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Sample records for bone regeneration

  1. Bone regeneration in dentistry

    OpenAIRE

    Tonelli, Paolo; Duvina, Marco; Barbato, Luigi; Biondi, Eleonora; Nuti, Niccolò; Brancato, Leila; Rose, Giovanna Delle

    2011-01-01

    The edentulism of the jaws and the periodontal disease represent conditions that frequently leads to disruption of the alveolar bone. The loss of the tooth and of its bone of support lead to the creation of crestal defects or situation of maxillary atrophy. The restoration of a functional condition involves the use of endosseous implants who require adequate bone volume, to deal with the masticatory load. In such situations the bone need to be regenerated, taking advantage of the biological p...

  2. Nanocomposites and bone regeneration

    Science.gov (United States)

    James, Roshan; Deng, Meng; Laurencin, Cato T.; Kumbar, Sangamesh G.

    2011-12-01

    This manuscript focuses on bone repair/regeneration using tissue engineering strategies, and highlights nanobiotechnology developments leading to novel nanocomposite systems. About 6.5 million fractures occur annually in USA, and about 550,000 of these individual cases required the application of a bone graft. Autogenous and allogenous bone have been most widely used for bone graft based therapies; however, there are significant problems such as donor shortage and risk of infection. Alternatives using synthetic and natural biomaterials have been developed, and some are commercially available for clinical applications requiring bone grafts. However, it remains a great challenge to design an ideal synthetic graft that very closely mimics the bone tissue structurally, and can modulate the desired function in osteoblast and progenitor cell populations. Nanobiomaterials, specifically nanocomposites composed of hydroxyapatite (HA) and/or collagen are extremely promising graft substitutes. The biocomposites can be fabricated to mimic the material composition of native bone tissue, and additionally, when using nano-HA (reduced grain size), one mimics the structural arrangement of native bone. A good understanding of bone biology and structure is critical to development of bone mimicking graft substitutes. HA and collagen exhibit excellent osteoconductive properties which can further modulate the regenerative/healing process following fracture injury. Combining with other polymeric biomaterials will reinforce the mechanical properties thus making the novel nano-HA based composites comparable to human bone. We report on recent studies using nanocomposites that have been fabricated as particles and nanofibers for regeneration of segmental bone defects. The research in nanocomposites, highlight a pivotal role in the future development of an ideal orthopaedic implant device, however further significant advancements are necessary to achieve clinical use.

  3. Bone morphogenetic proteins: Periodontal regeneration

    Directory of Open Access Journals (Sweden)

    Subramaniam M Rao

    2013-01-01

    Full Text Available Periodontitis is an infectious inflammatory disease that results in attachment loss and bone loss. Regeneration of the periodontal tissues entails de novo formation of cementum, periodontal ligament, and alveolar bone. Several different approaches are currently being explored to achieve complete, reliable, and reproducible regeneration of periodontal tissues. The therapeutic management of new bone formation is one of the key issues in successful periodontal regeneration. Bone morphogenetic proteins form a unique group of proteins within the transforming growth factor superfamily of genes and have a vital role in the regulation in the bone induction and maintenance. The activity of bone morphogenetic proteins was first identified in the 1960s, but the proteins responsible for bone induction were unknown until the purification and cloning of human bone morphogenetic proteins in the 1980s, because of their osteoinductive potential. Bone morphogenetic proteins have gained a lot of interest as therapeutic agents for treating periodontal defects. A systematic search for data related to the use of bone morphogenetic proteins for the regeneration of periodontal defects was performed to recognize studies on animals and human (PUBMED, MEDLINE, COCHRANE, and Google search. All the studies included showed noticeable regeneration of periodontal tissues with the use of BMP.

  4. Bone Regeneration in Odontostomatology

    OpenAIRE

    Tonelli, P; Duvina, M.; Brancato, L.; Delle Rose, G.; Biondi, E.; Civitelli, V.

    2010-01-01

    Maxillary edentulism, together with periodontal disease, is the condition that most frequently induces disruption of alveolar bone tissue. Indeed, the stimulus of the periodontal ligament is lost and the local bone tissue becomes subject to resorption processes that, in the six months following the loss of the tooth, result in alveolar defects or more extensive maxillary atrophy. In both cases, loss of vestibular cortical bone is followed by reduction in the vertical dimension of the alveolar...

  5. Molecular mechanism of bone formation and regeneration

    Institute of Scientific and Technical Information of China (English)

    Akira Yamaguchi

    2008-01-01

    @@ Bone formation and regeneration are mediated by the coordinate action of various factors. Among these, bone morphogenetic protein (BMP) and runt-related gene 2 (Runx2) play crucial roles in bone formation.

  6. Bone regeneration and stem cells

    DEFF Research Database (Denmark)

    Arvidson, K; Abdallah, B M; Applegate, L A;

    2011-01-01

    This invited review covers research areas of central importance for orthopedic and maxillofacial bone tissue repair, including normal fracture healing and healing problems, biomaterial scaffolds for tissue engineering, mesenchymal and fetal stem cells, effects of sex steroids on mesenchymal stem...... cells, use of platelet rich plasma for tissue repair, osteogenesis and its molecular markers. A variety of cells in addition to stem cells, as well as advances in materials science to meet specific requirements for bone and soft tissue regeneration by addition of bioactive molecules, are discussed....

  7. Circadian Gene Networks In Bone Regeneration

    OpenAIRE

    Hassan, Nathaniel

    2012-01-01

    BACKGROUND: Previous studies suggested that vitamin D played a significant role in bone regeneration, facilitating the establishment of implant osseointegration. A whole genome microarray study further suggested that the vitamin D axis might involve circadian rhythm gene expression in the bone peripheral tissue.OBJECTIVES: To identify key gene networks involved with vitamin D receptor in the bone regeneration process and to explore any correlation with circadian rhythm gene expression in bone...

  8. Regenerate augmentation with bone marrow concentrate after traumatic bone loss

    OpenAIRE

    Jan Gessmann; Manfred Köller; Holger Godry; Thomas Armin Schildhauer; Dominik Seybold

    2012-01-01

    Distraction osteogenesis after post-traumatic segmental bone loss of the tibia is a complex and time-consuming procedure that is often complicated due to prolonged consolidation or complete insufficiency of the regenerate. The aim of this feasibility study was to investigate the potential of bone marrow aspiration concentrate (BMAC) for percutaneous regenerate augmentation to accelerate bony consolidation of the regenerate. Eight patients (age 22-64) with an average posttraumatic bone defect ...

  9. Bone Regeneration Using Bone Morphogenetic Proteins and Various Biomaterial Carriers

    Directory of Open Access Journals (Sweden)

    Zeeshan Sheikh

    2015-04-01

    Full Text Available Trauma and disease frequently result in fractures or critical sized bone defects and their management at times necessitates bone grafting. The process of bone healing or regeneration involves intricate network of molecules including bone morphogenetic proteins (BMPs. BMPs belong to a larger superfamily of proteins and are very promising and intensively studied for in the enhancement of bone healing. More than 20 types of BMPs have been identified but only a subset of BMPs can induce de novo bone formation. Many research groups have shown that BMPs can induce differentiation of mesenchymal stem cells and stem cells into osteogenic cells which are capable of producing bone. This review introduces BMPs and discusses current advances in preclinical and clinical application of utilizing various biomaterial carriers for local delivery of BMPs to enhance bone regeneration.

  10. Carbon nanohorns accelerate bone regeneration in rat calvarial bone defect

    Energy Technology Data Exchange (ETDEWEB)

    Kasai, Takao; Iizuka, Tadashi; Kanamori, Takeshi; Yokoyama, Atsuro [Department of Oral Functional Prosthodontics, Division of Oral Functional Science, Graduate School of Dental Medicine, Hokkaido University, Kita 13, Nishi 7, Kita-ku, Sapporo, Hokkaido 060-8586 (Japan); Matsumura, Sachiko; Shiba, Kiyotaka [Division of Protein Engineering, Cancer Institute, Japanese Foundation for Cancer Research, 3-8-31, Ariake, koutou-ku, Tokyo 135-8550 (Japan); Yudasaka, Masako; Iijima, Sumio, E-mail: tkasai@den.hokudai.ac.jp [Nanotube Research Center, National Institute of Advanced Industrial Science and Technology, Central 5, 1-1-1, Higashi, Tsukuba, Ibaraki 305-8565 (Japan)

    2011-02-11

    A recent study showed that carbon nanohorns (CNHs) have biocompatibility and possible medical uses such as in drug delivery systems. It was reported that some kinds of carbon nanomaterials such as carbon nanotubes were useful for bone formation. However, the effect of CNHs on bone tissue has not been clarified. The purpose of this study was to evaluate the effect of CNHs on bone regeneration and their possible application for guided bone regeneration (GBR). CNHs dispersed in ethanol were fixed on a porous polytetrafluoroethylene membrane by vacuum filtration. Cranial defects were created in rats and covered by a membrane with/without CNHs. At two weeks, bone formation under the membrane with CNHs had progressed more than under that without CNHs and numerous macrophages were observed attached to CNHs. At eight weeks, there was no significant difference in the amount of newly formed bone between the groups and the appearance of macrophages was decreased compared with that at two weeks. Newly formed bone attached to some CNHs directly. These results suggest that macrophages induced by CNHs are related to bone regeneration. In conclusion, the present study indicates that CNHs are compatible with bone tissue and effective as a material for GBR.

  11. Regenerate augmentation with bone marrow concentrate after traumatic bone loss

    Directory of Open Access Journals (Sweden)

    Jan Gessmann

    2012-03-01

    Full Text Available Distraction osteogenesis after post-traumatic segmental bone loss of the tibia is a complex and time-consuming procedure that is often complicated due to prolonged consolidation or complete insufficiency of the regenerate. The aim of this feasibility study was to investigate the potential of bone marrow aspiration concentrate (BMAC for percutaneous regenerate augmentation to accelerate bony consolidation of the regenerate. Eight patients (age 22-64 with an average posttraumatic bone defect of 82.4 mm and concomitant risk factors (nicotine abuse, soft-tissue defects, obesity and/or circulatory disorders were treated with a modified Ilizarov external frame using an intramedullary cable transportation system. At the end of the distraction phase, each patient was treated with a percutaneously injection of autologous BMAC into the centre of the regenerate. The concentration factor was analysed using flow cytometry. The mean follow up after frame removal was 10 (4-15 months. With a mean healing index (HI of 36.9 d/cm, bony consolidation of the regenerate was achieved in all eight cases. The mean concentration factor of the bone marrow aspirate was 4.6 (SD 1.23. No further operations concerning the regenerate were needed and no adverse effects were observed with the BMAC procedure. This procedure can be used for augmentation of the regenerate in cases of segmental bone transport. Further studies with a larger number of patients and control groups are needed to evaluate a possible higher success rate and accelerating effects on regenerate healing.

  12. Effortless effort in bone regeneration: a review.

    Science.gov (United States)

    Nazirkar, Girish; Singh, Shailendra; Dole, Vinaykumar; Nikam, Akhilesh

    2014-06-01

    Since the beginning of the 20th century, the concept of osteoconduction in bony changes in the oral cavity showed a wide range of biomaterials and their osteoinductive potential that emerged gradually and has to a large extent improved the quality of the bone prior to the placement of an implant. Alveolar bone loss is a major concern after tooth extraction in patients and therefore atraumatic extraction procedures should be followed to avoid further bone loss. To overcome the alveolar bone loss and to augment support for placing dental implants, many bone regenerative substitutes are available such as allografts, autografts, xenografts, synthetic biomaterials and osteoactive agents. In light of the steady progress in bone grafting techniques and graft materials, it has become possible to improve the volume, width, and height of bone in deficient areas of the oral cavity. These advances in regenerative dentistry thus facilitate an easy and convenient placement of an implant in an ideal position and angulations resulting in superior esthetics and function. Bone grafting materials and their substitutes are the alternative filler materials, which facilitate to reduce additional surgical procedures, risks, chances of cross infection involved in placing autografts and allografts into the bony structures. This review literature highlights various biomaterials that are helpful in bone healing and thus create an anatomically favorable base for ideal implant placement. How to cite the article: Nazirkar G, Singh S, Dole V, Nikam A. Effortless effort in bone regeneration: A review. J Int Oral Health 2014;6(3):120-4. PMID:25083047

  13. Bone Adaptation and Regeneration - New Developments

    Science.gov (United States)

    Klein-Nulend, Jenneke; Bacabac, Rommel Gaud

    osteocytes sensing different canalicular flow patterns around cutting cone and reversal zone during loading, thus determining the bone's structure. Disturbances in architecture and permeability of the 3D porous network will affect transduction of mechanical loads to the mechanosensors. Uncovering the cellular and mechanical basis of the osteocyte's response to loading represents a significant challenge to our understanding of cellular mechanotransduction and bone remodeling. In view of the importance of mechanical stress for maintaining bone strength, mechanical stimuli have great potential for providing a therapeutic approach for bone (re)generation.

  14. Bone Regeneration Mediated by Biomimetic Mineralization of a Nanofiber Matrix

    OpenAIRE

    Mata, Alvaro; Geng, Yanbiao; Henrikson, Karl; Aparicio, Conrado; Stock, Stuart; Satcher, Robert L.; Stupp, Samuel I.

    2010-01-01

    Rapid bone regeneration within a three-dimensional defect without the use of bone grafts, exogenous growth factors, or cells remains a major challenge. We report here on the use of self-assembling peptide nanostructured gels to promote bone regeneration that have the capacity to mineralize in biomimetic fashion. The main molecular design was the use of phosphoserine residues in the sequence of a peptide amphiphile known to nucleate hydroxyapatite crystals on the surfaces of nanofibers. We tes...

  15. Effect of Polycaprolactone Scaffold Permeability on Bone Regeneration In Vivo

    OpenAIRE

    Mitsak, Anna G.; Kemppainen, Jessica M.; Harris, Matthew T.; Hollister, Scott J

    2011-01-01

    Successful bone tissue engineering depends on the scaffold's ability to allow nutrient diffusion to and waste removal from the regeneration site, as well as provide an appropriate mechanical environment. Since bone is highly vascularized, scaffolds that provide greater mass transport may support increased bone regeneration. Permeability encompasses the salient features of three-dimensional porous scaffold architecture effects on scaffold mass transport. We hypothesized that higher permeabilit...

  16. Biomaterials for orthopaedic implants and bone regeneration

    Science.gov (United States)

    Sargeant, Timothy David

    For bone regeneration, there is need for biodegradable, synthetic scaffolds that direct the formation of de novo mineralized tissue. Orthopaedic implants additionally require mechanical function. The work described herein attempts to address both of these needs. The general strategy involves integrating molecularly designed tissue engineering scaffolds with porous metallic foams to create hybrid materials to direct cellular behavior. Peptide amphiphiles (PAs) that self-assemble into nanofibers were designed to template hydroxyapatite mineral under biological conditions. The molecular design incorporated either serine (S) or phosphoserine S(P) and was mixed with RGDS-bearing PA to evaluate of the key parameters for mineral formation. This led to the discovery of nanoscale hydroxyapatite spheres templated on both S- and S(P)-bearing PA nanofibers. Stem cells were encapsulated in these gels and RT-PCR showed osteoblastic differentiation in all samples. Osteoblast maturation was increased in S-bearing PA compared to S(P)-bearing PA, although the reason is not yet understood. A method to create robust PA nanofiber coatings on NiTi was developed by optimizing the NiTi oxide surface chemistry, optimizing silane vapor deposition, and covalently attaching the PAs to the silanized substrate. The surfaces were characterized by XPS, SIMS, AFM, and fluorimetry. In vitro experiments demonstrated the importance of covalent attachment for cellular adhesion and proved the materials were not cytotoxic. Orthopaedic hybrid materials were created by triggering PA self-assembly within the interconnected pores of Ti foams developed by the Dunand research group. In vitro experiments demonstrate that pre-osteoblasts adhere to, proliferate on, and migrate into PA-Ti hybrids made with S(P)- and RGDS-bearing PA mixtures. The cells differentiate into mature osteoblasts and remain viable up to 28 days. In vivo studies using a rat model demonstrate osteointegration and boney ingrowth into bare

  17. In vivo bone regeneration using a novel porous bioactive composite

    Energy Technology Data Exchange (ETDEWEB)

    Xie En [Department of Orthopaedics and Traumatology, Xijing Hospital, Fourth Military Medical University, Xi' an (China); Hu Yunyu [Department of Orthopaedics and Traumatology, Xijing Hospital, Fourth Military Medical University, Xi' an (China)], E-mail: orth1@fmmn.edu.cn; Chen Xiaofeng [College of Materials Science and Engineering, South China University of Technology University, Guangzhou (China); Bai Xuedong; Li Dan [Department of Orthopaedics and Traumatology, Xijing Hospital, Fourth Military Medical University, Xi' an (China); Ren Li [College of Materials Science and Engineering, South China University of Technology University, Guangzhou (China); Zhang Ziru [Foreign Languages School, Northwest University Xi' an (China)

    2008-11-15

    Many commercial bone graft substitutes (BGS) and experimental bone tissue engineering scaffolds have been developed for bone repair and regeneration. This study reports the in vivo bone regeneration using a newly developed porous bioactive and resorbable composite that is composed of bioactive glass (BG), collagen (COL), hyaluronic acid (HYA) and phosphatidylserine (PS), BG-COL-HYA-PS. The composite was prepared by a combination of sol-gel and freeze-drying methods. A rabbit radius defect model was used to evaluate bone regeneration at time points of 2, 4 and 8 weeks. Techniques including radiography, histology, and micro-CT were applied to characterize the new bone formation. 8 weeks results showed that (1) nearly complete bone regeneration was achieved for the BG-COL-HYA-PS composite that was combined with a bovine bone morphogenetic protein (BMP); (2) partial bone regeneration was achieved for the BG-COL-HYA-PS composites alone; and (3) control remained empty. This study demonstrated that the novel BG-COL-HYA-PS, with or without the grafting of BMP incorporation, is a promising BGS or a tissue engineering scaffold for non-load bearing orthopaedic applications.

  18. Monitoring of bone regeneration process by means of texture analysis

    International Nuclear Information System (INIS)

    An image analysis method is proposed for the monitoring of the regeneration of the tibial bone. For this purpose, 130 digitized radiographs of 13 patients, who had undergone tibial lengthening by the Ilizarov method, were studied. For each patient, 10 radiographs, taken at an equal number of postoperative successive time moments, were available. Employing available software, 3 Regions Of Interest (ROIs), corresponding to the: (a) upper, (b) central, and (c) lower aspect of the gap, where bone regeneration was expected to occur, were determined on each radiograph. Employing custom developed algorithms: (i) a number of textural features were generated from each of the ROIs, and (ii) a texture-feature based regression model was designed for the quantitative monitoring of the bone regeneration process. Statistically significant differences (p 2 = 0.9, p < 0.001). The suggested method may contribute to the monitoring of the tibial bone regeneration process.

  19. Demineralized Bone Matrix Injection in Consolidation Phase Enhances Bone Regeneration in Distraction Osteogenesis via Endochondral Bone Formation

    OpenAIRE

    Kim, Ji-Beom; Lee, Dong Yeon; Seo, Sang Gyo; Kim, Eo Jin; Kim, Ji Hye; Yoo, Won Joon; Cho, Tae-Joon; Choi, In Ho

    2015-01-01

    Background Distraction osteogenesis (DO) is a promising tool for bone and tissue regeneration. However, prolonged healing time remains a major problem. Various materials including cells, cytokines, and growth factors have been used in an attempt to enhance bone formation. We examined the effect of percutaneous injection of demineralized bone matrix (DBM) during the consolidation phase on bone regeneration after distraction. Methods The immature rabbit tibial DO model (20 mm length-gain) was u...

  20. Vascularization of bone regeneration products in acute radiation sickness

    International Nuclear Information System (INIS)

    In 119 rabbits with acute radiation sickness the vascularization process in bone regeneration products was studied by microangiography. The formation of arteries and of bone structures was retarded in irradiated animals. The deficient formation of veins and capillaries did not cause conditions for venous blood circulation and resulted in a slow resorption of newly formed bone structures and gristle. That is one of the reasons for an extended healing process of fractures and for formation of false articulations in irradiated animals. (author)

  1. Biomechanical characteristics of regenerated cortical bone in the canine mandible

    OpenAIRE

    Zapata, Uriel; Opperman, Lynne A.; Kontogiorgos, Elias; Elsalanty, Mohammed E.; Dechow, Paul C.

    2011-01-01

    To test the mechanical properties of regenerate cortical bone created using Mandibular Bone Transport (MBT) distraction, five adult male American foxhound dogs underwent unilateral distraction of the mandible with a novel MBT device placed to linearly repair a 30-35 mm bone defect. The animals were sacrificed 12 weeks after the beginning of the consolidation period. Fourteen cylindrical specimens were taken from the inner (lingual) and outer (buccal) plates of the reconstructed mandible and 2...

  2. Adverse Effects of Hyperlipidemia on Bone Regeneration and Strength

    OpenAIRE

    Pirih, F; J. Lu; Ye, F; Bezouglaia, O.; Atti, E.; Ascenzi, MG; Tetradis, S; Demer, LL; Aghaloo, T; Tintut, Y

    2012-01-01

    Hyperlipidemia increases the risk for generation of lipid oxidation products, which accumulate in the subendothelial spaces of vasculature and bone. Atherogenic high-fat diets increase serum levels of oxidized lipids, which are known to attenuate osteogenesis in culture and to promote bone loss in mice. In this study, we investigated whether oxidized lipids affect bone regeneration and mechanical strength. Wild type and hyperlipidemic (Ldlr−/−) mice were placed on a high-fat (HF) diet for 13 ...

  3. Recent advances in bone regeneration using adult stemcells

    Institute of Scientific and Technical Information of China (English)

    Hadar Zigdon-Giladi; Utai Rudich; Gal Michaeli Geller; Ayelet Evron

    2015-01-01

    Bone is a highly vascularized tissue reliant on theclose spatial and temporal association between bloodvessels and bone cells. Therefore, cells that participatein vasculogenesis and osteogenesis play a pivotalrole in bone formation during prenatal and postnatalperiods. Nevertheless, spontaneous healing of bonefracture is occasionally impaired due to insufficientblood and cellular supply to the site of injury. In thesecases, bone regeneration process is interrupted, whichmight result in delayed union or even nonunion ofthe fracture. Nonunion fracture is difficult to treatand have a high financial impact. In the last decade,numerous technological advancements in bone tissueengineering and cell-therapy opened new horizon inthe field of bone regeneration. This review starts withpresentation of the biological processes involved inbone development, bone remodeling, fracture healingprocess and the microenvironment at bone healingsites. Then, we discuss the rationale for using adultstem cells and listed the characteristics of the availablecells for bone regeneration. The mechanism of actionand epigenetic regulations for osteogenic differentiationare also described. Finally, we review the literature fortranslational and clinical trials that investigated the useof adult stem cells (mesenchymal stem cells, endothelialprogenitor cells and CD34+ blood progenitors) for boneregeneration.

  4. Bone marrow-derived cell regulation of skeletal muscle regeneration

    OpenAIRE

    Sun, Dongxu; Martinez, Carlo O.; OCHOA, OSCAR; Ruiz-Willhite, Lourdes; Bonilla, Jose R.; Centonze, Victoria E.; Waite, Lindsay L.; Joel E. Michalek; McManus, Linda M.; Shireman, Paula K.

    2009-01-01

    Limb regeneration requires the coordination of multiple stem cell populations to recapitulate the process of tissue formation. Therefore, bone marrow (BM) -derived cell regulation of skeletal muscle regeneration was examined in mice lacking the CC chemokine receptor 2 (CCR2). Myofiber size, numbers of myogenic progenitor cells (MPCs), and recruitment of BM-derived cells and macrophages were assessed after cardiotoxin-induced injury of chimeric mice produced by transplanting BM from wild-type ...

  5. A tissue regeneration approach to bone and cartilage repair

    CERN Document Server

    Dunstan, Colin; Rosen, Vicki

    2015-01-01

    Reviewing exhaustively the current state of the art of tissue engineering strategies for regenerating bones and joints through the use of biomaterials, growth factors and stem cells, along with an investigation of the interactions between biomaterials, bone cells, growth factors and added stem cells and how together skeletal tissues can be optimised, this book serves to highlight the importance of biomaterials composition, surface topography, architectural and mechanical properties in providing support for tissue regeneration. Maximizing reader insights into the importance of the interplay of these attributes with bone cells (osteoblasts, osteocytes and osteoclasts) and cartilage cells (chondrocytes), this book also provides a detailed reference as to how key signalling pathways are activated. The contribution of growth factors to drive tissue regeneration and stem cell recruitment is discussed along with a review the potential and challenges of adult or embryonic mesenchymal stem cells to further enhance the...

  6. Tracheal cartilage regeneration and new bone formation by slow release of bone morphogenetic protein (BMP)-2.

    Science.gov (United States)

    Igai, Hitoshi; Chang, Sung Soo; Gotoh, Masashi; Yamamoto, Yasumichi; Yamamoto, Masaya; Tabata, Yasuhiko; Yokomise, Hiroyasu

    2008-01-01

    We investigated the efficiency of bone morphogenetic protein (BMP)-2 released slowly from gelatin sponge for tracheal cartilage regeneration. A 1-cm gap was made in the mid-ventral portion of each of 10 consecutive tracheal cartilages. In the control group (n = 4), the resulting gap was left untreated. In the gelatin group (n = 4), plain gelatin was implanted in the gap. In the BMP-2 group (n = 4), gelatin containing 100 microg BMP-2 was implanted. We euthanatized all dogs in each group at 1, 3, 6, and 12 months after the implantation, respectively, and then examined the implant site macro- and microscopically. In the BMP-2 group, regenerated fibrous cartilage and newly formed bone were observed at 1 and 12 months. Regenerated cartilage was observed at the ends of the host cartilage stumps, with newly formed bone in the middle portion. The gaps were filled with regenerated cartilage and newly formed bone. At 3 and 6 months, regenerated cartilage, but not newly formed bone, was evident. The regenerated cartilage was covered with perichondrium and showed continuity with the host cartilage. We succeeded in inducing cartilage regeneration and new bone formation in canine trachea by slow release of 100 microg BMP-2 from gelatin. PMID:18204324

  7. Three-Dimensional Evaluation of Mandibular Bone Regenerated By Bone Transport Distraction Osteogenesis

    OpenAIRE

    Kontogiorgos, Elias; Elsalanty, Mohammed E.; Zapata, Uriel; Zakhary, Ibrahim; Nagy, William W; Dechow, Paul C.; Opperman, Lynne A.

    2011-01-01

    The purpose of this study was to evaluate the structure and material properties of native mandibular bone and those of early regenerate bone, produced by bone transport distraction osteogenesis. Ten adult foxhounds were divided into two groups of five animals each. In all animals, a 3- to 4-cm defect was created on one side of the mandible. A bone transport reconstruction plate, consisting of a reconstruction plate with an attached intraoral transport unit, was utilized to stabilize the mandi...

  8. Mimicking the nanostructure of bone matrix to regenerate bone.

    Science.gov (United States)

    Kane, Robert; Ma1, Peter X

    2013-11-01

    Key features of bone tissue structure and composition are capable of directing cellular behavior towards the generation of new bone tissue. Bone tissue, as well as materials derived from bone, have a long and successful history of use as bone grafting materials. Recent developments in design and processing of synthetic scaffolding systems has allowed the replication of the bone's desirable biological activity in easy to fabricate polymeric materials with nano-scale features exposed on the surface. The biological response to these new tissue-engineering scaffold materials oftentimes exceeds that seen on scaffolds produced using biological materials. PMID:24688283

  9. Nanocomposite Membranes Enhance Bone Regeneration Through Restoring Physiological Electric Microenvironment.

    Science.gov (United States)

    Zhang, Xuehui; Zhang, Chenguang; Lin, Yuanhua; Hu, Penghao; Shen, Yang; Wang, Ke; Meng, Song; Chai, Yuan; Dai, Xiaohan; Liu, Xing; Liu, Yun; Mo, Xiaoju; Cao, Cen; Li, Shue; Deng, Xuliang; Chen, Lili

    2016-08-23

    Physiological electric potential is well-known for its indispensable role in maintaining bone volume and quality. Although implanted biomaterials simulating structural, morphological, mechanical, and chemical properties of natural tissue or organ has been introduced in the field of bone regeneration, the concept of restoring physiological electric microenvironment remains ignored in biomaterials design. In this work, a flexible nanocomposite membrane mimicking the endogenous electric potential is fabricated to explore its bone defect repair efficiency. BaTiO3 nanoparticles (BTO NPs) were first coated with polydopamine. Then the composite membranes are fabricated with homogeneous distribution of Dopa@BTO NPs in poly(vinylidene fluoridetrifluoroethylene) (P(VDF-TrFE)) matrix. The surface potential of the nanocomposite membranes could be tuned up to -76.8 mV by optimizing the composition ratio and corona poling treatment, which conform to the level of endogenous biopotential. Remarkably, the surface potential of polarized nanocomposite membranes exhibited a dramatic stability with more than half of original surface potential remained up to 12 weeks in the condition of bone defect. In vitro, the membranes encouraged bone marrow mesenchymal stem cells (BM-MSCs) activity and osteogenic differentiation. In vivo, the membranes sustainably maintained the electric microenvironment giving rise to rapid bone regeneration and complete mature bone-structure formation. Our findings evidence that physiological electric potential repair should be paid sufficient attention in biomaterials design, and this concept might provide an innovative and well-suited strategy for bone regenerative therapies. PMID:27389708

  10. Incomplete bone regeneration of rabbit calvarial defects using different membranes

    DEFF Research Database (Denmark)

    Aaboe, M; Pinholt, E M; Schou, S;

    1998-01-01

    The present study describes the use of a degradable and a non-degradable material for guided bone regeneration. Forty rabbits were divided into 5 groups. Bicortical defects 15 mm in diameter were prepared in rabbit calvaria. A titanium microplate was placed over the defect to prevent collapse of...

  11. Biophysical stimulation of bone fracture repair, regeneration and remodelling

    Directory of Open Access Journals (Sweden)

    Chao E. Y.S.

    2003-12-01

    Full Text Available Biophysical stimulation to enhance bone fracture repair and bone regenerate maturation to restore its structural strength must rely on both the biological and biomechanical principle according to the local tissue environment and the type of mechanical stress to be born by the skeletal joint system. This paper reviews the possible interactions between biophysical stimuli and cellular responses in healing bone fractures and proceeds to speculate the prospects and limitations of different experimental models in evaluating and optimising such non-invasive interventions. It is important to realize that bone fracture repair has several pathways with various combinations of bone formation mechanisms, but there may only be one bone remodeling principle regulated by the hypothesis proposed by Wolff. There are different mechanical and biophysical stimuli that could provide effective augmentation of fracture healing and bone regenerate maturation. The key requirements of establishing these positive interactions are to define the precise cellular response to the stimulation signal in an in vitro environment and to use well-established animal models to quantify and optimise the therapeutic regimen in a time-dependent manner. This can only be achieved through research collaboration among different disciplines using scientific methodologies. In addition, the specific forms of biophysical stimulation and its dose effect and application timing must be carefully determined and validated. Technological advances in achieving focalized stimulus delivery with adjustable signal type and intensity, in the ability to monitor healing callus mechanical property non-invasively, and in the establishment of a robust knowledgebase to develop effective and reliable treatment protocols are the essential pre-requisites to make biophysical stimulation acceptable in the main arena of health care. Finally, it is important to bear in mind that successful fracture repair or bone

  12. Mechanobiology of healing and regeneration of bone

    OpenAIRE

    Vetter, Andreas Christian

    2010-01-01

    Knochen ist ein multifunktionales Organ und zugleich ein biologisches Material. In dieser Arbeit wird der Heilungsverlauf eines Knochenbruchs (als biologisches Material) näher untersucht mit Hilfe von Computermodellen. Im menschlichen Körper kommt es nach einem Bruch zu einer vollständigen Regeneration des Knochens, ohne dass eine Narbe nach der Heilung zurückbleibt. In grob 10% der Frakturen kommt es jedoch zu Komplikationen bis zu einem Nicht-Heilen des Bruches. Das Ziel von intensiver inte...

  13. Bone marrow-derived cell regulation of skeletal muscle regeneration.

    Science.gov (United States)

    Sun, Dongxu; Martinez, Carlo O; Ochoa, Oscar; Ruiz-Willhite, Lourdes; Bonilla, Jose R; Centonze, Victoria E; Waite, Lindsay L; Michalek, Joel E; McManus, Linda M; Shireman, Paula K

    2009-02-01

    Limb regeneration requires the coordination of multiple stem cell populations to recapitulate the process of tissue formation. Therefore, bone marrow (BM) -derived cell regulation of skeletal muscle regeneration was examined in mice lacking the CC chemokine receptor 2 (CCR2). Myofiber size, numbers of myogenic progenitor cells (MPCs), and recruitment of BM-derived cells and macrophages were assessed after cardiotoxin-induced injury of chimeric mice produced by transplanting BM from wild-type (WT) or CCR2(-/-) mice into irradiated WT or CCR2(-/-) host mice. Regardless of the host genotype, muscle regeneration and recruitment of BM-derived cells and macrophages were similar in mice replenished with WT BM, whereas BM-derived cells and macrophage accumulation were decreased and muscle regeneration was impaired in all animals receiving CCR2(-/-) BM. Furthermore, numbers of MPCs (CD34(+)/Sca-1(-)/CD45(-) cells) were significantly increased in mice receiving CCR2(-/-) BM despite the decreased size of regenerated myofibers. Thus, the expression of CCR2 on BM-derived cells regulated macrophage recruitment into injured muscle, numbers of MPC, and the extent of regenerated myofiber size, all of which were independent of CCR2 expression on host-derived cells. Future studies in regenerative medicine must include consideration of the role of BM-derived cells, possibly macrophages, in CCR2-dependent events that regulate effective skeletal muscle regeneration. PMID:18827026

  14. Manufacture of degradable polymeric scaffolds for bone regeneration

    International Nuclear Information System (INIS)

    Many innovative technology platforms for promoting bone regeneration have been developed. A common theme among these is the use of scaffolds to provide mechanical support and osteoconduction. Scaffolds can be either ceramic or polymer-based, or composites of both classes of material. Both ceramics and polymers have their own merits and drawbacks, and a better solution may be to synergize the advantageous properties of both materials within composite scaffolds. In this current review, after a brief introduction of the anatomy and physiology of bone, different strategies of fabricating polymeric scaffolds for bone regeneration, including traditional and solid free-form fabrication, are critically discussed and compared, while focusing on the advantages and disadvantages of individual techniques. (topical review)

  15. Magnesium substitution in brushite cements for enhanced bone tissue regeneration

    Energy Technology Data Exchange (ETDEWEB)

    Cabrejos-Azama, Jatsue, E-mail: jacaza@farm.ucm.es [Departamento de Química-Física II, Facultad de Farmacia, UCM, Madrid (Spain); Departamento de Estomatología III, Facultad de Odontología UCM, Madrid (Spain); Alkhraisat, Mohammad Hamdan; Rueda, Carmen [Departamento de Química-Física II, Facultad de Farmacia, UCM, Madrid (Spain); Torres, Jesús [Facultad de Ciencias de la salud URJC, Alcorcón, Madrid (Spain); Blanco, Luis [Departamento de Estomatología III, Facultad de Odontología UCM, Madrid (Spain); López-Cabarcos, Enrique [Departamento de Química-Física II, Facultad de Farmacia, UCM, Madrid (Spain)

    2014-10-01

    We have synthesized calcium phosphate cements doped with different amounts of magnesium (Mg-CPC) with a twofold purpose: i) to evaluate in vitro the osteoblast cell response to this material, and ii) to compare the bone regeneration capacity of the doped material with a calcium cement prepared without magnesium (CPC). Cell proliferation and in vivo response increased in the Mg-CPCs in comparison with CPC. The Mg-CPCs have promoted higher new bone formation than the CPC (p < 0.05). The cytocompatibility and histomorfometric analysis performed in the rabbit calvaria showed that the incorporation of magnesium ions in CPC improves osteoblasts proliferation and provides higher new bone formation. The development of a bone substitute with controllable biodegradable properties and improved bone regeneration can be considered a step toward personalized therapy that can adapt to patient needs and clinical situations. - Highlights: • The Mg-CPCs promote higher new bone formation than the CPC. • The incorporation of magnesium ions in CPC improves osteoblasts proliferation. • Mg-CPC is a bone substitute with controllable biodegradable properties. • We suggest that the use of Mg ions could improve the clinical efficiency of CPCs.

  16. Magnesium substitution in brushite cements for enhanced bone tissue regeneration

    International Nuclear Information System (INIS)

    We have synthesized calcium phosphate cements doped with different amounts of magnesium (Mg-CPC) with a twofold purpose: i) to evaluate in vitro the osteoblast cell response to this material, and ii) to compare the bone regeneration capacity of the doped material with a calcium cement prepared without magnesium (CPC). Cell proliferation and in vivo response increased in the Mg-CPCs in comparison with CPC. The Mg-CPCs have promoted higher new bone formation than the CPC (p < 0.05). The cytocompatibility and histomorfometric analysis performed in the rabbit calvaria showed that the incorporation of magnesium ions in CPC improves osteoblasts proliferation and provides higher new bone formation. The development of a bone substitute with controllable biodegradable properties and improved bone regeneration can be considered a step toward personalized therapy that can adapt to patient needs and clinical situations. - Highlights: • The Mg-CPCs promote higher new bone formation than the CPC. • The incorporation of magnesium ions in CPC improves osteoblasts proliferation. • Mg-CPC is a bone substitute with controllable biodegradable properties. • We suggest that the use of Mg ions could improve the clinical efficiency of CPCs

  17. Nanotechnology in the targeted drug delivery for bone diseases and bone regeneration

    Directory of Open Access Journals (Sweden)

    Gu W

    2013-06-01

    Full Text Available Wenyi Gu,1,2 Chengtie Wu,3 Jiezhong Chen,1 Yin Xiao1 1Institute of Health and Biomedical Innovation, Queensland University of Technology, Brisbane, QLD, Australia; 2Australian Institute for Bioengineering and Nanotechnology, The University of Queensland, Brisbane, QLD, Australia; 3State Key Laboratory of High Performance Ceramics and Superfine Microstructure, Shanghai Institute of Ceramics, Chinese Academy of Sciences, Shanghai, People's Republic of China Abstract: Nanotechnology is a vigorous research area and one of its important applications is in biomedical sciences. Among biomedical applications, targeted drug delivery is one of the most extensively studied subjects. Nanostructured particles and scaffolds have been widely studied for increasing treatment efficacy and specificity of present treatment approaches. Similarly, this technique has been used for treating bone diseases including bone regeneration. In this review, we have summarized and highlighted the recent advancement of nanostructured particles and scaffolds for the treatment of cancer bone metastasis, osteosarcoma, bone infections and inflammatory diseases, osteoarthritis, as well as for bone regeneration. Nanoparticles used to deliver deoxyribonucleic acid and ribonucleic acid molecules to specific bone sites for gene therapies are also included. The investigation of the implications of nanoparticles in bone diseases have just begun, and has already shown some promising potential. Further studies have to be conducted, aimed specifically at assessing targeted delivery and bioactive scaffolds to further improve their efficacy before they can be used clinically. Keywords: nanoparticles, nanostructured scaffold, cancer bone metastasis, bone diseases, target drug delivery, bone regeneration

  18. Pullulan microcarriers for bone tissue regeneration.

    Science.gov (United States)

    Aydogdu, Hazal; Keskin, Dilek; Baran, Erkan Turker; Tezcaner, Aysen

    2016-06-01

    Microcarrier systems offer a convenient way to repair bone defects as injectable cell carriers that can be applied with small incisions owing to their small size and spherical shape. In this study, pullulan (PULL) microspheres were fabricated and characterized as cell carriers for bone tissue engineering applications. PULL was cross-linked by trisodium trimetaphosphate (STMP) to enhance the stability of the microspheres. Improved cytocompatibility was achieved by silk fibroin (SF) coating and biomimetic mineralization on the surface by incubating in simulated body fluid (SBF). X-ray diffraction (XRD), scanning electron microscopy (SEM) and fluorescent microscopy analysis confirmed biomimetic mineralization and SF coating on microspheres. The degradation analysis revealed that PULL microspheres had a slow degradation rate with 8% degradation in two weeks period indicating that the microspheres would support the formation of new bone tissue. Furthermore, the mechanical tests showed that the microspheres had a high mechanical stability that was significantly enhanced with the biomimetic mineralization. In vitro cell culture studies with SaOs-2 cells showed that cell viability was higher on SF and SBF coated microspheres on 7th day compared to PULL ones under dynamic conditions. Alkaline phosphatase activity was higher for SF coated microspheres in comparison to uncoated microspheres when dynamic culture condition was applied. The results suggest that both organic and inorganic surface modifications can be applied on PULL microspheres to prepare a biocompatible microcarrier system with suitable properties for bone tissue engineering. PMID:27040238

  19. Histomorphological evaluation of Compound bone of Granulated Ricinus in bone regeneration in rabbits

    International Nuclear Information System (INIS)

    Histological evaluation is an effective method in the behavioral description of the qualitative and quantitative implanted materials. The research validated the performance of Compound bone of Granulated Ricinus on bone regeneration with the histomorphological analysis results. Were selected 30 rabbits, females, divided into 3 groups of 10 animals (G1, G2, G3) with a postoperative time of 45, 70 and 120 days respectively. Each animal is undergone 2 bone lesions in the ilium, one implemented in the material: Compound bone of Granulated Ricinus and the other for control. After the euthanasia, the iliac bone was removed, identified and subjected to histological procedure. The evaluation histological, histomorphological results were interpreted and described by quantitative and qualitative analysis based facts verified in the three experimental groups evaluating the rate of absorption of the material in the tissue regeneration, based on the neo-bone formation. The histomorphologic results classified as a material biocompatible and biologically active. Action in regeneration by bone resorption occurs slowly and gradually. Knowing the time and rate of absorption and neo-formation bone biomaterial, which can be determined in the bone segment applicable in the clinical surgical area.

  20. Bone Regeneration from PLGA Micro-Nanoparticles

    Science.gov (United States)

    Ortega-Oller, Inmaculada; Padial-Molina, Miguel; Galindo-Moreno, Pablo; O'Valle, Francisco; Jódar-Reyes, Ana Belén; Peula-García, Jose Manuel

    2015-01-01

    Poly-lactic-co-glycolic acid (PLGA) is one of the most widely used synthetic polymers for development of delivery systems for drugs and therapeutic biomolecules and as component of tissue engineering applications. Its properties and versatility allow it to be a reference polymer in manufacturing of nano- and microparticles to encapsulate and deliver a wide variety of hydrophobic and hydrophilic molecules. It additionally facilitates and extends its use to encapsulate biomolecules such as proteins or nucleic acids that can be released in a controlled way. This review focuses on the use of nano/microparticles of PLGA as a delivery system of one of the most commonly used growth factors in bone tissue engineering, the bone morphogenetic protein 2 (BMP2). Thus, all the needed requirements to reach a controlled delivery of BMP2 using PLGA particles as a main component have been examined. The problems and solutions for the adequate development of this system with a great potential in cell differentiation and proliferation processes under a bone regenerative point of view are discussed. PMID:26509156

  1. Bone Regeneration from PLGA Micro-Nanoparticles

    Directory of Open Access Journals (Sweden)

    Inmaculada Ortega-Oller

    2015-01-01

    Full Text Available Poly-lactic-co-glycolic acid (PLGA is one of the most widely used synthetic polymers for development of delivery systems for drugs and therapeutic biomolecules and as component of tissue engineering applications. Its properties and versatility allow it to be a reference polymer in manufacturing of nano- and microparticles to encapsulate and deliver a wide variety of hydrophobic and hydrophilic molecules. It additionally facilitates and extends its use to encapsulate biomolecules such as proteins or nucleic acids that can be released in a controlled way. This review focuses on the use of nano/microparticles of PLGA as a delivery system of one of the most commonly used growth factors in bone tissue engineering, the bone morphogenetic protein 2 (BMP2. Thus, all the needed requirements to reach a controlled delivery of BMP2 using PLGA particles as a main component have been examined. The problems and solutions for the adequate development of this system with a great potential in cell differentiation and proliferation processes under a bone regenerative point of view are discussed.

  2. Bacterial Cellulose-Hydroxyapatite Nanocomposites for Bone Regeneration

    OpenAIRE

    Saska, S.; H.S. Barud; Gaspar, A. M. M.; Marchetto, R.; Ribeiro, S. J. L.; Y. Messaddeq

    2011-01-01

    The aim of this study was to develop and to evaluate the biological properties of bacterial cellulose-hydroxyapatite (BC-HA) nanocomposite membranes for bone regeneration. Nanocomposites were prepared from bacterial cellulose membranes sequentially incubated in solutions of CaCl2 followed by Na2HPO4. BC-HA membranes were evaluated in noncritical bone defects in rat tibiae at 1, 4, and 16 weeks. Thermogravimetric analyses showed that the amount of the mineral phase was 40%–50% of the total wei...

  3. Bacterial Cellulose-Hydroxyapatite Nanocomposites for Bone Regeneration

    Directory of Open Access Journals (Sweden)

    S. Saska

    2011-01-01

    Full Text Available The aim of this study was to develop and to evaluate the biological properties of bacterial cellulose-hydroxyapatite (BC-HA nanocomposite membranes for bone regeneration. Nanocomposites were prepared from bacterial cellulose membranes sequentially incubated in solutions of CaCl2 followed by Na2HPO4. BC-HA membranes were evaluated in noncritical bone defects in rat tibiae at 1, 4, and 16 weeks. Thermogravimetric analyses showed that the amount of the mineral phase was 40%–50% of the total weight. Spectroscopy, electronic microscopy/energy dispersive X-ray analyses, and X-ray diffraction showed formation of HA crystals on BC nanofibres. Low crystallinity HA crystals presented Ca/P a molar ratio of 1.5 (calcium-deficient HA, similar to physiological bone. Fourier transformed infrared spectroscopy analysis showed bands assigned to phosphate and carbonate ions. In vivo tests showed no inflammatory reaction after 1 week. After 4 weeks, defects were observed to be completely filled in by new bone tissue. The BC-HA membranes were effective for bone regeneration.

  4. Effect of rhBMP-2 Immobilized Anorganic Bovine Bone Matrix on Bone Regeneration

    OpenAIRE

    Jung-Bo Huh; June-Jip Yang; Kyung-Hee Choi; Ji Hyeon Bae; Jeong-Yeol Lee; Sung-Eun Kim; Sang-Wan Shin

    2015-01-01

    Anorganic bovine bone matrix (Bio-Oss®) has been used for a long time for bone graft regeneration, but has poor osteoinductive capability. The use of recombinant human bone morphogenetic protein-2 (rhBMP-2) has been suggested to overcome this limitation of Bio-Oss®. In the present study, heparin-mediated rhBMP-2 was combined with Bio-Oss® in animal experiments to investigate bone formation performance; heparin was used to control rhBMP-2 release. Two calvarial defects (8 mm diameter) were fo...

  5. Unbiased stereological methods used for the quantitative evaluation of guided bone regeneration

    DEFF Research Database (Denmark)

    Aaboe, Else Merete; Pinholt, E M; Schou, S;

    1998-01-01

    The present study describes the use of unbiased stereological methods for the quantitative evaluation of the amount of regenerated bone. Using the principle of guided bone regeneration the amount of regenerated bone after placement of degradable or non-degradable membranes covering defects in...... bicortically. Undecalcified sections were prepared for stereologic evaluation after an observation period of 8 weeks. Complete bone healing of the defects was not observed in any of the specimens. Unbiased stereologic estimates revealed 48% bone regeneration in defects covered by 2 ePTFE membranes, and 12% in...

  6. Hierarchically engineered fibrous scaffolds for bone regeneration

    Science.gov (United States)

    Sachot, Nadège; Castaño, Oscar; Mateos-Timoneda, Miguel A.; Engel, Elisabeth; Planell, Josep A.

    2013-01-01

    Surface properties of biomaterials play a major role in the governing of cell functionalities. It is well known that mechanical, chemical and nanotopographic cues, for example, influence cell proliferation and differentiation. Here, we present a novel coating protocol to produce hierarchically engineered fibrous scaffolds with tailorable surface characteristics, which mimic bone extracellular matrix. Based on the sol–gel method and a succession of surface treatments, hollow electrospun polylactic acid fibres were coated with a silicon–calcium–phosphate bioactive organic–inorganic glass. Compared with pure polymeric fibres that showed a completely smooth surface, the coated fibres exhibited a nanostructured topography and greater roughness. They also showed improved hydrophilic properties and a Young's modulus sixfold higher than non-coated ones, while remaining fully flexible and easy to handle. Rat mesenchymal stem cells cultured on these fibres showed great cellular spreading and interactions with the material. This protocol can be transferred to other structures and glasses, allowing the fabrication of various materials with well-defined features. This novel approach represents therefore a valuable improvement in the production of artificial matrices able to direct stem cell fate through physical and chemical interactions. PMID:23985738

  7. Histomorphometry of regenerated tibial bone tissue in rats of different age under violation of saltwater balance

    OpenAIRE

    Pogorelov M.V.

    2010-01-01

    Formation of regenerated bone tissue in rats of different age at normal conditions and at hyperhydration has beenstudied. It was revealed the features in composition of regenerated tissue at a different stages of bone repair process that dependson rat's age. The hypoosmolar hyperhydration cause disorders of regenerated tissue development and inhibit lamellarbone tissue formation. With the help of statistical methods it was shown the dependence of the age and hyperhydration degreeon regenerate...

  8. Histomorphometry of regenerated tibial bone tissue in rats of different age under violation of saltwater balance

    Directory of Open Access Journals (Sweden)

    Pogorelov M.V.

    2010-01-01

    Full Text Available Formation of regenerated bone tissue in rats of different age at normal conditions and at hyperhydration has beenstudied. It was revealed the features in composition of regenerated tissue at a different stages of bone repair process that dependson rat's age. The hypoosmolar hyperhydration cause disorders of regenerated tissue development and inhibit lamellarbone tissue formation. With the help of statistical methods it was shown the dependence of the age and hyperhydration degreeon regenerated tissue composition.

  9. Evaluation of Bone Regeneration on Polyhydroxyethyl-polymethyl Methacrylate Membrane in a Rabbit Calvarial Defect Model.

    Science.gov (United States)

    Kim, Somin; Hwang, Yawon; Kashif, Muhammad; Jeong, Dosun; Kim, Gonhyung

    This study was conducted to evaluate the capacity of guiding bone regeneration of polyhydroxyethyl-polymethyl methacrylate (PHEMA-PMMA) membrane as a guided tissue regeneration membrane for bone defects. Two 8-mm diameter transosseous round defects were made at the parietal bone of 18 New Zealand White rabbits. Defects were covered with or without PHEMA-PMMA membrane. Radiological and histological evaluation revealed that the bone tissue over the defect was more regenerated with time in both groups. However, there was significantly more bone regeneration at 8 weeks in the experimental group than the control group (p<0.05). There was no sign of membrane degradation or tissue inflammation and no invasion of muscle and fibrous tissue into defects. PHEMA-PMMA is a potential material for guided tissue regeneration membrane as it induces no adverse tissue reaction and effectively supports selective bone regeneration. PMID:27566076

  10. A biocomposite of collagen nanofibers and nanohydroxyapatite for bone regeneration

    International Nuclear Information System (INIS)

    This work aims to design a synthetic construct that mimics the natural bone extracellular matrix through innovative approaches based on simultaneous type I collagen electrospinning and nanophased hydroxyapatite (nanoHA) electrospraying using non-denaturating conditions and non-toxic reagents. The morphological results, assessed using scanning electron microscopy and atomic force microscopy (AFM), showed a mesh of collagen nanofibers embedded with crystals of HA with fiber diameters within the nanometer range (30 nm), thus significantly lower than those reported in the literature, over 200 nm. The mechanical properties, assessed by nanoindentation using AFM, exhibited elastic moduli between 0.3 and 2 GPa. Fourier transformed infrared spectrometry confirmed the collagenous integrity as well as the presence of nanoHA in the composite. The network architecture allows cell access to both collagen nanofibers and HA crystals as in the natural bone environment. The inclusion of nanoHA agglomerates by electrospraying in type I collagen nanofibers improved the adhesion and metabolic activity of MC3T3-E1 osteoblasts. This new nanostructured collagen–nanoHA composite holds great potential for healing bone defects or as a functional membrane for guided bone tissue regeneration and in treating bone diseases. (paper)

  11. Effect of rhBMP-2 Immobilized Anorganic Bovine Bone Matrix on Bone Regeneration

    Directory of Open Access Journals (Sweden)

    Jung-Bo Huh

    2015-07-01

    Full Text Available Anorganic bovine bone matrix (Bio-Oss® has been used for a long time for bone graft regeneration, but has poor osteoinductive capability. The use of recombinant human bone morphogenetic protein-2 (rhBMP-2 has been suggested to overcome this limitation of Bio-Oss®. In the present study, heparin-mediated rhBMP-2 was combined with Bio-Oss® in animal experiments to investigate bone formation performance; heparin was used to control rhBMP-2 release. Two calvarial defects (8 mm diameter were formed in a white rabbit model and then implanted or not (controls with Bio-Oss® or BMP-2/Bio-Oss®. The Bio-Oss® and BMP-2/Bio-Oss® groups had significantly greater new bone areas (expressed as percentages of augmented areas than the non-implanted controls at four and eight weeks after surgery, and the BMP-2/Bio-Oss® group (16.50 ± 2.87 (n = 6 had significantly greater new bone areas than the Bio-Oss® group (9.43 ± 3.73 (n = 6 at four weeks. These findings suggest that rhBMP-2 treated heparinized Bio-Oss® markedly enhances bone regeneration.

  12. Effect of rhBMP-2 Immobilized Anorganic Bovine Bone Matrix on Bone Regeneration.

    Science.gov (United States)

    Huh, Jung-Bo; Yang, June-Jip; Choi, Kyung-Hee; Bae, Ji Hyeon; Lee, Jeong-Yeol; Kim, Sung-Eun; Shin, Sang-Wan

    2015-01-01

    Anorganic bovine bone matrix (Bio-Oss®) has been used for a long time for bone graft regeneration, but has poor osteoinductive capability. The use of recombinant human bone morphogenetic protein-2 (rhBMP-2) has been suggested to overcome this limitation of Bio-Oss®. In the present study, heparin-mediated rhBMP-2 was combined with Bio-Oss® in animal experiments to investigate bone formation performance; heparin was used to control rhBMP-2 release. Two calvarial defects (8 mm diameter) were formed in a white rabbit model and then implanted or not (controls) with Bio-Oss® or BMP-2/Bio-Oss®. The Bio-Oss® and BMP-2/Bio-Oss® groups had significantly greater new bone areas (expressed as percentages of augmented areas) than the non-implanted controls at four and eight weeks after surgery, and the BMP-2/Bio-Oss® group (16.50 ± 2.87 (n = 6)) had significantly greater new bone areas than the Bio-Oss® group (9.43 ± 3.73 (n = 6)) at four weeks. These findings suggest that rhBMP-2 treated heparinized Bio-Oss® markedly enhances bone regeneration. PMID:26184187

  13. REGENERATION OF ARTICULAR CARTILAGE UNDER THE IMPLANTATION OF BONE MATRIX

    Directory of Open Access Journals (Sweden)

    Yuri M. Iryanov, Nikolay A. Kiryanov, Olga V. Dyuriagina , Tatiana Yu. Karaseva, Evgenii A. Karasev

    2015-07-01

    Full Text Available Background: The damage or loss of articular cartilage is costly medical problem. The purpose of this work – morphological analysis of reparative chondrogenesis when implanted in the area of the knee joint cartilage of granulated mineralized bone matrix. Material and Methods: The characteristic features of the knee cartilage regeneration studied experimentally in pubertal Wistar rats after modeling a marginal perforated defect and implantation of granulated mineralized bone matrix obtained according to original technology without heat and demineralizing processing into the injury zone. Results: This biomaterial established to have pronounced chondro- and osteoinductive properties, and to provide prolonged activation of reparative process, accelerated organotypical remodeling and restoration of the articular cartilage injured. Conclusion: The data obtained demonstrate the efficacy of МВМ in clinical practice for the treatment of diseases and injuries of the articular cartilage.

  14. [The progress in application of parathyroid hormone in craniomaxillofacial bone regeneration study].

    Science.gov (United States)

    Chen, X Y; Tang, Z L

    2016-06-01

    Parathyroid hormone(PTH)is synthesized and secreted by chief cell of Gley's glands which possesses dual functions of catabolism and anabolism. It regulates the proliferation and differentiation of multiple cell lines including osteoblast, osteoclast and skeletal lining cells. Furthermore, PTH activates various signaling pathways which control calcium, phosphorous' metabolism and bone conversion, accelerating the bone regeneration and reconstruction. However, the study of PTH in craniomaxillofacial bone regeneration is relatively less and whether the role of parathyroid glands and the mechanism of ossification are consistent with the long bone or not needs further investigation. This review focuses on the progress of PTH in craniomaxillofacial bone regeneration in recent years. PMID:27256534

  15. Fibromodulin reprogrammed cells: A novel cell source for bone regeneration.

    Science.gov (United States)

    Li, Chen-Shuang; Yang, Pu; Ting, Kang; Aghaloo, Tara; Lee, Soonchul; Zhang, Yulong; Khalilinejad, Kambiz; Murphy, Maxwell C; Pan, Hsin Chuan; Zhang, Xinli; Wu, Benjamin; Zhou, Yan-Heng; Zhao, Zhihe; Zheng, Zhong; Soo, Chia

    2016-03-01

    Pluripotent or multipotent cell-based therapeutics are vital for skeletal reconstruction in non-healing critical-sized defects since the local endogenous progenitor cells are not often adequate to restore tissue continuity or function. However, currently available cell-based regenerative strategies are hindered by numerous obstacles including inadequate cell availability, painful and invasive cell-harvesting procedures, and tumorigenesis. Previously, we established a novel platform technology for inducing a quiescent stem cell-like stage using only a single extracellular proteoglycan, fibromodulin (FMOD), circumventing gene transduction. In this study, we further purified and significantly increased the reprogramming rate of the yield multipotent FMOD reprogrammed (FReP) cells. We also exposed the 'molecular blueprint' of FReP cell osteogenic differentiation by gene profiling. Radiographic analysis showed that implantation of FReP cells into a critical-sized SCID mouse calvarial defect, contributed to the robust osteogenic capability of FReP cells in a challenging clinically relevant traumatic scenario in vivo. The persistence, engraftment, and osteogenesis of transplanted FReP cells without tumorigenesis in vivo were confirmed by histological and immunohistochemical staining. Taken together, we have provided an extended potency, safety, and molecular profile of FReP cell-based bone regeneration. Therefore, FReP cells present a high potential for cellular and gene therapy products for bone regeneration. PMID:26774565

  16. Efficacy of Honeycomb TCP-induced Microenvironment on Bone Tissue Regeneration in Craniofacial Area

    Science.gov (United States)

    Watanabe, Satoko; Takabatake, Kiyofumi; Tsujigiwa, Hidetsugu; Watanabe, Toshiyuki; Tokuyama, Eijiro; Ito, Satoshi; Nagatsuka, Hitoshi; Kimata, Yoshihiro

    2016-01-01

    Artificial bone materials that exhibit high biocompatibility have been developed and are being widely used for bone tissue regeneration. However, there are no biomaterials that are minimally invasive and safe. In a previous study, we succeeded in developing honeycomb β-tricalcium phosphate (β-TCP) which has through-and-through holes and is able to mimic the bone microenvironment for bone tissue regeneration. In the present study, we investigated how the difference in hole-diameter of honeycomb β-TCP (hole-diameter: 75, 300, 500, and 1600 μm) influences bone tissue regeneration histologically. Its osteoconductivity was also evaluated by implantation into zygomatic bone defects in rats. The results showed that the maximum bone formation was observed on the β-TCP with hole-diameter 300μm, included bone marrow-like tissue and the pattern of bone tissue formation similar to host bone. Therefore, the results indicated that we could control bone tissue formation by creating a bone microenvironment provided by β-TCP. Also, in zygomatic bone defect model with honeycomb β-TCP, the result showed there was osseous union and the continuity was reproduced between the both edges of resected bone and β-TCP, which indicated the zygomatic bone reproduction fully succeeded. It is thus thought that honeycomb β-TCP may serve as an excellent biomaterial for bone tissue regeneration in the head, neck and face regions, expected in clinical applications. PMID:27279797

  17. Efficacy of Honeycomb TCP-induced Microenvironment on Bone Tissue Regeneration in Craniofacial Area.

    Science.gov (United States)

    Watanabe, Satoko; Takabatake, Kiyofumi; Tsujigiwa, Hidetsugu; Watanabe, Toshiyuki; Tokuyama, Eijiro; Ito, Satoshi; Nagatsuka, Hitoshi; Kimata, Yoshihiro

    2016-01-01

    Artificial bone materials that exhibit high biocompatibility have been developed and are being widely used for bone tissue regeneration. However, there are no biomaterials that are minimally invasive and safe. In a previous study, we succeeded in developing honeycomb β-tricalcium phosphate (β-TCP) which has through-and-through holes and is able to mimic the bone microenvironment for bone tissue regeneration. In the present study, we investigated how the difference in hole-diameter of honeycomb β-TCP (hole-diameter: 75, 300, 500, and 1600 μm) influences bone tissue regeneration histologically. Its osteoconductivity was also evaluated by implantation into zygomatic bone defects in rats. The results showed that the maximum bone formation was observed on the β-TCP with hole-diameter 300μm, included bone marrow-like tissue and the pattern of bone tissue formation similar to host bone. Therefore, the results indicated that we could control bone tissue formation by creating a bone microenvironment provided by β-TCP. Also, in zygomatic bone defect model with honeycomb β-TCP, the result showed there was osseous union and the continuity was reproduced between the both edges of resected bone and β-TCP, which indicated the zygomatic bone reproduction fully succeeded. It is thus thought that honeycomb β-TCP may serve as an excellent biomaterial for bone tissue regeneration in the head, neck and face regions, expected in clinical applications. PMID:27279797

  18. Use of osteoplastic material to guide bone tissue regeneration deffect.

    Science.gov (United States)

    Machavariani, A; Mazmishvili, K; Grdzelidze, T; Menabde, G; Amiranashvili, I

    2011-12-01

    The goal of research was study of restoration processes in jaw-teeth bone defects by application of osteoplastic materials in the experiment. The experiment was performed over 32 white (6-12 month old) rats; the animals were divided into 2 groups; 16 animals were enrolled in the first group; the section was performed in the edge of lower jaw; the lower jaw body was revealed. Under the effect of the dental drilling machine and the # 1 cooling mean by the fissure bohrium (distilled water) the defect of the dimension of 2x2 mm was created; the defect was washed by 0/9% saline to remove the bone sawdust; the wound was sutured tightly, in layers. The second group of the experiment was staffed with 16 animals (main group); the similar bone defect of the size 2 x 2mm was created on the rat's jaw's body. After washing of modeled defect we inserted osteopathic materials PORESORB-TCP crystals with the size of 0,6-1.0 mm the wound was sutured tightly, in layers. After the 3-rd, 15-th, 30-th and 90-th days from the date of operation there was performed X-ray and morphological examination over the animals in the control as well as the main group. The analysis of the examination performed over the experimental materials showed that in the control group in samples taken at 90th day the defects were not completely restored. In the test group in samples taken at 90th day reparative regeneration is confirmed. This is stimulated by the factor that within the main group's animals the defect regeneration process is supported with the osteoplastic material PORESORB-TCP. PMID:22306506

  19. The paradoxes in patterns and mechanism of bone marrow regeneration after irradiation. 1

    International Nuclear Information System (INIS)

    Bone marrow regeneration following irradiation has been largely studied as a dose-effect phenomenon, however, a large literature has simultaneously developed utilizing a wide variety of volumes, both in clinical studies and in experimental studies. Volume factors, more than dose, determine patterns of suppression and regeneration which have been documented by a variety of assay systems. Experimental evidence is presented which indicates that high dose irradiation to large volumes of bone marrow does not completely suppress bone marrow regeneration but results in a rapid compensatory response. Comparisons are made between the small and larger volumes at similar doses and indicate a greater overall compensatory response after the larger field irradiation, being more rapid in onset particularly after the 1000 rad dose. Although in-field regeneration of bone marrow occurs after single dose radiation to different volumes of bone marrow, experimental and clinical evidence from protracted conventional doses of irradiation to different volumes of bone marrow indicate significantly different response mechanisms. (Auth.)

  20. Bone Regeneration in Artificial Jaw Cleft by Use of Carbonated Hydroxyapatite Particles and Mesenchymal Stem Cells Derived from Iliac Bone

    Directory of Open Access Journals (Sweden)

    Motoko Yoshioka

    2012-01-01

    Full Text Available Objectives of the Study. Cleft lip and palate (CLP is a prevalent congenital anomaly in the orofacial region. Autogenous iliac bone grafting has been frequently employed for the closure of bone defects at the jaw cleft site. Since the related surgical procedures are quite invasive for patients, it is of great importance to develop a new less invasive technique. The aim of this study was to examine bone regeneration with mesenchyme stem cells (MSCs for the treatment of bone defect in artificially created jaw cleft in dogs. Materials and Methods. A bone defect was prepared bilaterally in the upper incisor regions of beagle dogs. MSCs derived from iliac bone marrow were cultured and transplanted with carbonated hydroxyapatite (CAP particles into the bone defect area. The bone regeneration was evaluated by standardized occlusal X-ray examination and histological observation. Results. Six months after the transplantation, perfect closure of the jaw cleft was achieved on the experimental side. The X-ray and histological examination revealed that the regenerated bone on the experimental side was almost equivalent to the original bone adjoining the jaw cleft. Conclusion. It was suggested that the application of MSCs with CAP particles can become a new treatment modality for bone regeneration for CLP patients.

  1. A novel in vivo platform for studying alveolar bone regeneration in rat

    OpenAIRE

    Kim, Joong-Hyun; Moon, Ho-Jin; Kim, Tae-Hyun; Jo, Jong-Min; Yang, Sung Hee; Naskar, Deboki; Kundu, Subhas C.; Chrzanowski, Wojciech; Kim, Hae-Won

    2013-01-01

    Alveolar bone regeneration is a significant challenge in dental implantation. Novel biomaterials and tissue-engineered constructs are under extensive development and awaiting in vivo animal tests to find clinical endpoint. Here, we establish a novel in vivo model, modifying gingivoperiosteoplasty in rat for the alveolar bone regeneration. Rat premaxillary bone defects were filled with silk scaffold or remained empty during the implantation period (up to 6 weeks), and harvested samples were an...

  2. Preparation and Characterization of an Advanced Medical Device for Bone Regeneration

    OpenAIRE

    Dorati, Rossella; Colonna, Claudia; Genta, Ida; Bruni, Giovanna; Visai, Livia; Conti, Bice

    2013-01-01

    Tridimensional scaffolds can promote bone regeneration as a framework supporting the migration of cells from the surrounding tissue into the damaged tissue and as delivery systems for the controlled or prolonged release of cells, genes, and growth factors. The goal of the work was to obtain an advanced medical device for bone regeneration through coating a decellularized and deproteinized bone matrix of bovine origin with a biodegradable, biocompatible polymer, to improve the cell engraftment...

  3. Effects of bovine lactoferrin in surgically created bone defects on bone regeneration around implants.

    Science.gov (United States)

    Görmez, Ulaş; Kürkcü, Mehmet; E Benlidayi, Mehmet; Ulubayram, Kezban; Sertdemir, Yaşar; Dağlioğlu, Kenan

    2015-03-01

    The aim of this experimental study was to evaluate the effect of bovine lactoferrin (bLF)-loaded gelatin microspheres (GM) used in combination with anorganic bovine bone on bone regeneration in surgically created bone defects around tooth implants. Twenty-four uniform bone defects were created in the frontal bone via an extraoral approach in 12 domestic pigs. Twenty-four implants were placed at the center of the defects. In eight animals one of these defects was filled with 0.3 mL anorganic bovine bone while the other was left empty. In four animals, all defects were filled with 3 mg/defect bLF-loaded GM and anorganic bovine bone. All the defects were covered with collagen membranes. All animals were sacrificed after 10 weeks of healing, and the implants with the surrounding bone defects were removed en bloc. Undecalcified sections were prepared for histomorphometric analysis. The mean total area of hard tissue was 26.9 ± 6.0% in the empty defect group, 31.8 ± 8.4% in the graft group, and 47.6 ± 5.0% in the lactoferrin group (P < 0.001). The mean area of newly formed bone was 26.9 ± 6.0% in the empty defect group, 22.4 ± 8.2% in the graft group, and 46.1 ± 5.1% in the lactoferrin group (P < 0.001). The mean residual graft area was 9.4 ± 3.2% in the graft group and 1.5 ± 0.6% in the lactoferrin group (P < 0.001). The mean proportion of bone-implant contact in the defect region was 21.9 ± 8.4% in the empty defect group, 26.9 ± 10.1% in the graft group and 29.9 ± 10.3% in the lactoferrin group (P = 0.143). These data indicate that a combination of 3 mg bLF-loaded GM and bovine-derived HA promotes bone regeneration in defects around implants. PMID:25807903

  4. Bone tissue regeneration indento-alveolar surgery : clinical and experimental studies on biomaterials and bone graft substitutes

    OpenAIRE

    Sahlin-Platt, Annika

    2011-01-01

    Pathological processes in the alveolar and facial bones can lead to bone loss that may not heal with complete regeneration. Biomaterials can be used to facilitate the healing process and/or as a bone substitute, but the mechanisms are not fully understood. Persistent leakage of bacteria/bacterial toxins, after root canal treatment, may lead to a residual bone defect. The healing is dependent on a placed dental biomaterial providing a tight seal. The composition of the filling material may als...

  5. Chitosan and alginate scaffolds for bone tissue regeneration.

    Science.gov (United States)

    Olmez, S S; Korkusuz, P; Bilgili, H; Senel, S

    2007-06-01

    Polymeric scaffold for tissue regeneration was developed for veterinary applications. Oxytetracycline hydrochloride (OTC), which is a widely used antibiotic in veterinary medicine was chosen as the model compound. Gel formulations using chitosan and alginate were prepared in distilled water or in 1% (v/v) acetic acid solution. Sponges were also prepared by a freeze-drying process. Tripolyphosphate was used for cross-linking. Viscosity was decreased in the presence of OTC in chitosan gels whereas no difference was found with alginate gels. All gels showed pseudoplastic behaviour. Water absorption capacity was highest with chitosan/alginate sponges. The solvent used for preparation of the chitosan gels was found to affect the release of OTC. The release of OTC from the sponges was increased by cross-linking. Chitosan/alginate sponges showed the slowest and lowest drug release among the developed sponge formulations in this study. The formulations were found to be biocompatible, inducing no adverse reaction in vivo on surgically formed bone defects of radius of rabbits. The level of organization of the remodelled new bone in the treatment groups was better than that of control. Incorporation of OTC into formulations did not show any considerable enhancing effect. PMID:17663189

  6. Controlling dynamic mechanical properties and degradation of composites for bone regeneration by means of filler content

    NARCIS (Netherlands)

    Barbieri, Davide; de Bruijn, Joost D.; Luo, Xiaoman; Fare, Silvia; Grijpma, Dirk W.; Yuan, Huipin

    2013-01-01

    Bone tissue is a dynamic composite system that adapts itself, in response to the surrounding daily (cyclic) mechanical stimuli, through an equilibrium between growth and resorption processes. When there is need of synthetic bone grafts, the biggest issue is to support bone regeneration without causi

  7. Imaging regenerating bone tissue based on neural networks applied to micro-diffraction measurements

    Energy Technology Data Exchange (ETDEWEB)

    Campi, G.; Pezzotti, G. [Institute of Crystallography, CNR, via Salaria Km 29.300, I-00015, Monterotondo Roma (Italy); Fratini, M. [Centro Fermi -Museo Storico della Fisica e Centro Studi e Ricerche ' Enrico Fermi' , Roma (Italy); Ricci, A. [Deutsches Elektronen-Synchrotron DESY, Notkestraße 85, D-22607 Hamburg (Germany); Burghammer, M. [European Synchrotron Radiation Facility, B. P. 220, F-38043 Grenoble Cedex (France); Cancedda, R.; Mastrogiacomo, M. [Istituto Nazionale per la Ricerca sul Cancro, and Dipartimento di Medicina Sperimentale dell' Università di Genova and AUO San Martino Istituto Nazionale per la Ricerca sul Cancro, Largo R. Benzi 10, 16132, Genova (Italy); Bukreeva, I.; Cedola, A. [Institute for Chemical and Physical Process, CNR, c/o Physics Dep. at Sapienza University, P-le A. Moro 5, 00185, Roma (Italy)

    2013-12-16

    We monitored bone regeneration in a tissue engineering approach. To visualize and understand the structural evolution, the samples have been measured by X-ray micro-diffraction. We find that bone tissue regeneration proceeds through a multi-step mechanism, each step providing a specific diffraction signal. The large amount of data have been classified according to their structure and associated to the process they came from combining Neural Networks algorithms with least square pattern analysis. In this way, we obtain spatial maps of the different components of the tissues visualizing the complex kinetic at the base of the bone regeneration.

  8. Bone marrow stromal cells with a combined expression of BMP-2 and VEGF-165 enhanced bone regeneration

    Energy Technology Data Exchange (ETDEWEB)

    Xiao Caiwen; Zhou Huifang; Fu Yao; Gu Ping; Fan Xianqun [Department of Ophthalmology, Shanghai Ninth People' s Hospital, Shanghai JiaoTong University School of Medicine, Shanghai 200011 (China); Liu Guangpeng [Key Laboratory of Tissue Engineering, Shanghai Ninth People' s Hospital, Shanghai JiaoTong University School of Medicine, Shanghai 200011 (China); Zhang Peng [Center for Translational Medicine Research and Development, Shenzhen Institute of Advanced Technology, Chinese Academy of Science (China); Hou Hongliang; Tang Tingting, E-mail: drfanxianqun@126.com [Department of Orthopedics, Shanghai Ninth People' s Hospital, Shanghai JiaoTong University School of Medicine, Shanghai 200011 (China)

    2011-02-15

    Bone graft substitutes with osteogenic factors alone often exhibit poor bone regeneration due to inadequate vascularization. Combined delivery of osteogenic and angiogenic factors from biodegradable scaffolds may enhance bone regeneration. We evaluated the effects of bone morphogenetic protein 2 (BMP2) and vascular endothelial growth factor (VEGF), combined with natural coral scaffolds, on the repair of critical-sized bone defects in rabbit orbits. In vitro expanded rabbit bone marrow stromal cells (BMSCs) were transfected with human BMP2 and VEGF165 genes. Target protein expression and osteogenic differentiation were confirmed after gene transduction. Rabbit orbital defects were treated with a coral scaffold loaded with BMP2-transduced and VEGF-transduced BMSCs, BMP2-expressing BMSCs, VEGF-expressing BMSCs, or BMSCs without gene transduction. Volume and density of regenerated bone were determined by micro-computed tomography at 4, 8, and 16 weeks after implantation. Neovascularity, new bone deposition rate, and new bone formation were measured by immunostaining, tetracycline and calcein labelling, and histomorphometric analysis at different time points. The results showed that VEGF increased blood vessel formation relative to groups without VEGF. Combined delivery of BMP2 and VEGF increased new bone deposition and formation, compared with any single factor. These findings indicate that mimicking the natural bone development process by combined BMP2 and VEGF delivery improves healing of critical-sized orbital defects in rabbits.

  9. Bone marrow stromal cells with a combined expression of BMP-2 and VEGF-165 enhanced bone regeneration

    International Nuclear Information System (INIS)

    Bone graft substitutes with osteogenic factors alone often exhibit poor bone regeneration due to inadequate vascularization. Combined delivery of osteogenic and angiogenic factors from biodegradable scaffolds may enhance bone regeneration. We evaluated the effects of bone morphogenetic protein 2 (BMP2) and vascular endothelial growth factor (VEGF), combined with natural coral scaffolds, on the repair of critical-sized bone defects in rabbit orbits. In vitro expanded rabbit bone marrow stromal cells (BMSCs) were transfected with human BMP2 and VEGF165 genes. Target protein expression and osteogenic differentiation were confirmed after gene transduction. Rabbit orbital defects were treated with a coral scaffold loaded with BMP2-transduced and VEGF-transduced BMSCs, BMP2-expressing BMSCs, VEGF-expressing BMSCs, or BMSCs without gene transduction. Volume and density of regenerated bone were determined by micro-computed tomography at 4, 8, and 16 weeks after implantation. Neovascularity, new bone deposition rate, and new bone formation were measured by immunostaining, tetracycline and calcein labelling, and histomorphometric analysis at different time points. The results showed that VEGF increased blood vessel formation relative to groups without VEGF. Combined delivery of BMP2 and VEGF increased new bone deposition and formation, compared with any single factor. These findings indicate that mimicking the natural bone development process by combined BMP2 and VEGF delivery improves healing of critical-sized orbital defects in rabbits.

  10. Effect of porous polycaprolactone beads on bone regeneration: preliminary in vitro and in vivo studies

    OpenAIRE

    Byun, June-Ho; Lee, Han A Reum; Kim, Tae Ho; Lee, Jin Ho; Oh, Se Heang

    2014-01-01

    Background For the effective bone regeneration with appropriate pathological/physiological properties, a variety of bone fillers have been adapted as a therapeutic treatment. However, the development of ideal bone fillers is still remained as a big challenge in clinical practice. The main aims of this study are i) fabrication of a highly porous PCL beads; and ii) the estimation of the potential use of the porous PCL beads as a bone filler through preliminary animal study. Results The porous P...

  11. Improving gingival smile by means of guided bone regeneration principles

    Science.gov (United States)

    Ferreira, Carlos Eduardo de Almeida; Brandão, Roberto Carlos Bodart; Martinelli, Carolina Borges; Pignaton, Túlio Bonna

    2016-01-01

    ABSTRACT Objective: This study evaluated the effectiveness of guided bone regeneration (GBR) carried out with xenogenic bone substitute (Bio-OssTM) and collagen resorbable membrane (Bio-GideTM) to improve gingival smile (GS) in patients with excessive vertical maxillary growth (EVMG). Methods: Twelve healthy women aged between 20 and 49 years old (mean age of 26 years), with 5 mm or more of gingival exposure during fully posed smile (FPS) due to EVMG, were included. Baseline digital photographs were taken with standardized head position at rest and FPS. In eight out of 12 cases, crown lengthening procedure was indicated and the initial incision was made 2 to 4 mm from the gingival margin. In four cases, with no indication for crown lengthening procedure, a sulcular incision was performed. GBR was performed in all cases, using micro screws and/or titanium mesh associated with Bio-OssTM and Bio-GideTM. After 10 days, sutures were removed. Recall appointments were scheduled at 1, 6, and 12 months when standardized photographs were again taken. ImageToolTM software was used to measure the gingival exposure (GE) during FPS from the standardized close-up smile photographs at baseline and 12 months. Results: GE mean at baseline was 275.44 mm2. After 12 months, patients who undergone exclusively GBR procedure, presented GE reduction of 40.7%, ∆ = 112.01 mm2 (statistically significant, p = 0.12), and patients who had crown lengthening associated with the graft had a reduction of 60%, ∆ = 167.01 mm2. Conclusion: Our results using GBR to improve GS in cases of EVMG showed an exceptionally high patient acceptance and satisfaction. One-year follow-up confirmed stable results. PMID:27409660

  12. Mesenchymal Stem Cells as a Potent Cell Source for Bone Regeneration

    Directory of Open Access Journals (Sweden)

    Elham Zomorodian

    2012-01-01

    Full Text Available While small bone defects heal spontaneously, large bone defects need surgical intervention for bone transplantation. Autologous bone grafts are the best and safest strategy for bone repair. An alternative method is to use allogenic bone graft. Both methods have limitations, particularly when bone defects are of a critical size. In these cases, bone constructs created by tissue engineering technologies are of utmost importance. Cells are one main component in the manufacture of bone construct. A few cell types, including embryonic stem cells (ESCs, adult osteoblast, and adult stem cells, can be used for this purpose. Mesenchymal stem cells (MSCs, as adult stem cells, possess characteristics that make them good candidate for bone repair. This paper discusses different aspects of MSCs that render them an appropriate cell type for clinical use to promote bone regeneration.

  13. Calcium Sulfate and Platelet-Rich Plasma make a novel osteoinductive biomaterial for bone regeneration

    Directory of Open Access Journals (Sweden)

    Intini Francesco E

    2007-03-01

    Full Text Available Abstract Background With the present study we introduce a novel and simple biomaterial able to induce regeneration of bone. We theorized that nourishing a bone defect with calcium and with a large amount of activated platelets may initiate a series of biological processes that culminate in bone regeneration. Thus, we engineered CS-Platelet, a biomaterial based on the combination of Calcium Sulfate and Platelet-Rich Plasma in which Calcium Sulfate also acts as an activator of the platelets, therefore avoiding the need to activate the platelets with an agonist. Methods First, we tested CS-Platelet in heterotopic (muscle and orthotopic (bone bone regeneration bioassays. We then utilized CS-Platelet in a variety of dental and craniofacial clinical cases, where regeneration of bone was needed. Results The heterotopic bioassay showed formation of bone within the muscular tissue at the site of the implantation of CS-Platelet. Results of a quantitative orthotopic bioassay based on the rat calvaria critical size defect showed that only CS-Platelet and recombinant human BMP2 were able to induce a significant regeneration of bone. A non-human primate orthotopic bioassay also showed that CS-Platelet is completely resorbable. In all human clinical cases where CS-Platelet was used, a complete bone repair was achieved. Conclusion This study showed that CS-Platelet is a novel biomaterial able to induce formation of bone in heterotopic and orthotopic sites, in orthotopic critical size bone defects, and in various clinical situations. The discovery of CS-Platelet may represent a cost-effective breakthrough in bone regenerative therapy and an alternative or an adjuvant to the current treatments.

  14. Development and characterization of an injectable dextrin-based hydrogel for bone regeneration

    OpenAIRE

    Dina M. Silva; Daniella L. Morgado; Delair, T; David, L; Rouif, S.; López-Lacomba, J. L.; A C Maurício; Santos, J. D.; Gama, F. M.

    2014-01-01

    Bone is a dynamic, highly vascularized tissue that remodels itself continuously over an individual ́s lifetime. It plays several important roles in maintaining homeostasis of the body systems [ 1 , 2 ] . However, this regenerative capac ity is limited and, as in the case of large bone defects, where the template for an orchestrated regeneration is absent, surgical proce dures are needed [ 2...

  15. Evaluation of nanostructure and microstructure of bone regenerated by BMP-2-porous scaffolds.

    Science.gov (United States)

    Del Rosario, Carlos; Rodríguez-Evora, Maria; Reyes, Ricardo; González-Orive, Alejandro; Hernández-Creus, Alberto; Shakesheff, Kevin M; White, Lisa J; Delgado, Araceli; Evora, Carmen

    2015-09-01

    In this study, three systems containing BMP-2 were fabricated, including two electrospun sandwich-like-systems of PLGA 75:25 and PLGA 50:50 and a microsphere system of PLGA 50:50 to be implanted in a critical size defect in rat calvaria. The in vivo BMP-2 release profiles of the three systems were similar. The total dose was released during the first two weeks. To evaluate the nano and microstructure of the regenerated bone a multi-technique analysis was used, including stereo microscope, X-Ray; AFM, micro-CT, and histological analyses. The progression of bone regeneration was followed at 4, 8, and 12 weeks after the microsphere system implantation whereas the two electrospun systems were evaluated at fixed 12 weeks. All the techniques applied showed high bone regeneration. The average values of bone volume density, bone mineral density, Young's modulus, and the percent of bone repair were ∼70% of the values of the native bone. Besides, SEM-EDX analysis indicated that the main chemical elements in the new bone were oxygen, calcium, and phosphorus in a ratio similar to that of native bone. In comparison, the micro-CT may provide an alternative to histology for the evaluation of bone formation at the defect size. PMID:25689580

  16. Hydroxyapatite-calcium sulfate-hyaluronic acid composite encapsulated with collagenase as bone substitute for alveolar bone regeneration.

    Science.gov (United States)

    Subramaniam, Sadhasivam; Fang, Yen-Hsin; Sivasubramanian, Savitha; Lin, Feng-Huei; Lin, Chun-pin

    2016-01-01

    Periodontitis is a very severe inflammatory condition of the periodontium that progressively damages the soft tissue and destroys the alveolar bone that supports the teeth. The bone loss is naturally irreversible because of limited reparability of the teeth. Advancement in tissue engineering provides an effective regeneration of osseous defects with suitable dental implants or tissue-engineered constructs. This study reports a hydroxyapatite, calcium sulfate hemihydrate and hyaluronic acid laden collagenase (HAP/CS/HA-Col) as a bone substitute for the alveolar bone regeneration. The composite material was mechanically tested and the biocompatibility was evaluated by WST-1 assay. The in vivo bone formation was assessed in rat with alveolar bone defects and the bone augmentation by the HAP/CS/HA-Col composite was confirmed by micro-CT images and histological examination. The mechanical strength of 6.69 MPa with excellent biocompatibility was obtained for the HAP/CS/HA-Col composite. The collagenase release profile had facilitated the acceleration of bone remodeling process and it was confirmed by the findings of micro-CT and H&E staining. The bone defects implanted with HAP/CS/HA composite containing 2 mg/mL type I collagenase have shown improved new bone formation with matured bone morphology in comparison with the HAP/CS/HA composite that lacks the collagenase and the porous hydroxyapatite (p-HAP) granules. The said findings demonstrated that the collagenase inclusion in HAP/CS/HA composite is a feasible approach for the alveolar bone regeneration and the same design can also be applied to other defective tissues. PMID:26454048

  17. Exosome: A Novel Approach to Stimulate Bone Regeneration through Regulation of Osteogenesis and Angiogenesis

    Science.gov (United States)

    Qin, Yunhao; Sun, Ruixin; Wu, Chuanlong; Wang, Lian; Zhang, Changqing

    2016-01-01

    The clinical need for effective bone regeneration therapy remains in huge demands. However, the current “gold standard” treatments of autologous and allogeneic bone grafts may result in various complications. Furthermore, safety considerations of biomaterials and cell-based treatment require further clarification. Therefore, developing new therapies with stronger osteogenic potential and a lower incidence of complications is worthwhile. Recently, exosomes, small vesicles of endocytic origin, have attracted attention in bone regeneration field. The vesicles travel between cells and deliver functional cargoes, such as proteins and RNAs, thereby regulating targeted cells differentiation, commitment, function, and proliferation. Much evidence has demonstrated the important roles of exosomes in osteogenesis both in vitro and in vivo. In this review, we summarize the properties, origins and biogenesis of exosomes, and the recent reports using exosomes to regulate osteogenesis and promote bone regeneration. PMID:27213355

  18. Exosome: A Novel Approach to Stimulate Bone Regeneration through Regulation of Osteogenesis and Angiogenesis.

    Science.gov (United States)

    Qin, Yunhao; Sun, Ruixin; Wu, Chuanlong; Wang, Lian; Zhang, Changqing

    2016-01-01

    The clinical need for effective bone regeneration therapy remains in huge demands. However, the current "gold standard" treatments of autologous and allogeneic bone grafts may result in various complications. Furthermore, safety considerations of biomaterials and cell-based treatment require further clarification. Therefore, developing new therapies with stronger osteogenic potential and a lower incidence of complications is worthwhile. Recently, exosomes, small vesicles of endocytic origin, have attracted attention in bone regeneration field. The vesicles travel between cells and deliver functional cargoes, such as proteins and RNAs, thereby regulating targeted cells differentiation, commitment, function, and proliferation. Much evidence has demonstrated the important roles of exosomes in osteogenesis both in vitro and in vivo. In this review, we summarize the properties, origins and biogenesis of exosomes, and the recent reports using exosomes to regulate osteogenesis and promote bone regeneration. PMID:27213355

  19. Targeting the hypoxic response in bone tissue engineering: A balance between supply and consumption to improve bone regeneration.

    Science.gov (United States)

    Stiers, Pieter-Jan; van Gastel, Nick; Carmeliet, Geert

    2016-09-01

    Bone tissue engineering is a promising therapeutic alternative for bone grafting of large skeletal defects. It generally comprises an ex vivo engineered combination of a carrier structure, stem/progenitor cells and growth factors. However, the success of these regenerative implants largely depends on how well implanted cells will adapt to the hostile and hypoxic host environment they encounter after implantation. In this review, we will discuss how hypoxia signalling may be used to improve bone regeneration in a tissue-engineered construct. First, hypoxia signalling induces angiogenesis which increases the survival of the implanted cells as well as stimulates bone formation. Second, hypoxia signalling has also angiogenesis-independent effects on mesenchymal cells in vitro, offering exciting new possibilities to improve tissue-engineered bone regeneration in vivo. In addition, studies in other fields have shown that benefits of modulating hypoxia signalling include enhanced cell survival, proliferation and differentiation, culminating in a more potent regenerative implant. Finally, the stimulation of endochondral bone formation as a physiological pathway to circumvent the harmful effects of hypoxia will be briefly touched upon. Thus, angiogenic dependent and independent processes may counteract the deleterious hypoxic effects and we will discuss several therapeutic strategies that may be combined to withstand the hypoxia upon implantation and improve bone regeneration. PMID:26768117

  20. Osteogenic Potential of Multipotent Adult Progenitor Cells for Calvaria Bone Regeneration

    Science.gov (United States)

    Lee, Dong Joon; Park, Yonsil; Hu, Wei-Shou; Ko, Ching-Chang

    2016-01-01

    Osteogenic cells derived from rat multipotent adult progenitor cells (rMAPCs) were investigated for their potential use in bone regeneration. rMAPCs are adult stem cells derived from bone marrow that have a high proliferation capacity and the differentiation potential to multiple lineages. They may also offer immunomodulatory properties favorable for applications for regenerative medicine. rMAPCs were cultivated as single cells or as 3D aggregates in osteogenic media for up to 38 days, and their differentiation to bone lineage was then assessed by immunostaining of osteocalcin and collagen type I and by mineralization assays. The capability of rMAPCs in facilitating bone regeneration was evaluated in vivo by the direct implantation of multipotent adult progenitor cell (MAPC) aggregates in rat calvarial defects. Bone regeneration was examined radiographically, histologically, and histomorphometrically. Results showed that rMAPCs successfully differentiated into osteogenic lineage by demonstrating mineralized extracellular matrix formation in vitro and induced new bone formation by the effect of rMAPC aggregates in vivo. These outcomes confirm that rMAPCs have a good osteogenic potential and provide insights into rMAPCs as a novel adult stem cell source for bone regeneration. PMID:27239552

  1. BMP2 genetically engineered MSCs and EPCs promote vascularized bone regeneration in rat critical-sized calvarial bone defects.

    Directory of Open Access Journals (Sweden)

    Xiaoning He

    Full Text Available Current clinical therapies for critical-sized bone defects (CSBDs remain far from ideal. Previous studies have demonstrated that engineering bone tissue using mesenchymal stem cells (MSCs is feasible. However, this approach is not effective for CSBDs due to inadequate vascularization. In our previous study, we have developed an injectable and porous nano calcium sulfate/alginate (nCS/A scaffold and demonstrated that nCS/A composition is biocompatible and has proper biodegradability for bone regeneration. Here, we hypothesized that the combination of an injectable and porous nCS/A with bone morphogenetic protein 2 (BMP2 gene-modified MSCs and endothelial progenitor cells (EPCs could significantly enhance vascularized bone regeneration. Our results demonstrated that delivery of MSCs and EPCs with the injectable nCS/A scaffold did not affect cell viability. Moreover, co-culture of BMP2 gene-modified MSCs and EPCs dramatically increased osteoblast differentiation of MSCs and endothelial differentiation of EPCs in vitro. We further tested the multifunctional bone reconstruction system consisting of an injectable and porous nCS/A scaffold (mimicking the nano-calcium matrix of bone and BMP2 genetically-engineered MSCs and EPCs in a rat critical-sized (8 mm caviarial bone defect model. Our in vivo results showed that, compared to the groups of nCS/A, nCS/A+MSCs, nCS/A+MSCs+EPCs and nCS/A+BMP2 gene-modified MSCs, the combination of BMP2 gene -modified MSCs and EPCs in nCS/A dramatically increased the new bone and vascular formation. These results demonstrated that EPCs increase new vascular growth, and that BMP2 gene modification for MSCs and EPCs dramatically promotes bone regeneration. This system could ultimately enable clinicians to better reconstruct the craniofacial bone and avoid donor site morbidity for CSBDs.

  2. BMP2 Genetically Engineered MSCs and EPCs Promote Vascularized Bone Regeneration in Rat Critical-Sized Calvarial Bone Defects

    Science.gov (United States)

    He, Xiaoning; Dziak, Rosemary; Yuan, Xue; Mao, Keya; Genco, Robert; Swihart, Mark; Sarkar, Debanjan; Li, Chunyi; Wang, Changdong; Lu, Li; Andreadis, Stelios; Yang, Shuying

    2013-01-01

    Current clinical therapies for critical-sized bone defects (CSBDs) remain far from ideal. Previous studies have demonstrated that engineering bone tissue using mesenchymal stem cells (MSCs) is feasible. However, this approach is not effective for CSBDs due to inadequate vascularization. In our previous study, we have developed an injectable and porous nano calcium sulfate/alginate (nCS/A) scaffold and demonstrated that nCS/A composition is biocompatible and has proper biodegradability for bone regeneration. Here, we hypothesized that the combination of an injectable and porous nCS/A with bone morphogenetic protein 2 (BMP2) gene-modified MSCs and endothelial progenitor cells (EPCs) could significantly enhance vascularized bone regeneration. Our results demonstrated that delivery of MSCs and EPCs with the injectable nCS/A scaffold did not affect cell viability. Moreover, co-culture of BMP2 gene-modified MSCs and EPCs dramatically increased osteoblast differentiation of MSCs and endothelial differentiation of EPCs in vitro. We further tested the multifunctional bone reconstruction system consisting of an injectable and porous nCS/A scaffold (mimicking the nano-calcium matrix of bone) and BMP2 genetically-engineered MSCs and EPCs in a rat critical-sized (8 mm) caviarial bone defect model. Our in vivo results showed that, compared to the groups of nCS/A, nCS/A+MSCs, nCS/A+MSCs+EPCs and nCS/A+BMP2 gene-modified MSCs, the combination of BMP2 gene -modified MSCs and EPCs in nCS/A dramatically increased the new bone and vascular formation. These results demonstrated that EPCs increase new vascular growth, and that BMP2 gene modification for MSCs and EPCs dramatically promotes bone regeneration. This system could ultimately enable clinicians to better reconstruct the craniofacial bone and avoid donor site morbidity for CSBDs. PMID:23565253

  3. Effect of simvastatin versus low level laser therapy (LLLT) on bone regeneration in rabbit's tibia

    Science.gov (United States)

    Gheith, Mostafa E.; Khairy, Maggie A.

    2014-02-01

    Simvastatin is a cholesterol lowering drug which proved effective on promoting bone healing. Recently low level laser therapy (LLLT) proved its effect as a biostimulator promoting bone regeneration. This study aims to compare the effect of both Simvastatin versus low level laser on bone healing in surgically created bone defects in rabbit's tibia. Material and methods: The study included 12 New Zealand white rabbits. Three successive 3mm defects were created in rabbits tibia first defect was left as control, second defect was filled with Simvastatin while the third defect was acted on with Low Level Laser (optical fiber 320micrometer). Rabbits were sacrificed after 48 hours, 1 week and 2 weeks intervals. Histopathology was conducted on the three defects Results: The histopathologic studies showed that the bony defects treated with the Low Level Laser showed superior healing patterns and bone regeneration than those treated with Simvastatin. While the control defect showed the least healing pattern.

  4. Bone Regeneration Using Dentin Matrix Depends on the Degree of Demineralization and Particle Size.

    Directory of Open Access Journals (Sweden)

    Takamitsu Koga

    Full Text Available This study aimed to examine the influence of particle size and extent of demineralization of dentin matrix on bone regeneration.Extracted human teeth were pulverized and divided into 3 groups according to particle size; 200, 500, and 1000 μm. Each group was divided into 3 groups depending on the extent of demineralization; undemineralized dentin (UDD, partially demineralized dentin matrix (PDDM, and completely demineralized dentin matrix (CDDM. The dentin sample was implanted into rat calvarial bone defects. After 4 and 8 weeks, the bone regeneration was evaluated with micro-CT images, histomorphometric and immunohistochemical analyses. Osteoblasts were cultured on UDD and DDM to evaluate the cell attachment using electron microscope.Micro-CT images and histological observation revealed that CDDM had largely resorbed but UDD had not, and both of them induced little bone formation, whereas all particle sizes of PDDM induced more new bone, especially the 1000 μm. Electron microscopic observation showed osteoblasts attached to DDM but not to UDD.PDDM with larger particle size induced prominent bone regeneration, probably because PDDM possessed a suitable surface for cell attachment. There might be an exquisite balance between its resorption and bone formation on it. PDDM could be considered as a potential bone substitute.

  5. JAW CYSTS AND GUIDED BONE REGENERATION (a late complication after enucleation

    Directory of Open Access Journals (Sweden)

    Hristina Lalabonova

    2013-10-01

    Full Text Available Maxillary jaw bone possesses a high regenerative capacity. Yet sometimes the defects enucleation of jaw cysts leaves may regenerate only partially or not at all. For this reason some researchers advise treatment of the residual cavities after cystectomy using bone regeneration stimulation methods. We report a case of an atypical complication after enucleation of a maxillary cyst manifesting itself eight years after the initial treatment. The symptoms the patient reported were at first periodic sweating on the left sides of face and head. This was followed by a piercing pain in the left palpebral fissure radiating to the middle of the palate and felt in the left cheekbone, left eye and left supraorbital ridge. The patient has a history of maxillary cysts recurring three times and of three operations she had 20, 12 and 8 years previously. The multiple recurrences of the cysts after their enucleation indicates poor regenerative capacity of the body which resulted in the formation of cicatricial tissue. It is most probably this tissue that was responsible for the disruption of the nerve conduction capacity which can account for the reported symptoms. We filled the cavity with bone graft material which boosted the bone structure regeneration. Although maxillary jaws possess high regenerative capacity we advise the use of guided bone regeneration in cases of large bone defects that usually occur after enucleation of jaw cysts.

  6. Utilization of Guided Bone Regeneration Techniqes in Treatment of a Single Tooth Missing with Implant Supported Crown

    OpenAIRE

    Adamczyk, E.; Gladkowski, J.; Machnikowski, I.; Mierzwinska, E.; Spiechowicz, E.; Feder, T.; Wojtowicz, A.; Matenko, D.; Ciechowicz, K.

    2002-01-01

    Guided bone regeneration is developing very dynamically in dental surgery and in implantology. It relies on building up bone in places where it is lacking, utilizing a variety of grafting materials. Methods of guided bone regeneration utilize biological materials or synthetic specimens. The use of autogenous platelets rich plasma derived in the thromboforetic process (COBE spectra system) allows the employment of growth factors, which blood platelets contain in the formation of new bone tissu...

  7. Bone Regeneration Based on Tissue Engineering Conceptions-A 21st Century Perspective

    Institute of Scientific and Technical Information of China (English)

    Jan Henkel; Maria A. Woodruff; Devakara R. Epari; Roland Steck; Vaida Glatt; Ian C. Dickinson; Peter FM Choong; Michael A. Schuetz; Dietmar W. Hutmacher

    2013-01-01

    The role of Bone Tissue Engineering in the field of Regenerative Medicine has been the topic of substantial research over the past two decades. Technological advances have improved orthopaedic implants and surgical techniques for bone reconstruction. However, improvements in surgical techniques to reconstruct bone have been limited by the paucity of autologous materials available and donor site morbidity. Recent advances in the development of biomaterials have provided attractive alternatives to bone grafting expanding the surgical options for restoring the form and function of injured bone. Specifically, novel bioactive (second generation) biomaterials have been developed that are characterised by controlled action and reaction to the host tissue environment, whilst exhibiting controlled chemical breakdown and resorption with an ultimate replacement by regenerating tissue. Future generations of biomaterials (third generation) are designed to be not only osteo-conductive but also osteoinductive, i.e. to stimulate regeneration of host tissues by combining tissue engineer-ing and in situ tissue regeneration methods with a focus on novel applications. These techniques will lead to novel possibilities for tissue regeneration and repair. At present, tissue engineered constructs that may find future use as bone grafts for complex skeletal defects, whether from post-traumatic, degenerative, neoplastic or congenital/developmental“origin”require osseous reconstruction to ensure structural and functional integrity. Engineering functional bone using combinations of cells, scaffolds and bioactive factors is a promising strategy and a particular feature for future development in the area of hybrid materials which are able to exhibit suitable biomimetic and mechanical properties. This review will discuss the state of the art in this field and what we can expect from future generations of bone regeneration concepts.

  8. PATHOHISTOLOGICAL INVESTIGATION ON THE INFLUENCE OF INTRACANAL MEDICATION ON THE REGENERATION OF JAW BONE

    Directory of Open Access Journals (Sweden)

    Anatoliy Borysenko

    2012-12-01

    Full Text Available The results of histological investigation on the influence of the proposed drug composition (metronidazole, enterosgel (Sigma, alflutop (Biotehnos S.A., Romania for experimental mandible bone defect regeneration in rats were presented. The high efficiency and osteoregenerative properties of this paste were shown, and its significant clinical efficiency for temporary placement into the root canals in the treatment of chronic apical periodontitis, for stimulating regeneration of the damaged periapical tissues, was assessed.

  9. Current Progress in Bioactive Ceramic Scaffolds for Bone Repair and Regeneration

    Directory of Open Access Journals (Sweden)

    Chengde Gao

    2014-03-01

    Full Text Available Bioactive ceramics have received great attention in the past decades owing to their success in stimulating cell proliferation, differentiation and bone tissue regeneration. They can react and form chemical bonds with cells and tissues in human body. This paper provides a comprehensive review of the application of bioactive ceramics for bone repair and regeneration. The review systematically summarizes the types and characters of bioactive ceramics, the fabrication methods for nanostructure and hierarchically porous structure, typical toughness methods for ceramic scaffold and corresponding mechanisms such as fiber toughness, whisker toughness and particle toughness. Moreover, greater insights into the mechanisms of interaction between ceramics and cells are provided, as well as the development of ceramic-based composite materials. The development and challenges of bioactive ceramics are also discussed from the perspective of bone repair and regeneration.

  10. Myeloid regeneration after whole body irradiation, autologous bone marrow transplantation, and treatment with an anabolic steroid.

    Science.gov (United States)

    Ambrus, C M; Ambrus, J L

    1975-01-01

    Stumptail monkeys (Macaca speciosa) received lethal whole body radiation. Autologous bone marrow injection resulted in survival of the majority of the animals. Treatment with Deca-Durabolin, an anabolic steroid, caused more rapid recovery of colony-forming cell numbers in the bone marrow than in control animals. Both the Deca-Durabolin-treated and control groups were given autologous bone marrow transplantation. Anabolic steroid effect on transplanted bone marrow colonyforming cells may explain the increased rate of leukopoietic regeneration in anabolic steroid-treated animals as compared to controls. PMID:124758

  11. Myeloid regeneration after whole body irradiation, autologous bone marrow transplantation, and treatment with an anabolic steroid

    International Nuclear Information System (INIS)

    Stumptail monkeys (Macaca speciosa) received lethal whole-body radiation. Autologous bone marrow injection resulted in survival of the majority of the animals. Treatment with Deca-Durabolin, an anabolic steroid, caused more rapid recovery of colony-forming cell numbers in the bone marrow than in control animals. Both the Deca-Durabolin-treated and control groups were given autologous bone marrow transplantation. Anabolic steroid effect on transplanted bone marrow colony-forming cells may explain the increased rate of leukopoietic regeneration in anabolic steroid-treated animals as compared to controls

  12. Effects of Two Types of Anorganic Bovine Bone on Bone Regeneration: A Histological and Histomorphometric Study of Rabbit Calvaria

    OpenAIRE

    Mojgan Paknejad; Amir Reza Rokn; Siamak Yaghobee; Pantea Moradinejad; Mohadeseh Heidari; Ali Mehrfard

    2014-01-01

    Objective: The purpose of this study was to evaluate the efficacy of two types of bone substitutes, Bio-Oss and NuOss, for repair of bone defects. Materials and Methods: This study was performed on the calvaria of 14 New Zealand rabbits. The 6mm critical size defect (CSD) models of bone regeneration were used. Three CSDs were created in each surgical site. The first defect was filled with NuOss, the second one with Bio-Oss and the third one remained unfilled as the control. After healing peri...

  13. The role of synthetic biomaterials in resorptive alveolar bone regeneration

    Directory of Open Access Journals (Sweden)

    Kaličanin Biljana M.

    2007-01-01

    Full Text Available The alveolar bone tissue resorption defect has a significant role in dentistry. Because of the bone tissue deficit developed by alveolar resorption, the use of synthetic material CP/PLGA (calcium-phosphate/polylactide-co-gliycolide composite was introduced. Investigations were performed on rats with artificially produced resorption of the mandibular bone. The results show that the best effect on alveolar bone were attained by using nano-composite implants. The effect of the nanocomposite was ascertained by determining the calcium and phosphate content, as a basis of the hydroxyapatite structure. The results show that synthetic CP/PLGA nanocomposite alleviate the rehabilitation of weakened alveolar bone. Due to its osteoconductive effect, CP/PLGA can be the material of choice for bone substitution in the future.

  14. Relevance of fiber integrated gelatin-nanohydroxyapatite composite scaffold for bone tissue regeneration

    Science.gov (United States)

    Halima Shamaz, Bibi; Anitha, A.; Vijayamohan, Manju; Kuttappan, Shruthy; Nair, Shantikumar; Nair, Manitha B.

    2015-10-01

    Porous nanohydroxyapatite (nanoHA) is a promising bone substitute, but it is brittle, which limits its utility for load bearing applications. To address this issue, herein, biodegradable electrospun microfibrous sheets of poly(L-lactic acid)-(PLLA)-polyvinyl alcohol (PVA) were incorporated into a gelatin-nanoHA matrix which was investigated for its mechanical properties, the physical integration of the fibers with the matrix, cell infiltration, osteogenic differentiation and bone regeneration. The inclusion of sacrificial fibers like PVA along with PLLA and leaching resulted in improved cellular infiltration towards the center of the scaffold. Furthermore, the treatment of PLLA fibers with 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide enhanced their hydrophilicity, ensuring firm anchorage between the fibers and the gelatin-HA matrix. The incorporation of PLLA microfibers within the gelatin-nanoHA matrix reduced the brittleness of the scaffolds, the effect being proportional to the number of layers of fibrous sheets in the matrix. The proliferation and osteogenic differentiation of human adipose-derived mesenchymal stem cells was augmented on the fibrous scaffolds in comparison to those scaffolds devoid of fibers. Finally, the scaffold could promote cell infiltration, together with bone regeneration, upon implantation in a rabbit femoral cortical defect within 4 weeks. The bone regeneration potential was significantly higher when compared to commercially available HA (Surgiwear™). Thus, this biomimetic, porous, 3D composite scaffold could be offered as a promising candidate for bone regeneration in orthopedics.

  15. Biocompatibility, resorption and biofunctionality of a new synthetic biodegradable membrane for guided bone regeneration.

    Science.gov (United States)

    Hoornaert, Alain; d'Arros, Cyril; Heymann, Marie-Francoise; Layrolle, Pierre

    2016-01-01

    Membranes for guided bone regeneration (GBR) were prepared from the synthetic biodegradable polymer poly-D,L-lactic/glycolic acid (PLGA). This GBR membrane has a bi-layered structure with a dense film to prevent gingival fibroblast ingrowth and ensure mechanical function, and a micro-fibrous layer to support colonization by osteogenic cells and promote bone regeneration. Hydrolysis and biodegradation were both studied in vitro through soaking in phosphate buffered saline (PBS) and in vivo by implantation in the subcutis of rats for 4, 8, 16, 26, 48 and 52 weeks. Histology revealed an excellent colonization of the micro-fibrous layer by cells with a minimal inflammatory reaction during resorption. GBR using the synthetic PLGA membrane was evaluated on critical-size calvaria defects in rats for 4 and 8 weeks. Radiographs, micro-computed tomography and histology showed bone regeneration with the PLGA membrane, while the defects covered with a collagen membrane showed a limited amount of mineralized bone, similar to that of the defect left empty. The biofunctionality of the PLGA membranes was also compared to collagen membranes in mandible defects in rabbits, associated or not with beta-tricalcium phosphate granules. This study revealed that the bi-layered synthetic membrane made of PLGA was safer, more biocompatible, and had a greater controlled resorption rate and bone regeneration capacity than collagen membranes. This new PLGA membrane could be used in pre-implantology and peri-odontology surgery. PMID:27509180

  16. Small Players Ruling the Hard Game: siRNA in Bone Regeneration.

    Science.gov (United States)

    Ghadakzadeh, Saber; Mekhail, Mina; Aoude, Ahmed; Hamdy, Reggie; Tabrizian, Maryam

    2016-03-01

    Silencing gene expression through a sequence-specific manner can be achieved by small interfering RNAs (siRNAs). The discovery of this process has opened the doors to the development of siRNA therapeutics. Although several preclinical and clinical studies have shown great promise in the treatment of neurological disorders, cancers, dominant disorders, and viral infections with siRNA, siRNA therapy is still gaining ground in musculoskeletal tissue repair and bone regeneration. Here we present a comprehensive review of the literature to summarize different siRNA delivery strategies utilized to enhance bone regeneration. With advancement in understanding the targetable biological pathways involved in bone regeneration and also the rapid progress in siRNA technologies, application of siRNA for bone regeneration has great therapeutic potential. High rates of musculoskeletal injuries and diseases, and their inevitable consequences, impose a huge financial burden on individuals and healthcare systems worldwide. © 2016 American Society for Bone and Mineral Research. PMID:26890411

  17. CHANGING OF THE BIOCHEMICAL INDICES ON REGENERATION OF EXPERIMENTAL DEFECT OF THE MANDIBLE BONE

    Directory of Open Access Journals (Sweden)

    A. Borysenko

    2012-09-01

    Full Text Available Summary. The results of an experimental biochemical investigation on the influence of the proposed drug composition for the experimental mandible bone defect regeneration in rats were presented. The high efficiency and osteoregenerative properties of this paste were shown. The experimental investigations showed that the proposed drug composition exerts a considerable normalization influence upon the biochemical indicators of bone mineral metabolism, comparable to Collapan influence.

  18. Bioactive polymeric–ceramic hybrid 3D scaffold for application in bone tissue regeneration

    International Nuclear Information System (INIS)

    The regeneration of large bone defects remains a challenging scenario from a therapeutic point of view. In fact, the currently available bone substitutes are often limited by poor tissue integration and severe host inflammatory responses, which eventually lead to surgical removal. In an attempt to address these issues, herein we evaluated the importance of alginate incorporation in the production of improved and tunable β-tricalcium phosphate (β-TCP) and hydroxyapatite (HA) three-dimensional (3D) porous scaffolds to be used as temporary templates for bone regeneration. Different bioceramic combinations were tested in order to investigate optimal scaffold architectures. Additionally, 3D β-TCP/HA vacuum-coated with alginate, presented improved compressive strength, fracture toughness and Young's modulus, to values similar to those of native bone. The hybrid 3D polymeric–bioceramic scaffolds also supported osteoblast adhesion, maturation and proliferation, as demonstrated by fluorescence microscopy. To the best of our knowledge this is the first time that a 3D scaffold produced with this combination of biomaterials is described. Altogether, our results emphasize that this hybrid scaffold presents promising characteristics for its future application in bone regeneration. - Graphical abstract: B-TCP:HA–alginate hybrid 3D porous scaffolds for application in bone regeneration. - Highlights: • The produced hybrid 3D scaffolds are prone to be applied in bone tissue engineering. • Alginate coated 3D scaffolds present high mechanical and biological properties. • In vitro assays for evaluation of human osteoblast cell attachment in the presence of the scaffolds • The hybrid 3D scaffolds present suitable mechanical and biological properties for use in bone regenerative medicine

  19. Exosome: A Novel Approach to Stimulate Bone Regeneration through Regulation of Osteogenesis and Angiogenesis

    OpenAIRE

    Yunhao Qin; Ruixin Sun; Chuanlong Wu; Lian Wang; Changqing Zhang

    2016-01-01

    The clinical need for effective bone regeneration therapy remains in huge demands. However, the current “gold standard” treatments of autologous and allogeneic bone grafts may result in various complications. Furthermore, safety considerations of biomaterials and cell-based treatment require further clarification. Therefore, developing new therapies with stronger osteogenic potential and a lower incidence of complications is worthwhile. Recently, exosomes, small vesicles of endocytic origin, ...

  20. Bone marrow mesenchymal stem cells, platelet-rich plasma and nanohydroxyapatite-type I collagen beads were integral parts of biomimetic bone substitutes for bone regeneration.

    Science.gov (United States)

    Lin, Bo-Nian; Whu, Shu Wen; Chen, Chih-Hwa; Hsu, Fu-Yin; Chen, Jyh-Cheng; Liu, Hsia-Wei; Chen, Chien-Hao; Liou, Hau-Min

    2013-11-01

    Platelet rich plasma (PRP), which includes many growth factors, can activate osteoid production, collagen synthesis and cell proliferation. Nanohydroxyapatite-type I collagen beads (CIB), which mimetic natural bone components, are not only flexible fillers for bone defect but also encourage osteogenesis. Bone marrow mesenchymal stem cells (BMSCs) are often used as an abundant cell source for tissue engineering. We used a rabbit model to combine PRP, CIB and BMSCs (CIB+PRP+BMSC) into a bone-like substitute to study its impact on bone regeneration, when compared to defect alone, PRP, CIB+PRP, and PRP+BMSC. CIB+PRP upregulated more alkaline phosphatase (ALP) activity in BMSCs than PRP alone at 4 weeks postoperation. CIB+PRP+BMSC and PRP+BMSC did not differ significantly in DNA content, total collagen content, and ALP activity at 8 weeks. In histological assay, both CIB+PRP+BMSC and PRP+BMSC showed more bone regeneration at 4 and 8 weeks. Higher trabecular bone volume in tissue volume (BV/TV) (31.15±2.67% and 36.93±1.01%), fractal dimension (FD) (2.30±0.18 and 2.65±0.02) and lower trabecular separation (Tb.Sp) (2.30±0.18 and 1.35±0.16) of CIB+PRP+BMSC than of other groups at 4 and 8 weeks, and approach to of bone tissue (BV/TV=24.35±2.13%; FD=2.65±0.06; Tb.Sp=4.19±0.95). CIB+PRP+BMSC significantly enhanced new bone formation at 4 week. Therefore, nanohydroxyapatite-type I collagen beads combined with PRP and BMSCs produced a bone substitute with efficiently improved bone regeneration that shows promise to repair bone defects. PMID:22744907

  1. Laser Microablative Tunnel Formation to Initiate Alveolar Bone Regeneration. Pilot ex vivo Study

    Directory of Open Access Journals (Sweden)

    Karabut М.М.

    2013-12-01

    Full Text Available In recent years there has been demonstrated the ability of Erbium (Er laser to cause effective ablation of bone tissue with minimum collateral damage. Non-surgical treatment of periodontitis using Er laser improves probing depth and clinical attachment level. However, periodontal anti-inflammatory therapy should not be limited to these parameters, but also should initiate tissue regeneration including bone tissue damaged by the disease. The aim of the investigation was to evaluate feasibility and characterize the process of laser microablative tunnel formation in gingiva and alveolar bone using a pulse-periodic, single mode Er laser, and determine laser parameters providing appropriate size of the tunnel and coagulation zone needed to initiate healing and regeneration of the alveolar bone. Materials and Methods. Ex vivo pig jaw was used as a model for the study. To create a through-gingiva microperformation of the alveolar bone, we used a laboratory prototype of Er laser and delivery system Alta PE-AT (Dental Photonics, Inc.. Results. We performed a microperforation of a 1 mm thick gingiva and created a microcrater (tunnel in the underlying bone using a single pulse with energy 5, 10 and 30 mJ. The laser tunnel characteristics in the gingiva, bone and dentine were characterized as a function of laser irradiation parameters. Optical microscopy and histology examination did not reveal carbonization or significant collateral damage of the bone tissue. Conclusion. Using a laboratory prototype of Alta PE-AT Er laser we demonstrated feasibility of through gingiva laser microperforation of alveolar bone that can serve as the first step towards further study of healing and initiation of the alveolar bone regeneration.

  2. Graded porous polyurethane foam: A potential scaffold for oro-maxillary bone regeneration

    International Nuclear Information System (INIS)

    Bone tissue engineering applications demand for biomaterials offering a substrate for cell adhesion, migration, and proliferation, while inferring suitable mechanical properties to the construct. In the present study, polyurethane (PU) foams were synthesized to develop a graded porous material—characterized by a dense shell and a porous core—for the treatment of oro-maxillary bone defects. Foam was synthesized via a one-pot reaction starting from a polyisocyanate and a biocompatible polyester diol, using water as a foaming agent. Different foaming conditions were examined, with the aim of creating a dense/porous functional graded material that would perform at the same time as an osteoconductive scaffold for bone defect regeneration and as a membrane-barrier to gingival tissue ingrowth. The obtained PU was characterized in terms of morphological and mechanical properties. Biocompatibility assessment was performed in combination with bone-marrow-derived human mesenchymal stromal cells (hBMSCs). Our findings confirm that the material is potentially suitable for guided bone regeneration applications. - Highlights: • Graded porous polyurethane foams were synthesized via a one-pot foaming reaction. • The inner porous core might act as a scaffold for guided bone regeneration. • A dense outer shell was introduced to act as a barrier to gingival tissue ingrowth. • The synthesized foams were non-toxic and supportive of hBMSC adhesion

  3. Sulfated hyaluronan improves bone regeneration of diabetic rats by binding sclerostin and enhancing osteoblast function.

    Science.gov (United States)

    Picke, Ann-Kristin; Salbach-Hirsch, Juliane; Hintze, Vera; Rother, Sandra; Rauner, Martina; Kascholke, Christian; Möller, Stephanie; Bernhardt, Ricardo; Rammelt, Stefan; Pisabarro, M Teresa; Ruiz-Gómez, Gloria; Schnabelrauch, Matthias; Schulz-Siegmund, Michaela; Hacker, Michael C; Scharnweber, Dieter; Hofbauer, Christine; Hofbauer, Lorenz C

    2016-07-01

    Bone fractures in patients with diabetes mellitus heal poorly and require innovative therapies to support bone regeneration. Here, we assessed whether sulfated hyaluronan included in collagen-based scaffold coatings can improve fracture healing in diabetic rats. Macroporous thermopolymerized lactide-based scaffolds were coated with collagen including non-sulfated or sulfated hyaluronan (HA/sHA3) and inserted into 3 mm femoral defects of non-diabetic and diabetic ZDF rats. After 12 weeks, scaffolds coated with collagen/HA or collagen/sHA3 accelerated bone defect regeneration in diabetic, but not in non-diabetic rats as compared to their non-coated controls. At the tissue level, collagen/sHA3 promoted bone mineralization and decreased the amount of non-mineralized bone matrix. Moreover, collagen/sHA3-coated scaffolds from diabetic rats bound more sclerostin in vivo than the respective controls. Binding assays confirmed a high binding affinity of sHA3 to sclerostin. In vitro, sHA3 induced BMP-2 and lowered the RANKL/OPG expression ratio, regardless of the glucose concentration in osteoblastic cells. Both sHA3 and high glucose concentrations decreased the differentiation of osteoclastic cells. In summary, scaffolds coated with collagen/sHA3 represent a potentially suitable biomaterial to improve bone defect regeneration in diabetic conditions. The underlying mechanism involves improved osteoblast function and binding sclerostin, a potent inhibitor of Wnt signaling and osteoblast function. PMID:27131598

  4. Graded porous polyurethane foam: A potential scaffold for oro-maxillary bone regeneration

    Energy Technology Data Exchange (ETDEWEB)

    Giannitelli, S.M. [Department of Engineering, Tissue Engineering Unit, Università Campus Bio-Medico di Roma, Rome (Italy); Basoli, F. [Department of Chemical Science and Technology, University of Rome “Tor Vergata”, Rome (Italy); Mozetic, P. [Department of Engineering, Tissue Engineering Unit, Università Campus Bio-Medico di Roma, Rome (Italy); Piva, P.; Bartuli, F.N.; Luciani, F. [University of Rome “Tor Vergata”, Rome (Italy); Arcuri, C. [Department of Periodontics, University of Rome “Tor Vergata”, Rome (Italy); U.O.C.C. Odontostomatology, “S. Giovanni Calibita, Fatebenefratelli” Hospital, Rome (Italy); Trombetta, M. [Department of Engineering, Tissue Engineering Unit, Università Campus Bio-Medico di Roma, Rome (Italy); Rainer, A., E-mail: a.rainer@unicampus.it [Department of Engineering, Tissue Engineering Unit, Università Campus Bio-Medico di Roma, Rome (Italy); Licoccia, S. [Department of Chemical Science and Technology, University of Rome “Tor Vergata”, Rome (Italy)

    2015-06-01

    Bone tissue engineering applications demand for biomaterials offering a substrate for cell adhesion, migration, and proliferation, while inferring suitable mechanical properties to the construct. In the present study, polyurethane (PU) foams were synthesized to develop a graded porous material—characterized by a dense shell and a porous core—for the treatment of oro-maxillary bone defects. Foam was synthesized via a one-pot reaction starting from a polyisocyanate and a biocompatible polyester diol, using water as a foaming agent. Different foaming conditions were examined, with the aim of creating a dense/porous functional graded material that would perform at the same time as an osteoconductive scaffold for bone defect regeneration and as a membrane-barrier to gingival tissue ingrowth. The obtained PU was characterized in terms of morphological and mechanical properties. Biocompatibility assessment was performed in combination with bone-marrow-derived human mesenchymal stromal cells (hBMSCs). Our findings confirm that the material is potentially suitable for guided bone regeneration applications. - Highlights: • Graded porous polyurethane foams were synthesized via a one-pot foaming reaction. • The inner porous core might act as a scaffold for guided bone regeneration. • A dense outer shell was introduced to act as a barrier to gingival tissue ingrowth. • The synthesized foams were non-toxic and supportive of hBMSC adhesion.

  5. Bone Repair on Fractures Treated with Osteosynthesis, ir Laser, Bone Graft and Guided Bone Regeneration: Histomorfometric Study

    Science.gov (United States)

    dos Santos Aciole, Jouber Mateus; dos Santos Aciole, Gilberth Tadeu; Soares, Luiz Guilherme Pinheiro; Barbosa, Artur Felipe Santos; Santos, Jean Nunes; Pinheiro, Antonio Luiz Barbosa

    2011-08-01

    The aim of this study was to evaluate, through the analysis of histomorfometric, the repair of complete tibial fracture in rabbits fixed with osteosynthesis, treated or not with infrared laser light (λ780 nm, 50 mW, CW) associated or not to the use of hydroxyapatite and guided bone regeneration (GBR). Surgical fractures were created, under general anesthesia (Ketamina 0,4 ml/Kg IP and Xilazina 0,2 ml/Kg IP), on the dorsum of 15 Oryctolagus rabbits that were divided into 5 groups and maintained on individual cages, at day/night cycle, fed with solid laboratory pelted diet and had water ad libidum. On groups II, III, IV and V the fracture was fixed with wire osteosynthesis. Animals of groups III and V were grafted with hydroxyapatite and GBR technique used. Animals of groups IV and V were irradiated at every other day during two weeks (16 J/cm2, 4×4 J/cm2). Observation time was that of 30 days. After animal death (overdose of general anesthetics) the specimes were routinely processed to wax and underwent histological analysis by light microscopy. The histomorfometric analysis showed an increased bone neoformation, increased collagen deposition, less reabsorption and inflammation when laser was associated to the HATCP. It is concluded that IR laser light was able to accelerate fracture healing and the association with HATCP and GBR resulted on increased deposition of CHA.

  6. Pilot in vivo animal study of bone regeneration by fractional Er: YAG-laser

    Science.gov (United States)

    Altshuler, Gregory B.; Belikov, Andrey V.; Shatilova, Ksenia V.; Yaremenko, Andrey I.; Zernitskiy, Alexander Y.; Zernitckaia, Ekaterina A.

    2016-04-01

    The histological structure of the rabbit parietal bone during its regeneration after fractional Er: YAG-laser (λ=2.94μm) treatment was investigated by hematoxylin and eosin (H&E) stain. In 48 days after fractional laser treatment, bone samples contained micro-cavities and fragments of necrotic tissue with empty cellular lacuna and coagulated protein of bone matrix. In this case, necrotic lesions appeared around the periphery of micro-cavities created by laser radiation. Fragmentation of detrital mass and partial substitution of micro-cavities with fatty bone marrow were observed in bone samples in 100 days after fractional laser treatment, in contrast to the earlier period. Partial filling of micro-cavities edges by fibrous tissue with presence of osteoblasts on their inner surface was observed in 100 days also, that indicates regenerative processes in the bone.

  7. Development of high strength hydroxyapatite for bone tissue regeneration using nanobioactive glass composites

    Energy Technology Data Exchange (ETDEWEB)

    Shrivastava, Pragya; Dalai, Sridhar; Vijayalakshmi, S. [Centre for Research in Nanotechnology and Science, IIT Bombay (India); Sudera, Prerna; Sivam, Santosh Param [Amity Institute of Nanotechnology, Amity University, Noida, Uttar Pradesh-201303 (India); Sharma, Pratibha [Dept of Energy Science and Engineering, IIT Bombay (India)

    2013-02-05

    With an increasing demand of biocompatible bone substitutes for the treatment of bone diseases and bone tissue regeneration, bioactive glass composites are being tested to improvise the osteoconductive as well as osteoinductive properties. Nanobioactive glass (nBG) composites, having composition of SiO{sub 2} 70 mol%, CaO 26 mol % and P{sub 2}O{sub 5} 4 mol% were prepared by Freeze drying method using PEG-PPG-PEG co-polymer. Polymer addition improves the mechanical strength and porosity of the scaffold of nBG. Nano Bioactive glass composites upon implantation undergo specific reactions leading to the formation of crystalline hydroxyapatite (HA). This is tested in vitro using Simulated Body Fluid (SBF). This high strength hydroxyapatite (HA) layer acts as osteoconductive in cellular environment, by acting as mineral base of bones, onto which new bone cells proliferate leading to new bone formation. Strength of the nBG composites as well as HA is in the range of cortical and cancellous bone, thus proving significant for bone tissue regeneration substitutes.

  8. Development of high strength hydroxyapatite for bone tissue regeneration using nanobioactive glass composites

    International Nuclear Information System (INIS)

    With an increasing demand of biocompatible bone substitutes for the treatment of bone diseases and bone tissue regeneration, bioactive glass composites are being tested to improvise the osteoconductive as well as osteoinductive properties. Nanobioactive glass (nBG) composites, having composition of SiO2 70 mol%, CaO 26 mol % and P2O5 4 mol% were prepared by Freeze drying method using PEG-PPG-PEG co-polymer. Polymer addition improves the mechanical strength and porosity of the scaffold of nBG. Nano Bioactive glass composites upon implantation undergo specific reactions leading to the formation of crystalline hydroxyapatite (HA). This is tested in vitro using Simulated Body Fluid (SBF). This high strength hydroxyapatite (HA) layer acts as osteoconductive in cellular environment, by acting as mineral base of bones, onto which new bone cells proliferate leading to new bone formation. Strength of the nBG composites as well as HA is in the range of cortical and cancellous bone, thus proving significant for bone tissue regeneration substitutes.

  9. Bone morphogenetic protein-2 is a negative regulator of hepatocyte proliferation downregulated in the regenerating liver

    NARCIS (Netherlands)

    Xu, Cui-Ping; Ji, Wen-Min; van den Brink, Gijs R.; Peppelenbosch, Maikel P.

    2006-01-01

    AIM: To characterize the expression and dynamic changes of bone morphogenetic protein (BMP)-2 in hepatocytes in the regenerating liver in rats after partial hepatectomy (PH), and examine the effects of BMP-2 on proliferation of human Huh7 hepatoma cells. METHODS: Fifty-four adult male Wistar rats we

  10. Bioinspired nanocomposite structures for bone tissue regeneration based on collagen, gelatin, polyamide and hydroxyapatite

    Czech Academy of Sciences Publication Activity Database

    Suchý, Tomáš; Balík, Karel; Šupová, Monika; Hrušková, Daniela; Sucharda, Zbyněk; Černý, Martin; Sedláček, R.

    2009-01-01

    Roč. 12, 89-91 (2009), s. 13-15. ISSN 1429-7248 R&D Projects: GA ČR GA106/09/1000 Institutional research plan: CEZ:AV0Z30460519 Keywords : nanocomposite * bone regeneration * collagen Subject RIV: JI - Composite Materials

  11. Physicochemical properties and applications of poly(lactic-co-glycolic acid) for use in bone regeneration

    NARCIS (Netherlands)

    Lanao, R.P.; Jonker, A.M.; Wolke, J.G.C.; Jansen, J.A.; Hest, J.C. van; Leeuwenburgh, S.C.G.

    2013-01-01

    Poly(lactic-co-glycolic acid) (PLGA) is the most often used synthetic polymer within the field of bone regeneration owing to its biocompatibility and biodegradability. As a consequence, a large number of medical devices comprising PLGA have been approved for clinical use in humans by the American Fo

  12. Production and characterization of chitosan/gelatin/β-TCP scaffolds for improved bone tissue regeneration

    Energy Technology Data Exchange (ETDEWEB)

    Serra, I.R.; Fradique, R.; Vallejo, M.C.S.; Correia, T.R.; Miguel, S.P.; Correia, I.J., E-mail: icorreia@ubi.pt

    2015-10-01

    Recently, bone tissue engineering emerged as a viable therapeutic alternative, comprising bone implants and new personalized scaffolds to be used in bone replacement and regeneration. In this study, biocompatible scaffolds were produced by freeze-drying, using different formulations (chitosan, chitosan/gelatin, chitosan/β-TCP and chitosan/gelatin/β-TCP) to be used as temporary templates during bone tissue regeneration. Sample characterization was performed through attenuated total reflectance-Fourier transform infrared spectroscopy, X-ray diffraction and energy dispersive spectroscopy analysis. Mechanical characterization and porosity analysis were performed through uniaxial compression test and liquid displacement method, respectively. In vitro studies were also done to evaluate the biomineralization activity and the cytotoxic profile of the scaffolds. Scanning electron and confocal microscopy analysis were used to study cell adhesion and proliferation at the scaffold surface and within their structure. Moreover, the antibacterial activity of the scaffolds was also evaluated through the agar diffusion method. Overall, the results obtained revealed that the produced scaffolds are bioactive and biocompatible, allow cell internalization and show antimicrobial activity against Staphylococcus aureus. Such, make these 3D structures as potential candidates for being used on the bone tissue regeneration, since they promote cell adhesion and proliferation and also prevent biofilm development at their surfaces, which is usually the main cause of implant failure. - Highlights: • Production of 3D scaffolds composed by chitosan/gelatin/β-TCP by freeze-drying for bone regeneration • Physicochemical characterization of the bone substitutes by SEM, FTIR, XRD and EDS • Evaluation of the cytotoxic profile and antibacterial activity of the 3D structures through in vitro assays.

  13. Production and characterization of chitosan/gelatin/β-TCP scaffolds for improved bone tissue regeneration

    International Nuclear Information System (INIS)

    Recently, bone tissue engineering emerged as a viable therapeutic alternative, comprising bone implants and new personalized scaffolds to be used in bone replacement and regeneration. In this study, biocompatible scaffolds were produced by freeze-drying, using different formulations (chitosan, chitosan/gelatin, chitosan/β-TCP and chitosan/gelatin/β-TCP) to be used as temporary templates during bone tissue regeneration. Sample characterization was performed through attenuated total reflectance-Fourier transform infrared spectroscopy, X-ray diffraction and energy dispersive spectroscopy analysis. Mechanical characterization and porosity analysis were performed through uniaxial compression test and liquid displacement method, respectively. In vitro studies were also done to evaluate the biomineralization activity and the cytotoxic profile of the scaffolds. Scanning electron and confocal microscopy analysis were used to study cell adhesion and proliferation at the scaffold surface and within their structure. Moreover, the antibacterial activity of the scaffolds was also evaluated through the agar diffusion method. Overall, the results obtained revealed that the produced scaffolds are bioactive and biocompatible, allow cell internalization and show antimicrobial activity against Staphylococcus aureus. Such, make these 3D structures as potential candidates for being used on the bone tissue regeneration, since they promote cell adhesion and proliferation and also prevent biofilm development at their surfaces, which is usually the main cause of implant failure. - Highlights: • Production of 3D scaffolds composed by chitosan/gelatin/β-TCP by freeze-drying for bone regeneration • Physicochemical characterization of the bone substitutes by SEM, FTIR, XRD and EDS • Evaluation of the cytotoxic profile and antibacterial activity of the 3D structures through in vitro assays

  14. Effects of two types of anorganic bovine bone on bone regeneration: a histological and histomorphometric study of rabbit calvaria.

    Directory of Open Access Journals (Sweden)

    Mojgan Paknejad

    2014-12-01

    Full Text Available The purpose of this study was to evaluate the efficacy of two types of bone substitutes, Bio-Oss and NuOss, for repair of bone defects.This study was performed on the calvaria of 14 New Zealand rabbits. The 6mm critical size defect (CSD models of bone regeneration were used. Three CSDs were created in each surgical site. The first defect was filled with NuOss, the second one with Bio-Oss and the third one remained unfilled as the control. After healing periods of one and two months (seven animal for each time point, histological and histomorphometric analyses were carried out to assess the amount of new bone formation, presence of inflammation, foreign body reaction and type of new bone. Qualitative variables were analyzed by multiple comparisons, Wilcoxon, Friedman and Mann Whitney tests. Quantitative variables were analyzed using the Mann-Whitney and Wilcoxon tests. Level of statistical significance was set at 0.05.The level of inflammation was not significantly different at four and eight weeks in the Bio-Oss (P=0.944, NuOss (P=1.000 and control groups (P=0.71. At four weeks, foreign body reaction was not observed in Bio-Oss, NuOss and control groups. There was no significant difference in the type of the newly formed bone at four and eight weeks in any group (P=0.141 for Bio-Oss, P=0.06 for NuOss and P=0.389 for the control group.Deproteinized bovine bone mineral can be used as a scaffold in bone defects to induce bone regeneration.

  15. Evaluating the Bone Tissue Regeneration Capability of the Chinese Herbal Decoction Danggui Buxue Tang from a Molecular Biology Perspective

    OpenAIRE

    Wen-Ling Wang; Shi-Yuan Sheu; Yueh-Sheng Chen; Shung-Te Kao; Yuan-Tsung Fu; Tzong-Fu Kuo; Kuo-Yu Chen; Chun-Hsu Yao

    2014-01-01

    Large bone defects are a considerable challenge to reconstructive surgeons. Numerous traditional Chinese herbal medicines have been used to repair and regenerate bone tissue. This study investigated the bone regeneration potential of Danggui Buxue Tang (DBT), a Chinese herbal decoction prepared from Radix Astragali (RA) and Radix Angelicae Sinensis (RAS), from a molecular biology perspective. The optimal ratio of RA and RAS used in DBT for osteoblast culture was obtained by colorimetric and a...

  16. Bone Regeneration in Iliac Crestal Defects: An Experimental Study on Sheep

    Science.gov (United States)

    Lorusso, Felice; Ravera, Lorenzo; Mortellaro, Carmen; Piattelli, Adriano

    2016-01-01

    Background. Oral rehabilitation of partially fully edentulous patients with dental implants has become a routine procedure in clinical practice. In a site with a lack of bone GBR is a surgical procedure that provides an augmentation in terms of volume for the insertion of dental implants. Materials and Methods. In the iliac crest of six sheep 4 defects were created where an implant was inserted, three of them with different biomaterials and a control site. All animals were sacrificed after a 4-month healing period. All specimens were processed and analyzed with histomorphometry. Statistical evaluation was done to evaluate percentage of bone defect filled by new bone. Results. All experimental groups showed an increase of the new bone. Higher and highly statistically significant differences were found in the percentages of bone defect filled by new bone in group filled with corticocancellous 250–1000 microns particulate porcine bone mix. Conclusions. This study demonstrates that particulate porcine bone mix and porcine corticocancellous collagenate prehydrated bone mix when used as scaffold are able to induce bone regeneration. Moreover, these data suggest that these biomaterials have higher biocompatibility and are capable of inducing faster and greater bone formation. PMID:27413746

  17. LIVER AND BONE MARROW STEM/PROGENITOR CELLS AS REGULATORS OF REPARATIVE REGENERATION OF DAMAGED LIVER

    Directory of Open Access Journals (Sweden)

    А. V. Lundup

    2010-01-01

    Full Text Available In this review the modern information about effectiveness of liver insufficiency treatment by stem/ progenitor cells of liver (oval cells and bone marrow (hemopoietic cells and mesenchymal cells was presented. It is shown that medical action of these cells is referred on normalization of liver cell interaction and reorganization of processes of a reparative regeneration in damaged liver. It is believed that application of mesenchymal stromal cells from an autological bone marrow is the most perspective strategy. However, for definitive judgement about regenerative possibilities of the autological bone marrow cells it is necessary to carry out large-scale double blind clinical researches. 

  18. Development of electrospun nanofibrous-based scaffolds for bone regeneration

    OpenAIRE

    Martins, Albino

    2010-01-01

    Biomaterials and scaffolds play a significant role in many strategies followed in regenerative medicine and tissue engineering. Those systems are intended and designed to help and guide the cells to contribute for the tissue regeneration process. To achieve that goal, the system needs to actively participate in the signaling process for the cells. It is widely believed that a successful scaffold should mimic the main properties and structure of the extracellular matrix of the tiss...

  19. Bone defect regeneration and cortical bone parameters of type 2 diabetic rats are improved by insulin therapy.

    Science.gov (United States)

    Picke, A-K; Gordaliza Alaguero, I; Campbell, G M; Glüer, C-C; Salbach-Hirsch, J; Rauner, M; Hofbauer, L C; Hofbauer, C

    2016-01-01

    Zucker Diabetic Fatty (ZDF) rats represent an established model of type 2 diabetes mellitus (T2DM) and display several features of human diabetic bone disease, including impaired osteoblast function, decreased bone strength, and delayed bone healing. Here, we determined whether glycemic control by insulin treatment prevents skeletal complications associated with diabetes. Subcritical femur defects were created in diabetic (fa/fa) and non-diabetic (+/+) ZDF rats. Diabetic rats were treated once daily with long-lasting insulin glargin for 12weeks for glycemic control. Insulin treatment successfully maintained serum levels of glycated hemoglobin, while untreated diabetic rats showed a 2-fold increase. Trabecular and cortical bone mass measured by μCT were decreased in diabetic rats. Insulin treatment increased bone mass of the cortical, but not of the trabecular bone compartment. Dynamic histomorphometry revealed a lower bone formation rate at the trabecular and periosteal cortical bone in diabetic animals and decreased serum procollagen type 1 N-terminal propeptide (P1NP, -49%) levels. Insulin treatment partially improved these parameters. In T2DM, serum levels of tartrate-resistant acid phosphatase (TRAP, +32%) and C-terminal telopeptide (CTX, +49%) were increased. Insulin treatment further elevated TRAP levels, but did not affect CTX levels. While diabetes impaired bone defect healing, glycemic control with insulin fully reversed these negative effects. In conclusion, insulin treatment reversed the adverse effects of T2DM on bone defect regeneration in rats mainly by improving osteoblast function and bone formation. This article is part of a Special Issue entitled Bone and diabetes. PMID:26055107

  20. Surface Functionalization of Titanium Alloy with miR-29b Nanocapsules To Enhance Bone Regeneration.

    Science.gov (United States)

    Meng, Yubin; Li, Xue; Li, Zhaoyang; Liu, Chaoyong; Zhao, Jin; Wang, Jianwei; Liu, Yunde; Yuan, Xubo; Cui, Zhenduo; Yang, Xianjin

    2016-03-01

    Titanium and its alloys have been widely used over the past 3 decades as implants for healing bone defects. Nevertheless, the bioinert property of titanium alloy limits its clinical application and surface modification method is frequently performed to improve the biological and chemical properties. Recently, the delivery of microRNA with osteogenesis capability has been recognized as a promising tool to enhance bone regeneration of implants. Here, we developed a biodegradable coating to modify the titanium surface in order to enhance osteogenic bioactivity. The previous developed nanocapsules were used as the building blocks, and then a bioactive titanium coating was designed to entrap the miR-29b nanocapsules. This coating was not only favorable for cell adhesion and growth but also provided sufficient microRNA transfection efficacy and osteoinductive potential, resulting in a significant enhancement of bone regeneration on the surface of bioinert titanium alloy. PMID:26887789

  1. Dose-response for bone regeneration after single doses of 60Co irradiation

    International Nuclear Information System (INIS)

    The Bone Growth Chamber (BGC) methodology was used to establish a dose-response relationship for regeneration of mature bone tissue after irradiation of 5, 8, 11, 15 and 25 Gy single dose 60Co. The BGC, which is a titanium implant, was inserted in the proximal tibial metaphyses, bilaterally, of a rabbit immediately following local irradiation to one tibia. Each animal thus served as its own control. During a healing period of 4 weeks, the two canals penetrating the implant became filled with more or less newly formed bone. At the end of the healing period, the implants were removed and taken apart and the newly formed bone was collected and its volume measured by microradiography and microdensitometry. It was found that in the dose range of 5 to 8 Gy bone regeneration was reduced by about 20% as compared to non-irradiated controls. Between 8 and 11 Gy, there was a critical range in that a small increase in dose resulted in a greatly reduced bone formation. At 11 Gy and above, the depression in bone formation, as compared to non-irradiated controls, was about 65 to 75%

  2. Skeletal Cell Fate Decisions Within Periosteum and Bone Marrow During Bone Regeneration

    OpenAIRE

    Colnot, Céline

    2008-01-01

    Bone repair requires the mobilization of adult skeletal stem cells/progenitors to allow deposition of cartilage and bone at the injury site. These stem cells/progenitors are believed to come from multiple sources including the bone marrow and the periosteum. The goal of this study was to establish the cellular contributions of bone marrow and periosteum to bone healing in vivo and to assess the effect of the tissue environment on cell differentiation within bone marrow and periosteum. Results...

  3. Functionalized D-form self-assembling peptide hydrogels for bone regeneration

    Directory of Open Access Journals (Sweden)

    He B

    2016-04-01

    Full Text Available Bin He,1 Yunsheng Ou,1 Ao Zhou,1 Shuo Chen,1 Weikang Zhao,1 Jinqiu Zhao,2 Hong Li,3 Yong Zhu,1 Zenghui Zhao,1 Dianming Jiang1 1Department of Orthopedics, 2Department of Infectious Diseases, The First Affiliated Hospital of Chongqing Medical University, Chongqing, People’s Republic of China; 3School of Physical Science and Technology, Sichuan University, Chengdu, People’s Republic of China Abstract: Bone defects are very common in orthopedics, and there is great need to develop suitable bone grafts for transplantation in vivo. However, current bone grafts still encounter some limitations, including limited availability, immune rejection, poor osteoinduction and osteoconduction, poor biocompatibility and degradation properties, etc. Self-assembling peptide nanofiber scaffolds have emerged as an important substrate for cell culture and bone regeneration. We report on the structural features (eg, Congo red staining, circular dichroism spectroscopy, transmission electron microscopy, and rheometry assays and osteogenic ability of D-RADA16-RGD peptide hydrogels (with or without basic fibroblast growth factor due to the better stability of peptide bonds formed by these peptides compared with those formed by L-form peptides, and use them to fill the femoral condyle defect of Sprague Dawley rat model. The bone morphology change, two-dimensional reconstructions using microcomputed tomography, quantification of the microcomputed tomography analyses as well as histological analyses have demonstrated that RGD-modified D-form peptide scaffolds are able to enhance extensive bone regeneration. Keywords: bone defect, functionalized D-form self-assembling peptide, D-RADA16-RGD, peptide hydrogel, bone regeneration

  4. Optimization of tyrosine-derived polycarbonate terpolymers for bone regeneration scaffolds

    Science.gov (United States)

    Resurreccion-Magno, Maria Hanshella C.

    Tyrosine-derived polycarbonates (TyrPC) are a versatile class of polymers highly suitable for bone tissue engineering. Among the tyrosine-derived polycarbonates, poly(DTE carbonate) has an FDA masterfile that documents its biocompatibility and non-toxicity and has shown potential utility in orthopedics due to its osteoconductive properties and strength. DTE stands for desaminotyrosyl-tyrosine ethyl ester and is the most commonly used tyrosine-derived monomer. However, in vitro degradation studies showed that poly(DTE carbonate) did not completely resorb even after four years of incubation in phosphate buffered saline. Thus for bone regeneration, which only requires a temporary implant until the bone heals, poly(DTE carbonate) would not be the best choice. The goal of the present research was to optimize a scaffold composition for bone regeneration that is based on desaminotyrosyl-tyrosine alkyl ester (DTR), desaminotyrosyl-tyrosine (DT) and poly(ethylene glycol) (PEG). Five areas of research were presented: (1) synthesis and characterization of a focused library of TyrPC terpolymers; (2) evaluation of the effects of how small changes on the composition affected the mechanism and kinetics of polymer degradation and erosion; (3) fabrication of bioactive three-dimensional porous scaffold constructs for bone regeneration; (4) assessment of osteogenic properties in vitro using pre-osteoblasts; and (5) evaluation of bone regeneration potential, with or without recombinant human bone morphogenetic protein-2 (rhBMP-2), in vivo using a critical sized defect (CSD) rabbit calvaria (cranium) model. Small changes in the composition, such as changing the R group of DTR from ethyl to methyl, varying the mole percentages of DT and PEG, and using a different PEG block length, affected the overall properties of these polymers. Porous scaffolds were prepared by a combination of solvent casting, porogen leaching and phase separation techniques. Calcium phosphate was coated on the

  5. Composite biopolymers for bone regeneration enhancement in bony defects.

    Science.gov (United States)

    Jahan, K; Tabrizian, M

    2016-01-01

    For the past century, various biomaterials have been used in the treatment of bone defects and fractures. Their role as potential substitutes for human bone grafts increases as donors become scarce. Metals, ceramics and polymers are all materials that confer different advantages to bone scaffold development. For instance, biocompatibility is a highly desirable property for which naturally-derived polymers are renowned. While generally applied separately, the use of biomaterials, in particular natural polymers, is likely to change, as biomaterial research moves towards mixing different types of materials in order to maximize their individual strengths. This review focuses on osteoconductive biocomposite scaffolds which are constructed around natural polymers and their performance at the in vitro/in vivo stages and in clinical trials. PMID:26317131

  6. 3D-Printed Scaffolds and Biomaterials: Review of Alveolar Bone Augmentation and Periodontal Regeneration Applications

    Science.gov (United States)

    Asa'ad, Farah; Giannì, Aldo Bruno; Giannobile, William V.; Rasperini, Giulio

    2016-01-01

    To ensure a successful dental implant therapy, the presence of adequate vertical and horizontal alveolar bone is fundamental. However, an insufficient amount of alveolar ridge in both dimensions is often encountered in dental practice due to the consequences of oral diseases and tooth loss. Although postextraction socket preservation has been adopted to lessen the need for such invasive approaches, it utilizes bone grafting materials, which have limitations that could negatively affect the quality of bone formation. To overcome the drawbacks of routinely employed grafting materials, bone graft substitutes such as 3D scaffolds have been recently investigated in the dental field. In this review, we highlight different biomaterials suitable for 3D scaffold fabrication, with a focus on “3D-printed” ones as bone graft substitutes that might be convenient for various applications related to implant therapy. We also briefly discuss their possible adoption for periodontal regeneration. PMID:27366149

  7. In vivo evaluation of a simvastatin-loaded nanostructured lipid carrier for bone tissue regeneration

    Science.gov (United States)

    Yue, Xinxin; Niu, Mao; Zhang, Te; Wang, Cheng; Wang, Zhonglei; Wu, Wangxi; Zhang, Qi; Lai, Chunhua; Zhou, Lei

    2016-03-01

    Alveolar bone loss has long been a challenge in clinical dental implant therapy. Simvastatin (SV) has been demonstrated to exert excellent anabolic effects on bone. However, the successful use of SV to increase bone formation in vivo largely depends on the local concentration of SV at the site of action, and there have been continuing efforts to develop an appropriate delivery system. Specifically, nanostructured lipid carrier (NLC) systems have become a popular type of encapsulation carrier system. Therefore, SV-loaded NLCs (SNs) (179.4 nm in diameter) were fabricated in this study, and the osteogenic effect of the SNs was evaluated in a critical-sized rabbit calvarial defect. Our results revealed that the SNs significantly enhanced bone formation in vivo, as evaluated by hematoxylin and eosin (HE) staining, immunohistochemistry, and a fluorescence analysis. Thus, this novel nanostructured carrier system could be a potential encapsulation carrier system for SV in bone regeneration applications.

  8. Innovative Biomaterials Based on Collagen-Hydroxyapatite and Doxycycline for Bone Regeneration

    Directory of Open Access Journals (Sweden)

    Narcisa Mederle

    2016-01-01

    Full Text Available Bone regeneration is a serious challenge in orthopedic applications because of bone infections increase, tumor developing, and bone loss due to trauma. In this context, the aim of our study was to develop innovative biomaterials based on collagen and hydroxyapatite (25, 50, and 75% which mimic bone composition and prevent or treat infections due to doxycycline content. The biomaterials were obtained by freeze-drying in spongious forms and were characterized by water uptake capacity and microscopy. The in vitro release of doxycycline was also determined and established by non-Fickian drug transport mechanism. Among the studied biomaterials, the most suitable one to easily deliver the drug and mimic bone structure, having compact structure and lower capacity to uptake water, was the one with 75% hydroxyapatite and being cross-linked.

  9. Full regeneration of segmental bone defects using porous titanium implants loaded with BMP-2 containing fibrin gels

    Directory of Open Access Journals (Sweden)

    J van der Stok

    2015-03-01

    Full Text Available Regeneration of load-bearing segmental bone defects is a major challenge in trauma and orthopaedic surgery. The ideal bone graft substitute is a biomaterial that provides immediate mechanical stability, while stimulating bone regeneration to completely bridge defects over a short period. Therefore, selective laser melted porous titanium, designed and fine-tuned to tolerate full load-bearing, was filled with a physiologically concentrated fibrin gel loaded with bone morphogenetic protein-2 (BMP-2. This biomaterial was used to graft critical-sized segmental femoral bone defects in rats. As a control, porous titanium implants were either left empty or filled with a fibrin gels without BMP-2. We evaluated bone regeneration, bone quality and mechanical strength of grafted femora using in vivo and ex vivo µCT scanning, histology, and torsion testing. This biomaterial completely regenerated and bridged the critical-sized bone defects within eight weeks. After twelve weeks, femora were anatomically re-shaped and revealed open medullary cavities. More importantly, new bone was formed throughout the entire porous titanium implants and grafted femora regained more than their innate mechanical stability: torsional strength exceeded twice their original strength. In conclusion, combining porous titanium implants with a physiologically concentrated fibrin gels loaded with BMP-2 improved bone regeneration in load-bearing segmental defects. This material combination now awaits its evaluation in larger animal models to show its suitability for grafting load-bearing defects in trauma and orthopaedic surgery.

  10. Electrospun poly (3-hydroxybutyrate-co-3-hydroxyvalerate)/hydroxyapatite scaffold with unrestricted somatic stem cells for bone regeneration.

    Science.gov (United States)

    Biazar, Esmaeil; Heidari Keshel, Saeed

    2015-01-01

    The combination of scaffolds and cells can be useful in tissue reconstruction. In this study, nanofibrous poly (3-hydroxybutyrate-co-3-hydroxyvalerate) (PHBV)/nanohydroxyapatite (nano-HAp) scaffolds, filled with unrestricted somatic stem cells (USSCs), were used for healing calvarial bone in rat model. The healing effects of these scaffolds, with and without stem cells, in bone regeneration were investigated by computed tomography (CT) analysis and pathology assays after 28 days of grafting. The results of CT analysis showed that bone regeneration on the scaffolds, and the amounts of regenerated new bone for polymer/nano-HAp scaffold with USSC, was significantly greater than the scaffold without cell and untreated control samples. Therefore, the combination of scaffold especially with USSC could be considered as a useful method for bone regeneration. PMID:25710767

  11. Electrospun PVA-PCL-HAB scaffold for craniofacial bone regeneration

    DEFF Research Database (Denmark)

    Prabha, Rahul; Kraft, David Christian Evar; Melsen, Birte;

    2015-01-01

    Bone tissue engineering for craniofacial region is considered challenging owing to its physiologic and anatomical complexities. A porous bioactive scaffold promoting osteogenesis and angio- genesis is required for clinical applications. We have developed an electrospun polyvinyl alcohol (PVA) poly-caprolactone...

  12. Converted marine coral hydroxyapatite implants with growth factors: In vivo bone regeneration

    Energy Technology Data Exchange (ETDEWEB)

    Nandi, Samit K., E-mail: samitnandi1967@gmail.com [Department of Veterinary Surgery and Radiology, West Bengal University of Animal and Fishery Sciences, Kolkata (India); Kundu, Biswanath, E-mail: biswa_kundu@rediffmail.com [Bioceramics and Coating Division, CSIR-Central Glass and Ceramic Research Institute, Kolkata (India); Mukherjee, Jayanta [Institute of Animal Health and Veterinary Biologicals, Kolkata (India); Mahato, Arnab; Datta, Someswar; Balla, Vamsi Krishna [Bioceramics and Coating Division, CSIR-Central Glass and Ceramic Research Institute, Kolkata (India)

    2015-04-01

    Herein we report rabbit model in vivo bone regeneration of hydrothermally converted coralline hydroxyapatite (HCCHAp) scaffolds without (group I) and with growth factors namely insulin like growth factor-1 (IGF-1) (group II) and bone morphogenetic protein-2 (BMP-2) (group III). All HCCHAp scaffolds have been characterized for phase purity and morphology before implantation. Calcined marine coral was hydrothermally converted using a mineralizer/catalyst to phase pure HAp retaining original pore structure and geometry. After sintering at 1250 °C, the HCCHAp found to have ~ 87% crystallinity, 70–75% porosity and 2 ± 0.5 MPa compressive strength. In vitro growth factor release study at day 28 revealed 77 and 98% release for IGF-1 and BMP-2, respectively. The IGF-1 release was more sustained than BMP-2. In vivo bone healing of different groups was compared using chronological radiology, histological evaluations, scanning electron microscopy and fluorochrome labeling up to 90 days of implantation. In vivo studies showed substantial reduction in radiolucent zone and decreased radiodensity of implants in group II followed by group III and group I. These observations clearly suggest in-growth of osseous tissue, initiation of bone healing and complete union between implants and natural bone in group II implants. A statistical score sheet based on histological observations showed an excellent osseous tissue formation in group II and group III scaffolds and moderate bone regeneration in group I scaffolds. - Highlights: • In vivo bone regeneration of hydrothermally converted coralline hydroxyapatite • Scaffolds with and without growth factors (IGF-1 and BMP-2) • In vitro drug release was more sustained for IGF-1 than BMP-2. • Growth factor significantly improved osseous tissue formation of implanted scaffold. • Established through detailed statistical score sheet from histological observations.

  13. Converted marine coral hydroxyapatite implants with growth factors: In vivo bone regeneration

    International Nuclear Information System (INIS)

    Herein we report rabbit model in vivo bone regeneration of hydrothermally converted coralline hydroxyapatite (HCCHAp) scaffolds without (group I) and with growth factors namely insulin like growth factor-1 (IGF-1) (group II) and bone morphogenetic protein-2 (BMP-2) (group III). All HCCHAp scaffolds have been characterized for phase purity and morphology before implantation. Calcined marine coral was hydrothermally converted using a mineralizer/catalyst to phase pure HAp retaining original pore structure and geometry. After sintering at 1250 °C, the HCCHAp found to have ~ 87% crystallinity, 70–75% porosity and 2 ± 0.5 MPa compressive strength. In vitro growth factor release study at day 28 revealed 77 and 98% release for IGF-1 and BMP-2, respectively. The IGF-1 release was more sustained than BMP-2. In vivo bone healing of different groups was compared using chronological radiology, histological evaluations, scanning electron microscopy and fluorochrome labeling up to 90 days of implantation. In vivo studies showed substantial reduction in radiolucent zone and decreased radiodensity of implants in group II followed by group III and group I. These observations clearly suggest in-growth of osseous tissue, initiation of bone healing and complete union between implants and natural bone in group II implants. A statistical score sheet based on histological observations showed an excellent osseous tissue formation in group II and group III scaffolds and moderate bone regeneration in group I scaffolds. - Highlights: • In vivo bone regeneration of hydrothermally converted coralline hydroxyapatite • Scaffolds with and without growth factors (IGF-1 and BMP-2) • In vitro drug release was more sustained for IGF-1 than BMP-2. • Growth factor significantly improved osseous tissue formation of implanted scaffold. • Established through detailed statistical score sheet from histological observations

  14. Bone regeneration in cranioplasty and clinical complications in rabbits with alloxan-induced diabetes

    Directory of Open Access Journals (Sweden)

    Evanice Menezes Marçal Vieira

    2008-06-01

    Full Text Available This research evaluated the bone repair process in surgical defects created on the parietal bones of diabetic rabbits using the guided bone regeneration technique to observe the effects of alloxan in the induction of diabetes mellitus. Twenty-four adult rabbits were divided into three study groups: control (C, diabetic (D and diabetic associated to polytetrafluoroethylene (PTFE membrane (D-PTFE. For diabetes induction the animals received one dose of monohydrated alloxan (90 mg/kg by intravenous administration in the auricular or femoral vein. In group D-PTFE the membrane covered both the floor and the surface of the bone defect. In groups D and C, the bone defect was filled up with blood clot. The specimens were fixed in 10% formol and prepared for histomorphometric analysis. The results showed that the 90 mg/kg dose of monohydrate alloxan was sufficient to promote diabetes mellitus when administered in the auricular vein. Bone regeneration was slower in the diabetic group when compared with the control and diabetic-PTFE groups, but there was no significant statistical difference between the two experimental groups (D and D-PTFE. The oral and general clinical complications among the diabetics were weight loss, polyuria, polyphagia and severe chronic gingivitis.

  15. Biomimetic treatment on dental implants for short -term bone regeneration

    OpenAIRE

    Gil Mur, Francisco Javier; Manzanares, Norberto; Badet de Mena, Armando; Aparicio Bádenas, Conrado José; Ginebra Molins, Maria Pau

    2013-01-01

    Objectives The main purpose of this work was to assess the short-term bone regenerative potential of new osteoconductive implants. The novelty of the study lies in the analysis of the effectiveness of a novel two-step treatment which combines shot-blasting with a thermo-chemical treatment, at very short times after implant placement in a minipig model. Materials and methods Three hundred twenty implants with four different surface treatments, namely bioactivated sur...

  16. Titanium Foam-Bioactive Nanofiber Hybrids for Bone Regeneration

    OpenAIRE

    Sargeant, Timothy D; Oppenheimer, Scott M.; Dunand, David C.; Stupp, Samuel I.

    2008-01-01

    We have reported previously a method to introduce bioactive nanofiber networks through self-assembly into the pores of titanium alloy foams for bone repair. In this study we evaluate the in vitro colonization by mouse pre-osteoblastic cells of these metal-peptide amphiphile hybrids containing phosphoserine residues and the RGDS epitope. The aim was to determine the effect of varying the RGDS epitope concentration within a given range, and confirm the ability for cells to infiltrate and surviv...

  17. [Mandibular bone tissue regeneration after the introduction of the implantation system performed on the basis of carbon composite material].

    Science.gov (United States)

    Chetvertnykh, V A; Loginova, N P; Astashina, N B; Rogozhnikov, G I; Rapekta, S I

    2013-01-01

    The purpose of this study was to investigate the processes of regeneration of bone tissue after the introduction of new implant systems. In the experiment, performed on 10 male pigs of Landras breed aged 50-55 days and weighing 17-18.5 kg, the time course of histological changes was studied in the area of mandibular regeneration after the formation of tissue defect and the introduction of the implant of a proposed construction. Morphological analysis of the experimental results 90, 180 and 270 days after the operation demonstrated the process of reparative regeneration of damaged bone along implant-bone block boundaries. Bone repair proceeded through the stage of formation of the woven bone with its progressive substitution by the lamellar bone, with the maintenance of the shape, size and symmetry of the damaged organ. PMID:23805619

  18. Mandibular Jaw Bone Regeneration Using Human Dental Cell-Seeded Tyrosine-Derived Polycarbonate Scaffolds.

    Science.gov (United States)

    Zhang, Weibo; Zhang, Zheng; Chen, Shuang; Macri, Lauren; Kohn, Joachim; Yelick, Pamela C

    2016-07-01

    Here we present a new model for alveolar jaw bone regeneration, which uses human dental pulp cells (hDPCs) combined with tyrosine-derived polycarbonate polymer scaffolds [E1001(1k)] containing beta-tricalcium phosphate (β-TCP) [E1001(1k)/β-TCP]. E1001(1k)/β-TCP scaffolds (5 mm diameter × 1 mm thickness) were fabricated to fit a 5 mm rat mandibular ramus critical bone defect. Five experimental groups were examined in this study: (1) E1001(1k)/β-TCP scaffolds seeded with a high density of hDPCs, 5.0 × 10(5) hDPCs/scaffold (CH); (2) E1001(1k)/β-TCP scaffolds seeded with a lower density of hDPCs, 2.5 × 10(5) hDPCs/scaffold (CL); (3) acellular E1001(1k)/β-TCP scaffolds (SA); (4) acellular E1001(1k)/β-TCP scaffolds supplemented with 4 μg recombinant human bone morphogenetic protein-2 (BMP); and (5) empty defects (EDs). Replicate hDPC-seeded and acellular E1001(1k)/β-TCP scaffolds were cultured in vitro in osteogenic media for 1 week before implantation for 3 and 6 weeks. Live microcomputed tomography (μCT) imaging at 3 and 6 weeks postimplantation revealed robust bone regeneration in the BMP implant group. CH and CL groups exhibited similar uniformly distributed mineralized tissue coverage throughout the defects, but less than the BMP implants. In contrast, SA-treated defects exhibited sparse areas of mineralized tissue regeneration. The ED group exhibited slightly reduced defect size. Histological analyses revealed no indication of an immune response. In addition, robust expression of dentin and bone differentiation marker expression was observed in hDPC-seeded scaffolds, whereas, in contrast, BMP and SA implants exhibited only bone and not dentin differentiation marker expression. hDPCs were detected in 3-week but not in 6-week hDPC-seeded scaffold groups, indicating their survival for at least 3 weeks. Together, these results show that hDPC-seeded E1001(1k)/β-TCP scaffolds support the rapid regeneration of osteo

  19. Guided bone regeneration (GBR) using cortical bone pins in combination with leukocyte- and platelet-rich fibrin (L-PRF).

    Science.gov (United States)

    Toffler, Michael

    2014-03-01

    Two of the fundamental requisites for guided bone regeneration (GBR) are space maintenance and primary soft-tissue closure. Allogeneic cortical bone pins measuring 2 mm in diameter in customized lengths can protect surrounding graft materials, support bioresorbable membrane barriers, and resist wound compression from the overlying soft tissues. In addition, a second-generation platelet concentrate, leukocyte- and platelet-rich fibrin (L-PRF), may be incorporated into the augmentation procedure to provide multiple growth factors, accelerate wound healing, and aid in the maintenance of primary closure over the grafted materials. Highlighting two case reports, this article features a GBR technique that uses bone pins in combination with L-PRF membranes to provide both horizontal and vertical ridge augmentation at severely compromised implant sites. PMID:24773199

  20. A Comparative Study of Bioartificial Bone Tissue Poly-L-lactic Acid/Polycaprolactone and PLLA Scaffolds Applied in Bone Regeneration

    Directory of Open Access Journals (Sweden)

    Weizong Weng

    2014-01-01

    Full Text Available Bioartificial bone tissue engineering is an increasingly popular technique to repair bone defect caused by injury or disease. This study aimed to investigate the feasibility of PLLA/PCL (poly-L-lactic acid/polycaprolactone by a comparison study of PLLA/PCL and PLLA scaffolds applied in bone regeneration. Thirty healthy mature New Zealand rabbits on which 15 mm distal ulna defect model had been established were selected and then were divided into three groups randomly: group A (repaired with PLLA scaffold, group B (repaired with PLLA/PCL scaffold, and group C (no scaffold to evaluate the bone-remodeling ability of the implants. Micro-CT examination revealed the prime bone regeneration ability of group B in three groups. Bone mineral density of surgical site in group B was higher than group A but lower than group C. Meanwhile, the bone regeneration in both groups A and B proceeded with signs of inflammation for the initial fast degradation of scaffolds. As a whole, PLLA/PCL scaffolds in vivo initially degrade fast and were better suited to repair bone defect than PLLA in New Zealand rabbits. Furthermore, for the low mineral density of new bone and rapid degradation of the scaffolds, more researches were necessary to optimize the composite for bone regeneration.

  1. Extracellular matrix-inspired growth factor delivery systems for bone regeneration

    Energy Technology Data Exchange (ETDEWEB)

    Martino, Mikaël M. [Osaka Univ. (Japan). Immunology Frontier Research Center; Briquez, Priscilla S. [Ecole Polytechnique Federale de Lausanne (Switzerland). Inst. of Bioengineering; Maruyama, Kenta [Osaka Univ. (Japan). Immunology Frontier Research Center; Hubbell, Jeffrey A. [Ecole Polytechnique Federale de Lausanne (Switzerland). Inst. of Bioengineering; Univ. of Chicago, IL (United States). Inst. for Molecular Engineering; Argonne National Lab. (ANL), Argonne, IL (United States)

    2015-04-17

    Growth factors are very promising molecules to enhance bone regeneration. However, their translation to clinical use has been seriously limited, facing issues related to safety and cost-effectiveness. These problems derive from the vastly supra-physiological doses of growth factor used without optimized delivery systems. Therefore, these issues have motivated the development of new delivery systems allowing better control of the spatio-temporal release and signaling of growth factors. Because the extracellular matrix (ECM) naturally plays a fundamental role in coordinating growth factor activity in vivo, a number of novel delivery systems have been inspired by the growth factor regulatory function of the ECM. After introducing the role of growth factors during the bone regeneration process, this review exposes different issues that growth factor-based therapies have encountered in the clinic and highlights recent delivery approaches based on the natural interaction between growth factor and the ECM.

  2. Nanostructured Tendon-Derived Scaffolds for Enhanced Bone Regeneration by Human Adipose-Derived Stem Cells.

    Science.gov (United States)

    Ko, Eunkyung; Alberti, Kyle; Lee, Jong Seung; Yang, Kisuk; Jin, Yoonhee; Shin, Jisoo; Yang, Hee Seok; Xu, Qiaobing; Cho, Seung-Woo

    2016-09-01

    Decellularized matrix-based scaffolds can induce enhanced tissue regeneration due to their biochemical, biophysical, and mechanical similarity to native tissues. In this study, we report a nanostructured decellularized tendon scaffold with aligned, nanofibrous structures to enhance osteogenic differentiation and in vivo bone formation of human adipose-derived stem cells (hADSCs). Using a bioskiving method, we prepared decellularized tendon scaffolds from tissue slices of bovine Achilles and neck tendons with or without fixation, and investigated the effects on physical and mechanical properties of decellularized tendon scaffolds, based on the types and concentrations of cross-linking agents. In general, we found that decellularized tendon scaffolds without fixative treatments were more effective in inducing osteogenic differentiation and mineralization of hADSCs in vitro. When non-cross-linked decellularized tendon scaffolds were applied together with hydroxyapatite for hADSC transplantation in critical-sized bone defects, they promoted bone-specific collagen deposition and mineralized bone formation 4 and 8 weeks after hADSC transplantation, compared to conventional collagen type I scaffolds. Interestingly, stacking of decellularized tendon scaffolds cultured with osteogenically committed hADSCs and those containing human cord blood-derived endothelial progenitor cells (hEPCs) induced vascularized bone regeneration in the defects 8 weeks after transplantation. Our study suggests that biomimetic nanostructured scaffolds made of decellularized tissue matrices can serve as functional tissue-engineering scaffolds for enhanced osteogenesis of stem cells. PMID:27502160

  3. Effect of a novel load-bearing trabecular Nitinol scaffold on rabbit radius bone regeneration

    International Nuclear Information System (INIS)

    The research aim was to evaluate the bone regeneration capability of novel load-bearing NiTi alloy (Nitinol) scaffolds in a critical-size defect (CSD) model. High strength “trabecular Nitinol” scaffolds were prepared by PIRAC (Powder Immersion Reaction Assisted Coating) annealing of the highly porous Ni foam in Ti powder at 900°C. This was followed by PIRAC nitriding to mitigate the release of potentially toxic Ni ions. Scaffolds phase composition and microstructure were characterized by X-ray diffraction and scanning electron microscopy (SEM/EDS), and their mechanical properties were tested in compression. New Zealand white rabbits received bone defect in right radius and were divided in four groups randomly. In the control group, nothing was placed in the defect. In other groups, NiTi scaffolds were implanted in the defect: (i) as produced, (ii) loaded with bone marrow aspirate (BMA), and (iii) biomimetically CaP-coated. The animals were sacrificed after 12 weeks. The forelimbs with scaffolds were resected, fixed, sectioned and examined in SEM. New bone formation inside the scaffold was studied by EDS analysis and by the processing of backscattered electron images. Bone ingrowth into the scaffold was observed in all implant groups, mostly next to the ulna. New bone formation was strongly enhanced by BMA loading and biomimeatic CaP coating, the bone penetrating as much as 1–1.5 mm into the scaffold. The results of this preliminary study demonstrate that the newly developed high strength trabecular Nitinol scaffolds can be successfully used for bone regeneration in critical size defects

  4. Effect of a novel load-bearing trabecular Nitinol scaffold on rabbit radius bone regeneration

    Science.gov (United States)

    Gotman, Irena; Zaretzky, Asaph; Psakhie, Sergey G.; Gutmanas, Elazar Y.

    2015-10-01

    The research aim was to evaluate the bone regeneration capability of novel load-bearing NiTi alloy (Nitinol) scaffolds in a critical-size defect (CSD) model. High strength "trabecular Nitinol" scaffolds were prepared by PIRAC (Powder Immersion Reaction Assisted Coating) annealing of the highly porous Ni foam in Ti powder at 900°C. This was followed by PIRAC nitriding to mitigate the release of potentially toxic Ni ions. Scaffolds phase composition and microstructure were characterized by X-ray diffraction and scanning electron microscopy (SEM/EDS), and their mechanical properties were tested in compression. New Zealand white rabbits received bone defect in right radius and were divided in four groups randomly. In the control group, nothing was placed in the defect. In other groups, NiTi scaffolds were implanted in the defect: (i) as produced, (ii) loaded with bone marrow aspirate (BMA), and (iii) biomimetically CaP-coated. The animals were sacrificed after 12 weeks. The forelimbs with scaffolds were resected, fixed, sectioned and examined in SEM. New bone formation inside the scaffold was studied by EDS analysis and by the processing of backscattered electron images. Bone ingrowth into the scaffold was observed in all implant groups, mostly next to the ulna. New bone formation was strongly enhanced by BMA loading and biomimeatic CaP coating, the bone penetrating as much as 1-1.5 mm into the scaffold. The results of this preliminary study demonstrate that the newly developed high strength trabecular Nitinol scaffolds can be successfully used for bone regeneration in critical size defects.

  5. Effect of a novel load-bearing trabecular Nitinol scaffold on rabbit radius bone regeneration

    Energy Technology Data Exchange (ETDEWEB)

    Gotman, Irena, E-mail: gotman@technion.ac.il; Gutmanas, Elazar Y., E-mail: gutmanas@technion.ac.il [Department of Materials Science and Engineering, Techion-Israel Institute of Technology, Haifa, 32000 Israel (Israel); National Research Tomsk Polytechnic University, Tomsk, 634050 (Russian Federation); Zaretzky, Asaph [The Bruce Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, Haifa, 31096 Israel (Israel); Psakhie, Sergey G. [National Research Tomsk Polytechnic University, Tomsk, 634050 (Russian Federation); Institute of Strength Physics and Materials Science SB RAS, Tomsk, 634055 (Russian Federation)

    2015-10-27

    The research aim was to evaluate the bone regeneration capability of novel load-bearing NiTi alloy (Nitinol) scaffolds in a critical-size defect (CSD) model. High strength “trabecular Nitinol” scaffolds were prepared by PIRAC (Powder Immersion Reaction Assisted Coating) annealing of the highly porous Ni foam in Ti powder at 900°C. This was followed by PIRAC nitriding to mitigate the release of potentially toxic Ni ions. Scaffolds phase composition and microstructure were characterized by X-ray diffraction and scanning electron microscopy (SEM/EDS), and their mechanical properties were tested in compression. New Zealand white rabbits received bone defect in right radius and were divided in four groups randomly. In the control group, nothing was placed in the defect. In other groups, NiTi scaffolds were implanted in the defect: (i) as produced, (ii) loaded with bone marrow aspirate (BMA), and (iii) biomimetically CaP-coated. The animals were sacrificed after 12 weeks. The forelimbs with scaffolds were resected, fixed, sectioned and examined in SEM. New bone formation inside the scaffold was studied by EDS analysis and by the processing of backscattered electron images. Bone ingrowth into the scaffold was observed in all implant groups, mostly next to the ulna. New bone formation was strongly enhanced by BMA loading and biomimeatic CaP coating, the bone penetrating as much as 1–1.5 mm into the scaffold. The results of this preliminary study demonstrate that the newly developed high strength trabecular Nitinol scaffolds can be successfully used for bone regeneration in critical size defects.

  6. In vitro and in vivo investigations on bone regeneration potential of laminated hydroxyapatite/gelatin nanocomposite scaffold along with DBM

    International Nuclear Information System (INIS)

    Bone regeneration ability of a scaffold strongly depends on its structure and the size of its components. In this study, a nanostructured scaffold was designed for bone repair using nano hydroxyapatite (nHA) (8–16 nm × 50–80 nm) and gelatin (GEL) as main components. In vitro investigations of calcium matrix deposition and gene expression of the seeded cells for this scaffold, demineralized bone matrix (DBM), scaffold plus DBM, and the control group were carried out. Bone regeneration in rat calvarium with critical defect size after 1, 4, and 8 weeks post implantation was investigated. The calcium matrix depositions by the osteoblast and RUNX2, ALP, osteonectin, and osteocalcin gene expression in scaffold were more significant than in other groups. Histomorphometry analysis confirmed in vitro results. In vitro and in vivo bone regeneration were least in scaffold plus DBM group. Enhanced effects in scaffold could be attributed to the shape and size of nHA particles and good architecture of the scaffold. Reduction of bone regeneration might be due to tight bonding of BMPs and nHA particles in the third group. Results obtained from this study confirmed that nano-scale size of the main components and the scaffold architecture (pore diameter, interconnectivity pores, etc.) have significant effects on bone regeneration ability of the scaffold and are important parameters in designing a temporary bone substitute.

  7. Clonal Characterization of Bone Marrow Derived Stem Cells and Their Application for Bone Regeneration

    OpenAIRE

    Xiao, Yin; Mareddy, Shobha; Crawford, Ross

    2010-01-01

    Tissue engineering allows the design of functionally active cells within supportive bio-scaffolds to promote the development of new tissues such as cartilage and bone for the restoration of pathologically altered tissues. However, all bone tissue engineering applications are limited by a shortage of stem cells. The adult bone marrow stroma contains a subset of nonhematopoietic cells referred to as bone marrow mesenchymal stem cells (BMSCs). BMSCs are of interest because they are easily isolat...

  8. Bilayered construct for simultaneous regeneration of alveolar bone and periodontal ligament.

    Science.gov (United States)

    Sundaram, M Nivedhitha; Sowmya, S; Deepthi, S; Bumgardener, Joel D; Jayakumar, R

    2016-05-01

    Periodontitis is an inflammatory disease that causes destruction of tooth-supporting tissues and if left untreated leads to tooth loss. Current treatments have shown limited potential for simultaneous regeneration of the tooth-supporting tissues. To recreate the complex architecture of the periodontium, we developed a bilayered construct consisting of poly(caprolactone) (PCL) multiscale electrospun membrane (to mimic and regenerate periodontal ligament, PDL) and a chitosan/2wt % CaSO4 scaffold (to mimic and regenerate alveolar bone). Scanning electron microscopy results showed the porous nature of the scaffold and formation of beadless electrospun multiscale fibers. The fiber diameter of microfiber and nanofibers was in the range of 10 ± 3 µm and 377 ± 3 nm, respectively. The bilayered construct showed better protein adsorption compared to the control. Osteoblastic differentiation of human dental follicle stem cells (hDFCs) on chitosan/2wt % CaSO4 scaffold showed maximum alkaline phosphatase at seventh day followed by a decline thereafter when compared to chitosan control scaffold. Fibroblastic differentiation of hDFCs was confirmed by the expression of PLAP-1 and COL-1 proteins which were more prominent on PCL multiscale membrane in comparison to control membranes. Overall these results show that the developed bilayered construct might serve as a good candidate for the simultaneous regeneration of the alveolar bone and PDL. © 2015 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 104B: 761-770, 2016. PMID:26153674

  9. The chemical NMP as a potent BMP enhancer for bone tissue regeneration

    OpenAIRE

    San Miguel, B; Ghayor, C; Ehrbar, M.; Jung, R.E.; Zwahlen, R A; Hortschansky, P; Schmökel, H G; Weber, F. E.

    2009-01-01

    In medicine N-methylpyrrolidone (NMP) has a long track record as constituent in FDA approved medical devices and thus can be considered as safe and biological inactive small chemical. In the present study we report on the newly discovered pharmaceutical properties of NMP as it enhances bone regeneration in a rabbit calvarial defect model in vivo. At the cellular level, the pharmaceutical effect of NMP was confirmed, in particular, in combination with BMP-2, as NMP increased early and late mar...

  10. Bioactive composite scaffolds for bone regeneration:from the process to the biological validation

    OpenAIRE

    Ronca, Alfredo

    2010-01-01

    In this work, we have discussed the preparation and characterization of composite scaffolds for bone regeneration. The scaffolds were made with different techniques: salt leaching / phase inversion,filament winding and stereolithography. The phase of preparation is followed by a characterization from a morphological, mechanical and biological point of view. Results were very promising especially regarding the biological response of the substrates that appear to be promising for future in v...

  11. Incorporation of copper into chitosan scaffolds promotes bone regeneration in rat calvarial defects

    OpenAIRE

    D'Mello, Sheetal; Elangovan, Satheesh; Hong, Liu; Ross, Ryan D.; Sumner, D. Rick; Salem, Aliasger K.

    2014-01-01

    The objective of this study was to investigate the effects of a copper loaded chitosan scaffold on bone regeneration in critical-sized calvarial defects in rats. Chitosan scaffolds and copper-chitosan scaffolds were fabricated and characterized by scanning electron microscopy (SEM). Chitosan and copper-chitosan scaffolds were implanted into 5 mm diameter critical-sized calvarial defects in Fisher 344 male rats. Empty defects (no scaffolds) were included as a control. After 4 weeks, the rats w...

  12. β-Cell Regeneration Mediated by Human Bone Marrow Mesenchymal Stem Cells

    OpenAIRE

    Anna Milanesi; Jang-Won Lee; Zhenhua Li; Stefano Da Sacco; Valentina Villani; Vanessa Cervantes; Laura Perin; Yu, John S.

    2012-01-01

    Bone marrow mesenchymal stem cells (BMSCs) have been shown to ameliorate diabetes in animal models. The mechanism, however, remains largely unknown. An unanswered question is whether BMSCs are able to differentiate into β-cells in vivo, or whether BMSCs are able to mediate recovery and/or regeneration of endogenous β-cells. Here we examined these questions by testing the ability of hBMSCs genetically modified to transiently express vascular endothelial growth factor (VEGF) or pancreatic-duode...

  13. Triphasic scaffolds for the regeneration of the bone-ligament interface.

    Science.gov (United States)

    Criscenti, G; Longoni, A; Di Luca, A; De Maria, C; van Blitterswijk, C A; Vozzi, G; Moroni, L

    2016-03-01

    A triphasic scaffold (TPS) for the regeneration of the bone-ligament interface was fabricated combining a 3D fiber deposited polycaprolactone structure and a polylactic co-glycolic acid electrospun. The scaffold presented a gradient of physical and mechanical properties which elicited different biological responses from human mesenchymal stem cells. Biological test were performed on the whole TPS and on scaffolds comprised of each single part of the TPS, considered as the controls. The TPS showed an increase of the metabolic activity with culturing time that seemed to be an average of the controls at each time point. The importance of differentiation media for bone and ligament regeneration was further investigated. Metabolic activity analysis on the different areas of the TPS showed a similar trend after 7 days in both differentiation media. Total alkaline phosphatase (ALP) activity analysis showed a statistically higher activity of the TPS in mineralization medium compared to the controls. A different glycosaminoglycans amount between the TPS and its controls was detected, displaying a similar trend with respect to ALP activity. Results clearly indicated that the integration of electrospinning and additive manufacturing represents a promising approach for the fabrication of scaffolds for the regeneration of tissue interfaces, such as the bone-to-ligament one, because it allows mimicking the structural environment combining different biomaterials at different scales. PMID:26824799

  14. Clinical Application of Mesenchymal Stem Cells and Novel Supportive Therapies for Oral Bone Regeneration

    Directory of Open Access Journals (Sweden)

    Miguel Padial-Molina

    2015-01-01

    Full Text Available Bone regeneration is often needed prior to dental implant treatment due to the lack of adequate quantity and quality of the bone after infectious diseases, trauma, tumor, or congenital conditions. In these situations, cell transplantation technologies may help to overcome the limitations of autografts, xenografts, allografts, and alloplastic materials. A database search was conducted to include human clinical trials (randomized or controlled and case reports/series describing the clinical use of mesenchymal stem cells (MSCs in the oral cavity for bone regeneration only specifically excluding periodontal regeneration. Additionally, novel advances in related technologies are also described. 190 records were identified. 51 articles were selected for full-text assessment, and only 28 met the inclusion criteria: 9 case series, 10 case reports, and 9 randomized controlled clinical trials. Collectively, they evaluate the use of MSCs in a total of 290 patients in 342 interventions. The current published literature is very diverse in methodology and measurement of outcomes. Moreover, the clinical significance is limited. Therefore, the use of these techniques should be further studied in more challenging clinical scenarios with well-designed and standardized RCTs, potentially in combination with new scaffolding techniques and bioactive molecules to improve the final outcomes.

  15. Development of Thermosensitive Hydrogels of Chitosan, Sodium and Magnesium Glycerophosphate for Bone Regeneration Applications

    Science.gov (United States)

    Lisková, Jana; Bačaková, Lucie; Skwarczyńska, Agata L.; Musial, Olga; Bliznuk, Vitaliy; De Schamphelaere, Karel; Modrzejewska, Zofia; Douglas, Timothy E.L.

    2015-01-01

    Thermosensitive injectable hydrogels based on chitosan neutralized with sodium beta-glycerophosphate (Na-β-GP) have been studied as biomaterials for drug delivery and tissue regeneration. Magnesium (Mg) has been reported to stimulate adhesion and proliferation of bone forming cells. With the aim of improving the suitability of the aforementioned chitosan hydrogels as materials for bone regeneration, Mg was incorporated by partial substitution of Na-β-GP with magnesium glycerophosphate (Mg-GP). Chitosan/Na-β-GP and chitosan/Na-β-GP/Mg-GP hydrogels were also loaded with the enzyme alkaline phosphatase (ALP) which induces hydrogel mineralization. Hydrogels were characterized physicochemically with respect to mineralizability and gelation kinetics, and biologically with respect to cytocompatibility and cell adhesion. Substitution of Na-β-GP with Mg-GP did not negatively influence mineralizability. Cell biological testing showed that both chitosan/Na-β-GP and chitosan/Na-β-GP/Mg-GP hydrogels were cytocompatible towards MG63 osteoblast-like cells. Hence, chitosan/Na-β-GP/Mg-GP hydrogels can be used as an alternative to chitosan/Na-β-GP hydrogels for bone regeneration applications. However the incorporation of Mg in the hydrogels during hydrogel formation did not bring any appreciable physicochemical or biological benefit. PMID:25859630

  16. Development of Thermosensitive Hydrogels of Chitosan, Sodium and Magnesium Glycerophosphate for Bone Regeneration Applications

    Directory of Open Access Journals (Sweden)

    Jana Lisková

    2015-04-01

    Full Text Available Thermosensitive injectable hydrogels based on chitosan neutralized with sodium beta-glycerophosphate (Na-β-GP have been studied as biomaterials for drug delivery and tissue regeneration. Magnesium (Mg has been reported to stimulate adhesion and proliferation of bone forming cells. With the aim of improving the suitability of the aforementioned chitosan hydrogels as materials for bone regeneration, Mg was incorporated by partial substitution of Na-β-GP with magnesium glycerophosphate (Mg-GP. Chitosan/Na-β-GP and chitosan/Na-β-GP/Mg-GP hydrogels were also loaded with the enzyme alkaline phosphatase (ALP which induces hydrogel mineralization. Hydrogels were characterized physicochemically with respect to mineralizability and gelation kinetics, and biologically with respect to cytocompatibility and cell adhesion. Substitution of Na-β-GP with Mg-GP did not negatively influence mineralizability. Cell biological testing showed that both chitosan/Na-β-GP and chitosan/Na-β-GP/Mg-GP hydrogels were cytocompatible towards MG63 osteoblast-like cells. Hence, chitosan/Na-β-GP/Mg-GP hydrogels can be used as an alternative to chitosan/Na-β-GP hydrogels for bone regeneration applications. However the incorporation of Mg in the hydrogels during hydrogel formation did not bring any appreciable physicochemical or biological benefit.

  17. Biofabrication of bone tissue: approaches, challenges and translation for bone regeneration.

    Science.gov (United States)

    Tang, Daniel; Tare, Rahul S; Yang, Liang-Yo; Williams, David F; Ou, Keng-Liang; Oreffo, Richard O C

    2016-03-01

    The rising incidence of bone disorders has resulted in the need for more effective therapies to meet this demand, exacerbated by an increasing ageing population. Bone tissue engineering is seen as a means of developing alternatives to conventional bone grafts for repairing or reconstructing bone defects by combining biomaterials, cells and signalling factors. However, skeletal tissue engineering has not yet achieved full translation into clinical practice as a consequence of several challenges. The use of additive manufacturing techniques for bone biofabrication is seen as a potential solution, with its inherent capability for reproducibility, accuracy and customisation of scaffolds as well as cell and signalling factor delivery. This review highlights the current research in bone biofabrication, the necessary factors for successful bone biofabrication, in addition to the current limitations affecting biofabrication, some of which are a consequence of the limitations of the additive manufacturing technology itself. PMID:26803405

  18. Histopathological Comparison between Bone Marrow- and Periodontium-derived Stem Cells for Bone Regeneration in Rabbit Calvaria

    Science.gov (United States)

    Kadkhoda, Z.; Safarpour, A.; Azmoodeh, F.; Adibi, S.; Khoshzaban, A.; Bahrami, N.

    2016-01-01

    Background: Periodontitis is an important oral disease. Stem cell therapy has found its way in treatment of many diseases. Objective: To evaluate the regenerative potential of periodontal ligament-derived stem cells (PDLSCs) and osteoblast differentiated from PDLSC in comparison with bone marrow-derived mesenchymal stem cells (BM-MSCs) and pre-osteoblasts in calvarial defects. Methods: After proving the existence of surface markers by flow cytometry, BM-MSCs were differentiated into osteoblasts. 5 defects were made on rabbit calvaria. 3 of them were first covered with collagen membrane and then with BM-MSCs, PDLSCs, and pre-osteoblasts. The 4th defect was filled with collagen membrane and the 5th one was served as control. After 4 weeks, histological (quantitative) and histomorphological (qualitative) surveys were performed. Results: Both cell lineages were positive for CD-90 cell marker, which was specifically related to stem cells. Alizarin red staining was done for showing mineral material. RT-PCR set up for the expression of Cbfa1 gene, BMP4 gene, and PGLAP gene, confirmed osteoblast differentiation. The findings indicated that although PDLSCs and pre-osteoblasts could be used for bone regeneration, the rate of regeneration in BM-MSCs-treated cavities was more significant (p<0.0001). Conclusion: The obtained results are probably attributable to the effective micro-environmental signals caused by different bone types and the rate of cell maturation. PMID:26889369

  19. Short- and long-term effects of irradiation on bone regeneration

    International Nuclear Information System (INIS)

    The aim of the present study is to quantify bone-regenerative capacity directly and 1 year after administration of 15 Gy 60Co irradiation. A titanium implant, the bone growth chamber, which in nonirradiated cases becomes filled with newly formed bone over a 4-week period, was inserted into each tibial metaphysis of 20 rabbits. In 10 animals the chambers were installed directly after irradiation, while in 10 other rabbits the implants were installed 1 year after the 60Co trauma. In both groups the bone-forming capacity on the irradiated side was compared to that of the contralateral, nonirradiated, control tibia. The amount of bone formed was determined by microradiography and microdensitometry. It was found that bone regeneration was depressed by 70.9 percent within a 4-week period after irradiation. At a follow-up of 1 year, the average depression of bone-forming capacity was only 28.9 percent. This means a recovery by a factor of almost 2.5. The clinical implications of these findings are discussed

  20. The Kinetics of Ampicillin Release from Hydroxyapatite for Bones Regeneration

    Directory of Open Access Journals (Sweden)

    Giovanilton Ferreira da Silva

    2009-01-01

    Full Text Available Semisynthetic beta-lactam antibiotics are among the most used pharmaceuticals. Their use in veterinary and human medicine is in continuous expansion. There is a growing need for developing bioactive implants. Advantages of implantable drug delivery tools can include high release efficiency, precise dose control, low toxicity, and allow to overcome disadvantages connected with conventional methods. In this respect, hydroxyapatite (HA is an elective material. It enables to produce architectures similar to those of real bones. Here we studied a kinetic model to describe ampicillin release from HA. In the course of adsorption experiment, ampicillin was dissolved, maintained at 30∘C and shaken at 60 strokes/minute. Samples were withdrawn periodically for analysis and then returned to the mixture. Adsorbed amounts were measured by the difference of the concentration of the antibiotics before and after adsorption using UV adsorption at 225 nm. The aim of this work was to evaluate its application as ampicillin delivery carrier.

  1. Combination of simvastatin, calcium silicate/gypsum, and gelatin and bone regeneration in rabbit calvarial defects

    Science.gov (United States)

    Zhang, Jing; Wang, Huiming; Shi, Jue; Wang, Ying; Lai, Kaichen; Yang, Xianyan; Chen, Xiaoyi; Yang, Guoli

    2016-03-01

    The present study was performed to determine whether simvastatin improves bone regeneration when combined with calcium silicate/gypsum and gelatin (CS-GEL). The surface morphology was determined using field-emission scanning electron microscopy (FSEM). Degradation in vitro was evaluated by monitoring the weight change of the composites soaked in phosphate buffered saline (PBS). Drug release was evaluated using high-performance liquid chromatography (HPLC). Cytotoxicity testing was performed to assess the biocompatibility of composites. Four 5 mm-diameter bone defects were created in rabbit calvaria. Three sites were filled with CS-GEL, 0.5 mg simvastatin-loaded CS-GEL (SIM-0.5) and 1.0 mg simvastatin-loaded CS-GEL (SIM-1.0), respectively, and the fourth was left empty as the control group. Micro-computed tomography (micro-CT) and histological analysis were carried out at 4 and 12 weeks postoperatively. The composites all exhibited three-dimensional structures and showed the residue with nearly 80% after 4 weeks of immersion. Drug release was explosive on the first day and then the release rate remained stable. The composites did not induce any cytotoxicity. The results in vivo demonstrated that the new bone formation and the expressions of BMP-2, OC and type I collagen were improved in the simvastatin-loaded CS-GEL group. It was concluded that the simvastatin-loaded CS-GEL may improve bone regeneration.

  2. Combination of simvastatin, calcium silicate/gypsum, and gelatin and bone regeneration in rabbit calvarial defects.

    Science.gov (United States)

    Zhang, Jing; Wang, Huiming; Shi, Jue; Wang, Ying; Lai, Kaichen; Yang, Xianyan; Chen, Xiaoyi; Yang, Guoli

    2016-01-01

    The present study was performed to determine whether simvastatin improves bone regeneration when combined with calcium silicate/gypsum and gelatin (CS-GEL). The surface morphology was determined using field-emission scanning electron microscopy (FSEM). Degradation in vitro was evaluated by monitoring the weight change of the composites soaked in phosphate buffered saline (PBS). Drug release was evaluated using high-performance liquid chromatography (HPLC). Cytotoxicity testing was performed to assess the biocompatibility of composites. Four 5 mm-diameter bone defects were created in rabbit calvaria. Three sites were filled with CS-GEL, 0.5 mg simvastatin-loaded CS-GEL (SIM-0.5) and 1.0 mg simvastatin-loaded CS-GEL (SIM-1.0), respectively, and the fourth was left empty as the control group. Micro-computed tomography (micro-CT) and histological analysis were carried out at 4 and 12 weeks postoperatively. The composites all exhibited three-dimensional structures and showed the residue with nearly 80% after 4 weeks of immersion. Drug release was explosive on the first day and then the release rate remained stable. The composites did not induce any cytotoxicity. The results in vivo demonstrated that the new bone formation and the expressions of BMP-2, OC and type I collagen were improved in the simvastatin-loaded CS-GEL group. It was concluded that the simvastatin-loaded CS-GEL may improve bone regeneration. PMID:26996657

  3. Bone cement with a modified polyphosphate network structure stimulates hard tissue regeneration.

    Science.gov (United States)

    Lee, Byung-Hyun; Hong, Min-Ho; Kim, Min-Chul; Kwon, Jae-Sung; Ko, Yeong-Mu; Choi, Heon-Jin; Lee, Yong-Keun

    2016-09-01

    In this study, a calcium polyphosphate cement (CpPC) consisting of basic components was investigated to assess its potential for hard tissue regeneration. The added basic components for improving the structural stability, which controlled the setting time, where the setting reaction resulted in the formation of amorphous structure with a re-constructed polyphosphate. Moreover, the characteristics were controlled by the composition, which determined the polyphosphate structure. CpPC exhibited outstanding dissolution rate compared with the common biodegradable cement, brushite cement (2.5 times). Despite high amounts of dissolution products, no significant cytotoxicity ensued. Induction of calcification in MG-63 cells treated with CpPC, the level of calcification increased with increasing CpPC dissolution rate. Induced calcification was observed also in CpPC-treated ST2 cells, in contrast with MG-63 and ST2 treated with brushite cement, for which no calcification was observed. In vivo tests using a rat calvarial defect model showed that resorbed CpPC resulted in favorable host responses and promoted bone formation. Additionally, there was a significant increase in defect closure, and new bone formation progressed from CpPC mid-sites as well as defect margins. From these results, CpPC exhibits significant potential as biodegradable bone substitute for bone regeneration. PMID:27511981

  4. Bone regeneration in surgically created defects filled with autogenous bone: an epifluorescence microscopy analysis in rats

    OpenAIRE

    Marcos Heidy Guskuma; Eduardo Hochuli-Vieira; Flávia Priscila Pereira; Idelmo Rangel-Garcia Junior; Roberta Okamoto; Tetuo Okamoto; Osvaldo Magro Filho

    2010-01-01

    Although the search for the ideal bone substitute has been the focus of a large number of studies, autogenous bone is still the gold standard for the filling of defects caused by pathologies and traumas, and mainly, for alveolar ridge reconstruction, allowing the titanium implants installation. OBJECTIVES: The aim of this study was to evaluate the dynamics of autogenous bone graft incorporation process to surgically created defects in rat calvaria, using epifluorescence microscopy. MATERIAL A...

  5. Gelatin-Modified Bone Substitute with Bioactive Molecules Enhance Cellular Interactions and Bone Regeneration.

    Science.gov (United States)

    Teotia, Arun Kumar; Gupta, Ankur; Raina, Deepak Bushan; Lidgren, Lars; Kumar, Ashok

    2016-05-01

    In this work, we have synthesized injectable bone cement incorporated with gelatin to enhance cellular interaction. Human osteosarcoma Saos-2 cells derived bone morphogenetic proteins (BMP's) and a bisphosphonate (zoledronic acid (0.2 mM)) were also incorporated to cement. In vitro studies conducted using Saos-2 demonstrated enhanced cell proliferation on gelatin (0.2%w/v) cement. The differentiation of C2C12 mouse myoblast cells into bone forming cells showed 6-fold increase in ALP levels on gelatin cement. Polymerase chain reaction (PCR) for bone biomarkers showed osteoinductive potential of gelatin cement. We investigated efficacy for local delivery of these bioactive molecules in enhancing bone substitution qualities of bone cements by implanting in 3.5 mm critical size defect in tibial metaphysis of wistar rats. The rats were sacrificed after 12 weeks and 16 weeks post implantation. X-ray, micro-CT, histology, and histomorphometry analysis were performed to check bone healing. The cement materials slowly resorbed from the defect site leaving HAP creating porous matrix providing surface for bone formation. The materials showed high biocompatibility and initial bridging was observed in all the animals but maximum bone formation was observed in animals implanted with cement incorporated with zoledronic acid followed by cement with BMP's compared to other groups. PMID:27077816

  6. Cell-free scaffolds with different stiffness but same microstructure promote bone regeneration in rabbit large bone defect model.

    Science.gov (United States)

    Chen, Guobao; Yang, Li; Lv, Yonggang

    2016-04-01

    To promote bone healing, bone repair biomaterials are increasingly designed to incorporate growth factors. However, the impact of matrix mechanics of cell-free scaffold independent of microstructure on the osteogenic differentiation of endogenous osteoprogenitor cells orchestrating bone repair and regeneration remains not to be fully understood. In our recent study, three-dimensional (3D) scaffolds with different stiffness but same microstructure have been successfully fabricated by coating decellularized bone with collagen/hydroxyapatite (HA) mixture with different collagen rations. It has been demonstrated that the scaffold with optimal stiffness can induce the osteogenic differentiation of MSCs in vitro and in the subcutaneous tissue. The present in vivo study further investigated the repair efficiency of these scaffolds in a rabbit radius with a critical-sized segmental defect model and its potential mechanism. Micro-computed tomography (μ-CT), X-ray and histological analysis were carried out to evaluate the repair capacity of these scaffolds. The results demonstrated that the cell-free scaffold with optimal stiffness incorporation of endogenous osteoprogenitor cells significantly promoted the repair and reconstruction quality of mass bone defect. One of the crucial mechanisms was that hypoxia and stromal cell-derived factor-1α (SDF-1α) mediated mesenchymal stem cells (MSCs) migration by which matrix mechanics exerted influence on bone fracture healing. These findings suggested that only modulating the matrix stiffness of cell-free scaffold can be one of the most attractive strategies for promoting the progression of bone healing. © 2015 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 104A: 833-841, 2016. PMID:26650620

  7. Oily calcium hydroxide suspension (Osteoinductal) used as an adjunct to guided bone regeneration: an experimental study in rats.

    NARCIS (Netherlands)

    Stavropoulos, A.; Geenen, C.; Nyengaard, J.R.; Karring, T.; Sculean, A.

    2007-01-01

    OBJECTIVES: To evaluate whether an oily calcium hydroxide suspension (OCHS) promotes bone healing when used as an adjunct to guided bone regeneration (GBR). MATERIAL AND METHODS: Rigid, hemispherical, teflon capsules were placed with their open part facing the lateral surface of the ramus on both si

  8. Mechanical properties and osteogenic potential of hydroxyapatite-PLGA-collagen biomaterial for bone regeneration.

    Science.gov (United States)

    Bhuiyan, Didarul B; Middleton, John C; Tannenbaum, Rina; Wick, Timothy M

    2016-08-01

    A bone graft is a complicated structure that provides mechanical support and biological signals that regulate bone growth, reconstruction, and repair. A single-component material is inadequate to provide a suitable combination of structural support and biological stimuli to promote bone regeneration. Multicomponent composite biomaterials lack adequate bonding among the components to prevent phase separation after implantation. We have previously developed a novel multistep polymerization and fabrication process to construct a nano-hydroxyapatite-poly(D,L-lactide-co-glycolide)-collagen biomaterial (abbreviated nHAP-PLGA-collagen) with the components covalently bonded to each other. In the present study, the mechanical properties and osteogenic potential of nHAP-PLGA-collagen are characterized to assess the material's suitability to support bone regeneration. nHAP-PLGA-collagen films exhibit tensile strength very close to that of human cancellous bone. Human mesenchymal stem cells (hMSCs) are viable on 2D nHAP-PLGA-collagen films with a sevenfold increase in cell population after 7 days of culture. Over 5 weeks of culture, hMSCs deposit matrix and mineral consistent with osteogenic differentiation and bone formation. As a result of matrix deposition, nHAP-PLGA-collagen films cultured with hMSCs exhibit 48% higher tensile strength and fivefold higher moduli compared to nHAP-PLGA-collagen films without cells. More interestingly, secretion of matrix and minerals by differentiated hMSCs cultured on the nHAP-PLGA-collagen films for 5 weeks mitigates the loss of mechanical strength that accompanies PLGA hydrolysis. PMID:27120980

  9. Bone regeneration effect after the addition of a vitamin complex in two bio ceramics

    International Nuclear Information System (INIS)

    One of the goals of the Biomaterials research is the development of devices that help bone regeneration. Two synthetic ceramics has been widely used with that purpose: hydroxyapatite (HAp) and beta tricalcium phosphate (β-TCP). In many situations it is desirable that the resorption rate of these materials by the body matches the bone growth rate. In these cases, the use of a mixture between the two phases is beneficial. The material resorption and bone growth are complexes physiological processes, influenced amongst other things by the inflammatory response of the surgical site. That being said, an exacerbated inflammatory response is potentially hazardous, since it may induce an increase of the oxidative stress due to the free radicals production. The free radicals attack causes, amongst other hazardous effects, the cell membrane degeneration which in turn may lead to cell necrosis and/or apoptosis within the surgical site. In this work, two ceramics were implanted in rats femora: β-TCP or the biphasic mixture of 60:40% in mass of HAp:β-TCP. The bone growth was assessed by both optical and fluorescence microscopy, using fluorescent bone markers. Moreover, it was also evaluated the effect of the presence of a vitamin complex, mediator of the inflammatory response. It was concluded that the pure β-TCP was more readily absorbed when compared with the mixture β-TCP-HAp, and there it was signs that the presence of the vitamin complex may have helped in a favorable way the bone neo formation. (author)

  10. Bone regeneration in the presence of a synthetic hydroxyapatite/silica oxide-based and a xenogenic hydroxyapatite-based bone substitute materia

    OpenAIRE

    Kruse, A.; Jung, R.E.; Nicholls, F.; Zwahlen, R A; Hämmerle, C H F; Weber, F E

    2011-01-01

    Objectives: A comparison of synthetic hydroxyapatite/silica oxide, xenogenic hydroxyapatite-based bone substitute materials with empty control sites in terms of bone regeneration enhancement in a rabbit calvarial four non-critical-sized defect model. Methods: In each of six rabbits, four bicortical calvarial bone defects were generated. The following four treatment modalities were randomly allocated: (1) empty control site, (2) synthetic hydroxyapatite/silica oxide-based (HA/SiO) test granule...

  11. A comparison of the regeneration kinetics of radiation damage to mouse bone marrow in some skeleton regions

    International Nuclear Information System (INIS)

    The method of monitoring numbers of nucleated cells of the bone marrow in some skeleton regions was employed to determine the extent of radiation damage after whole-body irradiation of mice with 60Co-gamma rays in doses of 5, 7 and 9 Gy, and the regeneration kinetics of this radiation damage at intervals of 4, 6, 8 and 10 days post irradiation. The cellularity values found were expressed as per cents of control values of the respective bone marrow regions. The regeneration kinetics of radiation damage to hematopoietic tissue of the bone marrow was found to differ in the respective skeleton regions. (author)

  12. Bone Regeneration of Rat Tibial Defect by Zinc-Tricalcium Phosphate (Zn-TCP Synthesized from Porous Foraminifera Carbonate Macrospheres

    Directory of Open Access Journals (Sweden)

    Joshua Chou

    2013-12-01

    Full Text Available Foraminifera carbonate exoskeleton was hydrothermally converted to biocompatible and biodegradable zinc-tricalcium phosphate (Zn-TCP as an alternative biomimetic material for bone fracture repair. Zn-TCP samples implanted in a rat tibial defect model for eight weeks were compared with unfilled defect and beta-tricalcium phosphate showing accelerated bone regeneration compared with the control groups, with statistically significant bone mineral density and bone mineral content growth. CT images of the defect showed restoration of cancellous bone in Zn-TCP and only minimal growth in control group. Histological slices reveal bone in-growth within the pores and porous chamber of the material detailing good bone-material integration with the presence of blood vessels. These results exhibit the future potential of biomimetic Zn-TCP as bone grafts for bone fracture repair.

  13. Differentiation of rabbit bone mesenchymal stem cells into endothelial cells in vitro and promotion of defective bone regeneration in vivo.

    Science.gov (United States)

    Liu, Jinzhong; Liu, Chao; Sun, Bin; Shi, Ce; Qiao, Chunyan; Ke, Xiaoliang; Liu, Shutai; Liu, Xia; Sun, Hongchen

    2014-04-01

    Tissue engineering strategies often fail to regenerate bones because of inadequate vascularization, especially in the reconstruction of large segmental bone defects. Large volumes of vascular endothelial cells (ECs) that functionally interact with osteoblasts during osteogenesis are difficult to obtain. In this study, we simulated bone healing by co-culturing differentiated ECs and mesenchymal stem cells (MSCs) either on a culture plate or on a polylactide glycolic acid (PLGA) scaffold in vitro. We also evaluated the effect of osteogenesis in repairing rabbit mandible defects in vivo. In this study, MSCs were separated from rabbit as the seed cells. After passage, the MSCs were cultured in an EC-conditioned medium to differentiate into ECs. Immunohistochemical staining analysis with CD34 showed that the induced cells had the characteristics of ECs and MSC. The induced ECs were co-cultured in vitro, and the induction of MSCs to osteoblast served as the control. Alkaline phosphatase (ALP) and alizarin red (AZR) staining experiments were performed, and the Coomassie brilliant blue total protein and ALP activity were measured. The MSCs proliferated and differentiated into osteoblast-like cells through direct contact between the derived ECs and MSCs. The co-cultured cells were seeded on PLGA scaffold to repair 1 cm mandible defects in the rabbit. The effectiveness of the repairs was assessed through soft X-ray and histological analyses. The main findings indicated that MSCs survived well on the scaffold and that the scaffold is biocompatible and noncytotoxic. The results demonstrated that the co-cultured MSC-derived ECs improved MSC osteogenesis and promoted new bone formation. This study may serve as a basis for the use of in vitro co-culturing techniques as an improvisation to bone tissue engineering for the repair of large bone defects. PMID:23943083

  14. Injectable Hydrogel Composite Based Gelatin-PEG and Biphasic Calcium Phosphate Nanoparticles for Bone Regeneration

    Science.gov (United States)

    Van, Thuy Duong; Tran, Ngoc Quyen; Nguyen, Dai Hai; Nguyen, Cuu Khoa; Tran, Dai Lam; Nguyen, Phuong Thi

    2016-05-01

    Gelatin hydrogels have recently attracted much attention for tissue regeneration because of their biocompatibility. In this study, we introduce poly-ethylene glycol (PEG)—grafted gelatin containing tyramine moieties which have been utilized for in situ enzyme-mediated hydrogel preparation. The hydrogel can be used to load nanoparticles of biphasic calcium phosphate, a mixture of hydroxyapatite and β-tricalcium phosphate, and forming injectable bio-composites. Proton nuclear magnetic resonance (1H NMR) spectra indicated that tyramine-functionalized polyethylene glycol-nitrophenyl carbonate ester was conjugated to the gelatin. The hydrogel composite was rapidly formed in situ (within a few seconds) in the presence of horseradish peroxidase and hydrogen peroxide. In vitro experiments with bio-mineralization on the hydrogel composite surfaces was well-observed after 2 weeks soaking in simulated body fluid solution. The obtained results indicated that the hydrogel composite could be a potential injectable material for bone regeneration.

  15. Functionalization of a Collagen-Hydroxyapatite Scaffold with Osteostatin to Facilitate Enhanced Bone Regeneration.

    Science.gov (United States)

    Quinlan, Elaine; Thompson, Emmet M; Matsiko, Amos; O'Brien, Fergal J; López-Noriega, Adolfo

    2015-12-01

    Defects within bones caused by trauma and other pathological complications may often require the use of a range of therapeutics to facilitate tissue regeneration. A number of approaches have been widely utilized for the delivery of such therapeutics via physical encapsulation or chemical immobilization suggesting significant promise in the healing of bone defects. The study focuses on the chemical immobilization of osteostatin, a pentapeptide of the parathyroid hormone (PTHrP107-111), within a collagen-hydroxyapatite scaffold. The chemical attachment method via crosslinking supports as little as 4% release of the peptide from the scaffolds after 21 d whereas non-crosslinking leads to 100% of the peptide being released by as early as 4 d. In vitro characterization demonstrates that this cross-linking method of immobilization supports a pro-osteogenic effect on osteoblasts. Most importantly, when implanted in a critical-sized calvarial defect within a rat, these scaffolds promote significantly greater new bone volume and area compared to nonfunctionalized scaffolds (**p < 0.01) and an empty defect control (***p < 0.001). Collectively, this study suggests that such an approach of chemical immobilization offers greater spatiotemporal control over growth factors and can significantly modulate tissue regeneration. Such a system may be adopted for a range of different proteins and thus offers the potential for the treatment of various complex pathologies that require localized mediation of drug delivery. PMID:26414944

  16. The effect of bacterial cellulose membrane compared with collagen membrane on guided bone regeneration

    Science.gov (United States)

    Lim, Youn-Mook; Jeong, Sung In; An, Sung-Jun; Kang, Seong-Soo

    2015-01-01

    PURPOSE This study was to evaluate the effects of bacterial cellulose (BC) membranes as a barrier membrane on guided bone regeneration (GBR) in comparison with those of the resorbable collagen membranes. MATERIALS AND METHODS BC membranes were fabricated using biomimetic technology. Surface properties were analyzed, Mechanical properties were measured, in vitro cell proliferation test were performed with NIH3T3 cells and in vivo study were performed with rat calvarial defect and histomorphometric analysis was done. The Mann-Whitney U test and the Wilcoxon signed rank test was used (α<.05). RESULTS BC membrane showed significantly higher mechanical properties such as wet tensile strength than collagen membrane and represented a three-dimensional multilayered structure cross-linked by nano-fibers with 60 % porosity. In vitro study, cell adhesion and proliferation were observed on BC membrane. However, morphology of the cells was found to be less differentiated, and the cell proliferation rate was lower than those of the cells on collagen membrane. In vivo study, the grafted BC membrane did not induce inflammatory response, and maintained adequate space for bone regeneration. An amount of new bone formation in defect region loaded with BC membrane was significantly similar to that of collagen membrane application. CONCLUSION BC membrane has potential to be used as a barrier membrane, and efficacy of the membrane on GBR is comparable to that of collagen membrane. PMID:26816579

  17. Lyophilized Platelet-Rich Fibrin (PRF Promotes Craniofacial Bone Regeneration through Runx2

    Directory of Open Access Journals (Sweden)

    Qi Li

    2014-05-01

    Full Text Available Freeze-drying is an effective means to control scaffold pore size and preserve its composition. The purpose of the present study was to determine the applicability of lyophilized Platelet-rich fibrin (LPRF as a scaffold for craniofacial tissue regeneration and to compare its biological effects with commonly used fresh Platelet-rich fibrin (PRF. LPRF caused a 4.8-fold ± 0.4-fold elevation in Runt-related transcription factor 2 (Runx2 expression in alveolar bone cells, compared to a 3.6-fold ± 0.2-fold increase when using fresh PRF, and a more than 10-fold rise of alkaline phosphatase levels and mineralization markers. LPRF-induced Runx2 expression only occurred in alveolar bone and not in periodontal or dental follicle cells. LPRF also caused a 1.6-fold increase in osteoblast proliferation (p < 0.001 when compared to fresh PRF. When applied in a rat craniofacial defect model for six weeks, LPRF resulted in 97% bony coverage of the defect, compared to 84% for fresh PRF, 64% for fibrin, and 16% without scaffold. Moreover, LPRF thickened the trabecular diameter by 25% when compared to fresh PRF and fibrin, and only LPRF and fresh PRF resulted in the formation of interconnected trabeculae across the defect. Together, these studies support the application of lyophilized PRF as a biomimetic scaffold for craniofacial bone regeneration and mineralized tissue engineering.

  18. Selective laser melting-produced porous titanium scaffolds regenerate bone in critical size cortical bone defects.

    Science.gov (United States)

    Van der Stok, Johan; Van der Jagt, Olav P; Amin Yavari, Saber; De Haas, Mirthe F P; Waarsing, Jan H; Jahr, Holger; Van Lieshout, Esther M M; Patka, Peter; Verhaar, Jan A N; Zadpoor, Amir A; Weinans, Harrie

    2013-05-01

    Porous titanium scaffolds have good mechanical properties that make them an interesting bone substitute material for large bone defects. These scaffolds can be produced with selective laser melting, which has the advantage of tailoring the structure's architecture. Reducing the strut size reduces the stiffness of the structure and may have a positive effect on bone formation. Two scaffolds with struts of 120-µm (titanium-120) or 230-µm (titanium-230) were studied in a load-bearing critical femoral bone defect in rats. The defect was stabilized with an internal plate and treated with titanium-120, titanium-230, or left empty. In vivo micro-CT scans at 4, 8, and 12 weeks showed more bone in the defects treated with scaffolds. Finally, 18.4 ± 7.1 mm(3) (titanium-120, p = 0.015) and 18.7 ± 8.0 mm(3) (titanium-230, p = 0.012) of bone was formed in those defects, significantly more than in the empty defects (5.8 ± 5.1 mm(3) ). Bending tests on the excised femurs after 12 weeks showed that the fusion strength reached 62% (titanium-120) and 45% (titanium-230) of the intact contralateral femurs, but there was no significant difference between the two scaffolds. This study showed that in addition to adequate mechanical support, porous titanium scaffolds facilitate bone formation, which results in high mechanical integrity of the treated large bone defects. PMID:23255164

  19. Bone regeneration based on nano-hydroxyapatite and hydroxyapatite/chitosan nanocomposites: an in vitro and in vivo comparative study

    Energy Technology Data Exchange (ETDEWEB)

    Tavakol, S. [Tehran University of Medical Sciences, Department of Medical Nanotechnology, School of Advanced Technologies in Medicine (Iran, Islamic Republic of); Nikpour, M. R. [Babol University of Technology, Nanotechnology Research Institute, Nanobiotechnology Research Group (Iran, Islamic Republic of); Amani, A. [Tehran University of Medical Sciences, Department of Medical Nanotechnology, School of Advanced Technologies in Medicine (Iran, Islamic Republic of); Soltani, M. [University of Waterloo, Department of Chemical Engineering, Waterloo Institute for Nanotechnology (Canada); Rabiee, S. M. [Babol University of Technology, Nanotechnology Research Institute, Nanobiotechnology Research Group (Iran, Islamic Republic of); Rezayat, S. M. [Tehran University of Medical Sciences, Department of Medical Nanotechnology, School of Advanced Technologies in Medicine (Iran, Islamic Republic of); Chen, P., E-mail: p4chen@uwaterloo.ca [University of Waterloo, Department of Chemical Engineering, Waterloo Institute for Nanotechnology (Canada); Jahanshahi, M., E-mail: mjahan@nit.ac.ir [Babol University of Technology, Nanotechnology Research Institute, Nanobiotechnology Research Group (Iran, Islamic Republic of)

    2013-01-15

    Surface morphology, surface wettability, and size distribution of biomaterials affect their in vitro and in vivo bone regeneration potential. Since nano-hydroxyapatite has a great chemical and structural similarity to natural bone and dental tissues, incorporated biomaterial of such products could improve bioactivity and bone bonding ability. In this research, nano-hydroxyapatite (23 {+-} 0.09 nm) and its composites with variety of chitosan content [2, 4, and 6 g (45 {+-} 0.19, 32 {+-} 0.12, and 28 {+-} 0.12 nm, respectively)] were prepared via an in situ hybridization route. Size distribution of the particles, protein adsorption, and calcium deposition of powders by the osteoblast cells, gene expression and percentage of new bone formation area were investigated. The highest degree of bone regeneration potential was observed in nano-hydroxyapatite powder, while the bone regeneration was lowest in nano-hydroxyapatite with 6 g of chitosan. Regarding these data, suitable size distribution next to size distribution of hydroxyapatite in bone, smaller size, higher wettability, lower surface roughness of the nano-hydroxyapatite particles and homogeneity in surface resulted in higher protein adsorption, cell differentiation and percentage of bone formation area. Results obtained from in vivo and in vitro tests confirmed the role of surface morphology, surface wettability, mean size and size distribution of biomaterial besides surface chemistry as a temporary bone substitute.

  20. Bone regeneration based on nano-hydroxyapatite and hydroxyapatite/chitosan nanocomposites: an in vitro and in vivo comparative study

    International Nuclear Information System (INIS)

    Surface morphology, surface wettability, and size distribution of biomaterials affect their in vitro and in vivo bone regeneration potential. Since nano-hydroxyapatite has a great chemical and structural similarity to natural bone and dental tissues, incorporated biomaterial of such products could improve bioactivity and bone bonding ability. In this research, nano-hydroxyapatite (23 ± 0.09 nm) and its composites with variety of chitosan content [2, 4, and 6 g (45 ± 0.19, 32 ± 0.12, and 28 ± 0.12 nm, respectively)] were prepared via an in situ hybridization route. Size distribution of the particles, protein adsorption, and calcium deposition of powders by the osteoblast cells, gene expression and percentage of new bone formation area were investigated. The highest degree of bone regeneration potential was observed in nano-hydroxyapatite powder, while the bone regeneration was lowest in nano-hydroxyapatite with 6 g of chitosan. Regarding these data, suitable size distribution next to size distribution of hydroxyapatite in bone, smaller size, higher wettability, lower surface roughness of the nano-hydroxyapatite particles and homogeneity in surface resulted in higher protein adsorption, cell differentiation and percentage of bone formation area. Results obtained from in vivo and in vitro tests confirmed the role of surface morphology, surface wettability, mean size and size distribution of biomaterial besides surface chemistry as a temporary bone substitute.

  1. Role of Nanog in the maintenance of marrow stromal stem cells during post natal bone regeneration

    Energy Technology Data Exchange (ETDEWEB)

    Bais, Manish V.; Shabin, Zabrina M.; Young, Megan; Einhorn, Thomas A. [Orthopaedic Research Laboratory, Department of Orthopedic Surgery, Boston University School of Medicine, Boston, MA 02118 (United States); Kotton, Darrell N. [Pulmonary Center, Boston University School of Medicine, Boston, MA 02118 (United States); Gerstnefeld, Louis C., E-mail: lgersten@bu.edu [Orthopaedic Research Laboratory, Department of Orthopedic Surgery, Boston University School of Medicine, Boston, MA 02118 (United States)

    2012-01-06

    Highlights: Black-Right-Pointing-Pointer Nanog is related to marrow stromal stem cell maintenance. Black-Right-Pointing-Pointer Increasing Nanog expression is seen during post natal surgical bone repair. Black-Right-Pointing-Pointer Nanog knockdown decreases post surgical bone regeneration. -- Abstract: Post natal bone repair elicits a regenerative mechanism that restores the injured tissue to its pre-injury cellular composition and structure and is believed to recapitulate the embryological processes of bone formation. Prior studies showed that Nanog, a central epigenetic regulator associated with the maintenance of embryonic stem cells (ESC) was transiently expressed during fracture healing, Bais et al. . In this study, we show that murine bone marrow stromal cells (MSCs) before they are induced to undergo osteogenic differentiation express {approx}50 Multiplication-Sign the background levels of Nanog seen in murine embryonic fibroblasts (MEFs) and the W20-17 murine marrow stromal cell line stably expresses Nanog at {approx}80 Multiplication-Sign the MEF levels. Nanog expression in this cell line was inhibited by BMP7 treatment and Nanog lentivrial shRNA knockdown induced the expression of the terminal osteogenic gene osteocalcin. Lentivrial shRNA knockdown or lentiviral overexpression of Nanog in bone MSCs had inverse effects on proliferation, with knockdown decreasing and overexpression increasing MSC cell proliferation. Surgical marrow ablation of mouse tibia by medullary reaming led to a {approx}3-fold increase in Nanog that preceded osteogenic differentiation during intramembranous bone formation. Lentiviral shRNA knockdown of Nanog after surgical ablation led to an initial overexpression of osteogenic gene expression with no initial effect on bone formation but during subsequent remodeling of the newly formed bone a {approx}50% decrease was seen in the expression of terminal osteogenic gene expression and a {approx}50% loss in trabecular bone mass. This

  2. Role of Nanog in the maintenance of marrow stromal stem cells during post natal bone regeneration

    International Nuclear Information System (INIS)

    Highlights: ► Nanog is related to marrow stromal stem cell maintenance. ► Increasing Nanog expression is seen during post natal surgical bone repair. ► Nanog knockdown decreases post surgical bone regeneration. -- Abstract: Post natal bone repair elicits a regenerative mechanism that restores the injured tissue to its pre-injury cellular composition and structure and is believed to recapitulate the embryological processes of bone formation. Prior studies showed that Nanog, a central epigenetic regulator associated with the maintenance of embryonic stem cells (ESC) was transiently expressed during fracture healing, Bais et al. . In this study, we show that murine bone marrow stromal cells (MSCs) before they are induced to undergo osteogenic differentiation express ∼50× the background levels of Nanog seen in murine embryonic fibroblasts (MEFs) and the W20-17 murine marrow stromal cell line stably expresses Nanog at ∼80× the MEF levels. Nanog expression in this cell line was inhibited by BMP7 treatment and Nanog lentivrial shRNA knockdown induced the expression of the terminal osteogenic gene osteocalcin. Lentivrial shRNA knockdown or lentiviral overexpression of Nanog in bone MSCs had inverse effects on proliferation, with knockdown decreasing and overexpression increasing MSC cell proliferation. Surgical marrow ablation of mouse tibia by medullary reaming led to a ∼3-fold increase in Nanog that preceded osteogenic differentiation during intramembranous bone formation. Lentiviral shRNA knockdown of Nanog after surgical ablation led to an initial overexpression of osteogenic gene expression with no initial effect on bone formation but during subsequent remodeling of the newly formed bone a ∼50% decrease was seen in the expression of terminal osteogenic gene expression and a ∼50% loss in trabecular bone mass. This loss of bone mass was accompanied by an increased ∼2- to 5-fold adipogenic gene expression and observed increase of fat cells in the

  3. Evaluation of the Effect of Plasma Rich in Growth Factors (PRGF on Bone Regeneration

    Directory of Open Access Journals (Sweden)

    M. Paknejad

    2012-01-01

    Full Text Available Objective: Reconstruction methods are an essential prerequisite for functional rehabilitation of the stomatognathic system. Plasma rich in growth factors (PRGF offers a new and potentially useful adjunct to bone substitute materials in bone reconstructive surgery. This study was carried out to investigate the influ-ence of PRGF and fibrin membrane on regeneration of bony defects with and without deproteinized bovine bone mineral (DBBM on rabbit calvaria. Materials and Methods: Twelve New Zealand white rabbits were included in this randomized, blinded, prospective study. Four equal 3.3×6.6 mm cranial bone defects were created and immediately grafted with DBBM, PRGF+DBBM, PRGF+fibrin membrane and no treatment as control. The defects were evaluated with histologic and histomorphometric analysis performed 4 and 8 weeks later. Results: Adding PRGF to DBBM led to increased bone formation as compared with the control group in 4- and 8-week intervals. In DBBM and PRGF+fibrin membrane samples, no significant increase was seen compared to the control group. There was also a significant increase in the rate of biodegradation of DBBM particles with the addition of PRGF in the 8-week interval. Neither noti-ceable foreign body reaction nor any severe inflammation was seen in each of the specimens evaluated. Conclusion: Under the limitation of this study, adding PRGF to DBBM enhanced osteogenesis in rabbit calvarias. Applying autologous fibrin membrane in the de-fects was not helpful.

  4. Polycaprolactone nanofiber interspersed collagen type-I scaffold for bone regeneration: a unique injectable osteogenic scaffold

    International Nuclear Information System (INIS)

    promoting osteoblast phenotype progression for bone regeneration. (paper)

  5. Polycaprolactone nanofiber interspersed collagen type-I scaffold for bone regeneration: a unique injectable osteogenic scaffold.

    Science.gov (United States)

    Baylan, Nuray; Bhat, Samerna; Ditto, Maggie; Lawrence, Joseph G; Lecka-Czernik, Beata; Yildirim-Ayan, Eda

    2013-08-01

    promoting osteoblast phenotype progression for bone regeneration. PMID:23804651

  6. Bone marrow stromal/stem cell-derived extracellular vesicles regulate osteoblast activity and differentiation in vitro and promote bone regeneration in vivo

    OpenAIRE

    Yunhao Qin; Lian Wang; Zhengliang Gao; Genyin Chen; Changqing Zhang

    2016-01-01

    Emerging evidence suggests that extracellular vesicles (EVs) are secreted by diverse tissues and play important roles in cell-cell communication, organ interactions and tissue homeostasis. Studies have reported the use of EVs to stimulate tissue regeneration, such as hepatic cell regeneration, and to treat diseases, such as pulmonary hypertension. However, little is known about the osteogenic effect of EVs. In this study, we explore the role of bone marrow stromal cell-derived EVs in the regu...

  7. Microsphere-based scaffolds encapsulating tricalcium phosphate and hydroxyapatite for bone regeneration.

    Science.gov (United States)

    Gupta, Vineet; Lyne, Dina V; Barragan, Marilyn; Berkland, Cory J; Detamore, Michael S

    2016-07-01

    Bioceramic mixtures of tricalcium phosphate (TCP) and hydroxyapatite (HAp) are widely used for bone regeneration because of their excellent cytocompatibility, osteoconduction, and osteoinduction. Therefore, we hypothesized that incorporation of a mixture of TCP and HAp in microsphere-based scaffolds would enhance osteogenesis of rat bone marrow stromal cells (rBMSCs) compared to a positive control of scaffolds with encapsulated bone-morphogenic protein-2 (BMP-2). Poly(D,L-lactic-co-glycolic acid) (PLGA) microsphere-based scaffolds encapsulating TCP and HAp mixtures in two different ratios (7:3 and 1:1) were fabricated with the same net ceramic content (30 wt%) to evaluate how incorporation of these ceramic mixtures would affect the osteogenesis in rBMSCs. Encapsulation of TCP/HAp mixtures impacted microsphere morphologies and the compressive moduli of the scaffolds. Additionally, TCP/HAp mixtures enhanced the end-point secretion of extracellular matrix components relevant to bone tissue compared to the "blank" (PLGA-only) microsphere-based scaffolds as evidenced by the biochemical, gene expression, histology, and immunohistochemical characterization. Moreover, the TCP/HAp mixture groups even surpassed the BMP-2 positive control group in some instances in terms of matrix synthesis and gene expression. Lastly, gene expression data suggested that the rBMSCs responded differently to different TCP/HAp ratios presented to them. Altogether, it can be concluded that TCP/HAp mixtures stimulated the differentiation of rBMSCs toward an osteoblastic phenotype, and therefore may be beneficial in gradient microsphere-based scaffolds for osteochondral regeneration. PMID:27272903

  8. Surface delivery of tunable doses of BMP-2 from an adaptable polymeric scaffold induces volumetric bone regeneration.

    Science.gov (United States)

    Bouyer, Michael; Guillot, Raphael; Lavaud, Jonathan; Plettinx, Cedric; Olivier, Cécile; Curry, Véronique; Boutonnat, Jean; Coll, Jean-Luc; Peyrin, Françoise; Josserand, Véronique; Bettega, Georges; Picart, Catherine

    2016-10-01

    The rapid and effective bone regeneration of large non-healing defects remains challenging. Bioactive proteins, such as bone morphogenetic protein (BMP)-2, are proved their osteoinductivity, but their clinical use is currently limited to collagen as biomaterial. Being able to deliver BMP-2 from any other biomaterial would broaden its clinical use. This work presents a novel means for repairing a critical size volumetric bone femoral defect in the rat by combining a osteoinductive surface coating (2D) to a polymeric scaffold (3D hollow tube) made of commercially-available PLGA. Using a polyelectrolyte film as BMP-2 carrier, we tune the amount of BMP-2 loaded in and released from the polyelectrolyte film coating over a large extent by controlling the film crosslinking level and initial concentration of BMP-2 in solution. Using microcomputed tomography and quantitative analysis of the regenerated bone growth kinetics, we show that the amount of newly formed bone and kinetics can be modulated: an effective and fast repair was obtained in 1-2 weeks in the best conditions, including complete defect bridging, formation of vascularized and mineralized bone tissue. Histological staining and high-resolution computed tomography revealed the presence of bone regeneration inside and around the tube with spatially distinct organization for trabecular-like and cortical bones. The amount of cortical bone and its thickness increased with the BMP-2 dose. In view of the recent developments in additive manufacturing techniques, this surface-coating technology may be applied in combination with various types of polymeric or metallic scaffolds to offer new perspectives of bone regeneration in personalized medicine. PMID:27454063

  9. Chondrogenic Regeneration Using Bone Marrow Clots and a Porous Polycaprolactone-Hydroxyapatite Scaffold by Three-Dimensional Printing

    OpenAIRE

    Yao, Qingqiang; Wei, Bo; Liu, Nancy; Li, Chenshuang; Guo, Yang; Shamie, Arya Nick; Chen, James; TANG, Cheng; Jin, Chengzhe; Xu, Yan; Bian, Xiuwu; Zhang, Xinli; Wang, Liming

    2015-01-01

    Scaffolds play an important role in directing three-dimensional (3D) cartilage regeneration. Our recent study reported the potential advantages of bone marrow clots (MC) in promoting extracellular matrix (ECM) scaffold chondrogenic regeneration. The aim of this study is to build a new scaffold for MC, with improved characteristics in mechanics, shaping, and biodegradability, compared to our previous study. To address this issue, this study prepared a 3D porous polycaprolactone (PCL)-hydroxyap...

  10. Mesenchymal Stem Cells in Bone Tissue Regeneration and Application to Bone Healing

    Czech Academy of Sciences Publication Activity Database

    Crha, M.; Nečas, A.; Srnec, R.; Janovec, J.; Raušer, P.; Urbanová, L.; Plánka, L.; Jančář, J.; Amler, Evžen

    2009-01-01

    Roč. 78, č. 4 (2009), s. 635-642. ISSN 0001-7213 R&D Projects: GA MŠk 2B06130; GA AV ČR IAA500390702 Institutional research plan: CEZ:AV0Z50390703 Keywords : tissue engineering * biomaterials * segmental bone lesion Subject RIV: BO - Biophysics Impact factor: 0.403, year: 2009

  11. Human Urine Derived Stem Cells in Combination with β-TCP Can Be Applied for Bone Regeneration.

    Directory of Open Access Journals (Sweden)

    Junjie Guan

    Full Text Available Bone tissue engineering requires highly proliferative stem cells that are easy to isolate. Human urine stem cells (USCs are abundant and can be easily harvested without using an invasive procedure. In addition, in our previous studies, USCs have been proved to be able to differentiate into osteoblasts, chondrocytes, and adipocytes. Therefore, USCs may have great potential and advantages to be applied as a cell source for tissue engineering. However, there are no published studies that describe the interactions between USCs and biomaterials and applications of USCs for bone tissue engineering. Therefore, the objective of the present study was to evaluate the interactions between USCs with a typical bone tissue engineering scaffold, beta-Tricalcium Phosphate (β-TCP, and to determine whether the USCs seeded onto β-TCP scaffold can promote bone regeneration in a segmental femoral defect of rats. Primary USCs were isolated from urine and seeded on β-TCP scaffolds. Results showed that USCs remained viable and proliferated within β-TCP. The osteogenic differentiation of USCs within the scaffolds was demonstrated by increased alkaline phosphatase activity and calcium content. Furthermore, β-TCP with adherent USCs (USCs/β-TCP were implanted in a 6-mm critical size femoral defect of rats for 12 weeks. Bone regeneration was determined using X-ray, micro-CT, and histologic analyses. Results further demonstrated that USCs in the scaffolds could enhance new bone formation, which spanned bone defects in 5 out of 11 rats while β-TCP scaffold alone induced modest bone formation. The current study indicated that the USCs can be used as a cell source for bone tissue engineering as they are compatible with bone tissue engineering scaffolds and can stimulate the regeneration of bone in a critical size bone defect.

  12. Efficacy of guided bone regeneration using composite bone graft and resorbable collagen membrane in Seibert's Class I ridge defects: radiological evaluation.

    Science.gov (United States)

    Saravanan, Pushparajan; Ramakrishnan, T; Ambalavanan, N; Emmadi, Pamela; John, Thomas Libby

    2013-08-01

    The purpose of the study was to evaluate radiologically the efficacy of guided bone regeneration using composite bone graft (autogenous bone graft and anorganic bovine bone graft [Bio-Oss]) along with resorbable collagen membrane (BioMend Extend) in the augmentation of Seibert's class I ridge defects in maxilla. Bone width was evaluated using computerized tomography at day 0 and at day 180 at 2 mm, 4 mm, and 6 mm from the crest. There was a statistically significant increase in bone width between day 0 and day 180 at 2 mm, 4 mm, and 6 mm from the crest. The results of the study demonstrated an increase in bone width of Seibert's class I ridge defects in the maxilla of the study patients. PMID:23964779

  13. Preparation and characterization of fibrous chitosan-glued phosphate glass fiber scaffolds for bone regeneration.

    Science.gov (United States)

    Zheng, Kai; Wu, Zhaoying; Wei, Jie; Rűssel, Christian; Liang, Wen; Boccaccini, Aldo R

    2015-08-01

    Phosphate glass fibers (PGF) have emerged as promising building blocks for constructing bone scaffolds. In this study, fibrous scaffolds (PGFS) were fabricated using a facile binding method at room temperature. PGFS exhibited an extracellular matrix-like morphology and were composed of PGF as matrix and chitosan as the natural binding glue. They showed an interconnected porous structure with a porosity of ~87% and pore size of 100-500 µm. PGFS exhibited the typical compressive stress-strain behaviour of highly porous, low-density, open-cell scaffolds. Their yield stress and modulus were ~0.38 and ~2.84 MPa, respectively, with the strength being higher than the lower bound of the compressive strength of cancellous bone. PGFS were degradable and the weight loss was about 25% after immersion in stimulated body fluid (SBF) for 28 days. In addition, the yield stress and the modulus decreased with increasing immersion time in SBF. Apatite formation could be detected on the surface of PGFS within 7 days of immersion in SBF. MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay indicated that PGFS were non-cytotoxic against bone marrow stromal cells (bMSCs) after culture for up to 72 h. These results suggest that PGFS could be promising scaffolds for bone regeneration applications. PMID:26271217

  14. Highly porous polymer-derived wollastonite-hydroxycarbonate apatite ceramics for bone regeneration.

    Science.gov (United States)

    Fiocco, L; Li, S; Bernardo, E; Stevens, M M; Jones, J R

    2016-01-01

    A novel strategy was employed to synthesize highly porous wollastonite-hydroxycarbonate apatite ceramic scaffolds for bone regeneration. A commercial liquid preceramic polymer filled with micro-CaCO3 powders was foamed at low temperature (at 350 °C), using the decomposition of a hydrazine additive, and then converted into ceramic by a treatment at 700 °C. Hydroxycarbonate apatite was later developed by a phosphatization treatment of ceramized foams, in a P-rich solution, while wollastonite was obtained by a second firing, at 900 °C. The effectiveness of the method was proven by x-ray diffraction analysis, showing the presence of the two expected crystalline phases. Porosity, interconnect size distribution and mechanical strength were in the range that is thought to be suitable for bone regeneration in non-load bearing sites (compressive strength  ≈3 MPa, porosity  ≈90%, modal interconnect diameter  ≈130-160 μm). In addition, bioactivity and ion release rate were assessed in simulated body fluid (SBF). MC3T3 osteoblast precursor cells were able to colonize the material in vitro through the pore architecture and expressed osteogenic markers. PMID:27066770

  15. Preparation and Functional Assessment of Composite Chitosan-Nano-Hydroxyapatite Scaffolds for Bone Regeneration

    Directory of Open Access Journals (Sweden)

    Warren O. Haggard

    2012-02-01

    Full Text Available Composite chitosan-nano-hydroxyapatite microspheres and scaffolds prepared using a co-precipitation method have shown potential for use in bone regeneration. The goal of this research was to improve the functional properties of the composite scaffolds by modifying the fabrication parameters. The effects of degree of deacetylation (DDA, drying method, hydroxyapatite content and an acid wash on scaffold properties were investigated. Freeze-dried 61% DDA scaffolds degraded faster (3.5 ± 0.5% mass loss than air-dried 61% DDA scaffolds and 80% DDA scaffolds, but had a lower compressive modulus of 0.12 ± 0.01 MPa. Air-dried 80% DDA scaffolds displayed the highest compressive modulus (3.79 ± 0.51 MPa and these scaffolds were chosen as the best candidate for use in bone regeneration. Increasing the amount of hydroxyapatite in the air-dried 80% DDA scaffolds did not further increase the compressive modulus of the scaffolds. An acid wash procedure at pH 6.1 was found to increase the degradation of air-dried 80% DDA scaffolds from 1.3 ± 0.1% to 4.4 ± 0.4%. All of the formulations tested supported the proliferation of SAOS-2 cells.

  16. Effects of a chitosan membrane coated with polylactic and polyglycolic acid on bone regeneration in a rat calvarial defect

    International Nuclear Information System (INIS)

    The purpose of this study was to evaluate the effects of a chitosan membrane coated with polylactic and polyglycolic acid (PLGA) on bone regeneration in a rat calvarial defect. Surgical implantation of chitosan membranes resulted in enhanced local bone formation at both 2 and 8 weeks. In conclusion, the chitosan membrane coated with PLGA had a significant potential to induce bone formation in the rat calvarial defect model. Within the selected PLGA dose range and observation intervals, there appeared to be no meaningful differences in bone formation

  17. Effects of a chitosan membrane coated with polylactic and polyglycolic acid on bone regeneration in a rat calvarial defect

    Energy Technology Data Exchange (ETDEWEB)

    Jung, Ui-Won [Department of Periodontology, Research Institute for Periodontal Regeneration, College of Dentistry, Yonsei University, 134 Shinchon-Dong, Seodaemun-gu, Seoul 120-752l (Korea, Republic of); Song, Kun-Young [Department of Periodontology, Research Institute for Periodontal Regeneration, College of Dentistry, Yonsei University, 134 Shinchon-Dong, Seodaemun-gu, Seoul 120-752l (Korea, Republic of); Kim, Chang-Sung [Department of Periodontology, Research Institute for Periodontal Regeneration, College of Dentistry, Yonsei University, 134 Shinchon-Dong, Seodaemun-gu, Seoul 120-752l (Korea, Republic of); Lee, Yong-Keun [Department and Research Institute of Dental Biomaterials and Bioengineering, College of Dentistry, Yonsei University, 134 Shinchon-Dong, Seodaemun-gu, Seoul 120-750 (Korea, Republic of); Cho, Kyoo-Sung [Department of Periodontology, Research Institute for Periodontal Regeneration, College of Dentistry, Yonsei University, 134 Shinchon-Dong, Seodaemun-gu, Seoul 120-752l (Korea, Republic of); Kim, Chong-Kwan [Department of Periodontology, Research Institute for Periodontal Regeneration, College of Dentistry, Yonsei University, 134 Shinchon-Dong, Seodaemun-gu, Seoul 120-752l (Korea, Republic of); Choi, Seong-Ho [Department of Periodontology, Research Institute for Periodontal Regeneration, College of Dentistry, Yonsei University, 134 Shinchon-Dong, Seodaemun-gu, Seoul 120-752l (Korea, Republic of)

    2007-09-15

    The purpose of this study was to evaluate the effects of a chitosan membrane coated with polylactic and polyglycolic acid (PLGA) on bone regeneration in a rat calvarial defect. Surgical implantation of chitosan membranes resulted in enhanced local bone formation at both 2 and 8 weeks. In conclusion, the chitosan membrane coated with PLGA had a significant potential to induce bone formation in the rat calvarial defect model. Within the selected PLGA dose range and observation intervals, there appeared to be no meaningful differences in bone formation.

  18. Bone marrow-derived progenitor cells in de novo liver regeneration in liver transplant.

    Science.gov (United States)

    Lee, Sung-Gyu; Moon, Sung-Hwan; Kim, Hee-Je; Lee, Ji Yoon; Park, Soon-Jung; Chung, Hyung-Min; Ha, Tae-Yong; Song, Gi-Won; Jung, Dong-Hwan; Park, Hojong; Kwon, Tae-Won; Cho, Yong-Pil

    2015-09-01

    The study was designed (1) to examine the hypothesis that circulating progenitor cells play a role in the process of de novo regeneration in human liver transplants and that these cells arise from a cell population originating in, or associated with, the bone marrow and (2) to investigate whether the transplanted liver volume has an effect on the circulating recipient-derived progenitor cells that generate hepatocytes during this process. Clinical data and liver tissue characteristics were analyzed in male individuals who underwent sex-mismatched adult-to-adult living donor liver transplantation using dual left lobe grafts. Dual left lobe grafts were examined at the time of transplantation and 19 to 27 days after transplantation. All recipients showed recovery of normal liver function and a significant increase in the volume of the engrafted left lobes after transplantation. Double staining for a Y-chromosome probe and the CD31 antigen showed the presence of hybrid vessels composed of recipient-derived cells and donor cells within the transplanted liver tissues. Furthermore, CD34-expressing cells were observed commingling with Y-chromosome+ cells. The ratio of recipient-derived vessels and the number of Y+ CD34+ cells tended to be higher when smaller graft volumes underwent transplantation. These findings suggest that the recruitment of circulating bone marrow-derived progenitor cells could contribute to vessel formation and de novo regeneration in human liver transplants. Moreover, graft volume may be an important determinant for the active mobilization of circulating recipient-derived progenitor cells and their contribution to liver regeneration. PMID:25761987

  19. Siliceous mesostructured cellular foams/ poly(3-hydroxybutyrate-co-3-hydroxyhexanoate composite biomaterials for bone regeneration

    Directory of Open Access Journals (Sweden)

    Yang S

    2014-10-01

    Full Text Available Shengbing Yang,1,* Shuogui Xu,2,* Panyu Zhou,2,* Jing Wang,3 Honglue Tan,4 Yang Liu,5 TingTing Tang,4 ChangSheng Liu1,3,5 1The State Key Laboratory of Bioreactor Engineering, East China University of Science and Technology, Shanghai, People’s Republic of China; 2Changhai Hospital, Department of Orthopedics, the Second Military Medical University, Shanghai, People’s Republic of China; 3Key Laboratory for Ultrafine Materials of Ministry of Education, East China University of Science and Technology, Shanghai, People’s Republic of China; 4Shanghai Key Laboratory of Orthopedic Implant, Department of Orthopedic Surgery, Shanghai 9th People’s Hospital, Shanghai Jiao Tong University School of Medicine China, Shanghai, People’s Republic of China; 5Engineering Research Center for Biomedical Materials of Ministry of Education, East China University of Science and Technology, Shanghai, People’s Republic of China *These authors contributed equally to this workAbstract: Osteoinductive and biodegradable composite biomaterials for bone regeneration were prepared by combining poly(3-hydroxybutyrate-co-3-hydroxyhexanoate (PHBHHx with siliceous mesostructured cellular foams (SMC, using the porogen leaching method. Surface hydrophilicity, morphology, and recombinant human bone morphogenetic protein 2 adsorption/release behavior of the SMC/PHBHHx scaffolds were analyzed. Results of scanning electron microscopy indicated that the SMC was uniformly dispersed in the PHBHHx scaffolds, and SMC modification scaffolds have an interconnected porous architecture with pore sizes ranging from 200 to 400 µm. The measurements of the water contact angles suggested that the incorporation of SMC into PHBHHx improves the hydrophilicity of the composite. In vitro studies with simulated body fluid show great improvements to bioactivity and biodegradability versus pure PHBHHx scaffolds. Cell adhesion and cell proliferation on the scaffolds was also evaluated, and the new

  20. Inhibitory Smads and bone morphogenetic protein (BMP) modulate anterior photoreceptor cell number during planarian eye regeneration.

    Science.gov (United States)

    González-Sastre, Alejandro; Molina, Ma Dolores; Saló, Emili

    2012-01-01

    Planarians represent an excellent model to study the processes of body axis and organ re-specification during regeneration. Previous studies have revealed a conserved role for the bone morphogenetic protein (BMP) pathway and its intracellular mediators Smad1/5/8 and Smad4 in planarian dorsoventral (DV) axis re-establishment. In an attempt to gain further insight into the role of this signalling pathway in planarians, we have isolated and functionally characte-rized the inhibitory Smads (I-Smads) in Schmidtea mediterranea. Two I-Smad homologues have been identified: Smed-smad6/7-1 and Smed-smad6/7-2. Expression of smad6/7-1 was detected in the parenchyma, while smad6/7-2 was found to be ex-pressed in the central nervous system and the eyes. Neither single smad6/7-1 and smad6/7-2 nor double smad6/7-1,-2 silencing gave rise to any apparent disruption of the DV axis. However, both regenerating and intact smad6/7-2 (RNAi) planarians showed defects in eye morphogenesis and displayed small, rounded eyes that lacked the anterior subpopulation of photoreceptor cells. The number of pigment cells was also reduced in these animals at later stages of regeneration. In contrast, after low doses of Smed-bmp(RNAi), planarians regenerated larger eyes in which the anterior subpopulation of photoreceptor cells was expanded. Our results suggest that Smed-smad6/7-2 and Smed-bmp control the re-specification and maintenance of anterior photoreceptor cell number in S. mediterranea. PMID:22451003

  1. The use of a polycaprolactone-tricalcium phosphate scaffold for bone regeneration of tooth socket facial wall defects and simultaneous immediate dental implant placement in Macaca fascicularis

    NARCIS (Netherlands)

    Goh, B.T.; Chanchareonsook, N.; Tideman, H.; Teoh, S.H.; Chow, J.K.; Jansen, J.A.

    2014-01-01

    Bone regeneration and aesthetic outcomes may be compromised when immediate implants are placed at extraction sites with dehiscence defects. The aim of this study was to compare, in a monkey model, peri-implant bone regeneration and implant stability after immediate implant placement into tooth socke

  2. Bone Regeneration Using Hydroxyapatite Sponge Scaffolds with In Vivo Deposited Extracellular Matrix.

    Science.gov (United States)

    Ventura, Reiza Dolendo; Padalhin, Andrew Reyes; Min, Young-Ki; Lee, Byong-Taek

    2015-11-01

    There is currently an increased interest in studying the extracellular matrix (ECM) and its potential applications for tissue engineering and regenerative medicine. The ECM plays an important role by providing adhesive substrates to cells during migration, morphogenesis, differentiation, and homeostasis by signaling biochemical and biomechanical cues to cells. In this study, the ECM was incorporated into hydroxyapatite by implanting sponge replica scaffolds in subcutaneous pockets in rats, and the implants were tested for bone regeneration potential. The resulting scaffolds were characterized using scanning electron microscopy, confocal microscopy, DNA and RNA quantification, tissue staining, energy dispersive X-ray spectroscopy analysis, compressive strength testing, porosity, and pore size distribution analysis using bare scaffolds as a control reference. Biocompatibility was assessed using MC3T3-E1 preosteoblast cells and in vivo studies were carried out by implanting decellularized scaffolds in 11 mm radial defects in New Zealand rabbits for 4 and 8 weeks to determine the effect of the in vivo deposited ECM. Material characterization indicated that a 2-week decellularized scaffold was the best among the samples, with an evenly distributed ECM visible on hematoxylin and eosin-stained tissue sections, a compressive strength of 2.53 ± 0.68 MPa, a porosity of 58.08 ± 3.32% and a pore size distribution range of 10-150 μm. In vivo results showed no severe inflammation, with increased cell infiltration followed by dense matrix deposition after 4 weeks and new bone formation at 8 weeks. The results indicate that incorporation of an in vivo deposited ECM into ceramic scaffolds can potentially improve bone regeneration. PMID:26228909

  3. Concise review: bridging the gap: bone regeneration using skeletal stem cell-based strategies-where are we now?

    DEFF Research Database (Denmark)

    Dawson, Jonathan I; Kanczler, Janos; Kassem, Moustapha; Oreffo, Richard O.C.

    2014-01-01

    Skeletal stem cells confer to bone its innate capacity for regeneration and repair. Bone regeneration strategies seek to harness and enhance this regenerative capacity for the replacement of tissue damaged or lost through congenital defects, trauma, functional/esthetic problems, and a broad range...... of diseases associated with an increasingly aged population. This review describes the state of the field and current steps to translate and apply skeletal stem cell biology in the clinic and the problems therein. Challenges are described along with key strategies including the isolation and ex vivo...... expansion of multipotential populations, the targeting/delivery of regenerative populations to sites of repair, and their differentiation toward bone lineages. Finally, preclinical models of bone repair are discussed along with their implications for clinical translation and the opportunities to harness...

  4. Allogeneic stem cell transplantation for bone regeneration of a nonunion defect in a canine

    Directory of Open Access Journals (Sweden)

    Yaneselli K

    2013-10-01

    Full Text Available Kevin Yaneselli,1 Andrea Filomeno,1 Gabriel Semiglia,1 Carolina Arce,1 Analía Rial,2 Natalia Muñoz,2 María Moreno,2 Kent Erickson,3 Jacqueline Maisonnave11Universidad de la República, Facultad de Veterinaria, Montevideo, Uruguay; 2Laboratory for Vaccine Research, Department of Biotechnology, Instituto de Higiene, Facultad de Medicina, Universidad de la República, Montevideo, Uruguay; 3University of California, Davis, CA, USAAbstract: Nonunion bone defects occur frequently with local pain, functional limitations, muscular atrophy, and fistulas due to osteomyelitis. The application of mesenchymal stem cells (MSCs could improve regeneration of bone following bone defects. The objective of the present study was to evaluate the treatment of a nonunion defect due to chronic osteomyelitis in a greyhound female dog with allogeneic adipose tissue-derived mesenchymal stem cells (AT-MSCs. The implanted cells were adherent to plastic, were of fibroblast type, and expressed the canine stem cell markers CD90low, CD44high, and CD45-. Cell therapy consisted of five percutaneous weekly injections of 2 × 106 allogeneic AT-MSCs into the bone defect (total of 10 × 106 AT-MSCs. The patient was evaluated clinically and radiologically for up to 1 year. The results were clinical improvement, a light lameness score of 1 at week 16, return to use of its forearm, no pain, and increased muscular mass. No signs of osteomyelitis were observed radiologically and clinically there were no fistulas. There was no evidence of local or systemic adverse reactions caused by the aloimplants. The clinical relevance of the cell therapy contributing to repair of bone defects in small animals is a very promising future alternative. These results may have an important impact in new regenerative treatments for animal and human orthopedics.Keywords: allogeneic, AT-MSCs, treatment, nonunion, canine

  5. Osteogenesis effect of guided bone regeneration combined with alveolar cleft grafting: assessment by cone beam computed tomography.

    Science.gov (United States)

    Xiao, W-L; Zhang, D-Z; Chen, X-J; Yuan, C; Xue, L-F

    2016-06-01

    Cone beam computed tomography (CBCT) allows for a significantly lower radiation dose than conventional computed tomography (CT) scans and provides accurate images of the alveolar cleft area. The osteogenic effect of guided bone regeneration (GBR) vs. conventional alveolar bone grafting alone for alveolar cleft defects was evaluated in this study. Sixty alveolar cleft patients were divided randomly into two groups. One group underwent GBR using acellular dermal matrix film combined with alveolar bone grafting using iliac crest bone grafts (GBR group), while the other group underwent alveolar bone grafting only (non-GBR group). CBCT images were obtained at 1 week and at 3 months following the procedure. Using Simplant 11.04 software, the bone resorption rate was calculated and compared between the two groups. The bone resorption rate from 1 week to 3 months following bone grafting without the GBR technique was 36.50±5.04%, whereas the bone resorption rate using the GBR technique was 31.69±5.50% (P=0.017). The application of autogenous iliac bone combined with the GBR technique for alveolar bone grafting of alveolar cleft patients can reduce bone resorption and result in better osteogenesis. PMID:26876144

  6. In vitro and in vivo evaluation of electrospun PCL/PMMA fibrous scaffolds for bone regeneration

    Science.gov (United States)

    Son, So-Ra; Linh, Nguyen-Thuy Ba; Yang, Hun-Mo; Lee, Byong-Taek

    2013-02-01

    Scaffolds were fabricated by electrospinning using polycaprolactone (PCL) blended with poly(methyl methacrylate) (PMMA) in ratios of 10/0, 7/3, 5/5 and 3/7. The PCL/PMMA ratio affected the fiber diameter, contact angle, tensile strength and biological in vitro and in vivo properties of the scaffolds, and the 7/3 ratio resulted in a higher mechanical strength than 5/5 and 3/7. In vitro cytotoxicity and proliferation of MG-63 osteoblast cells on these blended scaffolds were examined by MTT assay, and it was found that PCL/PMMA blends are suitable for osteoblast cell proliferation. Confocal images and expression of proliferating cell nuclear antigen confirmed the good proliferation and expression of cells on the 7/3 PCL/PMMA fibrous scaffolds. In vivo bone formation was examined using rat models, and bone formation was observed on the 7/3 PCL/PMMA scaffold within 2 months. In vitro and in vivo results suggest that 7/3 PCL/PMMA scaffolds can be used for bone tissue regeneration.

  7. In vitro and in vivo evaluation of electrospun PCL/PMMA fibrous scaffolds for bone regeneration

    International Nuclear Information System (INIS)

    Scaffolds were fabricated by electrospinning using polycaprolactone (PCL) blended with poly(methyl methacrylate) (PMMA) in ratios of 10/0, 7/3, 5/5 and 3/7. The PCL/PMMA ratio affected the fiber diameter, contact angle, tensile strength and biological in vitro and in vivo properties of the scaffolds, and the 7/3 ratio resulted in a higher mechanical strength than 5/5 and 3/7. In vitro cytotoxicity and proliferation of MG-63 osteoblast cells on these blended scaffolds were examined by MTT assay, and it was found that PCL/PMMA blends are suitable for osteoblast cell proliferation. Confocal images and expression of proliferating cell nuclear antigen confirmed the good proliferation and expression of cells on the 7/3 PCL/PMMA fibrous scaffolds. In vivo bone formation was examined using rat models, and bone formation was observed on the 7/3 PCL/PMMA scaffold within 2 months. In vitro and in vivo results suggest that 7/3 PCL/PMMA scaffolds can be used for bone tissue regeneration. (paper)

  8. In vitro and in vivo evaluation of electrospun PCL/PMMA fibrous scaffolds for bone regeneration

    Directory of Open Access Journals (Sweden)

    So-Ra Son, Nguyen-Thuy Ba Linh, Hun-Mo Yang and Byong-Taek Lee

    2013-01-01

    Full Text Available Scaffolds were fabricated by electrospinning using polycaprolactone (PCL blended with poly(methyl methacrylate (PMMA in ratios of 10/0, 7/3, 5/5 and 3/7. The PCL/PMMA ratio affected the fiber diameter, contact angle, tensile strength and biological in vitro and in vivo properties of the scaffolds, and the 7/3 ratio resulted in a higher mechanical strength than 5/5 and 3/7. In vitro cytotoxicity and proliferation of MG-63 osteoblast cells on these blended scaffolds were examined by MTT assay, and it was found that PCL/PMMA blends are suitable for osteoblast cell proliferation. Confocal images and expression of proliferating cell nuclear antigen confirmed the good proliferation and expression of cells on the 7/3 PCL/PMMA fibrous scaffolds. In vivo bone formation was examined using rat models, and bone formation was observed on the 7/3 PCL/PMMA scaffold within 2 months. In vitro and in vivo results suggest that 7/3 PCL/PMMA scaffolds can be used for bone tissue regeneration.

  9. Strontium eluting nanofibers augment stem cell osteogenesis for bone tissue regeneration.

    Science.gov (United States)

    Meka, Sai Rama Krishna; Jain, Shubham; Chatterjee, Kaushik

    2016-10-01

    Strontium is known to offer a therapeutic benefit to osteoporotic patients by promoting bone formation. Thus, toward engineering scaffolds for bone tissue regeneration we have prepared polymer nanocomposite scaffolds by electrospinning. Strontium carbonate nanoparticles (nSrCO3) were added to poly(ε-caprolactone) (PCL) at 10 and 20wt% to develop nanocomposite fibrous scaffolds (PCL/SrC10 and PCL/SrC20) with fiber diameter in the range of 300-500nm. Incorporation of nSrCO3 decreased crystallinity and the elastic modulus of PCL. The composite scaffolds released Sr(2+) ions with up to 65ppm in 4days from the PCL/SrC20 scaffolds. Cell studies confirmed that the composite scaffold with 20% nSrCO3 enhanced proliferation of human mesenchymal stem cells in vitro. There was marked increase in mineral deposition up to four folds in PCL/SrC20 suggesting enhanced osteogenesis. This was corroborated by increased mRNA and protein expression of various osteogenic markers such as BMP-2, Osterix and Runx2 in the PCL/SrC20 fibers. Thus, incorporation of nSrCO3 in polymer scaffolds is a promising strategy for bone tissue engineering as an alternative to the use of labile growth factors to impart bioactivity to polymer scaffolds. PMID:27429299

  10. Nanoscale control of silica particle formation via silk-silica fusion proteins for bone regeneration.

    Science.gov (United States)

    Mieszawska, Aneta J; Nadkarni, Lauren D; Perry, Carole C; Kaplan, David L

    2010-10-26

    The biomimetic design of silk/silica fusion proteins was carried out, combining the self assembling domains of spider dragline silk (Nephila clavipes) and silaffin derived R5 peptide of Cylindrotheca fusiformis that is responsible for silica mineralization. Genetic engineering was used to generate the protein-based biomaterials incorporating the physical properties of both components. With genetic control over the nanodomain sizes and chemistry, as well as modification of synthetic conditions for silica formation, controlled mineralized silk films with different silica morphologies and distributions were successfully generated; generating 3D porous networks, clustered silica nanoparticles (SNPs), or single SNPs. Silk serves as the organic scaffolding to control the material stability and multiprocessing makes silk/silica biomaterials suitable for different tissue regenerative applications. The influence of these new silk-silica composite systems on osteogenesis was evaluated with human mesenchymal stem cells (hMSCs) subjected to osteogenic differentiation. hMSCs adhered, proliferated, and differentiated towards osteogenic lineages on the silk/silica films. The presence of the silica in the silk films influenced osteogenic gene expression, with the upregulation of alkaline phosphatase (ALP), bone sialoprotein (BSP), and collagen type 1 (Col 1) markers. Evidence for early bone formation as calcium deposits was observed on silk films with silica. These results indicate the potential utility of these new silk/silica systems towards bone regeneration. PMID:20976116

  11. Bone regeneration and infiltration of an anisotropic composite scaffold: an experimental study of rabbit cranial defect repair.

    Science.gov (United States)

    Li, Jidong; You, Fu; Li, Yubao; Zuo, Yi; Li, Limei; Jiang, Jiaxing; Qu, Yili; Lu, Minpeng; Man, Yi; Zou, Qin

    2016-01-01

    Tissue formation on scaffold outer edges after implantation may restrict cell infiltration and mass transfer to/from the scaffold center due to insufficient interconnectivity, leading to incidence of a necrotic core. Herein, a nano-hydroxyapatite/polyamide66 (n-HA/PA66) anisotropic scaffold with axially aligned channels was prepared with the aim to enhance pore interconnectivity. Bone tissue regeneration and infiltration inside of scaffold were assessed by rabbit cranial defect repair experiments. The amount of newly formed bone inside of anisotropic scaffold was much higher than isotropic scaffold, e.g., after 12 weeks, the new bone volume in the inner pores was greater in the anisotropic scaffolds (>50%) than the isotropic scaffolds (<30%). The results suggested that anisotropic scaffolds could accelerate the inducement of bone ingrowth into the inner pores in the non-load-bearing bone defects compared to isotropic scaffolds. Thus, anisotropic scaffolds hold promise for the application in bone tissue engineering. PMID:26775692

  12. Enhanced Bone Tissue Regeneration by Porous Gelatin Composites Loaded with the Chinese Herbal Decoction Danggui Buxue Tang.

    Directory of Open Access Journals (Sweden)

    Wen-Ling Wang

    Full Text Available Danggui Buxue Tang (DBT is a traditional Chinese herbal decoction containing Radix Astragali and Radix Angelicae sinensis. Pharmacological results indicate that DBT can stimulate bone cell proliferation and differentiation. The aim of the study was to investigate the efficacy of adding DBT to bone substitutes on bone regeneration following bone injury. DBT was incorporated into porous composites (GGT made from genipin-crosslinked gelatin and β-triclacium phosphates as bone substitutes (GGTDBT. The biological response of mouse calvarial bone to these composites was evaluated by in vivo imaging systems (IVIS, micro-computed tomography (micro-CT, and histology analysis. IVIS images revealed a stronger fluorescent signal in GGTDBT-treated defect than in GGT-treated defect at 8 weeks after implantation. Micro-CT analysis demonstrated that the level of repair from week 4 to 8 increased from 42.1% to 71.2% at the sites treated with GGTDBT, while that increased from 33.2% to 54.1% at GGT-treated sites. These findings suggest that the GGTDBT stimulates the innate regenerative capacity of bone, supporting their use in bone tissue regeneration.

  13. A Comparative Study of Bioartificial Bone Tissue Poly-L-lactic Acid/Polycaprolactone and PLLA Scaffolds Applied in Bone Regeneration

    OpenAIRE

    Weizong Weng; Shaojun Song; Liehu Cao; Xiao Chen; Yuanqi Cai; Haihang Li; Qirong Zhou; Jun Zhang; Jiacan Su

    2014-01-01

    Bioartificial bone tissue engineering is an increasingly popular technique to repair bone defect caused by injury or disease. This study aimed to investigate the feasibility of PLLA/PCL (poly-L-lactic acid/polycaprolactone) by a comparison study of PLLA/PCL and PLLA scaffolds applied in bone regeneration. Thirty healthy mature New Zealand rabbits on which 15 mm distal ulna defect model had been established were selected and then were divided into three groups randomly: group A (repaired with ...

  14. A conceptually new type of bio-hybrid scaffold for bone regeneration

    International Nuclear Information System (INIS)

    Magnetic bio-hybrid porous scaffolds have been synthesized, nucleating nano-apatite in situ on self-assembling collagen, in the presence of magnetite nano-particles. The magnetic phase acted as a sort of cross-linking agent for the collagen, inducing a chemico-physical-mechanical stabilization of the material and allowing us to control the porosity network of the scaffold. Gradients of bio-mineralization and magnetization were also developed for osteochondral application. The good potentiality of the material as a biomedical device, able to offer assistance to bone regeneration through scaffold reloading with specific factors guided by an external magnetic field, has been preliminarily investigated. Up to now the proof of this concept has been realized through in vitro assessments.

  15. A conceptually new type of bio-hybrid scaffold for bone regeneration

    Energy Technology Data Exchange (ETDEWEB)

    Tampieri, A; Landi, E; Valentini, F; Sandri, M; D' Alessandro, T [ISTEC-CNR, Institute of Science and Technology for Ceramics-National Research Council, via Granarolo, 64-48018 Faenza (RA) (Italy); Dediu, V [ISMN-CNR, Institute of Nanostructured Materials-National Research Council, via P Gobetti, 101-40135 Bologna (Italy); Marcacci, M, E-mail: elena.landi@istec.cnr.it [Istituti Ortopedici Rizzoli, Laboratorio di Biomeccanica, Via di Barbiano, 1/10-40136 Bologna (Italy)

    2011-01-07

    Magnetic bio-hybrid porous scaffolds have been synthesized, nucleating nano-apatite in situ on self-assembling collagen, in the presence of magnetite nano-particles. The magnetic phase acted as a sort of cross-linking agent for the collagen, inducing a chemico-physical-mechanical stabilization of the material and allowing us to control the porosity network of the scaffold. Gradients of bio-mineralization and magnetization were also developed for osteochondral application. The good potentiality of the material as a biomedical device, able to offer assistance to bone regeneration through scaffold reloading with specific factors guided by an external magnetic field, has been preliminarily investigated. Up to now the proof of this concept has been realized through in vitro assessments.

  16. Horizontal Guided Bone Regeneration in the Esthetic Area with rhPDGF-BB and Anorganic Bovine Bone Graft: A Case Report.

    Science.gov (United States)

    Chiantella, Giovanni Carlo

    2016-01-01

    The present article describes the treatment given to a patient who underwent horizontal ridge augmentation surgery in the maxillary anterior area due to the premature loss of the maxillary central incisors. The complete dehiscence of the buccal plate was detected after elevation of mucoperiosteal flaps. The lesion was overfilled with deproteinized bovine xenograft particles combined with recombinant human platelet-derived growth factor BB (rhPDGF-BB) and covered with a porcine collagen barrier hydrated with the same growth factor. The soft tissues healed with no adverse complications. After 12 months, reentry surgery was carried out to place endosseous implants. Complete bone regeneration with the presence of bone-like tissue was observed. Cross-sectional computed tomography scan images confirmed integration of the bone graft and reconstruction of the lost hard tissue volume. The implants were inserted in an optimal three-dimensional position, thus facilitating esthetic restoration. Two years after insertion of final crowns, cone beam computed tomography scans displayed the stability of regenerated hard tissues around the implants. Controlled clinical studies are necessary to determine the benefit of hydrating bovine bone particles and collagen barriers with rhPDGF-BB for predictable bone regeneration of horizontal lesions. PMID:26697562

  17. Bone morphogenetic protein-2 is a negative regulator of hepatocyte proliferation downregulated in the regenerating liver

    Institute of Scientific and Technical Information of China (English)

    Cui-Ping Xu; Wen-Min Ji; Gijs R van den Brink; Maikel P Peppelenbosch

    2006-01-01

    AIM: To characterize the expression and dynamic changes of bone morphogenetic protein (BMP)-2 in hepatocytes in the regenerating liver in rats after partial hepatectomy (PH), and examine the effects of BMP-2 on proliferation of human Huh7 hepatoma cells.METHODS: Fifty-four adult male Wistar rats were randomly divided into three groups: A normal control (NC) group, a partial hepatectomized (PH) group and a sham operated (SO) group. To study the effect of liver regeneration on BMP-2 expression, rats were sacrificed before and at different time points after PH or the sham intervention (6, 12, 24 and 48 h). For each time point, six rats were used in parallel. Expression and distribution of BMP-2 protein were determined in regenerating liver tissue by Western blot analysis and immunohistochemistry. Effects of BMP-2 on cell proliferation of human Huh7 hepatoma cell line were assessed using an MTT assay.RESULTS: In the normal liver strong BMP-2 expression was observed around the central and portal veins. The expression of BMP-2 decreased rapidly as measured by both immunohistochemistry and Western blot analysis.This decrease was at a maximum of 3.22 fold after 12 h and returned to normal levels at 48 h after PH. No significant changes in BMP-2 immunoreactivity were observed in the SO group. BMP-2 inhibited serum induced Huh7 cell proliferation.CONCLUSION: BMP-2 is expressed in normal adult rat liver and negatively regulates hepatocyte proliferation.The observed down regulation of BMP-2 following partial hepatectomy suggests that such down regulation may be necessary for hepatocyte proliferation.

  18. Wound models for periodontal and bone regeneration: the role of biologic research.

    Science.gov (United States)

    Sculean, Anton; Chapple, Iain L C; Giannobile, William V

    2015-06-01

    The ultimate goals of periodontal therapy remain the complete regeneration of those periodontal tissues lost to the destructive inflammatory-immune response, or to trauma, with tissues that possess the same structure and function, and the re-establishment of a sustainable health-promoting biofilm from one characterized by dysbiosis. This volume of Periodontology 2000 discusses the multiple facets of a transition from therapeutic empiricism during the late 1960s, toward regenerative therapies, which is founded on a clearer understanding of the biophysiology of normal structure and function. This introductory article provides an overview on the requirements of appropriate in vitro laboratory models (e.g. cell culture), of preclinical (i.e. animal) models and of human studies for periodontal wound and bone repair. Laboratory studies may provide valuable fundamental insights into basic mechanisms involved in wound repair and regeneration but also suffer from a unidimensional and simplistic approach that does not account for the complexities of the in vivo situation, in which multiple cell types and interactions all contribute to definitive outcomes. Therefore, such laboratory studies require validatory research, employing preclinical models specifically designed to demonstrate proof-of-concept efficacy, preliminary safety and adaptation to human disease scenarios. Small animal models provide the most economic and logistically feasible preliminary approaches but the outcomes do not necessarily translate to larger animal or human models. The advantages and limitations of all periodontal-regeneration models need to be carefully considered when planning investigations to ensure that the optimal design is adopted to answer the specific research question posed. Future challenges lie in the areas of stem cell research, scaffold designs, cell delivery and choice of growth factors, along with research to ensure appropriate gingival coverage in order to prevent gingival

  19. Guided tissue regeneration and bone grafts in the treatment of furcation defects.

    Science.gov (United States)

    Caffesse, R G; Nasjleti, C E; Plotzke, A E; Anderson, G B; Morrison, E C

    1993-11-01

    The present study evaluated the effects of guided tissue regeneration (GTR), with and without demineralized freeze-dried cortical bone grafts, in the treatment of furcation defects in 4 female beagle dogs with naturally occurring periodontal disease. The root surfaces were thoroughly debrided. Four weeks later, full thickness facial and lingual mucoperiosteal flaps were reflected using inverse bevel incisions on both sides of the mandible involving the 2nd, 3rd, and 4th premolar, and the 1st molar teeth. Following debridement, notches were placed on the roots at the level of supporting bone. Test quadrants were randomly selected and furcations were filled with reconstituted, demineralized, freeze-dried human cortical bone grafts. Following bone grafting, all defects were covered with an expanded polytetrafluoroethylene (ePTFE) membrane, which was sutured with 4-0 sutures. Afterward, interproximal sutures were placed through the flaps, assuring the flaps covered the membranes completely. The contralateral side, serving as control, was treated by debridement only and application of ePTFE membrane. All membranes were removed 6 weeks after surgery. Dogs were sacrificed at 4 months after surgery. Both mesio-distal and bucco-lingual histologic sections were evaluated by descriptive histology. Linear measurements and surface area determination of the furcal tissues were carried out using the microscope attached to a digitizer. Twelve to 20 nonserial sections were made of the mid-buccal aspects of each root of each treated tooth. Half of these sections were stained with Harris' hematoxylin and eosin (H&E) and the other half stained with Mallory's trichrome stain.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:8295103

  20. 3-Dimensional cell-laden nano-hydroxyapatite/protein hydrogels for bone regeneration applications

    Energy Technology Data Exchange (ETDEWEB)

    Sadat-Shojai, Mehdi, E-mail: msadatshojai@gmail.com [Department of Chemistry, College of Sciences, Shiraz University, Shiraz 71454 (Iran, Islamic Republic of); Department of Biomaterials, Iran Polymer and Petrochemical Institute, Tehran (Iran, Islamic Republic of); Khorasani, Mohammad-Taghi [Department of Biomaterials, Iran Polymer and Petrochemical Institute, Tehran (Iran, Islamic Republic of); Jamshidi, Ahmad [Department of Novel Drug Delivery Systems, Iran Polymer and Petrochemical Institute, Tehran (Iran, Islamic Republic of)

    2015-04-01

    The ability to encapsulate cells in three-dimensional (3D) protein-based hydrogels is potentially of benefit for tissue engineering and regenerative medicine. However, as a result of their poor mechanical strength, protein-based hydrogels have traditionally been considered for soft tissue engineering only. Hence, in this study we tried to render these hydrogels suitable for hard tissue regeneration, simply by incorporation of bioactive nano-hydroxyapatite (HAp) into a photocrosslinkable gelatin hydrogel. Different cell types were also encapsulated in three dimensions in the resulting composites to prepare cell-laden constructs. According to the results, HAp significantly improves the stiffness of gelatin hydrogels, while it maintains their structural integrity and swelling ratio. It was also found that while the bare hydrogel (control) was completely inert in terms of bioactivity, a homogeneous 3D mineralization occurs throughout the nanocomposites after incubation in simulated body fluid. Moreover, encapsulated cells readily elongated, proliferated, and formed a 3D interconnected network with neighboring cells in the nanocomposite, showing the suitability of the nano-HAp/protein hydrogels for cellular growth in 3D. Therefore, the hydrogel nanocomposites developed in this study may be promising candidates for preparing cell-laden tissue-like structures with enhanced stiffness and increased osteoconductivity to induce bone formation in vivo. - Highlights: • We tried to render protein-based hydrogels suitable for hard tissue regeneration. • We developed a three-component system comprising hydrogel, nano-HAp, and cells. • Nano-HAp significantly improved the mechanical strength of hydrogel. • Encapsulated cells readily elongated and proliferated in 3D cell-laden nanocomposite. • 3D deposition of bone crystals occurred in the hydrogel nanocomposites.

  1. Akermanite bioceramics promote osteogenesis, angiogenesis and suppress osteoclastogenesis for osteoporotic bone regeneration.

    Science.gov (United States)

    Xia, Lunguo; Yin, Zhilan; Mao, Lixia; Wang, Xiuhui; Liu, Jiaqiang; Jiang, Xinquan; Zhang, Zhiyuan; Lin, Kaili; Chang, Jiang; Fang, Bing

    2016-01-01

    It is a big challenge for bone healing under osteoporotic pathological condition with impaired angiogenesis, osteogenesis and remodeling. In the present study, the effect of Ca, Mg, Si containing akermanite bioceramics (Ca2MgSi2O7) extract on cell proliferation, osteogenic differentiation and angiogenic factor expression of BMSCs derived from ovariectomized rats (BMSCs-OVX) as well as the expression of osteoclastogenic factors was evaluated. The results showed that akermanite could enhance cell proliferation, ALP activity, expression of Runx2, BMP-2, BSP, OPN, OCN, OPG and angiogenic factors including VEGF and ANG-1. Meanwhile, akermanite could repress expression of osteoclastogenic factors including RANKL and TNF-α. Moreover, akermanite could activate ERK, P38, AKT and STAT3 signaling pathways, while crosstalk among these signaling pathways was evident. More importantly, the effect of akermanite extract on RANKL-induced osteoclastogenesis was evaluated by TRAP staining and real-time PCR assay. The results showed that akermanite could suppress osteoclast formation and expression of TRAP, cathepsin K and NFATc1. The in vivo experiments revealed that akermanite bioceramics dramatically stimulated osteogenesis and angiogenesis in an OVX rat critical-sized calvarial defect model. All these results suggest that akermanite bioceramics with the effects of Mg and Si ions on osteogenesis, angiogenesis and osteoclastogenesis are promising biomaterials for osteoporotic bone regeneration. PMID:26911441

  2. Nanocomposites of Polyacrylic Acid Nanogels and Biodegradable Polyhydroxybutyrate for Bone Regeneration and Drug Delivery

    Directory of Open Access Journals (Sweden)

    Mikael Larsson

    2014-01-01

    Full Text Available Biodegradable cell scaffolds and local drug delivery to stimulate cell response are currently receiving much scientific attention. Here we present a nanocomposite that combines biodegradation with controlled release of lithium, which is known to enhance bone growth. Nanogels of lithium neutralized polyacrylic acid were synthesized by microemulsion-templated polymerization and were incorporated into a biodegradable polyhydroxybutyrate (PHB matrix. Nanogel size was characterized using dynamic light scattering, and the nanocomposites were characterized with regard to structure using scanning electron microscopy, mechanical properties using tensile testing, permeability using tritiated water, and lithium release in PBS using a lithium specific electrode. The nanogels were well dispersed in the composites and the mechanical properties were good, with a decrease in elastic modulus being compensated by increased tolerance to strain in the wet state. Approximately half of the lithium was released over about three hours, with the remaining fraction being trapped in the PHB for subsequent slow release during biodegradation. The prepared nanocomposites seem promising for use as dual functional scaffolds for bone regeneration. Here lithium ions were chosen as model drug, but the nanogels could potentially act as carriers for larger and more complex drugs, possibly while still carrying lithium.

  3. Three-dimensional printing of strontium-containing mesoporous bioactive glass scaffolds for bone regeneration.

    Science.gov (United States)

    Zhang, Jianhua; Zhao, Shichang; Zhu, Yufang; Huang, Yinjun; Zhu, Min; Tao, Cuilian; Zhang, Changqing

    2014-05-01

    In this study, we fabricated strontium-containing mesoporous bioactive glass (Sr-MBG) scaffolds with controlled architecture and enhanced mechanical strength using a three-dimensional (3-D) printing technique. The study showed that Sr-MBG scaffolds had uniform interconnected macropores and high porosity, and their compressive strength was ∼170 times that of polyurethane foam templated MBG scaffolds. The physicochemical and biological properties of Sr-MBG scaffolds were evaluated by ion dissolution, apatite-forming ability and proliferation, alkaline phosphatase activity, osteogenic expression and extracelluar matrix mineralization of osteoblast-like cells MC3T3-E1. The results showed that Sr-MBG scaffolds exhibited a slower ion dissolution rate and more significant potential to stabilize the pH environment with increasing Sr substitution. Importantly, Sr-MBG scaffolds possessed good apatite-forming ability, and stimulated osteoblast cells' proliferation and differentiation. Using dexamethasone as a model drug, Sr-MBG scaffolds also showed a sustained drug delivery property for use in local drug delivery therapy, due to their mesoporous structure. Therefore, the 3-D printed Sr-MBG scaffolds combined the advantages of Sr-MBG such as good bone-forming bioactivity, controlled ion release and drug delivery and enhanced mechanical strength, and had potential application in bone regeneration. PMID:24412143

  4. Adequate hypoxia inducible factor 1α signaling is indispensable for bone regeneration.

    Science.gov (United States)

    Stegen, Steve; Deprez, Sanne; Eelen, Guy; Torrekens, Sophie; Van Looveren, Riet; Goveia, Jermaine; Ghesquière, Bart; Carmeliet, Peter; Carmeliet, Geert

    2016-06-01

    Engineered cell-based constructs are an appealing strategy to treat large skeletal defects. However, transplanted cells are often confronted with an environment that is deprived of oxygen and nutrients. Upon hypoxia, most cell types activate hypoxia-inducible factor 1α (HIF-1α) signaling, but its importance for implanted osteoprogenitor cells during bone regeneration is not elucidated. To this end, we specifically deleted the HIF--1α isoform in periosteal progenitor cells and show that activation of HIF-1α signaling in these cells is critical for bone repair by modulating angiogenic and metabolic processes. Activation of HIF-1α is not only crucial for blood vessel invasion, by enhancing angiogenic growth factor production, but also for periosteal cell survival early after implantation, when blood vessels have not yet invaded the construct. HIF-1α signaling limits oxygen consumption to avoid accumulation of harmful ROS and preserve redox balance, and additionally induces a switch to glycolysis to prevent energetic distress. Altogether, our results indicate that the proangiogenic capacity of implanted periosteal cells is HIF-1α regulated and that metabolic adaptations mediate post-implantation cell survival. PMID:27058876

  5. Clinical and radiological studies upon a combined method for guided bone regeneration in experimental mandibular defects in dogs - a preliminary communication

    International Nuclear Information System (INIS)

    The treated bone defects were compared clinically and radiologically. After a 3-month period of survey, the best results were obtained in the group treated with partially demineralized bone matrix, enzymatically processed and lyophilized dura mater and mucoperiosteal flap. The placement of titanium screw dental implants did not impair the guided bone regeneration, that was confirmed by their good osteointegration

  6. Tantalum coating of porous carbon scaffold supplemented with autologous bone marrow stromal stem cells for bone regeneration in vitro and in vivo.

    Science.gov (United States)

    Wei, Xiaowei; Zhao, Dewei; Wang, Benjie; Wang, Wei; Kang, Kai; Xie, Hui; Liu, Baoyi; Zhang, Xiuzhi; Zhang, Jinsong; Yang, Zhenming

    2016-03-01

    Porous tantalum metal with low elastic modulus is similar to cancellous bone. Reticulated vitreous carbon (RVC) can provide three-dimensional pore structure and serves as the ideal scaffold of tantalum coating. In this study, the biocompatibility of domestic porous tantalum was first successfully tested with bone marrow stromal stem cells (BMSCs) in vitro and for bone tissue repair in vivo. We evaluated cytotoxicity of RVC scaffold and tantalum coating using BMSCs. The morphology, adhesion, and proliferation of BMSCs were observed via laser scanning confocal microscope and scanning electron microscopy. In addition, porous tantalum rods with or without autologous BMSCs were implanted on hind legs in dogs, respectively. The osteogenic potential was observed by hard tissue slice examination. At three weeks and six weeks following implantation, new osteoblasts and new bone were observed at the tantalum-host bone interface and pores. At 12 weeks postporous tantalum with autologous BMSCs implantation, regenerated trabecular equivalent to mature bone was found in the pore of tantalum rods. Our results suggested that domestic porous tantalum had excellent biocompatibility and could promote new bone formation in vivo. Meanwhile, the osteogenesis of porous tantalum associated with autologous BMSCs was more excellent than only tantalum implantation. Future clinical studies are warranted to verify the clinical efficacy of combined implantation of this domestic porous tantalum associated with autologous BMSCs implantation and compare their efficacy with conventional autologous bone grafting carrying blood vessel in patients needing bone repairing. PMID:26843518

  7. In vitro study of manganese-doped bioactive glasses for bone regeneration

    International Nuclear Information System (INIS)

    A glass belonging to the system SiO2–P2O5–CaO–MgO–Na2O–K2O was modified by introducing two different amounts of manganese oxide (MnO). Mn-doped glasses were prepared by melt and quenching technique and characterized by means of X-ray diffraction (XRD), scanning electron microscopy (SEM) observation and energy dispersion spectrometry (EDS) analysis. In vitro bioactivity test in simulated body fluid (SBF) showed a slight decrease in the reactivity kinetics of Mn-doped glasses compared to the glass used as control; however the glasses maintained a good degree of bioactivity. Mn-leaching test in SBF and minimum essential medium (MEM) revealed fluctuating trends probably due to a re-precipitation of Mn compounds during the bioactivity process. Cellular tests showed that all the Mn-doped glasses, up to a concentration of 50 μg/cm2 (μg of glass powders/cm2 of cell monolayer), did not produce cytotoxic effects on human MG-63 osteoblasts cultured for up to 5 days. Finally, biocompatibility tests demonstrated a good osteoblast proliferation and spreading on Mn-doped glasses and most of all that the Mn-doping can promote the expression of alkaline phosphatase (ALP) and some bone morphogenetic proteins (BMPs). - Highlights: • Novel bioactive glasses doped with manganese were prepared. • Mn-doped bioactive glasses were not cytotoxic towards human MG-63 osteoblasts. • The Mn introduction promotes the expression of ALP and bone morphogenetic proteins. • Mn-doped glass may be a promising material for bone regeneration procedures

  8. In vitro study of manganese-doped bioactive glasses for bone regeneration

    Energy Technology Data Exchange (ETDEWEB)

    Miola, Marta, E-mail: marta.miola@polito.it [Applied Science and Technology Department, Politecnico di Torino, C.so Duca degli Abruzzi 24, 10129 Turin (Italy); Brovarone, Chiara Vitale [Applied Science and Technology Department, Politecnico di Torino, C.so Duca degli Abruzzi 24, 10129 Turin (Italy); Maina, Giovanni [Department of Clinical and Biological Sciences, University of Turin, Via Zuretti 29, 10126 Turin (Italy); Rossi, Federica [Department of Public Health and Pediatric Sciences, Piazza Polonia, 94, 10126 Torino (Italy); Bergandi, Loredana; Ghigo, Dario [Department of Oncology, University of Turin, Via Santena 5/bis, 10126 Turin (Italy); Saracino, Silvia; Maggiora, Marina; Canuto, Rosa Angela; Muzio, Giuliana [Department of Clinical and Biological Sciences, University of Turin, Corso Raffaello 30, 10125 Turin (Italy); Vernè, Enrica [Applied Science and Technology Department, Politecnico di Torino, C.so Duca degli Abruzzi 24, 10129 Turin (Italy)

    2014-05-01

    A glass belonging to the system SiO{sub 2}–P{sub 2}O{sub 5}–CaO–MgO–Na{sub 2}O–K{sub 2}O was modified by introducing two different amounts of manganese oxide (MnO). Mn-doped glasses were prepared by melt and quenching technique and characterized by means of X-ray diffraction (XRD), scanning electron microscopy (SEM) observation and energy dispersion spectrometry (EDS) analysis. In vitro bioactivity test in simulated body fluid (SBF) showed a slight decrease in the reactivity kinetics of Mn-doped glasses compared to the glass used as control; however the glasses maintained a good degree of bioactivity. Mn-leaching test in SBF and minimum essential medium (MEM) revealed fluctuating trends probably due to a re-precipitation of Mn compounds during the bioactivity process. Cellular tests showed that all the Mn-doped glasses, up to a concentration of 50 μg/cm{sup 2} (μg of glass powders/cm{sup 2} of cell monolayer), did not produce cytotoxic effects on human MG-63 osteoblasts cultured for up to 5 days. Finally, biocompatibility tests demonstrated a good osteoblast proliferation and spreading on Mn-doped glasses and most of all that the Mn-doping can promote the expression of alkaline phosphatase (ALP) and some bone morphogenetic proteins (BMPs). - Highlights: • Novel bioactive glasses doped with manganese were prepared. • Mn-doped bioactive glasses were not cytotoxic towards human MG-63 osteoblasts. • The Mn introduction promotes the expression of ALP and bone morphogenetic proteins. • Mn-doped glass may be a promising material for bone regeneration procedures.

  9. Autologous bone marrow-derived progenitor cell transplantation for myocardial regeneration after acute infarction

    Directory of Open Access Journals (Sweden)

    Obradović Slobodan

    2004-01-01

    Full Text Available Background. Experimental and first clinical studies suggest that the transplantation of bone marrow derived, or circulating blood progenitor cells, may beneficially affect postinfarction remodelling processes after acute myocardial infarction. Aim. This pilot trial reports investigation of safety and feasibility of autologous bone marrow-derived progenitor cell therapy for faster regeneration of the myocardium after infarction. Methods and results. Four male patients (age range 47-68 years with the first extensive anterior, ST elevation, acute myocardial infarction (AMI, were treated by primary angioplasty. Bone marrow mononuclear cells were administered by intracoronary infusion 3-5 days after the infarction. Bone marrow was harvested by multiple aspirations from posterior cristae iliacae under general anesthesia, and under aseptic conditions. After that, cells were filtered through stainless steel mesh, centrifuged and resuspended in serum-free culture medium, and 3 hours later infused through the catheter into the infarct-related artery in 8 equal boluses of 20 ml. Myocardial viability in the infarcted area was confirmed by dobutamin stress echocardiography testing and single-photon emission computed tomography (SPECT 10-14 days after infarction. One patient had early stent thrombosis immediately before cell transplantation, and was treated successfully with second angioplasty. Single average ECG revealed one positive finding at discharge, and 24-hour Holter ECG showed only isolated ventricular ectopic beats during the follow-up period. Early findings in two patients showed significant improvement of left ventricular systolic function 3 months after the infarction. There were no major cardiac events after the transplantation during further follow-up period (30-120 days after infarction. Control SPECT for the detection of ischemia showed significant improvement in myocardial perfusion in two patients 4 months after the infarction

  10. The role of miR-135-modified adipose-derived mesenchymal stem cells in bone regeneration.

    Science.gov (United States)

    Xie, Qing; Wang, Zi; Zhou, Huifang; Yu, Zhang; Huang, Yazhuo; Sun, Hao; Bi, Xiaoping; Wang, Yefei; Shi, Wodong; Gu, Ping; Fan, Xianqun

    2016-01-01

    Tissue-engineering technology employing genetically-modified mesenchymal stem cells combined with proper scaffolds represents a promising strategy for bone regeneration. Elucidating the underlying mechanisms that govern the osteogenesis of mesenchymal stem cells will give deeper insights into the regulatory patterns, as well as provide more effective methods to enhance bone regeneration. In this study, miR-135 was identified as an osteogenesis-related microRNA that was up-regulated during the osteogenesis of rat adipose-derived stem cells (ADSCs). Gain- and loss-of-function experiments using a lentiviral expression system showed that Homeobox A2 (Hoxa2) was negatively regulated by miR-135, and luciferase reporter assay further indicated that miR-135 repressed Hoxa2 expression through binding to the 3'-untranslated region (3'-UTR) of the Hoxa2 mRNA. In vitro analyses showed that the overexpression of miR-135 significantly enhanced the expression of bone markers and extracellular matrix calcium deposition, whereas the knockdown of miR-135 suppressed these processes. Transduced ADSCs were then combined with poly(sebacoyl diglyceride) (PSeD) scaffold to repair a critical-sized calvarial defects in rats. The results showed that the overexpression of miR-135 significantly promoted new bone formation with higher bone mineral density (BMD) and number of trabeculae (Tb.N), as well as larger areas of newly formed bone and mineralization labeled by tetracycline, calcein and alizarin red. In contrast, the knockdown of miR-135 attenuated these processes. Additionally, immunohistochemical analyses showed that transduced ADSCs participated in new bone formation and a miR-135/Hoxa2/Runx2 pathway might contribute to the regulation of ADSC osteogenesis and bone regeneration. Taken together, our data suggested that miR-135 positively regulated the osteogenesis and bone regeneration of ADSCs both in vitro and in vivo. Thus, the combination of miR-135-modified ADSCs and the PSe

  11. A composited PEG-silk hydrogel combining with polymeric particles delivering rhBMP-2 for bone regeneration.

    Science.gov (United States)

    Ma, Dakun; An, Gang; Liang, Min; Liu, Yugang; Zhang, Bin; Wang, Yansong

    2016-08-01

    Given the fabulous potential of promoting bone regeneration, BMP-2 has been investigated widely in the bone tissue engineering field. A sophisticated biomaterial loaded with BMP-2, which could avoid the required supraphysiological dose leading to high medical costs and risks of complications, has been considered as a promising strategy to treat non-healing bone defects. In this study, we developed a simple approach to engineer a composited hydrogel consisting polymeric particles (PLA/PLGA) used as a BMP-2 delivery vehicle. Compared with other groups, the introduction of PLA into PEG-silk gels endowed the hydrogel new physicochemical characteristics especially hydrophobicity which inhibited the burst release of BMP-2 and enhanced gel's structural stability. Moreover, such composited gels could stabilize entrapped proteins and maintain their bioactivity fully in vitro. In vivo, the bio-degradability experiment demonstrated this system was biocompatible and the reinforced hydrophobicity significantly decreased degradation rate, and in rat critical-sized cranial defects model, the gel containing PLA promoted the most bone formation. These findings demonstrated the introduction of PLA changed physicochemical features of gels more suitable as a BMP-2 carrier indicated by inducing bone regeneration efficiently in large bone defects at low delivered dose and this system may own translational potential. PMID:27157747

  12. Hierarchical Structure and Mechanical Improvement of an n-HA/GCO-PU Composite Scaffold for Bone Regeneration.

    Science.gov (United States)

    Li, Limei; Zuo, Yi; Zou, Qin; Yang, Boyuan; Lin, Lili; Li, Jidong; Li, Yubao

    2015-10-14

    To improve the mechanical properties of bone tissue and achieve the desired bone tissue regeneration for orthopedic surgery, newly designed hydroxyapatite/polyurethane (HA/PU) porous scaffolds were developed via in situ polymerization. The results showed that the molecular modification of PU soft segments by glyceride of castor oil (GCO) can increase the scaffold compressive strength by 48% and the elastic modulus by 96%. When nano-HA (n-HA) particles were incorporated into the GCO-PU matrix, the compressive strength and elastic modulus further increased by 49 and 74%, from 2.91 to 4.34 MPa and from 95 to 165.36 MPa, respectively. The n-HA particles with fine dispersity not only improved the interface bonding with the GCO-PU matrix but also provided effective bioactivity for bonding with bone tissue. The hierarchical structure and mechanical quality of the n-HA/GCO-PU composite scaffold were determined to be appropriate for the growth of cells and the regeneration of bony tissues, demonstrating promising prospects for bone repair and regeneration. PMID:26406396

  13. Segmental bone regeneration using rhBMP-2-loaded collagen/chitosan microspheres composite scaffold in a rabbit model

    International Nuclear Information System (INIS)

    The reconstruction of segmental bone defects remains an urgent problem in the orthopaedic field, and bone morphogenetic protein-2 (BMP-2) is known for its potent osteoinductive properties in bone regeneration. In this study, chitosan microspheres (CMs) were prepared and combined with absorbable collagen sponge to maintain controlled-release recombinant human bone morphogenetic protein-2 (rhBMP-2). The rhBMP-2-loaded composite scaffolds were implanted into 15 mm radius defects of rabbits and the bone-repair ability was evaluated systematically. CMs were spherical in shape and had a polyporous surface, according to SEM images. The complex scaffold exhibited an ideal releasing profile in vitro. The micro-computed tomographic analysis revealed that the rhBMP-2-loaded composite scaffold not only bridged the defects as early as 4 weeks, but also healed the defects and presented recanalization of the bone-marrow cavity at 12 weeks. These results were confirmed by x-ray. When compared with other control groups, the composite scaffold group remarkably enhanced new bone formation and mechanical properties, as evidenced by bone mineral content evaluation, histological observations and biomechanical testing. Moreover, the biocompatibility and appropriate degradation of the composite scaffold could be obtained. All of these results clearly demonstrated that the composite scaffold is a promising carrier of BMP-2 for the treatment of segmental bone defects. (paper)

  14. Bone marrow-derived fibroblast growth factor-2 induces glial cell proliferation in the regenerating peripheral nervous system

    Directory of Open Access Journals (Sweden)

    Ribeiro-Resende Victor

    2012-07-01

    Full Text Available Abstract Background Among the essential biological roles of bone marrow-derived cells, secretion of many soluble factors is included and these small molecules can act upon specific receptors present in many tissues including the nervous system. Some of the released molecules can induce proliferation of Schwann cells (SC, satellite cells and lumbar spinal cord astrocytes during early steps of regeneration in a rat model of sciatic nerve transection. These are the major glial cell types that support neuronal survival and axonal growth following peripheral nerve injury. Fibroblast growth factor-2 (FGF-2 is the main mitogenic factor for SCs and is released in large amounts by bone marrow-derived cells, as well as by growing axons and endoneurial fibroblasts during development and regeneration of the peripheral nervous system (PNS. Results Here we show that bone marrow-derived cell treatment induce an increase in the expression of FGF-2 in the sciatic nerve, dorsal root ganglia and the dorsolateral (DL region of the lumbar spinal cord (LSC in a model of sciatic nerve transection and connection into a hollow tube. SCs in culture in the presence of bone marrow derived conditioned media (CM resulted in increased proliferation and migration. This effect was reduced when FGF-2 was neutralized by pretreating BMMC or CM with a specific antibody. The increased expression of FGF-2 was validated by RT-PCR and immunocytochemistry in co-cultures of bone marrow derived cells with sciatic nerve explants and regenerating nerve tissue respectivelly. Conclusion We conclude that FGF-2 secreted by BMMC strongly increases early glial proliferation, which can potentially improve PNS regeneration.

  15. β-Cell Regeneration Mediated by Human Bone Marrow Mesenchymal Stem Cells

    Science.gov (United States)

    Milanesi, Anna; Lee, Jang-Won; Li, Zhenhua; Da Sacco, Stefano; Villani, Valentina; Cervantes, Vanessa; Perin, Laura; Yu, John S.

    2012-01-01

    Bone marrow mesenchymal stem cells (BMSCs) have been shown to ameliorate diabetes in animal models. The mechanism, however, remains largely unknown. An unanswered question is whether BMSCs are able to differentiate into β-cells in vivo, or whether BMSCs are able to mediate recovery and/or regeneration of endogenous β-cells. Here we examined these questions by testing the ability of hBMSCs genetically modified to transiently express vascular endothelial growth factor (VEGF) or pancreatic-duodenal homeobox 1 (PDX1) to reverse diabetes and whether these cells were differentiated into β-cells or mediated recovery through alternative mechanisms. Human BMSCs expressing VEGF and PDX1 reversed hyperglycemia in more than half of the diabetic mice and induced overall improved survival and weight maintenance in all mice. Recovery was sustained only in the mice treated with hBMSCs-VEGF. However, de novo β-cell differentiation from human cells was observed in mice in both cases, treated with either hBMSCs-VEGF or hBMSCs- PDX1, confirmed by detectable level of serum human insulin. Sustained reversion of diabetes mediated by hBMSCs-VEGF was secondary to endogenous β-cell regeneration and correlated with activation of the insulin/IGF receptor signaling pathway involved in maintaining β-cell mass and function. Our study demonstrated the possible benefit of hBMSCs for the treatment of insulin-dependent diabetes and gives new insight into the mechanism of β-cell recovery after injury mediated by hBMSC therapy. PMID:22879915

  16. β-Cell regeneration mediated by human bone marrow mesenchymal stem cells.

    Directory of Open Access Journals (Sweden)

    Anna Milanesi

    Full Text Available Bone marrow mesenchymal stem cells (BMSCs have been shown to ameliorate diabetes in animal models. The mechanism, however, remains largely unknown. An unanswered question is whether BMSCs are able to differentiate into β-cells in vivo, or whether BMSCs are able to mediate recovery and/or regeneration of endogenous β-cells. Here we examined these questions by testing the ability of hBMSCs genetically modified to transiently express vascular endothelial growth factor (VEGF or pancreatic-duodenal homeobox 1 (PDX1 to reverse diabetes and whether these cells were differentiated into β-cells or mediated recovery through alternative mechanisms. Human BMSCs expressing VEGF and PDX1 reversed hyperglycemia in more than half of the diabetic mice and induced overall improved survival and weight maintenance in all mice. Recovery was sustained only in the mice treated with hBMSCs-VEGF. However, de novo β-cell differentiation from human cells was observed in mice in both cases, treated with either hBMSCs-VEGF or hBMSCs- PDX1, confirmed by detectable level of serum human insulin. Sustained reversion of diabetes mediated by hBMSCs-VEGF was secondary to endogenous β-cell regeneration and correlated with activation of the insulin/IGF receptor signaling pathway involved in maintaining β-cell mass and function. Our study demonstrated the possible benefit of hBMSCs for the treatment of insulin-dependent diabetes and gives new insight into the mechanism of β-cell recovery after injury mediated by hBMSC therapy.

  17. Biomimetic three-dimensional nanocrystalline hydroxyapatite and magnetically synthesized single-walled carbon nanotube chitosan nanocomposite for bone regeneration

    Directory of Open Access Journals (Sweden)

    Im O

    2012-04-01

    Full Text Available Owen Im1, Jian Li2, Mian Wang2, Lijie Grace Zhang2,3, Michael Keidar2,31Department of Biomedical Engineering, Duke University, Durham, NC; 2Department of Mechanical and Aerospace Engineering, 3Institute for Biomedical Engineering and Institute for Nanotechnology, The George Washington University, Washington, DC, USABackground: Many shortcomings exist in the traditional methods of treating bone defects, such as donor tissue shortages for autografts and disease transmission for allografts. The objective of this study was to design a novel three-dimensional nanostructured bone substitute based on magnetically synthesized single-walled carbon nanotubes (SWCNT, biomimetic hydrothermally treated nanocrystalline hydroxyapatite, and a biocompatible hydrogel (chitosan. Both nanocrystalline hydroxyapatite and SWCNT have a biomimetic nanostructure, excellent osteoconductivity, and high potential to improve the load-bearing capacity of hydrogels.Methods: Specifically, three-dimensional porous chitosan scaffolds with different concentrations of nanocrystalline hydroxyapatite and SWCNT were created to support the growth of human osteoblasts (bone-forming cells using a lyophilization procedure. Two types of SWCNT were synthesized in an arc discharge with a magnetic field (B-SWCNT and without a magnetic field (N-SWCNT for improving bone regeneration.Results: Nanocomposites containing magnetically synthesized B-SWCNT had superior cytocompatibility properties when compared with nonmagnetically synthesized N-SWCNT. B-SWCNT have much smaller diameters and are twice as long as their nonmagnetically prepared counterparts, indicating that the dimensions of carbon nanotubes can have a substantial effect on osteoblast attachment.Conclusion: This study demonstrated that a chitosan nanocomposite with both B-SWCNT and 20% nanocrystalline hydroxyapatite could achieve a higher osteoblast density when compared with the other experimental groups, thus making this nanocomposite

  18. The chorioallantoic membrane (CAM) assay for the study of human bone regeneration: a refinement animal model for tissue engineering

    Science.gov (United States)

    Moreno-Jiménez, Inés; Hulsart-Billstrom, Gry; Lanham, Stuart A.; Janeczek, Agnieszka A.; Kontouli, Nasia; Kanczler, Janos M.; Evans, Nicholas D.; Oreffo, Richard OC

    2016-01-01

    Biomaterial development for tissue engineering applications is rapidly increasing but necessitates efficacy and safety testing prior to clinical application. Current in vitro and in vivo models hold a number of limitations, including expense, lack of correlation between animal models and human outcomes and the need to perform invasive procedures on animals; hence requiring new predictive screening methods. In the present study we tested the hypothesis that the chick embryo chorioallantoic membrane (CAM) can be used as a bioreactor to culture and study the regeneration of human living bone. We extracted bone cylinders from human femoral heads, simulated an injury using a drill-hole defect, and implanted the bone on CAM or in vitro control-culture. Micro-computed tomography (μCT) was used to quantify the magnitude and location of bone volume changes followed by histological analyses to assess bone repair. CAM blood vessels were observed to infiltrate the human bone cylinder and maintain human cell viability. Histological evaluation revealed extensive extracellular matrix deposition in proximity to endochondral condensations (Sox9+) on the CAM-implanted bone cylinders, correlating with a significant increase in bone volume by μCT analysis (p animal research and a step towards a humanized in vivo model for tissue engineering. PMID:27577960

  19. The chorioallantoic membrane (CAM) assay for the study of human bone regeneration: a refinement animal model for tissue engineering.

    Science.gov (United States)

    Moreno-Jiménez, Inés; Hulsart-Billstrom, Gry; Lanham, Stuart A; Janeczek, Agnieszka A; Kontouli, Nasia; Kanczler, Janos M; Evans, Nicholas D; Oreffo, Richard Oc

    2016-01-01

    Biomaterial development for tissue engineering applications is rapidly increasing but necessitates efficacy and safety testing prior to clinical application. Current in vitro and in vivo models hold a number of limitations, including expense, lack of correlation between animal models and human outcomes and the need to perform invasive procedures on animals; hence requiring new predictive screening methods. In the present study we tested the hypothesis that the chick embryo chorioallantoic membrane (CAM) can be used as a bioreactor to culture and study the regeneration of human living bone. We extracted bone cylinders from human femoral heads, simulated an injury using a drill-hole defect, and implanted the bone on CAM or in vitro control-culture. Micro-computed tomography (μCT) was used to quantify the magnitude and location of bone volume changes followed by histological analyses to assess bone repair. CAM blood vessels were observed to infiltrate the human bone cylinder and maintain human cell viability. Histological evaluation revealed extensive extracellular matrix deposition in proximity to endochondral condensations (Sox9+) on the CAM-implanted bone cylinders, correlating with a significant increase in bone volume by μCT analysis (p animal research and a step towards a humanized in vivo model for tissue engineering. PMID:27577960

  20. A computer-designed scaffold for bone regeneration within cranial defect using human dental pulp stem cells

    OpenAIRE

    Doo Yeon Kwon; Jin Seon Kwon; Seung Hun Park; Ji Hun Park; So Hee Jang; Xiang Yun Yin; Jeong-Ho Yun; Jae Ho Kim; Byoung Hyun Min; Jun Hee Lee; Wan-Doo Kim; Moon Suk Kim

    2015-01-01

    A computer-designed, solvent-free scaffold offer several potential advantages such as ease of customized manufacture and in vivo safety. In this work, we firstly used a computer-designed, solvent-free scaffold and human dental pulp stem cells (hDPSCs) to regenerate neo-bone within cranial bone defects. The hDPSCs expressed mesenchymal stem cell markers and served as an abundant source of stem cells with a high proliferation rate. In addition, hDPSCs showed a phenotype of differentiated osteob...

  1. Scaffolds for bone regeneration made of hydroxyapatite microspheres in a collagen matrix.

    Science.gov (United States)

    Cholas, Rahmatullah; Kunjalukkal Padmanabhan, Sanosh; Gervaso, Francesca; Udayan, Gayatri; Monaco, Graziana; Sannino, Alessandro; Licciulli, Antonio

    2016-06-01

    Biomimetic scaffolds with a structural and chemical composition similar to native bone tissue may be promising for bone tissue regeneration. In the present work hydroxyapatite mesoporous microspheres (mHA) were incorporated into collagen scaffolds containing an ordered interconnected macroporosity. The mHA were obtained by spray drying of a nano hydroxyapatite slurry prepared by the precipitation technique. X-ray diffraction (XRD) analysis revealed that the microspheres were composed only of hydroxyapatite (HA) phase, and energy-dispersive x-ray spectroscopy (EDS) analysis revealed the Ca/P ratio to be 1.69 which is near the value for pure HA. The obtained microspheres had an average diameter of 6μm, a specific surface area of 40m(2)/g as measured by Brunauer-Emmett-Teller (BET) analysis, and Barrett-Joyner-Halenda (BJH) analysis showed a mesoporous structure with an average pore diameter of 16nm. Collagen/HA-microsphere (Col/mHA) composite scaffolds were prepared by freeze-drying followed by dehydrothermal crosslinking. SEM observations of Col/mHA scaffolds revealed HA microspheres embedded within a porous collagen matrix with a pore size ranging from a few microns up to 200μm, which was also confirmed by histological staining of sections of paraffin embedded scaffolds. The compressive modulus of the composite scaffold at low and high strain values was 1.7 and 2.8 times, respectively, that of pure collagen scaffolds. Cell proliferation measured by the MTT assay showed more than a 3-fold increase in cell number within the scaffolds after 15days of culture for both pure collagen scaffolds and Col/mHA composite scaffolds. Attractive properties of this composite scaffold include the potential to load the microspheres for drug delivery and the controllability of the pore structure at various length scales. PMID:27040244

  2. Effect of neurotransmitters and bone marrow cells for neuronal regeneration in iatrogenic spinal cord injury: An experimental study

    OpenAIRE

    John P; Paulose C; Sreekanth R

    2010-01-01

    Background: Spinal cord trauma is a major health problem with associated physical, social, economic and psychological sequelae. Despite many advances in research and treatment modalities, the pathophysiology of spinal cord injury remains unclear, and morbidity and mortality among these patients remain high. This experimental study investigates the regenerative cell proliferation effects of bone marrow supplemented with neurotransmitters combinations in the regeneration of spinal cord injury ...

  3. Bone marrow-derived fibroblast growth factor-2 induces glial cell proliferation in the regenerating peripheral nervous system

    OpenAIRE

    Ribeiro-Resende Victor; Carrier-Ruiz Alvaro; R Lemes Robertha M; Reis Ricardo A M; Mendez-Otero Rosalia

    2012-01-01

    Abstract Background Among the essential biological roles of bone marrow-derived cells, secretion of many soluble factors is included and these small molecules can act upon specific receptors present in many tissues including the nervous system. Some of the released molecules can induce proliferation of Schwann cells (SC), satellite cells and lumbar spinal cord astrocytes during early steps of regeneration in a rat model of sciatic nerve transection. These are the major glial cell types that s...

  4. Synergistic intrafibrillar/extrafibrillar mineralization of collagen scaffolds based on a biomimetic strategy to promote the regeneration of bone defects

    OpenAIRE

    Wang Y; Van Manh H; Wang H; Zhong X; Zhang X; Li C

    2016-01-01

    Yao Wang,1 Ngo Van Manh,1,2 Haorong Wang,1 Xue Zhong,1 Xu Zhang,1 Changyi Li1 1School of Dentistry, Hospital of Stomatology, Tianjin Medical University, Tianjin, People’s Republic of China; 2Thaibinh University of Medicine and Pharmacy, Thaibinh, Vietnam Abstract: The mineralization of collagen scaffolds can improve their mechanical properties and biocompatibility, thereby providing an appropriate microenvironment for bone regeneration. The primary purpose of the present study is ...

  5. Toward guided tissue and bone regeneration: morphology, attachment, proliferation, and migration of cells cultured on collagen barrier membranes. A systematic review.

    NARCIS (Netherlands)

    Behring, J.; Junker, R.; Walboomers, X.F.; Chessnut, B.; Jansen, J.A.

    2008-01-01

    Collagen barrier membranes are frequently used in both guided tissue regeneration (GTR) and guided bone regeneration (GBR). Collagen used for these devices is available from different species and is often processed to alter the properties of the final product. This is necessary because unprocessed c

  6. Bone Regeneration Using a Mixture of Silicon-Substituted Coral HA and β-TCP in a Rat Calvarial Bone Defect Model

    Directory of Open Access Journals (Sweden)

    Jiyeon Roh

    2016-02-01

    Full Text Available The demand of bone graft materials has been increasing. Among various origins of bone graft materials, natural coral composed of up to 99% calcium carbonate was chosen and converted into hydroxyapatite (HA; silicon was then substituted into the HA. Then, the Si-HA was mixed with β-tricalcium phosphate (TCP in the ratios 100:0 (S100T0, 70:30 (S70T30, 60:40 (S60T40, and 50:50 (S50T50. The materials were implanted for four and eight weeks in a rat calvarial bone defect model (8 mm. The MBCPTM (HA:β-TCP = 60:40, Biomatalante, Vigneux de Bretagne, France was used as a control. After euthanasia, the bone tissue was analyzed by making histological slides. From the results, S60T40 showed the fastest bone regeneration in four weeks (p < 0.05. In addition, S60T40, S50T50, and MBCPTM showed significant new bone formation in eight weeks (p < 0.05. In conclusion, Si-HA/TCP showed potential as a bone graft material.

  7. Properties and in vitro biological evaluation of nano-hydroxyapatite/chitosan membranes for bone guided regeneration

    International Nuclear Information System (INIS)

    Nano-hydroxyapatite(n-HA)/chitosan(CS) composite membranes were prepared by solvent casting and evaporation methods for the function of guided bone regeneration (GBR). The effect of n-HA content and solvent evaporation temperature on the properties of the composite membranes was studied. The n-HA/CS membranes were analyzed by scanning electron microscopy, Fourier transformed infrared spectroscopy, X-ray diffraction, swelling measurement, mechanical test, cell culture and MTT (3-[4,5-dimethylthiazol-2-yl]-2,5-diphenylte-2H-tetrazolium bromide) assay. The results show that the surface roughness and micropores of the composite membranes increase with the rise of n-HA content, suitable for adhesion, crawl and growth of cells. The hydroxyapatite holds nano size and distributes uniformly in the composite membranes. Chemical bond interaction exists between Ca ions and -OH groups of n-HA and -NH2 or -OH groups of CS. The n-HA content and solvent evaporation temperature have obvious influence on the swelling ratio, tensile strength and elongation rate of the composite membranes. Cell culture and MTT assays show that n-HA and its content can affect the proliferation of cells. The n-HA/CS composite membranes have no negative effect on the cell morphology, viability and proliferation and possess good biocompatibility. This study makes the n-HA/CS composite membrane be a prospective biodegradable GBR membrane for future applications

  8. Dimensionally stable and bioactive membrane for guided bone regeneration: An in vitro study.

    Science.gov (United States)

    Rowe, Matthew J; Kamocki, Krzysztof; Pankajakshan, Divya; Li, Ding; Bruzzaniti, Angela; Thomas, Vinoy; Blanchard, Steve B; Bottino, Marco C

    2016-04-01

    Composite fibrous electrospun membranes based on poly(dl-lactide) (PLA) and poly(ε-caprolactone) (PCL) were engineered to include borate bioactive glass (BBG) for the potential purposes of guided bone regeneration (GBR). The fibers were characterized using scanning and transmission electron microscopies, which respectively confirmed the submicron fibrous arrangement of the membranes and the successful incorporation of BBG particles. Selected mechanical properties of the membranes were evaluated using the suture pullout test. The addition of BBG at 10 wt % led to similar stiffness, but more importantly, it led to a significantly stronger (2.37 ± 0.51 N mm) membrane when compared with the commercially available Epiguide® (1.06 ± 0.24 N mm) under hydrated conditions. Stability (shrinkage) was determined after incubation in a phosphate buffer solution from 24 h up to 9 days. The dimensional stability of the PLA:PCL-based membranes with or without BBG incorporation (10.07-16.08%) was similar to that of Epiguide (14.28%). Cell proliferation assays demonstrated a higher rate of preosteoblasts proliferation on BBG-containing membranes (6.4-fold) over BBG-free membranes (4- to 5.8-fold) and EpiGuide (4.5-fold), following 7 days of in vitro culture. Collectively, our results demonstrated the ability to synthesize, via electrospinning, stable, polymer-based submicron fibrous BBG-containing membranes capable of sustaining osteoblastic attachment and proliferation-a promising attribute in GBR. PMID:25953329

  9. Cellular reactions of osteoblast-like cells to a novel nanocomposite membrane for guided bone regeneration

    Energy Technology Data Exchange (ETDEWEB)

    Meng Yao [State Key Laboratory of Oral Diseases, West China Stomatology Hospital, Sichuan University, Chengdu 610041 (China); Department of Orthodontics, West China Stomatology Hospital, Sichuan University, Chengdu 610041 (China); Liu Man [State Key Laboratory of Oral Diseases, West China Stomatology Hospital, Sichuan University, Chengdu 610041 (China); Stomatology Health Care Center, Shenzhen Maternity and Child Healthcare Hospital, Shenzhen 518048 (China); Wang Shaoan [State Key Laboratory of Oral Diseases, West China Stomatology Hospital, Sichuan University, Chengdu 610041 (China); Mo Anchun [State Key Laboratory of Oral Diseases, West China Stomatology Hospital, Sichuan University, Chengdu 610041 (China)], E-mail: moanchun@163.com; Huang, Cui [State Key Laboratory of Oral Diseases, West China Stomatology Hospital, Sichuan University, Chengdu 610041 (China); Zuo Yi; Li Jidong [Research Center for Nano-biomaterials, Sichuan University, Chengdu 610041 (China)

    2008-11-15

    This study investigated the bioactivity and biocompatibility of hydroxyapatite nanoparticles (n-HA)/Polyamide-66 (PA66) nanocomposite membrane and expanded-polytetrafluoroethylene (e-PTFE) membrane (as control) to MG63 osteoblast-like cells. The attachment and proliferation of the cells on the porous surface of nHA/PA66 membrane and the surface of e-PTFE membrane were evaluated by scanning electron microscope (SEM) observation and the MTT assay. The bioactivity of the cells on the surface of the two membranes was evaluated by testing cell viability and alkaline phosphatase (ALP) activities. The results suggested that the bioresponse of MG63 osteoblast-like cells on the porous surface of nHA/PA66 membrane was better than the bioresponse on the opposite surface of e-PTFE membrane. Because of a better cell attachment manner, there is a potential utilization of the guided bone regeneration (GBR) membrane to substitute nHA/PA66 membrane for e-PTFE membra0008.

  10. MAPLE deposition of polypyrrole-based composite layers for bone regeneration

    Science.gov (United States)

    Paun, Irina Alexandra; Acasandrei, Adriana Maria; Luculescu, Catalin Romeo; Mustaciosu, Cosmin Catalin; Ion, Valentin; Mihailescu, Mona; Vasile, Eugenia; Dinescu, Maria

    2015-12-01

    We report on biocompatible, electrically conductive layers of polypyrrole (PPy)-based composites obtained by Matrix Assisted Pulsed Laser Evaporation (MAPLE) for envisioned bone regeneration. In order to preserve the conductivity of the PPy while overcoming its lack of biodegradability and low mechanical resilience, conductive PPy nanograins were embedded in two biocompatible, insulating polymeric matrices, i.e. poly(lactic-co-glycolic)acid (PLGA) and polyurethane (PU). PLGA offers the advantage of full biodegradability into non-toxic products, while PU provides toughness and elasticity. The PPy nanograins formed micro-domains and networks within the PLGA and PU matrices, in a compact spatial arrangement favorable for electrical percolation. The proposed approach allowed us to obtain PPy-based composite layers with biologically meaningful conductivities up to 10-2 S/cm for PPy loadings as low as 1:10 weight ratios. Fluorescent staining and viability assays showed that the MG63 osteoblast-like cells cultured on the PPy-based layers deposited by MAPLE were viable and retained their capacity to proliferate. The performance of the proposed method was demonstrated by quantitative evaluation of the calcium phosphate deposits from the cultured cells, as indicative for cell mineralization. Electrical stimulation using 200 μA currents passing through the PPy-based layers, during a time interval of 4 h, enhanced the osteogenesis in the cultured cells. Despite their lowest conductivity, the PPy/PU layers showed the best biocompatibility and the highest osteogenic potential.

  11. Attachment and growth of human bone marrow derived mesenchymal stem cells on regenerated antheraea pernyi silk fibroin films.

    Science.gov (United States)

    Luan, Xi-Ying; Wang, Yong; Duan, Xiang; Duan, Qiao-Yan; Li, Ming-Zhong; Lu, Shen-Zhou; Zhang, Huan-Xiang; Zhang, Xue-Guang

    2006-12-01

    Silk fibroin of the silkworm Bombyx mori has been studied extensively, while the research on Antheraea pernyi silk fibroin (A. pernyi SF) in biomaterials is only at an early stage. In this study, the attachment, morphology, growth and phenotype of human bone marrow derived mesenchymal stem cells (hBMSCs) cultured on the regenerated A. pernyi SF films were studied in vitro. The results indicated that the attachment of hBMSCs on the regenerated A. pernyi SF films was almost the same as that on the collagen films. MTT and cell counting analyses demonstrated that the growth of hBMSCs on the regenerated A. pernyi SF films was better than that on controls. Moreover, electron scanning microscopy and fluorescence-activated cell sorting assays showed that the regenerated A. pernyi SF supported hBMSCs growth and functional maintenance compared with the controls. These data suggest that the regenerated A. pernyi SF, like Bombyx mori silk fibroin (B. mori SF) and collagen, can support hBMSCs attachment, growth and phenotypic maintenance, and has better biocompatibilities for hBMSCs in vitro culture. PMID:18458403

  12. Attachment and growth of human bone marrow derived mesenchymal stem cells on regenerated antheraea pernyi silk fibroin films

    Energy Technology Data Exchange (ETDEWEB)

    Luan Xiying [Institute of Medical Biotechnology, Jiangsu Province Key Laboratory of Stem Cell, Suzhou University, Suzhou 215007 (China); Wang Yong [Institute of Medical Biotechnology, Jiangsu Province Key Laboratory of Stem Cell, Suzhou University, Suzhou 215007 (China); Duan Xiang [Institute of Medical Biotechnology, Jiangsu Province Key Laboratory of Stem Cell, Suzhou University, Suzhou 215007 (China); Duan Qiaoyan [Institute of Medical Biotechnology, Jiangsu Province Key Laboratory of Stem Cell, Suzhou University, Suzhou 215007 (China); Li Mingzhong [School of Materials Engineering, Suzhou University, Suzhou 215006 (China); Lu Shenzhou [School of Materials Engineering, Suzhou University, Suzhou 215006 (China); Zhang Huanxiang [Institute of Medical Biotechnology, Jiangsu Province Key Laboratory of Stem Cell, Suzhou University, Suzhou 215007 (China); Zhang Xueguang [Institute of Medical Biotechnology, Jiangsu Province Key Laboratory of Stem Cell, Suzhou University, Suzhou 215007 (China)

    2006-12-15

    Silk fibroin of the silkworm Bombyx mori has been studied extensively, while the research on Antheraea pernyi silk fibroin (A. pernyi SF) in biomaterials is only at an early stage. In this study, the attachment, morphology, growth and phenotype of human bone marrow derived mesenchymal stem cells (hBMSCs) cultured on the regenerated A. pernyi SF films were studied in vitro. The results indicated that the attachment of hBMSCs on the regenerated A. pernyi SF films was almost the same as that on the collagen films. MTT and cell counting analyses demonstrated that the growth of hBMSCs on the regenerated A. pernyi SF films was better than that on controls. Moreover, electron scanning microscopy and fluorescence-activated cell sorting assays showed that the regenerated A. pernyi SF supported hBMSCs growth and functional maintenance compared with the controls. These data suggest that the regenerated A. pernyi SF, like Bombyx mori silk fibroin (B. mori SF) and collagen, can support hBMSCs attachment, growth and phenotypic maintenance, and has better biocompatibilities for hBMSCs in vitro culture.

  13. Compound soft regenerated skull material for repairing dog skull defects using bone morphogenetic protein as an inductor and nanohydroxyapatite as a scaffold

    Institute of Scientific and Technical Information of China (English)

    Zhidong Shi; Mingwang Liu; Zhongzong Qin; Qinmei Wang; Ying Guo; Haiyong He; Zhonghe Yu

    2008-01-01

    BACKGROUND: In previous studies of skull defects and regeneration, bone morphogenetic protein as an inductor and nanohydroxyapatite as a scaffold have been cocultured with osteoblasts.OBJECTIVE: To verify the characteristics of the new skull regenerated material after compound soft regenerated skull material implantatiom.DESIGN, TIME AND SETTING: The self-control and inter-group control animal experiment was perfurmed at the Sun Yat-sen University, China from February to July 2007.MATERIALS: Twenty-tour healthy adult dogs of both genders weighing 15-20 kg were used in this study. Nanohydroxyapatite as a scaffold was cocultured with osteoblasts. Using demineralized canine bone matrix as a carrier, recombinant human bone morphogenetic protein-2 was employed to prepare compound soft regenerated skull material. Self-designed compound soft regenerated skull material was implanted in models of skull defects.METHODS: Animals were randomly assigned into two groups, Group A (n = 16) and Group B (n = 8).Bilateral 2.5-cm-diameter full-thickness parietal skull defects were made in all animals. In Group A, the right side was reconstructed with calcium alginate gel, osteoblasts, and nanomcter bone meal composite;the left side was reconstructed with calcium alginate gel, osteoblasts, nanometer bone meal and recombinant human bone morphogenetic protein-2 composite. In Group B, the right side was kept as a simple skull detect, and the left side was reconstructed with calcium alginate gel, osteoblasts, nanometer bone meal and recombinant human bone morphogenetic protein-2 composite.MAIN OUTCOME MEASURES: Bone regeneration and histopathological changes at the site of the skull defect were observed with an optical microscope and a scanning electron microscope after surgery.The ability to form bone was measured by alizarin red S staining. In vitro cultured osteoblasts were observed for morphology.RESULTS: One month following surgery, newly formed bone trabeculae mostly covered the

  14. Wollastonite nanofiber–doped self-setting calcium phosphate bioactive cement for bone tissue regeneration

    Directory of Open Access Journals (Sweden)

    Guo H

    2012-07-01

    incorporation of WNFs into CPC improved the biological properties for wnf-CPC. Following the implantation of wnf-CPC into bone defects of rabbits, histological evaluation showed that wnf-CPC enhanced the efficiency of new bone formation in comparison with CPC, indicating excellent biocompatibility and osteogenesis of wnf-CPC. In conclusion, wnf-CPC exhibited promising prospects in bone regeneration.Keywords: calcium phosphate cement, degradability, cell and tissue responses, biocompatibility

  15. Surface modification of porous polycaprolactone/biphasic calcium phosphate scaffolds for bone regeneration in rat calvaria defect.

    Science.gov (United States)

    Kim, Ji-Hyun; Linh, Nguyen T B; Min, Young K; Lee, Byong-Taek

    2014-10-01

    In this study, polycaprolactone scaffolds fabricated by a salt-leaching process were loaded with biphasic calcium phosphate successfully to improve the osteoconductivity in bone regeneration. The surface of polycaprolactone/biphasic calcium phosphate scaffolds was aminolyzed by 1,6-hexamethylenediamine to introduce amino groups onto the surface, which was verified qualitatively by ninhyrin staining. Collagen was further immobilized on the aminolyzed porous polycaprolactone via N-ethyl-N'-(3-dimethylaminopropy) carbodiimide hydrochloride/hydroxy-2,5-dioxopyrolidine-3-sulfonic acid sodium cross-linking. The pore size of polycaprolactone/biphasic calcium phosphate-collagen scaffolds was 200-300 µm, which was suitable for bone in-growth. The X-ray photoelectron spectroscopy confirmed the coupling of collagen immobilized on the surface of polycaprolactone/biphasic calcium phosphate. In vitro results demonstrated that the spreading and viability of MC3T3-E1 cells were remarkably improved in the polycaprolactone/biphasic calcium phosphate-collagen scaffolds. The in vivo study was carried out by implanting the porous polycaprolactone, polycaprolactone/biphasic calcium phosphate, and polycaprolactone/biphasic calcium phosphate-collagen to the skulls of rats. Although the addition of biphasic calcium phosphate particles in the polycaprolactone scaffolds does not have a strong effect on the new bone formation, the immobilization of collagen on the polycaprolactone/biphasic calcium phosphate scaffolds significantly improved the bone regeneration even though the implantation time was short, 6 weeks. The present results provide more evidence that functionalizing polycaprolactone with biphasic calcium phosphate and collagen may be a feasible way to improve the osteoconduction in bone regeneration. PMID:24939961

  16. Porous tantalum coatings prepared by vacuum plasma spraying enhance bmscs osteogenic differentiation and bone regeneration in vitro and in vivo.

    Directory of Open Access Journals (Sweden)

    Ze Tang

    Full Text Available Tantalum, as a potential metallic implant biomaterial, is attracting more and more attention because of its excellent anticorrosion and biocompatibility. However, its significantly high elastic modulus and large mechanical incompatibility with bone tissue make it unsuitable for load-bearing implants. In this study, porous tantalum coatings were first successfully fabricated on titanium substrates by vacuum plasma spraying (VPS, which would exert the excellent biocompatibility of tantalum and alleviate the elastic modulus of tantalum for bone tissue. We evaluated cytocompatibility and osteogenesis activity of the porous tantalum coatings using human bone marrow stromal cells (hBMSCs and its ability to repair rabbit femur bone defects. The morphology and actin cytoskeletons of hBMSCs were observed via electron microscopy and confocal, and the cell viability, proliferation and osteogenic differentiation potential of hBMSCs were examined quantitatively by PrestoBlue assay, Ki67 immunofluorescence assay, real-time PCR technology and ALP staining. For in vivo detection, the repaired femur were evaluated by histomorphology and double fluorescence labeling 3 months postoperation. Porous tantalum coating surfaces promoted hBMSCs adhesion, proliferation, osteogenesis activity and had better osseointegration and faster new bone formation rate than titanium coating control. Our observation suggested that the porous tantalum coatings had good biocompatibility and could enhance osseoinductivity in vitro and promote new bone formation in vivo. The porous tantalum coatings prepared by VPS is a promising strategy for bone regeneration.

  17. Porous tantalum coatings prepared by vacuum plasma spraying enhance bmscs osteogenic differentiation and bone regeneration in vitro and in vivo.

    Science.gov (United States)

    Tang, Ze; Xie, Youtao; Yang, Fei; Huang, Yan; Wang, Chuandong; Dai, Kerong; Zheng, Xuebin; Zhang, Xiaoling

    2013-01-01

    Tantalum, as a potential metallic implant biomaterial, is attracting more and more attention because of its excellent anticorrosion and biocompatibility. However, its significantly high elastic modulus and large mechanical incompatibility with bone tissue make it unsuitable for load-bearing implants. In this study, porous tantalum coatings were first successfully fabricated on titanium substrates by vacuum plasma spraying (VPS), which would exert the excellent biocompatibility of tantalum and alleviate the elastic modulus of tantalum for bone tissue. We evaluated cytocompatibility and osteogenesis activity of the porous tantalum coatings using human bone marrow stromal cells (hBMSCs) and its ability to repair rabbit femur bone defects. The morphology and actin cytoskeletons of hBMSCs were observed via electron microscopy and confocal, and the cell viability, proliferation and osteogenic differentiation potential of hBMSCs were examined quantitatively by PrestoBlue assay, Ki67 immunofluorescence assay, real-time PCR technology and ALP staining. For in vivo detection, the repaired femur were evaluated by histomorphology and double fluorescence labeling 3 months postoperation. Porous tantalum coating surfaces promoted hBMSCs adhesion, proliferation, osteogenesis activity and had better osseointegration and faster new bone formation rate than titanium coating control. Our observation suggested that the porous tantalum coatings had good biocompatibility and could enhance osseoinductivity in vitro and promote new bone formation in vivo. The porous tantalum coatings prepared by VPS is a promising strategy for bone regeneration. PMID:23776648

  18. Osseointegration of subperiosteal implants using bovine bone substitute and various membranes

    DEFF Research Database (Denmark)

    Aaboe, Merete; Schou, S.; Hjørting-Hansen, E.; Helbo, M.; Vikjær, D.

    Osseointegration, subperiosteal implant, bone substitute, bovine bone, guided bone, regeneration, histology, rabbits......Osseointegration, subperiosteal implant, bone substitute, bovine bone, guided bone, regeneration, histology, rabbits...

  19. In silico Mechano-Chemical Model of Bone Healing for the Regeneration of Critical Defects: The Effect of BMP-2.

    Directory of Open Access Journals (Sweden)

    Frederico O Ribeiro

    Full Text Available The healing of bone defects is a challenge for both tissue engineering and modern orthopaedics. This problem has been addressed through the study of scaffold constructs combined with mechanoregulatory theories, disregarding the influence of chemical factors and their respective delivery devices. Of the chemical factors involved in the bone healing process, bone morphogenetic protein-2 (BMP-2 has been identified as one of the most powerful osteoinductive proteins. The aim of this work is to develop and validate a mechano-chemical regulatory model to study the effect of BMP-2 on the healing of large bone defects in silico. We first collected a range of quantitative experimental data from the literature concerning the effects of BMP-2 on cellular activity, specifically proliferation, migration, differentiation, maturation and extracellular matrix production. These data were then used to define a model governed by mechano-chemical stimuli to simulate the healing of large bone defects under the following conditions: natural healing, an empty hydrogel implanted in the defect and a hydrogel soaked with BMP-2 implanted in the defect. For the latter condition, successful defect healing was predicted, in agreement with previous in vivo experiments. Further in vivo comparisons showed the potential of the model, which accurately predicted bone tissue formation during healing, bone tissue distribution across the defect and the quantity of bone inside the defect. The proposed mechano-chemical model also estimated the effect of BMP-2 on cells and the evolution of healing in large bone defects. This novel in silico tool provides valuable insight for bone tissue regeneration strategies.

  20. Evaluating the Bone Tissue Regeneration Capability of the Chinese Herbal Decoction Danggui Buxue Tang from a Molecular Biology Perspective

    Directory of Open Access Journals (Sweden)

    Wen-Ling Wang

    2014-01-01

    Full Text Available Large bone defects are a considerable challenge to reconstructive surgeons. Numerous traditional Chinese herbal medicines have been used to repair and regenerate bone tissue. This study investigated the bone regeneration potential of Danggui Buxue Tang (DBT, a Chinese herbal decoction prepared from Radix Astragali (RA and Radix Angelicae Sinensis (RAS, from a molecular biology perspective. The optimal ratio of RA and RAS used in DBT for osteoblast culture was obtained by colorimetric and alkaline phosphatase (ALP activity assays. Moreover, the optimal concentration of DBT for bone cell culture was also determined by colorimetric, ALP activity, nodule formation, Western blotting, wound-healing, and tartrate-resistant acid phosphatase activity assays. Consequently, the most appropriate weight ratio of RA to RAS for the proliferation and differentiation of osteoblasts was 5 : 1. Moreover, the most effective concentration of DBT was 1,000 μg/mL, which significantly increased the number of osteoblasts, intracellular ALP levels, and nodule numbers, while inhibiting osteoclast activity. Additionally, 1,000 μg/mL of DBT was able to stimulate p-ERK and p-JNK signal pathway. Therefore, DBT is highly promising for use in accelerating fracture healing in the middle or late healing periods.

  1. A Preliminary Evaluation of Lyophilized Gelatin Sponges, Enhanced with Platelet-Rich Plasma, Hydroxyapatite and Chitin Whiskers for Bone Regeneration

    Directory of Open Access Journals (Sweden)

    Andrew J. Spence

    2013-04-01

    Full Text Available The purpose of this study was to perform a number of preliminary in vitro evaluations on an array of modified gelatin gel sponge scaffolds for use in a bone graft application. The gelatin gels were modified through the addition of a number of components which each possess unique properties conducive to the creation and regeneration of bone: a preparation rich in growth factors (PRGF, a bioactive, lyophilized form of platelet-rich plasma, hydroxyapatite, and chitin whiskers. Platelet-rich plasma therapy is an emerging practice that has proven effective in a number of clinical applications, including enhancing bone repair through improved deposition of new bony matrix and angiogenesis. As such, the inclusion of PRGF in our gelatin scaffolds was intended to significantly enhance scaffold bioactivity, while the addition of hydroxyapatite and chitin whiskers were anticipated to increase scaffold strength. Additionally, the gelatin sponges, which readily dissolve in aqueous solutions, were subjected to 1-Ethyl-3-[3-dimethylaminopropyl]carbodiimide hydrochloride (EDC cross-linking, either during or post-gelation, to control their rate of degradation. Scaffolds were evaluated in vitro with respect to compressive strength, mass loss/degradation, protein release, and cellular interaction, with results demonstrating the potential of the gelatin gel sponge scaffold for use in the regeneration of bone.

  2. Functionalized PCL/HA nanocomposites as microporous membranes for bone regeneration

    International Nuclear Information System (INIS)

    In the present work, microporous membranes based on poly(ε-caprolactone) (PCL) and PCL functionalized with amine (PCL-DMAEA) or anhydride groups (PCL-MAGMA) were realized by solvent–non solvent phase inversion and proposed for use in Guided Tissue Regeneration (GTR). Nanowhiskers of hydroxyapatite (HA) were also incorporated in the polymer matrix to realize nanocomposite membranes. Scanning Electron Microscopy (SEM) showed improved interfacial adhesion with HA for functionalized polymers, and highlighted substantial differences in the porosity. A relationship between the developed porous structure of the membrane and the chemical nature of grafted groups was proposed. Compared to virgin PCL, hydrophilicity increases for functionalized PCL, while the addition of HA influences significantly the hydrophilic characteristics only in the case of virgin polymer. A significant increase of in vitro degradation rate was found for PCL-MAGMA based membranes, and at lower extent of PCL-DMAEA membranes. The novel materials were investigated regarding their potential as support for cell growth in bone repair using multipotent mesenchymal stromal cells (MSC) as a model. MSC plated onto the various membranes were analyzed in terms of adhesion, proliferation and osteogenic capacity that resulted to be related to chemical as well as porous structure. In particular, PCL-DMAEA and the relative nanocomposite membranes are the most promising in terms of cell-biomaterial interactions. - Graphical abstract: Functionalized PCL is used to realize nanocomposites with hydroxyapatite (HA) in the form of microporous membranes. The influence of different grafted groups on mechanical properties, in vitro degradation, porous membrane structure and interaction with mesenchymal stromal cells (MSC) is discussed. - Highlights: • Functionalized PCL shows faster in vitro degradation rate. • Functionalized PCL shows superior cell adhesion, proliferation and differentiation. • Nanocomposites based

  3. Functionalized PCL/HA nanocomposites as microporous membranes for bone regeneration

    Energy Technology Data Exchange (ETDEWEB)

    Basile, Maria Assunta; Gomez d' Ayala, Giovanna; Malinconico, Mario [Institute for Polymers, Composites and Biomaterials, CNR, Via Campi Flegrei 34, Pozzuoli (Naples) (Italy); Laurienzo, Paola, E-mail: paola.laurienzo@ipcb.cnr.it [Institute for Polymers, Composites and Biomaterials, CNR, Via Campi Flegrei 34, Pozzuoli (Naples) (Italy); Coudane, Jean; Nottelet, Benjamin [Institut des Biomolécules Max Mousseron (IBMM), Artificial Biopolymers Group, CNRS UMR 5247, University of Montpellier 1, Faculty of Pharmacy, 15 Av. C. Flahault, Montpellier 34093 (France); Ragione, Fulvio Della [Department of Biochemistry and Biophysics, Second University of Naples, Via L. De Crecchio 7, Naples (Italy); Oliva, Adriana, E-mail: adriana.oliva@unina2.it [Department of Biochemistry and Biophysics, Second University of Naples, Via L. De Crecchio 7, Naples (Italy)

    2015-03-01

    In the present work, microporous membranes based on poly(ε-caprolactone) (PCL) and PCL functionalized with amine (PCL-DMAEA) or anhydride groups (PCL-MAGMA) were realized by solvent–non solvent phase inversion and proposed for use in Guided Tissue Regeneration (GTR). Nanowhiskers of hydroxyapatite (HA) were also incorporated in the polymer matrix to realize nanocomposite membranes. Scanning Electron Microscopy (SEM) showed improved interfacial adhesion with HA for functionalized polymers, and highlighted substantial differences in the porosity. A relationship between the developed porous structure of the membrane and the chemical nature of grafted groups was proposed. Compared to virgin PCL, hydrophilicity increases for functionalized PCL, while the addition of HA influences significantly the hydrophilic characteristics only in the case of virgin polymer. A significant increase of in vitro degradation rate was found for PCL-MAGMA based membranes, and at lower extent of PCL-DMAEA membranes. The novel materials were investigated regarding their potential as support for cell growth in bone repair using multipotent mesenchymal stromal cells (MSC) as a model. MSC plated onto the various membranes were analyzed in terms of adhesion, proliferation and osteogenic capacity that resulted to be related to chemical as well as porous structure. In particular, PCL-DMAEA and the relative nanocomposite membranes are the most promising in terms of cell-biomaterial interactions. - Graphical abstract: Functionalized PCL is used to realize nanocomposites with hydroxyapatite (HA) in the form of microporous membranes. The influence of different grafted groups on mechanical properties, in vitro degradation, porous membrane structure and interaction with mesenchymal stromal cells (MSC) is discussed. - Highlights: • Functionalized PCL shows faster in vitro degradation rate. • Functionalized PCL shows superior cell adhesion, proliferation and differentiation. • Nanocomposites based

  4. Hydroxyapatite fiber reinforced poly(alpha-hydroxy ester) foams for bone regeneration

    Science.gov (United States)

    Thomson, R. C.; Yaszemski, M. J.; Powers, J. M.; Mikos, A. G.; McIntire, L. V. (Principal Investigator)

    1998-01-01

    A process has been developed to manufacture biodegradable composite foams of poly(DL-lactic-co-glycolic acid) (PLGA) and hydroxyapatite short fibers for use in bone regeneration. The processing technique allows the manufacture of three-dimensional foam scaffolds and involves the formation of a composite material consisting of a porogen material (either gelatin microspheres or salt particles) and hydroxyapatite short fibers embedded in a PLGA matrix. After the porogen is leached out, an open-cell composite foam remains which has a pore size and morphology defined by the porogen. By changing the weight fraction of the leachable component it was possible to produce composite foams with controlled porosities ranging from 0.47 +/- 0.02 to 0.85 +/- 0.01 (n = 3). Up to a polymer:fiber ratio of 7:6, short hydroxyapatite fibers served to reinforce low-porosity PLGA foams manufactured using gelatin microspheres as a porogen. Foams with a compressive yield strength up to 2.82 +/- 0.63 MPa (n = 3) and a porosity of 0.47 +/- 0.02 (n = 3) were manufactured using a polymer:fiber weight ratio of 7:6. In contrast, high-porosity composite foams (up to 0.81 +/- 0.02, n = 3) suitable for cell seeding were not reinforced by the introduction of increasing quantities of hydroxyapatite short fibers. We were therefore able to manufacture high-porosity foams which may be seeded with cells but which have minimal compressive yield strength, or low porosity foams with enhanced osteoconductivity and compressive yield strength.

  5. Mechanical and cytotoxicity evaluation of nanostructured hydroxyapatite-bredigite scaffolds for bone regeneration.

    Science.gov (United States)

    Eilbagi, Marjan; Emadi, Rahmatollah; Raeissi, Keyvan; Kharaziha, Mahshid; Valiani, Ali

    2016-11-01

    Despite the attractive characteristics of three-dimensional pure hydroxyapatite (HA) scaffolds, due to their weak mechanical properties, researches have focused on the development of composite scaffolds via introducing suitable secondary components. The aim of this study was to develop, for the first time, three-dimensional HA-bredigite (Ca7MgSi4O16) scaffolds containing various amounts of bredigite nanopowder (0, 5, 10 and 15wt.%) using space holder technique. Transmission electron microscopy, scanning electron microscopy, energy-dispersive X-ray spectroscopy and X-ray diffraction spectroscopy were applied in order to study the morphology, fracture surface and phase compositions of nanopowders and scaffolds. Furthermore, the effects of scaffold composition on the mechanical properties, bioactivity, biodegradability, and cytotoxicity were also evaluated. Results showed that the composite scaffolds with average pore size in the range of 220-310μm, appearance porosity of 63.1-75.9% and appearance density of 1.1±0.04g/cm(3) were successfully developed, depending on bredigite content. Indeed, the micropore size of the scaffolds reduced with increasing bredigite content confirming that the sinterability of the scaffolds was improved. Furthermore, the compression strength and modulus of the scaffolds significantly enhanced via incorporation of bredigite content from 0 to 15wt.%. The composite scaffolds revealed superior bioactivity and biodegradability with increasing bredigite content. Moreover, MTT assay confirmed that HA-15wt.% bredigite scaffold significantly promoted cell proliferation compared to tissue culture plate (control) and HA scaffold. Based on these results, three-dimensional HA-bredigite scaffolds could be promising replacements for HA scaffolds in bone regeneration. PMID:27524060

  6. Bone marrow cells contribute to tissue regeneration in the intestine and skin.

    OpenAIRE

    Brittan, M

    2005-01-01

    Adult bone marrow contains progenitor cells that can extricate themselves from their bone marrow cavity niche, and engraft within foreign tissues, whereupon they produce specific differentiated adult lineages. Bone marrow engraftment is upregulated with increasing regenerative pressure, which has triggered speculation as to the therapeutic potential of bone marrow cells. In this thesis, I describe for the first time, that transplanted adult bone marrow cells engraft within the intestines of m...

  7. Craniofacial Distraction Osteogenesis: Effects of rhythm of distraction on bone regeneration

    OpenAIRE

    Djasim, Urville

    2008-01-01

    textabstractDistraction osteogenesis is defined as the formation of new bone tissue between bone segments that are divided by an osteotomy and then gradually separated by exerting an external force to the mobile bone segment(s). The resulting callus tissue in the distraction gap will eventually mineralize, creating a new bridge of bone between the osteotomy edges of the original bone segments. Nowadays, distraction osteogenesis is a widely accepted tool for the treatment of acquired and conge...

  8. Mesoporous bioactive glass surface modified poly(lactic-co-glycolic acid) electrospun fibrous scaffold for bone regeneration.

    Science.gov (United States)

    Chen, Shijie; Jian, Zhiyuan; Huang, Linsheng; Xu, Wei; Liu, Shaohua; Song, Dajiang; Wan, Zongmiao; Vaughn, Amanda; Zhan, Ruisen; Zhang, Chaoyue; Wu, Song; Hu, Minghua; Li, Jinsong

    2015-01-01

    A mesoporous bioactive glass (MBG) surface modified with poly(lactic-co-glycolic acid) (PLGA) electrospun fibrous scaffold for bone regeneration was prepared by dip-coating a PLGA electrospun fibrous scaffold into MBG precursor solution. Different surface structures and properties were acquired by different coating times. Surface morphology, chemical composition, microstructure, pore size distribution, and hydrophilicity of the PLGA-MBG scaffold were characterized. Results of scanning electron microscopy indicated that MBG surface coating made the scaffold rougher with the increase of MBG content. Scaffolds after MBG modification possessed mesoporous architecture on the surface. The measurements of the water contact angles suggested that the incorporation of MBG into the PLGA scaffold improved the surface hydrophilicity. An energy dispersive spectrometer evidenced that calcium-deficient carbonated hydroxyapatite formed on the PLGA-MBG scaffolds after a 7-day immersion in simulated body fluid. In vitro studies showed that the incorporation of MBG favored cell proliferation and osteogenic differentiation of human mesenchymal stem cells on the PLGA scaffolds. Moreover, the MBG surface-modified PLGA (PLGA-MBG) scaffolds were shown to be capable of providing the improved adsorption/release behaviors of bone morphogenetic protein-2 (BMP-2). It is very significant that PLGA-MBG scaffolds could be effective for BMP-2 delivery and bone regeneration. PMID:26082632

  9. Vitapex can promote the expression of BMP-2 during the bone regeneration of periapical lesions in rats

    Directory of Open Access Journals (Sweden)

    Xianyin Xia

    2013-01-01

    Full Text Available Purpose: To investigate the effect of Vitapex on the healing of periapical lesions and the expression of bone morphogenetic protein (BMP-2 during the periapical bone regeneration. Materials and Methods: Periapical lesions were induced in Sprague-Dawley (S-D rats by an occlusal pulp exposure in the mandibular first molars and were verified by X-ray. Total of 36 rats were randomly divided into three groups, and they were obturated with Zinc Oxide Eugenol (ZOE, or with Vitapex, or non-treated as negative control group. The rats of three groups were randomly killed at week 0, 2, 4, and 8 after root canal therapy, and then the mandibles were processed for histological examination and immunohistochemistry analysis. Results: At week 0, only a few BMP-2 positive cells could be observed in all rats. While the expression of BMP-2 was dramatically increased in case of Vitapex group at week 2 and week 4, and then climaxed at week 8. However, no apparent changes were observed in ZOE group and negative group at week 2, 4, and 8. Conclusion: These observations suggested that Vitapex has a greater ability in inducing bone regeneration than ZOE by the expression of BMP-2 induction in the treatment of rats experimental periapical lesions.

  10. Comparative Efficacies of a 3D-Printed PCL/PLGA/β-TCP Membrane and a Titanium Membrane for Guided Bone Regeneration in Beagle Dogs

    Directory of Open Access Journals (Sweden)

    Jin-Hyung Shim

    2015-10-01

    Full Text Available This study was conducted to evaluate the effects of a 3D-printed resorbable polycaprolactone/poly(lactic-co-glycolic acid/β-tricalcium phosphate (PCL/PLGA/β-TCP membrane on bone regeneration and osseointegration in areas surrounding implants and to compare results with those of a non-resorbable titanium mesh membrane. After preparation of PCL/PLGA/β-TCP membranes using extrusion-based 3D printing technology; mechanical tensile testing and in vitro cell proliferation testing were performed. Implant surgery and guided bone regeneration were performed randomly in three groups (a no membrane group, a titanium membrane group, and a PCL/PLGA/β-TCP membrane group (n = 8 per group. Histological and histometric analyses were conducted to evaluate effects on bone regeneration and osseointegration. Using the results of mechanical testing; a PCL/PLGA/β-TCP ratio of 2:6:2 was selected. The new bone areas (% in buccal defects around implants were highest in the PCL/PLGA/β-TCP group and significantly higher than in the control group (p < 0.05. Bone-to-implant contact ratios (% were also significantly higher in the PCL/PLGA/β-TCP and titanium groups than in the control group (p < 0.05. When the guided bone regeneration procedure was performed using the PCL/PLGA/β-TCP membrane; new bone formation around the implant and osseointegration were not inferior to those of the non-resorbable pre-formed titanium mesh membrane.

  11. A bioceramic with enhanced osteogenic properties to regulate the function of osteoblastic and osteocalastic cells for bone tissue regeneration.

    Science.gov (United States)

    Roohani-Esfahani, Seyed-Iman; No, Young Jung; Lu, Zufu; Ng, Pei Ying; Chen, Yongjuan; Shi, Jeffrey; Pavlos, Nathan J; Zreiqat, Hala

    2016-01-01

    Bioceramics for regenerative medicine applications should have the ability to promote adhesion, proliferation and differentiation of osteoblast and osteoclast cells. Osteogenic properties of the material are essential for rapid bone regeneration and new bone formation. The aim of this study was to develop a silicate-based ceramic, gehlenite (GLN, Ca2Al2SiO7), and characterise its physiochemical, biocompatibility and osteogenic properties. A pure GLN powder was synthesised by a facile reactive sintering method and compacted to disc-shaped specimens. The sintering behaviour and degradation of the GLN discs in various buffer solutions were fully characterised. The cytotoxicity of GLN was evaluated by direct and indirect methods. In the indirect method, primary human osteoblast cells (HOBs) were exposed to diluted extracts (100, 50, 25, 12.5 and 6.25 mg ml(-1)) of fine GLN particles in culture medium. The results showed that the extracts did not cause any cytotoxic effect on the HOBs with the number of cells increasing significantly from day 1 to day 7. GLN-supported HOB attachment and proliferation, and significantly enhanced osteogenic gene expression levels (Runx2, osteocalcin, osteopontin and bone sialoprotein) were compared with biphasic calcium phosphate groups (BCP, a mixture of hydroxyapatite (60wt.%) and β-tricalcium phosphate(40wt.%)). We also demonstrated that in addition to supporting HOB attachment and proliferation, GLN promoted the formation of tartrate-acid resistance phosphatase (TRAP) positive multinucleated osteoclastic cells (OCs) derived from mouse bone marrow cells. Results also demonstrated the ability of GLN to support the polarisation of OCs, a prerequisite for their functional resorptive activity which is mainly influenced by the composition and degradability of biomaterials. Overall, the developed GLN is a prospective candidate to be used in bone regeneration applications due its effective osteogenic properties and biocompatibility. PMID

  12. A contribution to the study of damage and regeneration of hemopoiesis during fractionated irradiation and repeated bone marrow transplantation

    International Nuclear Information System (INIS)

    The experiment was aimed at studying two contradictory actions: damage to hemopoietic organs during application of radiation doses per fraction and regenerative efforts of the organism support by repeated bone marrow transplantation. The mice received doses of 3 Gy or 60Co-gamma rays total body irradiation at four-day intervals up to a total dose of 18 Gy. After each dose per fraction half of the animals were injected with 106 bone marrow cells. At four-day intervals evaluations were made of the blood count, bone marrow and spleen cellularities, and spleen mass. In animals subjected only to irradiation the damage to hemopoietic organs was becoming deeper until the end of observation. In bone marrow recipients the decrease in bone marrow cellularity and the number of leukocytes stopped after day 16, and there was a steep growth of splenic cellularity and mass; the decrease in erythrocyte count stopped on day 20. Obviously a certain recovery of hemopoiesis occurred after the total dose of 12 Gy between days 12 and 16. The lodging of injected hemopoietic stem cells and their proliferation had to be preceeded by a regeneration of the hemopoietic microenvironment. (orig.)

  13. Effects of low-level laser therapy on bone regeneration of the midpalatal suture after rapid maxillary expansion.

    Science.gov (United States)

    Ferreira, Fabíola Nogueira Holanda; Gondim, Juliana Oliveira; Neto, José Jeová Siebra Moreira; Dos Santos, Pedro Cesar Fernandes; de Freitas Pontes, Karina Matthes; Kurita, Lúcio Mitsuo; de Araújo, Maria Walderez Andrade

    2016-07-01

    This study evaluated the effect of low-level laser therapy (LLLT) on bone regeneration at the midpalatal suture (MPS) after rapid maxillary expansion (RME), using cone beam computed tomography. Fourteen 8-14-year-old patients with transverse maxillary deficiency underwent RME with a Hyrax-type expander activated with one full turn after installation and two half turn daily activations until achieving overcorrection. Patients were randomly assigned to either a control group (RME alone, n = 4) or an experimental group (n = 10) in which RME was followed by 12 LLLT sessions (GaAlAs, p = 70 mW, λ = 780 nm, Ø = 0.04 cm(2)). Two tomographic images of the MPS were obtained-T0, after disjunction and T1, after 4 months. Bone regeneration was evaluated by measuring the optical density (OD) on the tomographic images using InVivo Dental 5.0 software. Data were analyzed by the paired Student's t test (α = 0.05 %). A statistically significant difference between T0 and T1 OD values was observed in the laser-treated group (p = 0.00), but this difference was not significant in the control group (p = 0.20). Intergroup comparison of OD values at T1 revealed higher OD in the laser-treated group (p = 0.05). In conclusion, LLLT had a positive influence on bone regeneration of the midpalatal suture by accelerating the repair process. PMID:27056702

  14. Efficacy of Platelet-Rich-Plasma (PRP and Highly Purified Bovine Xenograft (Laddec® Combination in Bone Regeneration after Cyst Enucleation: Radiological and Histological Evaluation

    Directory of Open Access Journals (Sweden)

    Sabrina Pappalardo

    2013-10-01

    Full Text Available Objectives: The purpose of the present study was to evaluate the efficacy of adding platelet-rich plasma (PRP to a new highly purified bovine allograft (Laddec® in the bone regeneration of cystic bony defects augmented following cystectomy.Material and Methods: Study sample included 20 patients undergoing cystectomy in which the bone defect was filled with PRP and Laddec®. All patients were examined with periapical radiographs before operation and at follow-up. After 3 months, at re-entry surgery for implant placement, bone core was taken for histological and histomorphometric analysis.Results: The postoperative successive radiographs showed a good regeneration of bone in the height of bony defects with application of PRP to bone graft. By the first postoperative month, about 48% of the defect was filled, which gradually increased in each month and showed about 90% of defect-fill by 6 months. Histological and histomorphometric analysis, showed a significant presence of bone tissue and vessels, with newly formed bone in contact with anorganic bone particles. The mean volume of vital bone was 68 ± 1.6% and the mean percentage of vital bone was 48 ± 2.4%. The mean percentage of inorganic particles in tissues was 20 ± 1.2% of the total volume. All the samples analyzed did not evidence the presence of inflammatory cells.Conclusions: The results of this study showed how the use of Laddec® in association with platelet-rich plasma allows bone regeneration and has a potential for routine clinical use for regeneration of cystic bony defects.

  15. VEGF-sdf1 recruitment of CXCR7+ bone marrow progenitors of liver sinusoidal endothelial cells promotes rat liver regeneration.

    Science.gov (United States)

    DeLeve, Laurie D; Wang, Xiangdong; Wang, Lei

    2016-05-01

    In liver injury, recruitment of bone marrow (BM) progenitors of liver sinusoidal endothelial cells (sprocs) is necessary for normal liver regeneration. Hepatic vascular endothelial growth factor (VEGF) is a central regulator of the recruitment process. We examine whether stromal cell-derived factor 1 [sdf1, or CXC ligand 12 (CXCL12)] acts downstream from VEGF to mediate recruitment of BM sprocs, what the sdf1 receptor type [CXC receptor (CXCR)-4 or CXCR7] is on sprocs, and whether sdf1 signaling is required for normal liver regeneration. Studies were performed in the rat partial hepatectomy model. Tracking studies of BM sprocs were performed in wild-type Lewis rats that had undergone BM transplantation from transgenic enhanced green fluorescent protein-positive Lewis rats. Knockdown studies were performed using antisense oligonucleotides (ASOs). Expression of sdf1 doubles in liver and liver sinusoidal endothelial cells (LSECs) after partial hepatectomy. Upregulation of sdf1 expression increases proliferation of sprocs in the BM, mobilization of CXCR7(+) BM sprocs to the circulation, and engraftment of CXCR7(+) BM sprocs in the liver and promotes liver regeneration. Knockdown of hepatic VEGF with ASOs decreases hepatic sdf1 expression and plasma sdf1 levels. When the effect of VEGF knockdown on sdf1 is offset by infusion of sdf1, VEGF knockdown-induced impairment of BM sproc recruitment after partial hepatectomy is completely attenuated and liver regeneration is normalized. These data demonstrate that the VEGF-sdf1 pathway regulates recruitment of CXCR7(+) BM sprocs to the hepatic sinusoid after partial hepatectomy and is required for normal liver regeneration. PMID:26939868

  16. Comparative study on the role of gelatin, chitosan and their combination as tissue engineered scaffolds on healing and regeneration of critical sized bone defects: an in vivo study.

    Science.gov (United States)

    Oryan, Ahmad; Alidadi, Soodeh; Bigham-Sadegh, Amin; Moshiri, Ali

    2016-10-01

    Gelatin and chitosan are natural polymers that have extensively been used in tissue engineering applications. The present study aimed to evaluate the effectiveness of chitosan and gelatin or combination of the two biopolymers (chitosan-gelatin) as bone scaffold on bone regeneration process in an experimentally induced critical sized radial bone defect model in rats. Fifty radial bone defects were bilaterally created in 25 Wistar rats. The defects were randomly filled with chitosan, gelatin and chitosan-gelatin and autograft or left empty without any treatment (n = 10 in each group). The animals were examined by radiology and clinical evaluation before euthanasia. After 8 weeks, the rats were euthanized and their harvested healing bone samples were evaluated by radiology, CT-scan, biomechanical testing, gross pathology, histopathology, histomorphometry and scanning electron microscopy. Gelatin was biocompatible and biodegradable in vivo and showed superior biodegradation and biocompatibility when compared with chitosan and chitosan-gelatin scaffolds. Implantation of both the gelatin and chitosan-gelatin scaffolds in bone defects significantly increased new bone formation and mechanical properties compared with the untreated defects (P  0.05). In conclusion, application of the gelatin alone or its combination with chitosan had beneficial effects on bone regeneration and could be considered as good options for bone tissue engineering strategies. However, chitosan alone was not able to promote considerable new bone formation in the experimentally induced critical-size radial bone defects. PMID:27590825

  17. Preparation and characterization of bioactive composite scaffolds from polycaprolactone nanofibers-chitosan-oxidized starch for bone regeneration.

    Science.gov (United States)

    Nourmohammadi, Jhamak; Ghaee, Azadeh; Liavali, Samira Hosseini

    2016-03-15

    The objective of this study was to fabricate and investigate the characteristics of a suitable scaffold for bone regeneration. Therefore, chitosan was combined with various amounts of oxidized starch through reductive alkylation process. Afterwards, chopped CaP-coated PCL nanofibers were added into the chitosan-starch composite scaffolds in order to obtain bioactivity and mimic bone extracellular matrix structure. Scanning electron microscopy confirmed that all scaffolds had well-interconnected porous structure. The mean pore size, porosity, and water uptake of the composite scaffolds increased by incorporation of higher amounts of starch, while this trend was opposite for compressive modulus and strength. Osteoblast-like cells (MG63) culturing on the scaffolds demonstrated that higher starch content could improve cell viability. Moreover, the cells spread and anchored well on the scaffolds, on which the surface was covered with a monolayer of cells. PMID:26794750

  18. Hyaluronic Acid Hydrogels with Controlled Degradation Properties for Oriented Bone Regeneration

    OpenAIRE

    J. Patterson; Siew, R; Herring, SW; Lin, ASP; Guldberg, R; Stayton, PS

    2010-01-01

    Non-healing fractures can result from trauma, disease, or age-related bone loss. While many treatments focus on restoring bone volume, few try to recapitulate bone organization. However, the native architecture of bone is optimized to provide its necessary mechanical properties. Hyaluronic acid (HA) hydrogel scaffold systems with tunable degradation properties were developed for the controlled delivery of osteoinductive and angiogenic growth factors, thus affecting the quantity and quality of...

  19. Hard tissue regeneration using bone substitutes: an update on innovations in materials

    OpenAIRE

    Sarkar, Swapan Kumar; Lee, Byong Taek

    2015-01-01

    Bone is a unique organ composed of mineralized hard tissue, unlike any other body part. The unique manner in which bone can constantly undergo self-remodeling has created interesting clinical approaches to the healing of damaged bone. Healing of large bone defects is achieved using implant materials that gradually integrate with the body after healing is completed. Such strategies require a multidisciplinary approach by material scientists, biological scientists, and clinicians. Development o...

  20. Concise Review: Diabetes, the Bone Marrow Niche, and Impaired Vascular Regeneration

    OpenAIRE

    Fadini, Gian Paolo; Ferraro, Francesca; Quaini, Federico; Asahara, Takayuki; Madeddu, Paolo

    2014-01-01

    This review examines the physiological and molecular bone marrow abnormalities associated with diabetes and discusses how bone marrow dysfunction represents a potential root for the development of the multiorgan failure characteristic of advanced diabetes. The notion of diabetes as a bone marrow and stem cell disease opens new avenues for therapeutic interventions ultimately aimed at improving the outcome of diabetic patients.

  1. Acceleration of bone development and regeneration through the Wnt/β-catenin signaling pathway in mice heterozygously deficient for GSK-3β

    Energy Technology Data Exchange (ETDEWEB)

    Arioka, Masaki [Department of Clinical Pharmacology, Faculty of Medical Sciences, Kyushu University, Fukuoka (Japan); Department of Oral and Maxillofacial Surgery, Faculty of Dental Science, Kyushu University, Fukuoka (Japan); Takahashi-Yanaga, Fumi, E-mail: yanaga@clipharm.med.kyushu-u.ac.jp [Department of Clinical Pharmacology, Faculty of Medical Sciences, Kyushu University, Fukuoka (Japan); Global Medical Science Education Unit, Faculty of Medical Sciences, Kyushu University, Fukuoka (Japan); Sasaki, Masanori [Department of Oral and Maxillofacial Surgery, Faculty of Dental Science, Kyushu University, Fukuoka (Japan); Yoshihara, Tatsuya; Morimoto, Sachio [Department of Clinical Pharmacology, Faculty of Medical Sciences, Kyushu University, Fukuoka (Japan); Takashima, Akihiko [Department of Aging Neurobiology, National Center for Geriatrics and Gerontology, Oobu (Japan); Mori, Yoshihide [Department of Oral and Maxillofacial Surgery, Faculty of Dental Science, Kyushu University, Fukuoka (Japan); Sasaguri, Toshiyuki [Department of Clinical Pharmacology, Faculty of Medical Sciences, Kyushu University, Fukuoka (Japan)

    2013-11-01

    Highlights: •The Wnt/β-catenin signaling pathway was activated in GSK-3β{sup +/−} mice. •The cortical and trabecular bone volumes were increased in GSK-3β{sup +/−} mice. •Regeneration of a partial bone defect was accelerated in GSK-3β{sup +/−} mice. -- Abstract: Glycogen synthase kinase (GSK)-3β plays an important role in osteoblastogenesis by regulating the Wnt/β-catenin signaling pathway. Therefore, we investigated whether GSK-3β deficiency affects bone development and regeneration using mice heterozygously deficient for GSK-3β (GSK-3β{sup +/−}). The amounts of β-catenin, c-Myc, cyclin D1, and runt-related transcription factor-2 (Runx2) in the bone marrow cells of GSK-3β{sup +/−} mice were significantly increased compared with those of wild-type mice, indicating that Wnt/β-catenin signals were enhanced in GSK-3β{sup +/−} mice. Microcomputed tomography of the distal femoral metaphyses demonstrated that the volumes of both the cortical and trabecular bones were increased in GSK-3β{sup +/−} mice compared with those in wild-type mice. Subsequently, to investigate the effect of GSK-3β deficiency on bone regeneration, we established a partial bone defect in the femur and observed new bone at 14 days after surgery. The volume and mineral density of the new bone were significantly higher in GSK-3β{sup +/−} mice than those in wild-type mice. These results suggest that bone formation and regeneration in vivo are accelerated by inhibition of GSK-3β, probably through activation of the Wnt/β-catenin signaling pathway.

  2. Bone regeneration by implantation of adipose-derived stromal cells expressing BMP-2

    International Nuclear Information System (INIS)

    In this study, we reported that the adipose-derived stromal cells (ADSCs) genetically modified by bone morphogenetic protein 2 (BMP-2) healed critical-sized canine ulnar bone defects. First, the osteogenic and adipogenic differentiation potential of the ADSCs derived from canine adipose tissue were demonstrated. And then the cells were modified by the BMP-2 gene and the expression and bone-induction ability of BMP-2 were identified. Finally, the cells modified by BMP-2 gene were applied to a β-tricalcium phosphate (TCP) carrier and implanted into ulnar bone defects in the canine model. After 16 weeks, radiographic, histological, and histomorphometry analysis showed that ADSCs modified by BMP-2 gene produced a significant increase of newly formed bone area and healed or partly healed all of the bone defects. We conclude that ADSCs modified by the BMP-2 gene can enhance the repair of critical-sized bone defects in large animals

  3. Assessment of regeneration in meniscal lesions by use of mesenchymal stem cells derived from equine bone marrow and adipose tissue.

    Science.gov (United States)

    González-Fernández, Maria L; Pérez-Castrillo, Saúl; Sánchez-Lázaro, Jaime A; Prieto-Fernández, Julio G; López-González, Maria E; Lobato-Pérez, Sandra; Colaço, Bruno J; Olivera, Elías R; Villar-Suárez, Vega

    2016-07-01

    OBJECTIVE To assess the ability to regenerate an equine meniscus by use of a collagen repair patch (scaffold) seeded with mesenchymal stem cells (MSCs) derived from bone marrow (BM) or adipose tissue (AT). SAMPLE 6 female Hispano-Breton horses between 4 and 7 years of age; MSCs from BM and AT were obtained for the in vitro experiment, and the horses were subsequently used for the in vivo experiment. PROCEDURES Similarities and differences between MSCs derived from BM or AT were investigated in vitro by use of cell culture. In vivo assessment involved use of a meniscus defect and implantation on a scaffold. Horses were allocated into 2 groups. In one group, defects in the medial meniscus were treated with MSCs derived from BM, whereas in the other group, defects were treated with MSCs derived from AT. Defects were created in the contralateral stifle joint but were not treated (control samples). RESULTS Both types of MSCs had universal stem cell characteristics. For in vivo testing, at 12 months after treatment, treated defects were regenerated with fibrocartilaginous tissue, whereas untreated defects were partially repaired or not repaired. CONCLUSIONS AND CLINICAL RELEVANCE Results indicated that MSCs derived from AT could be a good alternative to MSCs derived from BM for use in regenerative treatments. Results also were promising for a stem cell-based implant for use in regeneration in meniscal lesions. IMPACT FOR HUMAN MEDICINE Because of similarities in joint disease between horses and humans, these results could have applications in humans. PMID:27347833

  4. A nanoparticulate injectable hydrogel as a tissue engineering scaffold for multiple growth factor delivery for bone regeneration

    Directory of Open Access Journals (Sweden)

    Dyondi D

    2012-12-01

    Full Text Available Deepti Dyondi,1 Thomas J Webster,2 Rinti Banerjee11Department of Biosciences and Bioengineering, Indian Institute of Technology Bombay, Mumbai, Maharashtra, India; 2Nanomedicine Laboratories, Division of Engineering and Department of Orthopedics, Brown University, Providence, RI, USAAbstract: Gellan xanthan gels have been shown to be excellent carriers for growth factors and as matrices for several tissue engineering applications. Gellan xanthan gels along with chitosan nanoparticles of 297 ± 61 nm diameter, basic fibroblast growth factor (bFGF, and bone morphogenetic protein 7 (BMP7 were employed in a dual growth factor delivery system to promote the differentiation of human fetal osteoblasts. An injectable system with ionic and temperature gelation was optimized and characterized. The nanoparticle loaded gels showed significantly improved cell proliferation and differentiation due to the sustained release of growth factors. A differentiation marker study was conducted, analyzed, and compared to understand the effect of single vs dual growth factors and free vs encapsulated growth factors. Dual growth factor loaded gels showed a higher alkaline phosphatase and calcium deposition compared to single growth factor loaded gels. The results suggest that encapsulation and stabilization of growth factors within nanoparticles and gels are promising for bone regeneration. Gellan xanthan gels also showed antibacterial effects against Pseudomonas aeruginosa, Staphylococcus aureus, and Staphylococcus epidermidis, the common pathogens in implant failure.Keywords: bone tissue engineering, bone morphogenetic protein 7 (BMP7, basic fibroblast growth factor (bFGF, hydrogel, nanoparticles, osteoblasts

  5. Multiwall carbon nanotubes/polycaprolactone scaffolds seeded with human dental pulp stem cells for bone tissue regeneration.

    Science.gov (United States)

    Flores-Cedillo, M L; Alvarado-Estrada, K N; Pozos-Guillén, A J; Murguía-Ibarra, J S; Vidal, M A; Cervantes-Uc, J M; Rosales-Ibáñez, R; Cauich-Rodríguez, J V

    2016-02-01

    Conventional approaches to bone regeneration rarely use multiwall carbon nanotubes (MWCNTs) but instead use polymeric matrices filled with hydroxyapatite, calcium phosphates and bioactive glasses. In this study, we prepared composites of MWCNTs/polycaprolactone (PCL) for bone regeneration as follows: (a) MWCNTs randomly dispersed on PCL, (b) MWCNTs aligned with an electrical field to determine if the orientation favors the growing of human dental pulp stem cells (HDPSCs), and (c) MWCNTs modified with β-glycerol phosphate (BGP) to analyze its osteogenic potential. Raman spectroscopy confirmed the presence of MWCNTs and BGP on PCL, whereas the increase in crystallinity by the addition of MWCNTs to PCL was confirmed by X-ray diffraction and differential scanning calorimetry. A higher elastic modulus (608 ± 4.3 MPa), maximum stress (42 ± 6.1 MPa) and electrical conductivity (1.67 × 10(-7) S/m) were observed in non-aligned MWCNTs compared with the pristine PCL. Cell viability at 14 days was similar in all samples according to the live/dead assay, but the 21 day cell proliferation, measured by MTT was higher in MWCNTs aligned with BGP. Von Kossa and Alizarin red showed larger amounts of mineral deposits on MWCNTs aligned with BGP, indicating that at 21 days, this scaffold promotes osteogenic differentiation of HDPSCs. PMID:26704552

  6. BMP2 Genetically Engineered MSCs and EPCs Promote Vascularized Bone Regeneration in Rat Critical-Sized Calvarial Bone Defects

    OpenAIRE

    He, Xiaoning; Dziak, Rosemary; Yuan, Xue; Mao, Keya; Genco, Robert; Swihart, Mark; Sarkar, Debanjan; Li, Chunyi; Wang, Changdong; Lu, Li; Andreadis, Stelios; Yang, Shuying

    2013-01-01

    Current clinical therapies for critical-sized bone defects (CSBDs) remain far from ideal. Previous studies have demonstrated that engineering bone tissue using mesenchymal stem cells (MSCs) is feasible. However, this approach is not effective for CSBDs due to inadequate vascularization. In our previous study, we have developed an injectable and porous nano calcium sulfate/alginate (nCS/A) scaffold and demonstrated that nCS/A composition is biocompatible and has proper biodegradability for bon...

  7. Chondrogenic regeneration using bone marrow clots and a porous polycaprolactone-hydroxyapatite scaffold by three-dimensional printing.

    Science.gov (United States)

    Yao, Qingqiang; Wei, Bo; Liu, Nancy; Li, Chenshuang; Guo, Yang; Shamie, Arya Nick; Chen, James; Tang, Cheng; Jin, Chengzhe; Xu, Yan; Bian, Xiuwu; Zhang, Xinli; Wang, Liming

    2015-04-01

    Scaffolds play an important role in directing three-dimensional (3D) cartilage regeneration. Our recent study reported the potential advantages of bone marrow clots (MC) in promoting extracellular matrix (ECM) scaffold chondrogenic regeneration. The aim of this study is to build a new scaffold for MC, with improved characteristics in mechanics, shaping, and biodegradability, compared to our previous study. To address this issue, this study prepared a 3D porous polycaprolactone (PCL)-hydroxyapatite (HA) scaffold combined with MC (Group A), while the control group (Group B) utilized a bone marrow stem cell seeded PCL-HA scaffold. The results of in vitro cultures and in vivo implantation demonstrated that although an initial obstruction of nutrient exchange caused by large amounts of fibrin and erythrocytes led to a decrease in the ratio of live cells in Group A, these scaffolds also showed significant improvements in cell adhesion, proliferation, and chondrogenic differentiation with porous recanalization in the later culture, compared to Group B. After 4 weeks of in vivo implantation, Group A scaffolds have a superior performance in DNA content, Sox9 and RunX2 expression, cartilage lacuna-like cell and ECM accumulation, when compared to Group B. Furthermore, Group A scaffold size and mechanics were stable during in vitro and in vivo experiments, unlike the scaffolds in our previous study. Our results suggest that the combination with MC proved to be a highly efficient, reliable, and simple new method that improves the biological performance of 3D PCL-HA scaffold. The MC-PCL-HA scaffold is a candidate for future cartilage regeneration studies. PMID:25530453

  8. Mesoporous bioactive glass surface modified poly(lactic-co-glycolic acid electrospun fibrous scaffold for bone regeneration

    Directory of Open Access Journals (Sweden)

    Chen SJ

    2015-06-01

    Full Text Available Shijie Chen,1,* Zhiyuan Jian,2,* Linsheng Huang,2,* Wei Xu,3,* Shaohua Liu,4 Dajiang Song,3 Zongmiao Wan,3 Amanda Vaughn,5 Ruisen Zhan,1 Chaoyue Zhang,1 Song Wu,1 Minghua Hu,6 Jinsong Li1 1Department of Orthopaedics, The Third Xiangya Hospital of Central South University, Changsha, Hunan, People’s Republic of China; 2The First General Surgery Department of Shiyan Taihe Hospital Affiliated to Hubei University of Medicine, Shiyan, People’s Republic of China; 3Department of Orthopedic Oncology, Changzheng Hospital, The Second Military Medical University, Shanghai, People’s Republic of China; 4Department of Spine Surgery, Xiangya Hospital of Central South University, Changsha, Hunan, People’s Republic of China; 5Department of Molecular Biosciences, Institute of Cellular and Molecular Biology, The University of Texas at Austin, Austin, TX, USA; 6Department of Anthropotomy, Changsha Medical College, Changsha, Hunan, People’s Republic of China *These authors contributed equally to this work Abstract: A mesoporous bioactive glass (MBG surface modified with poly(lactic-co-glycolic acid (PLGA electrospun fibrous scaffold for bone regeneration was prepared by dip-coating a PLGA electrospun fibrous scaffold into MBG precursor solution. Different surface structures and properties were acquired by different coating times. Surface morphology, chemical composition, microstructure, pore size distribution, and hydrophilicity of the PLGA-MBG scaffold were characterized. Results of scanning electron microscopy indicated that MBG surface coating made the scaffold rougher with the increase of MBG content. Scaffolds after MBG modification possessed mesoporous architecture on the surface. The measurements of the water contact angles suggested that the incorporation of MBG into the PLGA scaffold improved the surface hydrophilicity. An energy dispersive spectrometer evidenced that calcium-deficient carbonated hydroxyapatite formed on the PLGA-MBG scaffolds

  9. Advanced BMP Gene Therapies for Temporal and Spatial Control of Bone Regeneration

    OpenAIRE

    Wilson, C.G.; Martín-Saavedra, F.M.; Vilaboa, N.; Franceschi, R.T.

    2013-01-01

    Spatial and temporal patterns of bone morphogenetic protein (BMP) signaling are crucial to the assembly of appropriately positioned and shaped bones of the face and head. This review advances the hypothesis that reconstitution of such patterns with cutting-edge gene therapies will transform the clinical management of craniofacial bone defects attributed to trauma, disease, or surgical resection. Gradients in BMP signaling within developing limbs and orofacial primordia regulate proliferation ...

  10. Intravenous transplantation of bone marrow mesenchymal stem cells promotes neural regeneration after traumatic brain injury

    OpenAIRE

    Anbari, Fatemeh; Khalili, Mohammad Ali; Bahrami, Ahmad Reza; Khoradmehr, Arezoo; Sadeghian, Fatemeh; Fesahat, Farzaneh; Nabi, Ali

    2014-01-01

    To investigate the supplement of lost nerve cells in rats with traumatic brain injury by intravenous administration of allogenic bone marrow mesenchymal stem cells, this study established a Wistar rat model of traumatic brain injury by weight drop impact acceleration method and administered 3 × 106 rat bone marrow mesenchymal stem cells via the lateral tail vein. At 14 days after cell transplantation, bone marrow mesenchymal stem cells differentiated into neurons and astrocytes in injured rat...

  11. Bone regeneration with resorbable polylactide membrane and sponge in an unstable fracture model in rabbit radius

    OpenAIRE

    Gogolewski, S.; Tsui, K.; Ip, WY

    2003-01-01

    BACKGROUND: Healing of segmental diaphyseal bone defects in animals can be enhanced by covering the defects with resorbable polylactide membranes. Based on the results of bone healing in defects 10 mm long in the rabbit radii, it was suggested that the membranes prevents muscle and soft tissue from invading the defect and maintains osteogenic cells and osteogenic substances within the space covered with membrane, thus promoting new bone formation. OBJECTIVES: 1. To investigate and …

  12. ECM Inspired Coating of Embroidered 3D Scaffolds Enhances Calvaria Bone Regeneration

    OpenAIRE

    C. Rentsch; Rentsch, B.; Heinemann, S.; Bernhardt, R; Bischoff, B; Förster, Y; Scharnweber, D.; Rammelt, S

    2014-01-01

    Resorbable polymeric implants and surface coatings are an emerging technology to treat bone defects and increase bone formation. This approach is of special interest in anatomical regions like the calvaria since adults lose the capacity to heal large calvarial defects. The present study assesses the potential of extracellular matrix inspired, embroidered polycaprolactone-co-lactide (PCL) scaffolds for the treatment of 13 mm full thickness calvarial bone defects in rabbits. Moreover the influe...

  13. Biphasic calcium phosphate–casein bone graft fortified with Cassia occidentalis for bone tissue engineering and regeneration

    Indian Academy of Sciences (India)

    B Santhosh Kumar; T Hemalatha; R Deepachitra; R Narasimha Raghavan; P Prabu; T P Sastry

    2015-02-01

    Research on traditional herbs is gaining momentum owing to their potent medical properties, among which Cassia occidentalis (CO) is a promising herb, with osteogenic potential. The study investigates the efficacy of CO extract incorporated biphasic calcium phosphate as an osteoinductive material. Prepared bone implants were characterized physico-chemically using FT-IR, TGA, XRD, SEM and EDX. The implants were analysed further for mechanical and biological properties. The results revealed that CO extract-incorporated bone implants possessed better compression strength and it was able to induce proliferation and enhance alkaline phosphatase activity in SaOS-2 cells. The implant proves to be promising for bone tissue engineering, and hence it demands further in vivo evaluation.

  14. Degradability of injectable calcium sulfate/mineralized collagen-based bone repair material and its effect on bone tissue regeneration

    Energy Technology Data Exchange (ETDEWEB)

    Chen, Zonggang, E-mail: chenzg@sdu.edu.cn [National Glycoengineering Research Center, Shandong University, Jinan 250100 (China); Department of Materials Science and Engineering, Tsinghua University, Beijing 100084 (China); Kang, Lingzhi [National Glycoengineering Research Center, Shandong University, Jinan 250100 (China); Meng, Qing-Yuan [Department of Materials Science and Engineering, Tsinghua University, Beijing 100084 (China); Liu, Huanye [Department of Prosthodontics, School of Stomatology, China Medical University, Shenyang 110001 (China); Wang, Zhaoliang [Jinan Military General Hospital of PLA, Jinan 250031 (China); Guo, Zhongwu, E-mail: zwguo@sdu.edu.cn [National Glycoengineering Research Center, Shandong University, Jinan 250100 (China); Cui, Fu-Zhai, E-mail: cuifz@mail.tsinghua.edu.cn [Department of Materials Science and Engineering, Tsinghua University, Beijing 100084 (China)

    2014-12-01

    The nHAC/CSH composite is an injectable bone repair material with controllable injectability and self-setting properties prepared by introducing calcium sulfate hemihydrate (CSH) into mineralized collagen (nHAC). When mixed with water, the nHAC/CSH composites can be transformed into mineralized collagen/calcium sulfate dihydrate (nHAC/CSD) composites. The nHAC/CSD composites have good biocompatibility and osteogenic capability. Considering that the degradation behavior of bone repair material is another important factor for its clinical applications, the degradability of nHAC/CSD composites was studied. The results showed that the degradation ratio of the nHAC/CSD composites with lower nHAC content increased with the L/S ratio increase of injectable materials, but the variety of L/S ratio had no significant effect on the degradation ratio of the nHAC/CSD composites with higher nHAC content. Increasing nHAC content in the composites could slow down the degradation of nHAC/CSD composite. Setting accelerator had no significant effect on the degradability of nHAC/CSD composites. In vivo histological analysis suggests that the degradation rate of materials can match the growth rate of new mandibular bone tissues in the implanted site of rabbit. The regulable degradability of materials resulting from the special prescriptions of injectable nHAC/CSH composites will further improve the workability of nHAC/CSD composites. - Highlights: • The nHAC/CSH composite can be as an injectable bone repair material. • The L/S ratio and nHAC content have a significant effect on material degradability. • The degradability of bone materials can be regulated to match tissue repair. • The regulable degradability will further improve the workability of bone materials.

  15. Degradability of injectable calcium sulfate/mineralized collagen-based bone repair material and its effect on bone tissue regeneration

    International Nuclear Information System (INIS)

    The nHAC/CSH composite is an injectable bone repair material with controllable injectability and self-setting properties prepared by introducing calcium sulfate hemihydrate (CSH) into mineralized collagen (nHAC). When mixed with water, the nHAC/CSH composites can be transformed into mineralized collagen/calcium sulfate dihydrate (nHAC/CSD) composites. The nHAC/CSD composites have good biocompatibility and osteogenic capability. Considering that the degradation behavior of bone repair material is another important factor for its clinical applications, the degradability of nHAC/CSD composites was studied. The results showed that the degradation ratio of the nHAC/CSD composites with lower nHAC content increased with the L/S ratio increase of injectable materials, but the variety of L/S ratio had no significant effect on the degradation ratio of the nHAC/CSD composites with higher nHAC content. Increasing nHAC content in the composites could slow down the degradation of nHAC/CSD composite. Setting accelerator had no significant effect on the degradability of nHAC/CSD composites. In vivo histological analysis suggests that the degradation rate of materials can match the growth rate of new mandibular bone tissues in the implanted site of rabbit. The regulable degradability of materials resulting from the special prescriptions of injectable nHAC/CSH composites will further improve the workability of nHAC/CSD composites. - Highlights: • The nHAC/CSH composite can be as an injectable bone repair material. • The L/S ratio and nHAC content have a significant effect on material degradability. • The degradability of bone materials can be regulated to match tissue repair. • The regulable degradability will further improve the workability of bone materials

  16. Cellular regeneration in bone marrow with synthesized semiconductor polymers by plasma

    International Nuclear Information System (INIS)

    In this work the intervention of polymers with capacity of conducting electric current for the regeneration of the spinal marrow in rats of laboratory is studied. It is a focus different from the one that up to now has taken in account since it involves medical, biological, physical and chemical sciences. Inside the properties of transporting electric charges, the polymers would have to respond before the biological media with ionic mechanisms of conduction, besides the electronic ones, to promote the regeneration of the spinal marrow. They should also be biocompatible to avoid the rejection of the media before the implantation. (Author)

  17. Beta-tricalcium phosphate granules improve osteogenesis in vitro and establish innovative osteo-regenerators for bone tissue engineering in vivo

    Science.gov (United States)

    Gao, Peng; Zhang, Haoqiang; Liu, Yun; Fan, Bo; Li, Xiaokang; Xiao, Xin; Lan, Pingheng; Li, Minghui; Geng, Lei; Liu, Dong; Yuan, Yulin; Lian, Qin; Lu, Jianxi; Guo, Zheng; Wang, Zhen

    2016-01-01

    The drawbacks of traditional bone-defect treatments have prompted the exploration of bone tissue engineering. This study aimed to explore suitable β-tricalcium phosphate (β-TCP) granules for bone regeneration and identify an efficient method to establish β-TCP-based osteo-regenerators. β-TCP granules with diameters of 1 mm and 1–2.5 mm were evaluated in vitro. The β-TCP granules with superior osteogenic properties were used to establish in vivo bioreactors, referred to as osteo-regenerators, which were fabricated using two different methods. Improved proliferation of bone mesenchymal stem cells (BMSCs), glucose consumption and ALP activity were observed for 1–2.5 mm β-TCP compared with 1-mm granules (P < 0.05). In addition, BMSCs incubated with 1–2.5 mm β-TCP expressed significantly higher levels of the genes for runt-related transcription factor-2, alkaline phosphatase, osteocalcin, osteopontin, and collagen type-1 and the osteogenesis-related proteins alkaline phosphatase, collagen type-1 and runt-related transcription factor-2 compared with BMSCs incubated with 1 mm β-TCP (P < 0.05). Fluorochrome labelling, micro-computed tomography and histological staining analyses indicated that the osteo-regenerator with two holes perforating the femur promoted significantly greater bone regeneration compared with the osteo-regenerator with a periosteum incision (P < 0.05). This study provides an alternative to biofunctionalized bioreactors that exhibits improved osteogenesis. PMID:27000963

  18. Effect of neurotransmitters and bone marrow cells for neuronal regeneration in iatrogenic spinal cord injury: An experimental study

    Directory of Open Access Journals (Sweden)

    John P

    2010-01-01

    Full Text Available Background: Spinal cord trauma is a major health problem with associated physical, social, economic and psychological sequelae. Despite many advances in research and treatment modalities, the pathophysiology of spinal cord injury remains unclear, and morbidity and mortality among these patients remain high. This experimental study investigates the regenerative cell proliferation effects of bone marrow supplemented with neurotransmitters combinations in the regeneration of spinal cord injury Materials and Methods: Ethical Committee Clearance was obtained for animal study. All animal care and procedures were in accordance with the CPCSEA and National Institute of Health guidelines. Thirty Wistar rats with monoplegia following surgical hemitransection of the spinal cord were used for the study. Half of them were randomly selected as the test group and the rest as the control group. Spinal cord injury model of Wistar rats in the test group were treated by infusing a combination of neurotransmitters and bone marrow at the site of injury using a special polythene tube and reservoir for 21 days. In the control group of rats with monoplegia, normal saline was infused at the site of injury for 21 days. The observations are recorded along with results. Results: The monoplegia in the test group of rats recovered significantly (P value < 0.01 with supplementation of the bone marrow cells and neurotransmitters combination. In the control group of rats, there was no recovery. The reward-seeking locomotor test and sensory recovery test confirmed recovery from spinal cord injury in the test group with significance. Conclusions: The neurotransmitters and bone marrow combination was responsible for functional recovery in the test group of rats with experimental spinal cord injury We believe that the combination of neurotransmitters along with bone marrow may be a scope of future research in patients with spinal cord injury.

  19. Efficacy of Platelet-Rich-Plasma (PRP) and Highly Purified Bovine Xenograft (Laddec®) Combination in Bone Regeneration after Cyst Enucleation: Radiological and Histological Evaluation

    OpenAIRE

    Pappalardo, Sabrina; Guarnieri, Renzo

    2013-01-01

    ABSTRACT Objectives The purpose of the present study was to evaluate the efficacy of adding platelet-rich plasma (PRP) to a new highly purified bovine allograft (Laddec®) in the bone regeneration of cystic bony defects augmented following cystectomy. Material and Methods Study sample included 20 patients undergoing cystectomy in which the bone defect was filled with PRP and Laddec®. All patients were examined with periapical radiographs before operation and at follow-up. After 3 months, at re...

  20. Evaluations of guided bone regeneration in canine radius segmental defects using autologous periosteum combined with fascia lata under stable external fixation

    OpenAIRE

    Yu, Zhe; Geng, Jie; Gao, Haoran; Zhao, Xinwen; Chen, Jingyuan

    2014-01-01

    Background Although bone defect is one of the most common orthopaedic diseases, treatment remains a challenge and an issue of debate. Guided bone regeneration (GBR) is primarily accompanied by barrier membranes; however, optional membranes show some inherent flaws in clinical application. The purpose of this study was to observe the healing velocity and quality of repairing canine radius segmental defect using transferred autologous periosteum combined with fascia lata, which can provide bett...

  1. Integration of a Novel Injectable Nano Calcium Sulfate/Alginate Scaffold and BMP2 Gene-Modified Mesenchymal Stem Cells for Bone Regeneration

    OpenAIRE

    He, Xiaoning; Dziak, Rosemary; Mao, Keya; Genco, Robert; Swithart, Mark; Li, Chunyi; Yang, Shuying

    2012-01-01

    The repair of craniofacial bone defects is surgically challenging due to the complex anatomical structure of the craniofacial skeleton. Current strategies for bone tissue engineering using a preformed scaffold have not resulted in the expected clinical regeneration due to difficulty in seeding cells into the deep internal space of scaffold, and the inability to inject them in minimally invasive surgeries. In this study, we used the osteoconductive and mechanical properties of nano-scale calci...

  2. A Novel Injectable Magnesium/Calcium Sulfate Hemihydrate Composite Cement for Bone Regeneration

    Directory of Open Access Journals (Sweden)

    Shanchuan Zhang

    2015-01-01

    Full Text Available Objective. A novel injectable magnesium/calcium sulfate hemihydrate (Mg/CSH composite with improved properties was reported here. Methods. Composition, setting time, injectability, compressive strength, and bioactivity in simulated body fluid (SBF of the Mg/CSH composite were evaluated. Furthermore, the cellular responses of canine bone marrow stromal cells (cBMSCs and bone formation capacity after the implantation of Mg/CSH in tibia defects of canine were investigated. Results. Mg/CSH possessed a prolonged setting time and markedly improved injectability and mechanical property p<0.05. Mg/CSH samples showed better degradability than CSH in SBF after 21 days of soaking p<0.05. Moreover, the degrees of cell attachment, proliferation, and capability of osteogenic differentiation on the Mg/CSH specimens were higher than those on CSH, without significant cytotoxicity and with the increased proliferation index, ALP activity, and expression levels of integrin β1 and Coll I in cBMSCs p<0.05. Mg/CSH enhanced the efficiency of new bone formation at the tibia defect area, including the significantly elevated bone mineral density, bone area fraction, and Coll I expression level p<0.05. Conclusions. The results implied that this new injectable bone scaffold exhibited promising prospects for bone repair and had a great potential in bone tissue engineering.

  3. Effects of adding resorbable chitosan microspheres to calcium phosphate cements for bone regeneration

    Energy Technology Data Exchange (ETDEWEB)

    Meng, Dan [Department of Prosthodontics, Beijing Stomatological Hospital, Capital Medical University, Beijing 100050 (China); Dong, Limin [Beijing Key Lab of Fine Ceramics, Institute of Nuclear and New Energy Technology, Tsinghua University, Energy Science Building, Beijing 100084 (China); Wen, Ying [Department of Prosthodontics, Beijing Stomatological Hospital, Capital Medical University, Beijing 100050 (China); Xie, Qiufei, E-mail: xieqiuf@163.com [Department of Prosthodontics, Peking University School and Hospital of Stomatology, Beijing 100081 (China)

    2015-02-01

    Calcium phosphate cements (CPCs) have been widely used as bone graft substitutes. However, the undesirable osteoinductivity and slow degradability of CPCs greatly hamper their clinical application. The aim of this study was to synthesize a type of injectable, bioactive cement. This was accomplished by incorporating chitosan microspheres into CPC. CPC containing chitosan microspheres was analyzed by X-ray diffraction (XRD) and scanning electron microscope (SEM). XRD showed that the hardened chitosan microsphere/CPC with different proportions of microspheres contained diffraction peaks of hydroxyapatite and chitosan. Compressive strength and dissolution in simulated body fluid were measured. The chitosan microsphere/CPC containing 10% (w/w) chitosan microspheres had a compressive strength of 14.78 ± 0.67 MPa. Cavity defects were created in both femoral condylar regions of New Zealand White rabbits. Chitosan microsphere/CPC (composite group) and α-TCP/CPC (control group) were implanted separately into the bone defects of both femurs. X-ray analysis was performed to observe the filling of these bone defects 3 days after surgery. The extent of bone substitute degradation and new bone formation were evaluated by SEM and histological examination at 8, 16, and 24 weeks after implantation. These results showed far more new bone formation and degradation of the chitosan microsphere/CPC composite in the bone defects. These data indicate that a chitosan microsphere/CPC composite might be considered as a promising injectable material for the generation of new bone tissue. - Highlights: • We synthesized an injectable, bioactive chitosan microsphere/CPC for the first time. • 100–400 μm chitosan microspheres were incorporated into the cement solid phase. • XRD showed the construct contained diffraction peaks of hydroxyapatite and chitosan. • Compressive strength of the composite was about 15 MPa comparable to cancellous bone. • The new construct shows better bone

  4. Effects of adding resorbable chitosan microspheres to calcium phosphate cements for bone regeneration

    International Nuclear Information System (INIS)

    Calcium phosphate cements (CPCs) have been widely used as bone graft substitutes. However, the undesirable osteoinductivity and slow degradability of CPCs greatly hamper their clinical application. The aim of this study was to synthesize a type of injectable, bioactive cement. This was accomplished by incorporating chitosan microspheres into CPC. CPC containing chitosan microspheres was analyzed by X-ray diffraction (XRD) and scanning electron microscope (SEM). XRD showed that the hardened chitosan microsphere/CPC with different proportions of microspheres contained diffraction peaks of hydroxyapatite and chitosan. Compressive strength and dissolution in simulated body fluid were measured. The chitosan microsphere/CPC containing 10% (w/w) chitosan microspheres had a compressive strength of 14.78 ± 0.67 MPa. Cavity defects were created in both femoral condylar regions of New Zealand White rabbits. Chitosan microsphere/CPC (composite group) and α-TCP/CPC (control group) were implanted separately into the bone defects of both femurs. X-ray analysis was performed to observe the filling of these bone defects 3 days after surgery. The extent of bone substitute degradation and new bone formation were evaluated by SEM and histological examination at 8, 16, and 24 weeks after implantation. These results showed far more new bone formation and degradation of the chitosan microsphere/CPC composite in the bone defects. These data indicate that a chitosan microsphere/CPC composite might be considered as a promising injectable material for the generation of new bone tissue. - Highlights: • We synthesized an injectable, bioactive chitosan microsphere/CPC for the first time. • 100–400 μm chitosan microspheres were incorporated into the cement solid phase. • XRD showed the construct contained diffraction peaks of hydroxyapatite and chitosan. • Compressive strength of the composite was about 15 MPa comparable to cancellous bone. • The new construct shows better bone

  5. ECM Inspired Coating of Embroidered 3D Scaffolds Enhances Calvaria Bone Regeneration

    Directory of Open Access Journals (Sweden)

    C. Rentsch

    2014-01-01

    Full Text Available Resorbable polymeric implants and surface coatings are an emerging technology to treat bone defects and increase bone formation. This approach is of special interest in anatomical regions like the calvaria since adults lose the capacity to heal large calvarial defects. The present study assesses the potential of extracellular matrix inspired, embroidered polycaprolactone-co-lactide (PCL scaffolds for the treatment of 13 mm full thickness calvarial bone defects in rabbits. Moreover the influence of a collagen/chondroitin sulfate (coll I/cs coating of PCL scaffolds was evaluated. Defect areas filled with autologous bone and empty defects served as reference. The healing process was monitored over 6 months by combining a novel ultrasonographic method, radiographic imaging, biomechanical testing, and histology. The PCL coll I/cs treated group reached 68% new bone volume compared to the autologous group (100% and the biomechanical stability of the defect area was similar to that of the gold standard. Histological investigations revealed a significantly more homogenous bone distribution over the whole defect area in the PCL coll I/cs group compared to the noncoated group. The bioactive, coll I/cs coated, highly porous, 3-dimensional PCL scaffold acted as a guide rail for new skull bone formation along and into the implant.

  6. ECM inspired coating of embroidered 3D scaffolds enhances calvaria bone regeneration.

    Science.gov (United States)

    Rentsch, C; Rentsch, B; Heinemann, S; Bernhardt, R; Bischoff, B; Förster, Y; Scharnweber, D; Rammelt, S

    2014-01-01

    Resorbable polymeric implants and surface coatings are an emerging technology to treat bone defects and increase bone formation. This approach is of special interest in anatomical regions like the calvaria since adults lose the capacity to heal large calvarial defects. The present study assesses the potential of extracellular matrix inspired, embroidered polycaprolactone-co-lactide (PCL) scaffolds for the treatment of 13 mm full thickness calvarial bone defects in rabbits. Moreover the influence of a collagen/chondroitin sulfate (coll I/cs) coating of PCL scaffolds was evaluated. Defect areas filled with autologous bone and empty defects served as reference. The healing process was monitored over 6 months by combining a novel ultrasonographic method, radiographic imaging, biomechanical testing, and histology. The PCL coll I/cs treated group reached 68% new bone volume compared to the autologous group (100%) and the biomechanical stability of the defect area was similar to that of the gold standard. Histological investigations revealed a significantly more homogenous bone distribution over the whole defect area in the PCL coll I/cs group compared to the noncoated group. The bioactive, coll I/cs coated, highly porous, 3-dimensional PCL scaffold acted as a guide rail for new skull bone formation along and into the implant. PMID:25013767

  7. Minimal guided bone regeneration procedure for immediate implant placement in the esthetic zone

    Directory of Open Access Journals (Sweden)

    Nettemu Sunil Kumar

    2013-01-01

    Full Text Available The anterior maxilla presents a challenging milieu interior for ideal placement of implants because of the compromised bone quality. With the advent of intraoral bone harvesting and augmentation techniques, immediate implant placement into fresh extraction sockets have become more predictable. Immediate implant placement has numerous advantages compared to the delayed procedure including superior esthetic and functional outcomes, maintenance of soft and hard tissue integrity and increased patient compliance. This case report exhibits immediate implant placement in the maxillary esthetic zone by combining a minimal invasive autogenous block bone graft harvest technique for ensuring successful osseointegration of the implant at the extraction site.

  8. Collagen/hydroxyapatite scaffold enriched with polycaprolactone nanofibers, thrombocyte-rich solution and mesenchymal stem cells promotes regeneration in large bone defect in vivo

    Czech Academy of Sciences Publication Activity Database

    Prosecká, Eva; Rampichová, Michala; Litvinec, Andrej; Tonar, Z.; Králíčková, M.; Vojtová, L.; Kochová, P.; Plencner, Martin; Buzgo, Matej; Míčková, Andrea; Jančář, J.; Amler, Evžen

    2015-01-01

    Roč. 103, č. 2 (2015), s. 671-682. ISSN 1549-3296 Institutional support: RVO:68378041 Keywords : bone regeneration * mesenchymal stem cells * collagen/hydroxyapatite scaffold Subject RIV: FP - Other Medical Disciplines Impact factor: 3.369, year: 2014

  9. Novel osteoinductive photo-cross-linkable chitosan-lactide-fibrinogen hydrogels enhance bone regeneration in critical size segmental bone defects

    OpenAIRE

    Kim, Sungwoo; Bedigrew, Katherine; Guda, Teja; Maloney, William J.; Park, Sangwon; Wenke, Joseph C.; Yang, Yunzhi Peter

    2014-01-01

    The purpose of this study was to develop and characterize a novel photo-cross-linkable chitosan-lactide-fibrinogen (CLF) hydrogel and evaluate the efficacy of bone morphogenetic protein-2 (BMP-2) containing CLF hydrogel for osteogenesis in vitro and in vivo. We synthesized the CLF hydrogels and characterized their chemical structure, degradation rate, compressive modulus, and in vitro BMP-2 release kinetics. We evaluated bioactivities of the BMP-2 containing CLF hydrogels (0, 50, 100, and 500...

  10. Effect of preliminary fluorization on posttraumatic regeneration of bone tissue in combined radiation injury (external irradiation and fracture)

    International Nuclear Information System (INIS)

    Experiments with 65 male Wistar rats with body mass 0.160 0.180 kg were made. Preliminary fluorization has been carried out in the course of 3 months. Fluorine content, dissolved in drinking water as Na-fluoride, amounted to 4 mg/l. Every animal was given about 11 mg fluorine, which is equal to LD50/3. Immediately after fluorization a gamma irradiation (270 cGy) was made, followed by manually made fracture. On days 14, 21 and 28 after the fracture X-ray and histological studies were performed. The results showed that fluorization did not delay bone regeneration process. On the other hand, external irradiation with nonlethal doses delayed the process of callus formation

  11. Hydrogel/bioactive glass composites for bone regeneration applications: Synthesis and characterisation

    Energy Technology Data Exchange (ETDEWEB)

    Killion, John A., E-mail: jkillion@research.ait.ie [Materials Research Institute, Athlone Institute of Technology, Dublin Rd, Athlone, Co. Westmeath (Ireland); Kehoe, Sharon, E-mail: sh625116@dal.ca [Department of Applied Oral Sciences, Dalhousie University, Halifax, NS B3H 34R2 (Canada); Geever, Luke M., E-mail: lgeever@ait.ie [Materials Research Institute, Athlone Institute of Technology, Dublin Rd, Athlone, Co. Westmeath (Ireland); Devine, Declan M., E-mail: ddevine@ait.ie [Materials Research Institute, Athlone Institute of Technology, Dublin Rd, Athlone, Co. Westmeath (Ireland); Sheehan, Eoin, E-mail: eoinsheehan@aol.com [Department of Trauma and Orthopaedics, MRHT, Tullamore, Co. Offaly (Ireland); Boyd, Daniel, E-mail: d.boyd@dal.ca [Department of Applied Oral Sciences, Dalhousie University, Halifax, NS B3H 34R2 (Canada); Higginbotham, Clement L., E-mail: chigginbotham@ait.ie [Materials Research Institute, Athlone Institute of Technology, Dublin Rd, Athlone, Co. Westmeath (Ireland)

    2013-10-15

    Due to the deficiencies of current commercially available biological bone grafts, alternative bone graft substitutes have come to the forefront of tissue engineering in recent times. The main challenge for scientists in manufacturing bone graft substitutes is to obtain a scaffold that has sufficient mechanical strength and bioactive properties to promote formation of new tissue. The ability to synthesise hydrogel based composite scaffolds using photopolymerisation has been demonstrated in this study. The prepared hydrogel based composites were characterised using techniques including Fourier Transform Infrared Spectroscopy (FTIR), X-ray diffraction (XRD), scanning electron microscopy (SEM), Energy-dispersive X-ray spectrometry (EDX), rheological studies and compression testing. In addition, gel fraction, differential scanning calorimetry (DSC), thermogravimetric analysis (TGA), porosity and swelling studies of the composites were carried out. It was found that these novel hydrogel bioglass composite formulations did not display the inherent brittleness that is typically associated with bioactive glass based bone graft materials and exhibited enhanced biomechanical properties compared to the polyethylene glycol hydrogel scaffolds along. Together, the combination of enhanced mechanical properties and the deposition of apatite on the surface of these hydrogel based composites make them an ideal candidate as bone graft substitutes in cancellous bone defects or low load bearing applications. Highlights: • Young's modulus increases with the addition of bioactive glasses. • Hydrogel based composites formed an apatite layer in simulated body fluid. • Storage modulus increases with addition of bioactive glasses. • Compressive strength is dependent on molecular weight and bioactive glass loading.

  12. Hydrogel/bioactive glass composites for bone regeneration applications: Synthesis and characterisation

    International Nuclear Information System (INIS)

    Due to the deficiencies of current commercially available biological bone grafts, alternative bone graft substitutes have come to the forefront of tissue engineering in recent times. The main challenge for scientists in manufacturing bone graft substitutes is to obtain a scaffold that has sufficient mechanical strength and bioactive properties to promote formation of new tissue. The ability to synthesise hydrogel based composite scaffolds using photopolymerisation has been demonstrated in this study. The prepared hydrogel based composites were characterised using techniques including Fourier Transform Infrared Spectroscopy (FTIR), X-ray diffraction (XRD), scanning electron microscopy (SEM), Energy-dispersive X-ray spectrometry (EDX), rheological studies and compression testing. In addition, gel fraction, differential scanning calorimetry (DSC), thermogravimetric analysis (TGA), porosity and swelling studies of the composites were carried out. It was found that these novel hydrogel bioglass composite formulations did not display the inherent brittleness that is typically associated with bioactive glass based bone graft materials and exhibited enhanced biomechanical properties compared to the polyethylene glycol hydrogel scaffolds along. Together, the combination of enhanced mechanical properties and the deposition of apatite on the surface of these hydrogel based composites make them an ideal candidate as bone graft substitutes in cancellous bone defects or low load bearing applications. Highlights: • Young's modulus increases with the addition of bioactive glasses. • Hydrogel based composites formed an apatite layer in simulated body fluid. • Storage modulus increases with addition of bioactive glasses. • Compressive strength is dependent on molecular weight and bioactive glass loading

  13. Zebrafish sp7:EGFP: a transgenic for studying otic vesicle formation, skeletogenesis, and bone regeneration

    Science.gov (United States)

    DeLaurier, April; Eames, B. Frank; Blanco-Sánchez, Bernardo; Peng, Gang; He, Xinjun; Swartz, Mary E.; Ullmann, Bonnie; Westerfield, Monte; Kimmel, Charles B.

    2010-01-01

    Summary We report the expression pattern and construction of a transgenic zebrafish line for a transcription factor involved in otic vesicle formation and skeletogenesis. The zinc finger transcription factor sp7 (formerly called osterix) is reported as a marker of osteoblasts. Using bacterial artificial chromosome (BAC)-mediated transgenesis, we generated a zebrafish transgenic line for studying skeletal development, Tg(sp7:EGFP)b1212. Using a zebrafish BAC, EGFP was introduced downstream of the regulatory regions of sp7 and injected into 1 cell-stage embryos. In this transgenic line, GFP expression reproduces endogenous sp7 gene expression in the otic placode and vesicle, and in forming skeletal structures. GFP-positive cells were also detected in adult fish, and were found associated with regenerating fin rays post-amputation. This line provides an essential tool for the further study of zebrafish otic vesicle formation and the development and regeneration of the skeleton. PMID:20506187

  14. Bone marrow mesenchymal stem cell aggregate: an optimal cell therapy for full-layer cutaneous wound vascularization and regeneration

    Science.gov (United States)

    An, Yulin; wei, Wei; Jing, Huan; Ming, Leiguo; Liu, Shiyu; Jin, Yan

    2015-01-01

    Cutaneous wounds are among the most common soft tissue injuries. Wounds involving dermis suffer more from outside influence and higher risk of chronic inflammation. Therefore the appearance and function restoration has become an imperative in tissue engineering research. In this study, cell-aggregates constructed with green fluorescent protein-expressing (GFP+) rat bone marrow mesenchymal stem cells (BMMSCs) were applied to rat acute full-layer cutaneous wound model to confirm its pro-regeneration ability and compare its regenerative efficacy with the currently thriving subcutaneous and intravenous stem cell administration strategy, with a view to sensing the advantages, disadvantages and the mechanism behind. According to results, cell-aggregates cultured in vitro enjoyed higher expression of several pro-healing genes than adherent cultured cells. Animal experiments showed better vascularization along with more regular dermal collagen deposition for cell-aggregate transplanted models. Immunofluorescence staining on inflammatory cells indicated a shorter inflammatory phase for cell-aggregate group, which was backed up by further RT-PCR. The in situ immunofluorescence staining manifested a higher GFP+-cell engraftment for cell-aggregate transplanted models versus cell administered ones. Thus it is safe to say the BMMSCs aggregate could bring superior cutaneous regeneration for full layer cutaneous wound to BMMSCs administration, both intravenous and subcutaneous. PMID:26594024

  15. Synergistic intrafibrillar/extrafibrillar mineralization of collagen scaffolds based on a biomimetic strategy to promote the regeneration of bone defects

    Directory of Open Access Journals (Sweden)

    Wang Y

    2016-05-01

    Full Text Available Yao Wang,1 Ngo Van Manh,1,2 Haorong Wang,1 Xue Zhong,1 Xu Zhang,1 Changyi Li1 1School of Dentistry, Hospital of Stomatology, Tianjin Medical University, Tianjin, People’s Republic of China; 2Thaibinh University of Medicine and Pharmacy, Thaibinh, Vietnam Abstract: The mineralization of collagen scaffolds can improve their mechanical properties and biocompatibility, thereby providing an appropriate microenvironment for bone regeneration. The primary purpose of the present study is to fabricate a synergistically intra- and extrafibrillar mineralized collagen scaffold, which has many advantages in terms of biocompatibility, biomechanical properties, and further osteogenic potential. In this study, mineralized collagen scaffolds were fabricated using a traditional mineralization method (ie, immersed in simulated body fluid as a control group and using a biomimetic method based on the polymer-induced liquid precursor process as an experimental group. In the polymer-induced liquid precursor process, a negatively charged polymer, carboxymethyl chitosan (CMC, was used to stabilize amorphous calcium phosphate (ACP to form nanocomplexes of CMC/ACP. Collagen scaffolds mineralized based on the polymer-induced liquid precursor process were in gel form such that nanocomplexes of CMC/ACP can easily be drawn into the interstices of the collagen fibrils. Scanning electron microscopy and transmission electron microscopy were used to examine the porous micromorphology and synergistic mineralization pattern of the collagen scaffolds. Compared with simulated body fluid, nanocomplexes of CMC/ACP significantly increased the modulus of the collagen scaffolds. The results of in vitro experiments showed that the cell count and differentiated degrees in the experimental group were higher than those in the control group. Histological staining and micro-computed tomography showed that the amount of new bone regenerated in the experimental group was larger than that in the

  16. Synergistic intrafibrillar/extrafibrillar mineralization of collagen scaffolds based on a biomimetic strategy to promote the regeneration of bone defects

    Science.gov (United States)

    Wang, Yao; Van Manh, Ngo; Wang, Haorong; Zhong, Xue; Zhang, Xu; Li, Changyi

    2016-01-01

    The mineralization of collagen scaffolds can improve their mechanical properties and biocompatibility, thereby providing an appropriate microenvironment for bone regeneration. The primary purpose of the present study is to fabricate a synergistically intra- and extrafibrillar mineralized collagen scaffold, which has many advantages in terms of biocompatibility, biomechanical properties, and further osteogenic potential. In this study, mineralized collagen scaffolds were fabricated using a traditional mineralization method (ie, immersed in simulated body fluid) as a control group and using a biomimetic method based on the polymer-induced liquid precursor process as an experimental group. In the polymer-induced liquid precursor process, a negatively charged polymer, carboxymethyl chitosan (CMC), was used to stabilize amorphous calcium phosphate (ACP) to form nanocomplexes of CMC/ACP. Collagen scaffolds mineralized based on the polymer-induced liquid precursor process were in gel form such that nanocomplexes of CMC/ACP can easily be drawn into the interstices of the collagen fibrils. Scanning electron microscopy and transmission electron microscopy were used to examine the porous micromorphology and synergistic mineralization pattern of the collagen scaffolds. Compared with simulated body fluid, nanocomplexes of CMC/ACP significantly increased the modulus of the collagen scaffolds. The results of in vitro experiments showed that the cell count and differentiated degrees in the experimental group were higher than those in the control group. Histological staining and micro-computed tomography showed that the amount of new bone regenerated in the experimental group was larger than that in the control group. The biomimetic mineralization will assist us in fabricating a novel collagen scaffold for clinical applications. PMID:27274235

  17. In vivo experimental study on bone regeneration in critical bone defects using PIB nanogels/boron-containing mesoporous bioactive glass composite scaffold

    Directory of Open Access Journals (Sweden)

    Chen XH

    2015-01-01

    Full Text Available Xiaohui Chen,1,2,* Yanbing Zhao,3,* Shinan Geng,3 Richard J Miron,1 Qiao Zhang,1 Chengtie Wu,4 Yufeng Zhang1,2 1State Key Laboratory Breeding Base of Basic Science of Stomatology (Hubei-MOST and Key Laboratory of Oral Biomedicine Ministry of Education, School and Hospital of Stomatology, Wuhan University, People’s Republic of China; 2Department of Dental Implantology, School and Hospital of Stomatology, Wuhan University, People’s Republic of China; 3National Engineering Research Center for Nanomedicine, College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan, People’s Republic of China; 4State Key Laboratory of High Performance Ceramics and Superfine Microstructure, Shanghai Institute of Ceramics, Chinese Academy of Sciences, Shanghai, People’s Republic of China *These authors contributed equally to this work Purpose: In the present study, the fabrication of novel p(N-isopropylacrylamide-co-butyl methylacrylate (PIB nanogels was combined with boron-containing mesoporous bioactive glass (B-MBG scaffolds in order to improve the mechanical properties of PIB nanogels alone. Scaffolds were tested for mechanical strength and the ability to promote new bone formation in vivo.Patients and methods: To evaluate the potential of each scaffold in bone regeneration, ovariectomized rats were chosen as a study model to determine the ability of PIB nanogels to stimulate bone formation in a complicated anatomical bone defect. PIB nanogels and PIB nanogels/B-MBG composites were respectively implanted into ovariectomized rats with critical-sized femur defects following treatment periods of 2, 4, and 8 weeks post-implantation.Results: Results from the present study demonstrate that PIB nanogels/B-MBG composites showed greater improvement in mechanical strength when compared to PIB nanogels alone. In vivo, hematoxylin and eosin staining revealed significantly more newly formed bone in defects containing PIB

  18. Regeneration of a Compromized Masticatory Unit in a Large Mandibular Defect Caused by a Huge Solitary Bone Cyst: A Case Report and Review of the Regenerative Literature.

    Science.gov (United States)

    Muhammad, Joseph Kamal; Akhtar, Shakeel; Abu Al Nassar, Hiba; Al Khoury, Nabil

    2016-07-01

    The reconstructive options for large expansive cystic lesion affecting the jaws are many. The first stage of treatment may involve enucleation or marsupialization of the cyst. Attempted reconstruction of large osseous defects arising from the destruction of local tissue can present formidable challenges. The literature reports the use of bone grafts, free tissue transfer, bone morphogenic protein and reconstruction plates to assist in the healing and rehabilitation process. The management of huge mandibular cysts needs to take into account the preservation of existing intact structures, removal of the pathology and the reconstructive objectives which focus both on aesthetic and functional rehabilitation. The planning and execution of such treatment requires not only the compliance of the patient and family but also their assent as customers with a voice in determining their surgical destiny. The authors would like to report a unique case of a huge solitary bone cyst that had reduced the ramus, angle and part of the body of one side of the mandible to a pencil-thin-like strut of bone. A combination of decompression through marsupialization, serial packing, and the fabrication of a custom made obturator facilitated the regeneration of the myo-osseous components of the masticatory unit of this patient. Serial CT scans showed evidence of concurrent periosteal and endosteal bone formation and, quite elegantly, the regeneration of the first branchial arch components of the right myo-osseous masticatory complex. The microenvironmental factors that may have favored regeneration of these complex structures are discussed. PMID:27408457

  19. Bacterial cellulose-hydroxyapatite composites with osteogenic growth peptide (OGP) or pentapeptide OGP on bone regeneration in critical-size calvarial defect model.

    Science.gov (United States)

    Pigossi, Suzane C; de Oliveira, Guilherme J P L; Finoti, Livia S; Nepomuceno, Rafael; Spolidorio, Luis Carlos; Rossa, C; Ribeiro, Sidney J L; Saska, Sybele; Scarel-Caminaga, Raquel M

    2015-10-01

    This study aimed to evaluate the potential of bacterial cellulose-hydroxyapatite (BC-HA) composites associated with osteogenic growth peptide (OGP) or pentapeptide OGP(10-14) in bone regeneration in critical-size calvarial defects in mice. In this study, the BC-HA, BC-HA-OGP, and BC-HA-OGP(10-14) membranes were analyzed at 3, 7, 15, 30, 60, and 90 days. In each period, the specimens were evaluated by micro-computed tomography (µCT), descriptive histology, gene expression of bone biomarkers by qPCR and VEGFR-2 (vascular endothelial growth factor) quantification by ELISA. Three days post-operative, Runx2, Tnfrsf11b and Bglap bone biomarkers were upregulated mainly by BC-HA OGP and BC-HA OGP(10-14) membranes, suggesting an acceleration of the osteoblast differentiation/activity with the use of these biomaterials. At 60 and 90 days, a high percentage of bone formation was observed by µCT for BC-HA and BC-HA OGP(10-14) membranes. High expression of some bone biomarkers, such as Alpl, Spp1, and Tnfrsf11b, was also observed for the same membranes on days 60 and 90. In conclusion, the BC-HA membrane promoted a better bone formation in critical-size mice calvarial defects. Nevertheless, incorporation of the peptides at the concentration of 10(-9) mol L(-1) did not improve bone regeneration potential in the long-term. PMID:25850694

  20. Enhanced differentiation of osteoblastic cells on novel chitosan/β-1,3-glucan/bioceramic scaffolds for bone tissue regeneration

    International Nuclear Information System (INIS)

    Bone scaffolds for regenerative medicine applications should have the ability to promote adhesion, proliferation and differentiation of osteoblast cells. Osteoconductive, osteoinductive and osteopromotive properties of the material are essential for rapid bone regeneration and new bone formation. In this study, the osteogenic potential of two novel tri-component scaffolds composed of krill chitosan, bacterial β-1,3-glucan and bioceramics (HAp or a mix of HAp/β-TCP granules) was investigated. The typical markers of the first (type I collagen), second (bone alkaline phosphatase) and third stages (osteocalcin) of the osteoblast differentiation process were evaluated during in vitro experimentation. The study was carried out using three various osteoblastic cell lines (normal human fetal osteoblast cells hFOB 1.19, human osteoblast-like cells derived from osteosarcoma Saos-2 and mouse calvarial preosteoblast cells MC3T3-E1 Subclone 4). The bone alkaline phosphatase (bALP) and osteocalcin (OC) were determined quantitatively using enzyme-linked immunosorbent assays, and type I collagen (Col I) was evaluated qualitatively using the direct immunofluorescence (DIF) method. The data obtained clearly prove that novel scaffolds have the ability to increase bALP activity, to enhance extracellular matrix synthesis (Col I and OC) and to induce mineralized nodule formation during osteogenic differentiation. In conclusion, novel tri-component materials have osteoconductive and osteopromotive properties, and thus are promising materials in bone tissue engineering applications to accelerate the bone regeneration process. (paper)

  1. A novel open-porous magnesium scaffold with controllable microstructures and properties for bone regeneration

    Science.gov (United States)

    Cheng, Meng-Qi; Wahafu, Tuerhongjiang; Jiang, Guo-Feng; Liu, Wei; Qiao, Yu-Qin; Peng, Xiao-Chun; Cheng, Tao; Zhang, Xian-Long; He, Guo; Liu, Xuan-Yong

    2016-04-01

    The traditional production methods of porous magnesium scaffolds are difficult to accurately control the pore morphologies and simultaneously obtain appropriate mechanical properties. In this work, two open-porous magnesium scaffolds with different pore size but in the nearly same porosity are successfully fabricated with high-purity Mg ingots through the titanium wire space holder (TWSH) method. The porosity and pore size can be easily, precisely and individually controlled, as well as the mechanical properties also can be regulated to be within the range of human cancellous bone by changing the orientation of pores without sacrifice the requisite porous structures. In vitro cell tests indicate that the scaffolds have good cytocompatibility and osteoblastic differentiation properties. In vivo findings demonstrate that both scaffolds exhibit acceptable inflammatory responses and can be almost fully degraded and replaced by newly formed bone. More importantly, under the same porosity, the scaffolds with larger pore size can promote early vascularization and up-regulate collagen type 1 and OPN expression, leading to higher bone mass and more mature bone formation. In conclusion, a new method is introduced to develop an open-porous magnesium scaffold with controllable microstructures and mechanical properties, which has great potential clinical application for bone reconstruction in the future.

  2. Different bone regeneration patterns in periimplant circumferential gap defects grafted with two types of osteoconductive biomaterial.

    Science.gov (United States)

    Lee, Jung-Seok; Sohn, Joo-Yeon; Lim, Hyun-Chang; Jung, Ui-Won; Choi, Seong-Ho

    2016-08-01

    This study aimed to determine healing patterns in periimplant gap defect grafted with demineralized bovine bone mineral (DBBM) and porous titanium granules (PTG), which are known to induce a minimal tissue reaction and to undergo minimal biodegradation in healing process. Experiments were performed using a standardized periimplant gap-defect model in dogs with two observational periods: 4 and 8 weeks. Circumferential defects were surgically induced around dental implants on unilateral mandibles in five dogs, and collagen barrier membranes were placed over the DBBM and PTG grafts at two experimental sites and over a nongrafted site. Four weeks later, the same procedures were performed on the contralateral mandible, and the animals allowed to heal for a further 4 weeks, after which they were sacrificed and their mandibles with graft/control sites harvested for histologic evaluation. Both types of grafted biomaterials significantly enhanced the defect fill with newly formed bone, but the bone-to-implant contact (BIC) was significantly increased only at sites that had been grafted with DBBM. The two experimental sites exhibited different healing patterns, with new bone formation being observed on the surface of the DBBM particles throughout the defect, while there was no de novo bone formation on the PTG surface, but rather appositional bone growth from the base and lateral walls of the defect. It has been suggested that gap-defect filling with DBBM around dental implants may enhance both BIC and defect fill; however, the present findings show that defect grafting with PTG enhances only defect fill and not BIC. © 2015 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 104B: 1202-1209, 2016. PMID:26087247

  3. Low-Temperature Additive Manufacturing of Biomimic Three-Dimensional Hydroxyapatite/Collagen Scaffolds for Bone Regeneration.

    Science.gov (United States)

    Lin, Kai-Feng; He, Shu; Song, Yue; Wang, Chun-Mei; Gao, Yi; Li, Jun-Qin; Tang, Peng; Wang, Zheng; Bi, Long; Pei, Guo-Xian

    2016-03-23

    Low-temperature additive manufacturing (AM) holds promise for fabrication of three-dimensional (3D) scaffolds containing bioactive molecules and/or drugs. Due to the strict technical limitations of current approaches, few materials are suitable for printing at low temperature. Here, a low-temperature robocasting method was employed to print biomimic 3D scaffolds for bone regeneration using a routine collagen-hydroxyapatite (CHA) composite material, which is too viscous to be printed via normal 3D printing methods at low temperature. The CHA scaffolds had excellent 3D structure and maintained most raw material properties after printing. Compared to nonprinted scaffolds, printed scaffolds promoted bone marrow stromal cell proliferation and improved osteogenic outcome in vitro. In a rabbit femoral condyle defect model, the interconnecting pores within the printed scaffolds facilitated cell penetration and mineralization before the scaffolds degraded and enhanced repair, compared to nonprinted CHA scaffolds. Additionally, the optimal printing parameters for 3D CHA scaffolds were investigated; 600-μm-diameter rods were optimal in terms of moderate mechanical strength and better repair outcome in vivo. This low-temperature robocasting method could enable a variety of bioactive molecules to be incorporated into printed CHA materials and provides a method of bioprinting biomaterials without compromising their natural properties. PMID:26930140

  4. ToF-SIMS evaluation of calcium-containing silica/γ-PGA hybrid systems for bone regeneration

    Science.gov (United States)

    Wang, Daming; Nakamura, Jin; Poologasundarampillai, Gowsihan; Kasuga, Toshihiro; Jones, Julian R.; McPhail, David S.

    2014-08-01

    Inorganic/organic hybrids have great potential for the production of bioactive scaffolds which have tailored mechanical properties and degradation rates suitable for tissue engineering. For bone regeneration, calcium incorporation into hybrids at low temperatures is important due to its ability to stimulate new bone formation. As a consequence, understanding the homogeneity of the critical inorganic and organic components will be the key to the development of such hybrids. The aim of this interdisciplinary study was to use time-of-flight secondary ion mass spectrometry (ToF-SIMS) to determine the homogeneity of these critical components. We evaluated various sol-gel silica/γ-polyglutamic acid (γ-PGA) hybrid systems produced using different routes to introduce the calcium, thereby tailoring and optimizing hybrid syntheses and processing routes. Dimethyl carbonate (DMC) was used to improve the inorganic/organic coupling and its influence on the homogeneity of the hybrid structures was also examined. The results revealed that the calcium salt form of γ-PGA was promising for calcium incorporation since homogeneous products could be obtained. The ToF-SIMS data also indicated that the reaction time of hybrid synthesis and the timing of the addition of DMC can affect the homogeneity of hybrids.

  5. Integration of Rabbit Adipose Derived Mesenchymal Stem Cells to Hydroxyapatite Burr Hole Button Device for Bone Interface Regeneration

    Science.gov (United States)

    Gayathri, Viswanathan; Harikrishnan, Varma; Mohanan, Parayanthala Valappil

    2016-01-01

    Adipose Derived Mesenchymal Stem Cells, multipotent stem cells isolated from adipose tissue, present close resemblance to the natural in vivo milieu and microenvironment of bone tissue and hence widely used for in bone tissue engineering applications. The present study evaluates the compatibility of tissue engineered hydroxyapatite burr hole button device (HAP-BHB) seeded with Rabbit Adipose Derived Mesenchymal Stem Cells (ADMSCs). Cytotoxicity, oxidative stress response, apoptotic behavior, attachment, and adherence of adipose MSC seeded on the device were evaluated by scanning electron and confocal microscopy. The results of the MTT (3-(4,5-dimethylthiazol)-2,5-diphenyl tetrazolium bromide) assay indicated that powdered device material was noncytotoxic up to 0.5 g/mL on cultured cells. It was also observed that oxidative stress related reactive oxygen species production and apoptosis on cell seeded device were similar to those of control (cells alone) except in 3-day period which showed increased reactive oxygen species generation. Further scanning electron and confocal microscopy indicated a uniform attachment of cells and viability up to 200 μm deep inside the device, respectively. Based on the results, it can be concluded that the in-house developed HAP-BHB device seeded with ADMSCs is nontoxic/safe compatible device for biomedical application and an attractive tissue engineered device for calvarial defect regeneration. PMID:26880922

  6. A composite scaffold of MSC affinity peptide-modified demineralized bone matrix particles and chitosan hydrogel for cartilage regeneration

    Science.gov (United States)

    Meng, Qingyang; Man, Zhentao; Dai, Linghui; Huang, Hongjie; Zhang, Xin; Hu, Xiaoqing; Shao, Zhenxing; Zhu, Jingxian; Zhang, Jiying; Fu, Xin; Duan, Xiaoning; Ao, Yingfang

    2015-12-01

    Articular cartilage injury is still a significant challenge because of the poor intrinsic healing potential of cartilage. Stem cell-based tissue engineering is a promising technique for cartilage repair. As cartilage defects are usually irregular in clinical settings, scaffolds with moldability that can fill any shape of cartilage defects and closely integrate with the host cartilage are desirable. In this study, we constructed a composite scaffold combining mesenchymal stem cells (MSCs) E7 affinity peptide-modified demineralized bone matrix (DBM) particles and chitosan (CS) hydrogel for cartilage engineering. This solid-supported composite scaffold exhibited appropriate porosity, which provided a 3D microenvironment that supports cell adhesion and proliferation. Cell proliferation and DNA content analysis indicated that the DBM-E7/CS scaffold promoted better rat bone marrow-derived MSCs (BMMSCs) survival than the CS or DBM/CS groups. Meanwhile, the DBM-E7/CS scaffold increased matrix production and improved chondrogenic differentiation ability of BMMSCs in vitro. Furthermore, after implantation in vivo for four weeks, compared to those in control groups, the regenerated issue in the DBM-E7/CS group exhibited translucent and superior cartilage-like structures, as indicated by gross observation, histological examination, and assessment of matrix staining. Overall, the functional composite scaffold of DBM-E7/CS is a promising option for repairing irregularly shaped cartilage defects.

  7. Fabrication of polycaprolactone collagen hydrogel constructs seeded with mesenchymal stem cells for bone regeneration

    Energy Technology Data Exchange (ETDEWEB)

    Reichert, J C; Berner, A [Institute of Health and Biomedical Innovation, Queensland University of Technology, Brisbane (Australia); Heymer, A; Eulert, J; Noeth, U, E-mail: johannes.reichert@qut.edu.a [Orthopaedic Institute, Division of Tissue Engineering, Koenig-Ludwig-Haus, Julius-Maximilians-University, Wuerzburg (Germany)

    2009-12-15

    The osteogenic differentiation of bone marrow-derived human mesenchymal stem cells (MSCs) in a collagen I hydrogel was investigated. Collagen hydrogels with 7.5 x 10{sup 5} MSCs ml{sup -1} were fabricated and cultured for 6 weeks in a defined, osteogenic differentiation medium. Histochemistry revealed morphologically distinct, chondrocyte-like cells, surrounded by a sulfated proteoglycan-rich extracellular matrix in the group treated with bone morphogenetic protein 2 (BMP-2), while cells cultured with dexamethasone, ascorbate-2-phosphate, and beta-glycerophosphate displayed a spindle-shaped morphology and deposited a mineralized matrix. Real-time polymerase chain reaction (RT-PCR) analyses revealed a specific chondrogenic differentiation with the expression of cartilage-specific markers in the BMP-2-treated group and a distinct expression pattern of the osteogenic markers alkaline phosphatase (ALP), type I collagen, osteocalcin (OC), and cbfa-1 in the group treated with an osteogenic standard medium. The collagen gels were used to engineer a cell laden medical grade epsilon-polycaprolactone (PCL)-hydrogel construct for segmental bone repair showing good bonding at the scaffold hydrogel interface and even cell distribution. The results show that MSCs cultured in a collagen I hydrogel are able to undergo a distinct osteogenic differentiation pathway when stimulated with specific differentiation factors and suggest that collagen I hydrogels are a suitable means to facilitate cell seeding of scaffolds for bone tissue engineering applications.

  8. Fabrication of polycaprolactone collagen hydrogel constructs seeded with mesenchymal stem cells for bone regeneration

    International Nuclear Information System (INIS)

    The osteogenic differentiation of bone marrow-derived human mesenchymal stem cells (MSCs) in a collagen I hydrogel was investigated. Collagen hydrogels with 7.5 x 105 MSCs ml-1 were fabricated and cultured for 6 weeks in a defined, osteogenic differentiation medium. Histochemistry revealed morphologically distinct, chondrocyte-like cells, surrounded by a sulfated proteoglycan-rich extracellular matrix in the group treated with bone morphogenetic protein 2 (BMP-2), while cells cultured with dexamethasone, ascorbate-2-phosphate, and β-glycerophosphate displayed a spindle-shaped morphology and deposited a mineralized matrix. Real-time polymerase chain reaction (RT-PCR) analyses revealed a specific chondrogenic differentiation with the expression of cartilage-specific markers in the BMP-2-treated group and a distinct expression pattern of the osteogenic markers alkaline phosphatase (ALP), type I collagen, osteocalcin (OC), and cbfa-1 in the group treated with an osteogenic standard medium. The collagen gels were used to engineer a cell laden medical grade ε-polycaprolactone (PCL)-hydrogel construct for segmental bone repair showing good bonding at the scaffold hydrogel interface and even cell distribution. The results show that MSCs cultured in a collagen I hydrogel are able to undergo a distinct osteogenic differentiation pathway when stimulated with specific differentiation factors and suggest that collagen I hydrogels are a suitable means to facilitate cell seeding of scaffolds for bone tissue engineering applications.

  9. Enhanced bone regeneration with carbon nanotube reinforced hydroxyapatite in animal model.

    Science.gov (United States)

    Mukherjee, Susmita; Nandi, Samit Kumar; Kundu, Biswanath; Chanda, Abhijit; Sen, Swarnendu; Das, Pradip Kumar

    2016-07-01

    In order to improve the inherently poor mechanical properties of hydroxyapatite (HAp) and to increase its feasibility as load bearing implant material, in the present investigation, functionalised (HFC1 and HFC2) and non-functionalized (HC1 and HC2) multi-walled carbon nanotubes were used as reinforcing material with HAp. Significant improvement with respect to fracture toughness, flexural strength and impact strength of the composites was noticed. In vitro biological properties of HAp-carbon nanotube (CNT) biocomposites have also favored uniform and systematic apatite growth on their surface. Subsequently, in vivo osseous ingrowth at bone defect of rabbit femur was evaluated and compared using radiology, push out test, fluorochrome labeling, histology and scanning electron microscopy after 2 and 4 months respectively. The results demonstrated growth of web like soft callus from the host bone towards the implant, ensuring strong host bone interaction. Toxicological studies of the liver and kidney cells exhibited no abnormality, thereby confirming non-toxicity of the CNT in the animal body. Host-implant biomechanical strength showed high interfacial strength of the composites, indicating their high potentials to be used for bone remodeling applications. PMID:26907099

  10. Guided bone regeneration in distal mandibular atrophy by means of a preformed titanium foil: a case series.

    Science.gov (United States)

    Andreasi Bassi, M; Andrisani, C; Lopez, M A; Gaudio, R M; Lombardo, L; Lauritano, D

    2016-01-01

    The aim of this case series was to evaluate the clinical outcome of preformed titanium foil (PTF) to perform guided bone regeneration (GBR) in posterior mandibular atrophies. Thirteen patients (4 male; 9 female; mean age 58.85±10.16 years), with class II division C atrophy, according to Misch, were selected to perform GBR by means of PTF, using a moldable allograft paste as graft material. The devices, made of a 0.2mm thick pure titanium foil, were pre-shaped using stereolithographic models obtained from CT-scan of the patients’ recipient sites. In the second stage, performed at 6.35±2.15 months, 23 cylindrical two-piece implants were placed and the devices removed. At four months, the implants were exposed and submitted to progressive prosthetic load for a span of 4 months. The cases were finalized by means of metal-ceramic cementable restorations. The post finalization follow-up was at 12 months. Survival rate (i.e. SVR) was 100% since no fixtures were lost. At the one-year follow up, the clinical appearance of the soft tissues was optimal and no pathological signs on probing were recorded. The success rate (i.e. SCR) was 82.6% and the average peri-implant bone reabsorption was 0.99±0.59 mm. The results suggest good potentialities of this method for bone volume augmentation in distal mandibular atrophies, allowing to maximize the outcome and simplifying the surgical phase. PMID:27469550

  11. Improved bioactivity of selective laser melting titanium: Surface modification with micro-/nano-textured hierarchical topography and bone regeneration performance evaluation.

    Science.gov (United States)

    Xu, Jia-Yun; Chen, Xian-Shuai; Zhang, Chun-Yu; Liu, Yun; Wang, Jing; Deng, Fei-Long

    2016-11-01

    Selective laser melting (SLM) titanium requires surface modification to improve its bioactivity. The microrough surface of it can be utilized as the micro primary substrate to create a micro-/nano-textured topography for improved bone regeneration. In this study, the microrough SLM titanium substrate was optimized by sandblasting, and nano-porous features of orderly arranged nanotubes and disorderly arranged nanonet were produced by anodization (SAN) and alkali-heat treatment (SAH), respectively. The results were compared with the control group of an untreated surface (native-SLM) and a microtopography only surface treated by acid etching (SLA). The effects of the different topographies on cell functions and bone formation performance were evaluated in vitro and in vivo. It was found that micro-/nano-textured topographies of SAN and SAH showed enhanced cell behaviour relative to the microtopography of SLA with significantly higher proliferation on the 1st, 3rd, 5th and 7th day (P<0.05) and higher total protein contents on the 14th day (P<0.05). In vivo, SAN and SAH formed more successively regenerated bone, which resulted in higher bone-implant contact (BIC%) and bone-bonding force than native-SLM and SLA. In addition, the three-dimensional nanonet of SAH was expected to be more similar to native extracellular matrix (ECM) and thus led to better bone formation. The alkaline phosphatase activity of SAH was significantly higher than the other three groups at an earlier stage of the 7th day (P<0.05) and the BIC% was nearly double that of native-SLM and SLA in the 8th week. In conclusion, the addition of nano-porous features on the microrough SLM titanium surface is effective in improving the bioactivity and bone regeneration performance, in which the ECM-like nanonet with a disorderly arranged biomimetic feature is suggested to be more efficient than nanotubes. PMID:27524017

  12. Effects of rhBMP-2 on Sandblasted and Acid Etched Titanium Implant Surfaces on Bone Regeneration and Osseointegration: Spilt-Mouth Designed Pilot Study

    Science.gov (United States)

    Kim, Nam-Ho; Lee, So-Hyoun; Ryu, Jae-Jun; Choi, Kyung-Hee; Huh, Jung-Bo

    2015-01-01

    This study was conducted to evaluate effects of rhBMP-2 applied at different concentrations to sandblasted and acid etched (SLA) implants on osseointegration and bone regeneration in a bone defect of beagle dogs as pilot study using split-mouth design. Methods. For experimental groups, SLA implants were coated with different concentrations of rhBMP-2 (0.1, 0.5, and 1 mg/mL). After assessment of surface characteristics and rhBMP-2 releasing profile, the experimental groups and untreated control groups (n = 6 in each group, two animals in each group) were placed in split-mouth designed animal models with buccal open defect. At 8 weeks after implant placement, implant stability quotients (ISQ) values were recorded and vertical bone height (VBH, mm), bone-to-implant contact ratio (BIC, %), and bone volume (BV, %) in the upper 3 mm defect areas were measured. Results. The ISQ values were highest in the 1.0 group. Mean values of VBH (mm), BIC (%), and BV (%) were greater in the 0.5 mg/mL and 1.0 mg/mL groups than those in 0.1 and control groups in buccal defect areas. Conclusion. In the open defect area surrounding the SLA implant, coating with 0.5 and 1.0 mg/mL concentrations of rhBMP-2 was more effective, compared with untreated group, in promoting bone regeneration and osseointegration. PMID:26504807

  13. The Axolotl Fibula as a Model for the Induction of Regeneration across Large Segment Defects in Long Bones of the Extremities.

    Directory of Open Access Journals (Sweden)

    Xiaoping Chen

    Full Text Available We tested the ability of the axolotl (Ambystoma mexicanum fibula to regenerate across segment defects of different size in the absence of intervention or after implant of a unique 8-braid pig small intestine submucosa (SIS scaffold, with or without incorporated growth factor combinations or tissue protein extract. Fractures and defects of 10% and 20% of the total limb length regenerated well without any intervention, but 40% and 50% defects failed to regenerate after either simple removal of bone or implanting SIS scaffold alone. By contrast, scaffold soaked in the growth factor combination BMP-4/HGF or in protein extract of intact limb tissue promoted partial or extensive induction of cartilage and bone across 50% segment defects in 30%-33% of cases. These results show that BMP-4/HGF and intact tissue protein extract can promote the events required to induce cartilage and bone formation across a segment defect larger than critical size and that the long bones of axolotl limbs are an inexpensive model to screen soluble factors and natural and synthetic scaffolds for their efficacy in stimulating this process.

  14. Gene delivery nanocarriers of bioactive glass with unique potential to load BMP2 plasmid DNA and to internalize into mesenchymal stem cells for osteogenesis and bone regeneration

    Science.gov (United States)

    Kim, Tae-Hyun; Singh, Rajendra K.; Kang, Min Sil; Kim, Joong-Hyun; Kim, Hae-Won

    2016-04-01

    The recent development of bioactive glasses with nanoscale morphologies has spurred their specific applications in bone regeneration, for example as drug and gene delivery carriers. Bone engineering with stem cells genetically modified with this unique class of nanocarriers thus holds great promise in this avenue. Here we report the potential of the bioactive glass nanoparticle (BGN) system for the gene delivery of mesenchymal stem cells (MSCs) targeting bone. The composition of 15% Ca-added silica, proven to be bone-bioactive, was formulated into surface aminated mesoporous nanospheres with enlarged pore sizes, to effectively load and deliver bone morphogenetic protein-2 (BMP2) plasmid DNA. The enlarged mesopores were highly effective in loading BMP2-pDNA with an efficiency as high as 3.5 wt% (pDNA w.r.t. BGN), a level more than twice than for small-sized mesopores. The BGN nanocarriers released the genetic molecules in a highly sustained manner (for as long as 2 weeks). The BMP2-pDNA/BGN complexes were effectively internalized to rat MSCs with a cell uptake level of ~73%, and the majority of cells were transfected to express the BMP2 protein. Subsequent osteogenesis of the transfected MSCs was demonstrated by the expression of bone-related genes, including bone sialoprotein, osteopontin, and osteocalcin. The MSCs transfected with BMP2-pDNA/BGN were locally delivered inside a collagen gel to the target calvarium defects. The results showed significantly improved bone regeneration, as evidenced by the micro-computed tomographic, histomorphometric and immunohistochemical analyses. This study supports the excellent capacity of the BGN system as a pDNA-delivery nanocarrier in MSCs, and the engineered system, BMP2-pDNA/BGN with MSCs, may be considered a new promising candidate to advance the therapeutic potential of stem cells through genetic modification, targeting bone defects and diseases.The recent development of bioactive glasses with nanoscale morphologies has

  15. Bone regeneration by the osteoconductivity of porous titanium implants manufactured by selective laser melting: a histological and micro computed tomography study in the rabbit.

    Science.gov (United States)

    de Wild, Michael; Schumacher, Ralf; Mayer, Kyrill; Schkommodau, Erik; Thoma, Daniel; Bredell, Marius; Kruse Gujer, Astrid; Grätz, Klaus W; Weber, Franz E

    2013-12-01

    augmentation purposes. Therefore, designed porous, lightweight structures have potential for bone regeneration and augmentation purposes, especially when complex and patient-specific geometries are essential. PMID:23895118

  16. Synthesis and Characterization of Nano Hydroxyapatite with Poly Vinyl Pyrrolidone Nano Composite for Bone Tissue Regeneration

    Directory of Open Access Journals (Sweden)

    A. Ragu

    2014-07-01

    Full Text Available Hydroxyapatite (Ca10 (PO46(OH2 , the main mineral component of bone and teeth, is native to the human body. Hydroxyapatite (HAp is a desirable implant material due to its biocompatibility and osteoconductivity properties. In this study, nano hydroxyapatite (nHAp with poly vinyl pyrrolidone (PVP was synthesized at room temperature condition. The synthetic nano hydroxyapatite (nHAp prepared by wet chemical precipitation method was investigated. Hydroxyapatite is biocompatible with the human organism and is capable of integrating biologically into bone tissue. The synthesized sample were characterized by Fourier transformed infrared spectroscopy (FTIR, X-ray diffraction (XRD, Transmission electron microscope (TEM, Energy dispersive analysis of x-rays techniques (EDAX and Micro hardness test.

  17. Design and production of sintered β-tricalcium phosphate 3D scaffolds for bone tissue regeneration

    International Nuclear Information System (INIS)

    The characteristics of sintered β-tricalcium phosphate (β-TCP) scaffolds produced by 3D printing were studied by means of X-ray diffraction, Scanning Electron Microscopy, Fourier transform infrared spectroscopy, uniaxial compression tests and cytotoxicity tests, using human osteoblast cells. The results reported include details of the β-TCP scaffolds' porosity, density, phase stability, mechanical behavior and cytotoxic profile. Collectively, these properties are fundamental for the future application of these scaffolds as bone substitutes for individualized therapy. Highlights: ► β-Tricalcium phosphate (β-TCP) 3D scaffolds were produced by rapid prototyping. ► Scaffold properties were assessed by SEM, FTIR, XRD and by mechanical tests. ► The cytotoxic profile of the scaffolds was characterized by in vitro assays. ► Scaffolds have good properties for its application as bone substitutes for individualized therapy.

  18. Design and production of sintered {beta}-tricalcium phosphate 3D scaffolds for bone tissue regeneration

    Energy Technology Data Exchange (ETDEWEB)

    Santos, Carlos F.L. [CICS-UBI - Centro de Investigacao em Ciencias da Saude, Universidade da Beira Interior, Covilha (Portugal); Silva, Abilio P. [Centro de Ciencia e Tecnologia Aeroespaciais, Universidade da Beira Interior, Covilha (Portugal); Lopes, Luis [CICS-UBI - Centro de Investigacao em Ciencias da Saude, Universidade da Beira Interior, Covilha (Portugal); Pires, Ines [Instituto de Engenharia Mecanica - Lisboa (IDMEC Lisboa/IST/UTL), Avenida Rovisco Pais, 1049-001 Lisboa (Portugal); Correia, Ilidio J., E-mail: icorreia@ubi.pt [CICS-UBI - Centro de Investigacao em Ciencias da Saude, Universidade da Beira Interior, Covilha (Portugal)

    2012-07-01

    The characteristics of sintered {beta}-tricalcium phosphate ({beta}-TCP) scaffolds produced by 3D printing were studied by means of X-ray diffraction, Scanning Electron Microscopy, Fourier transform infrared spectroscopy, uniaxial compression tests and cytotoxicity tests, using human osteoblast cells. The results reported include details of the {beta}-TCP scaffolds' porosity, density, phase stability, mechanical behavior and cytotoxic profile. Collectively, these properties are fundamental for the future application of these scaffolds as bone substitutes for individualized therapy. Highlights: Black-Right-Pointing-Pointer {beta}-Tricalcium phosphate ({beta}-TCP) 3D scaffolds were produced by rapid prototyping. Black-Right-Pointing-Pointer Scaffold properties were assessed by SEM, FTIR, XRD and by mechanical tests. Black-Right-Pointing-Pointer The cytotoxic profile of the scaffolds was characterized by in vitro assays. Black-Right-Pointing-Pointer Scaffolds have good properties for its application as bone substitutes for individualized therapy.

  19. Stem cells of the suture mesenchyme in craniofacial bone development, repair and regeneration

    OpenAIRE

    Maruyama, Takamitsu; Jeong, Jaeim; Sheu, Tzong-jen; Hsu, Wei

    2016-01-01

    The suture mesenchyme serves as a growth centre for calvarial morphogenesis and has been postulated to act as the niche for skeletal stem cells. Aberrant gene regulation causes suture dysmorphogenesis resulting in craniosynostosis, one of the most common craniofacial deformities. Owing to various limitations, especially the lack of suture stem cell isolation, reconstruction of large craniofacial bone defects remains highly challenging. Here we provide the first evidence for an Axin2-expressin...

  20. Small molecule stimulation enhances bone regeneration but not titanium implant osseointegration

    OpenAIRE

    Gellynck, K.; Shah, R.; Parkar, M.; Young, A; Buxton, P.; Brett, P. (Peter)

    2013-01-01

    Abstract The osteogenic and osseointegrative potential of a small molecule was examined to assess its usefulness in regenerative procedures. Purmorphamine was used to stimulate bone growth and repair in an in vitro cell based assay and an in vivo chick embryo CAM-assay with and without the presence of an implant. Purmorphamine adhered to precipitated hydroxyapatite coating, could activate the sonic hedgehog pathway and thereby stimulated osteodifferentiation. Porous calcium phosphate beads we...

  1. Synthesis and Characterization of Nano Hydroxyapatite with Poly Vinyl Pyrrolidone Nano Composite for Bone Tissue Regeneration

    OpenAIRE

    Ragu, A.; K. Senthilarasan

    2014-01-01

    Hydroxyapatite (Ca10 (PO4)6(OH)2 ), the main mineral component of bone and teeth, is native to the human body. Hydroxyapatite (HAp) is a desirable implant material due to its biocompatibility and osteoconductivity properties. In this study, nano hydroxyapatite (nHAp) with poly vinyl pyrrolidone (PVP was synthesized at room temperature condition. The synthetic nano hydroxyapatite (nHAp) prepared by wet chemical precipitation method was investigated. Hydroxyapatite is biocompatib...

  2. Allogeneic stem cell transplantation for bone regeneration of a nonunion defect in a canine

    OpenAIRE

    Yaneselli K; Filomeno A; Semiglia G; Arce C; Rial A.; Muñoz N; Moreno M; Erickson K; Maisonnave J

    2013-01-01

    Kevin Yaneselli,1 Andrea Filomeno,1 Gabriel Semiglia,1 Carolina Arce,1 Analía Rial,2 Natalia Muñoz,2 María Moreno,2 Kent Erickson,3 Jacqueline Maisonnave11Universidad de la República, Facultad de Veterinaria, Montevideo, Uruguay; 2Laboratory for Vaccine Research, Department of Biotechnology, Instituto de Higiene, Facultad de Medicina, Universidad de la República, Montevideo, Uruguay; 3University of California, Davis, CA, USAAbstract: Nonunion bone defects oc...

  3. In vitro prominent bone regeneration by release zinc ion from Zn-modified implant

    Energy Technology Data Exchange (ETDEWEB)

    Yusa, Kazuyuki [Department of Biochemistry, Akita University Graduate School of Medicine, Akita (Japan); Yamamoto, Osamu [Department of Bio-System Engineering, Graduate School of Science and Engineering, Yamagata University, Yonezawa (Japan); Fukuda, Masayuki [Division of Dentistry and Oral Surgery, Akita University Hospital, Akita (Japan); Koyota, Souichi; Koizumi, Yukio [Department of Biochemistry, Akita University Graduate School of Medicine, Akita (Japan); Sugiyama, Toshihiro, E-mail: sugiyama@med.akita-u.ac.jp [Department of Biochemistry, Akita University Graduate School of Medicine, Akita (Japan)

    2011-08-26

    Highlights: {yields} We isolated the Zn{sup 2+} ions (eluted Zn{sup 2+} ion; EZ) from zinc-incorporated titanium implant. {yields} The EZ promoted the cell viability in hBMCs. {yields} The EZ stimulated preosteoblast and osteoblast marker gene expression in hBMCs. {yields} The hBMCs supplemented with EZ showed typically cell morphology when osteoblast maturing. {yields} It is revealed that the EZ also stimulates the calcium deposition of hBMCs. -- Abstract: Zinc is one of the trace elements which induce the proliferation and the differentiation of the osteoblast. In the previous study, we found that zinc ions (Zn{sup 2+} ion)-releasing titanium implants had excellent bone fixation using a rabbit femurs model. In this study, we isolated the Zn{sup 2+} ions (eluted Zn{sup 2+} ion; EZ) released from the implant surface, and evaluated the effect of EZ on the osteogenesis of human bone marrow-derived mesenchymal cells (hBMCs). In the result, it was found that the EZ stimulated cell viability, osteoblast marker gene (type I collagen, osteocalcin (OC), alkaline phosphatase (ALP) and bone sialoprotein (BSP)) expressions and calcium deposition in hBMCs.

  4. In vitro prominent bone regeneration by release zinc ion from Zn-modified implant

    International Nuclear Information System (INIS)

    Highlights: → We isolated the Zn2+ ions (eluted Zn2+ ion; EZ) from zinc-incorporated titanium implant. → The EZ promoted the cell viability in hBMCs. → The EZ stimulated preosteoblast and osteoblast marker gene expression in hBMCs. → The hBMCs supplemented with EZ showed typically cell morphology when osteoblast maturing. → It is revealed that the EZ also stimulates the calcium deposition of hBMCs. -- Abstract: Zinc is one of the trace elements which induce the proliferation and the differentiation of the osteoblast. In the previous study, we found that zinc ions (Zn2+ ion)-releasing titanium implants had excellent bone fixation using a rabbit femurs model. In this study, we isolated the Zn2+ ions (eluted Zn2+ ion; EZ) released from the implant surface, and evaluated the effect of EZ on the osteogenesis of human bone marrow-derived mesenchymal cells (hBMCs). In the result, it was found that the EZ stimulated cell viability, osteoblast marker gene (type I collagen, osteocalcin (OC), alkaline phosphatase (ALP) and bone sialoprotein (BSP)) expressions and calcium deposition in hBMCs.

  5. Melt-electrospun polycaprolactone strontium-substituted bioactive glass scaffolds for bone regeneration.

    Science.gov (United States)

    Ren, Jiongyu; Blackwood, Keith A; Doustgani, Amir; Poh, Patrina P; Steck, Roland; Stevens, Molly M; Woodruff, Maria A

    2014-09-01

    Polycaprolactone (PCL) is a resorbable polymer used extensively in bone tissue engineering owing to good structural properties and processability. Strontium-substituted bioactive glass (SrBG) has the ability to promote osteogenesis and may be incorporated into scaffolds intended for bone repair. Here, we describe for the first time, the development of a PCL-SrBG composite scaffold incorporating 10% (weight) of SrBG particles into PCL bulk, produced by the technique of melt electrospinning. We show that we are able to reproducibly manufacture composite scaffolds with an interconnected porous structure and, furthermore, these scaffolds were demonstrated to be noncytotoxic in vitro. Ions present in the SrBG component were shown to dissolve into cell culture media and promoted precipitation of a calcium phosphate layer on the scaffold surface which in turn led to noticeably enhanced alkaline phosphatase activity in MC3T3-E1 cells compared to PLC-only scaffolds. These results suggest that melt-electrospun PCL-SrBG composite scaffolds show potential to become effective bone graft substitutes. PMID:24133006

  6. Bone marrow-derived mesenchymal stem cells in three-dimensional culture promote neuronal regeneration by neurotrophic protection and immunomodulation.

    Science.gov (United States)

    Han, Sufang; Wang, Bin; Li, Xing; Xiao, Zhifeng; Han, Jin; Zhao, Yannan; Fang, Yongxiang; Yin, Yanyun; Chen, Bing; Dai, Jianwu

    2016-07-01

    Accumulating evidence has revealed three-dimensional (3D) culture could better mimic the stem cell niche in vivo in comparison with conventional two-dimensional (2D) culture. In this study, we found that bone marrow derived mesenchymal stem cells (BMSCs) cultured in 3D collagen scaffold (3D BMSCs) exhibited distinctive features including significantly enhancing neurotrophic factor secretions and reducing macrophage activations challenged by lipopolysaccharide (LPS) in vitro. To further evaluate 3D BMSCs' potential benefits to the regeneration of spinal cord injury (SCI), the 3D and 2D BMSCs were respectively implanted in rat hemisected SCI. Compared with 2D cohort, 3D BMSCs transplantation significantly reduced the expressions of inflammatory cytokines such as TNF-α, IL-1β, and IL-6 at 5 days after transplantation, markedly enhanced axonal regeneration, and promoted motor functional recovery during 8 weeks of observation. When Nocodazole was used to depolymerize the cytoskeleton of 3D BMSCs, the changed expressions of neurotrophic factors and inflammatory cytokines were blunted, at least partially. Thus synergistic effects of neuronal protection and immunomodulation of 3D BMSCs may lead to a better functional recovery of SCI and the underlying mechanism may involve the alteration of their cellular morphology because of 3D culture. This study contributes to a better understanding of the cellular characteristics of 3D BMSCs and provides a novel strategy to promote the repair of the injured spinal cord. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 104A: 1759-1769, 2016. PMID:26990583

  7. Autologous bone marrow mesenchymal stromal cells for regeneration of injured equine ligaments and tendons: a clinical report.

    Science.gov (United States)

    Renzi, S; Riccò, S; Dotti, S; Sesso, L; Grolli, S; Cornali, M; Carlin, S; Patruno, M; Cinotti, S; Ferrari, M

    2013-08-01

    The use of Mesenchymal Stromal Cells (MSCs) in orthopedic practice has recently and rapidly acquired an important role. Therapies based on the use of MSCs for the treatment of acute injuries as well as chronic inflammatory disorders are gradually becoming clinical routine. These cells have demonstrated intriguing therapeutic potentialities (i.e.: inflammation control, tissue regeneration and pathological scar prevention), that have been taken into consideration for use in both human and veterinary medicine. In particular, horses represent high performance athletes considered models for human pathologies since musculo-skeletal disorders frequently occur in this species. In the past, repair of tendon injures were performed by different methods. In particular, clinical therapy was based on ice application, bandage, box rest and controlled exercise. An alternative approach consisted on the use of corticosteroid (inflammation reduction) and other drugs (sodium hyaluronate, polysulphated glycosaminoglycans, beta aminoproprionitrile fumarate). Furthermore, surgical treatments like accessory ligament desmotomy, local irritation by line firing or pin firing were commonly used. More recently ultrasound, laser therapy, electromagnetic field therapy have been considered. Unfortunately, they did not allow complete tissue healing and quite often animals did not regain competitiveness. In order to minimize this inconvenience, the use of MSCs has been introduced as an alternative to the traditional approach since it represents a potential tool to improve tissue regeneration. Aim of this study was to evaluate the capability of MSCs to improve the functional outcome of horses affected by tendonitis and desmitis. Thirty-three breed and activity-matched horses affected by tendonitis or desmitis, were included in clinical trial scored for lesions and subdivided into two groups. Group 1 animals were treated with autologous MSCs, associated with platelet rich plasma (group 1). Bone

  8. Mineralization and Characterization of Composite Lyophilized Gelatin Sponges Intended for Early Bone Regeneration

    Directory of Open Access Journals (Sweden)

    Isaac Rodriguez

    2014-01-01

    Full Text Available The application of freeze-dried gelatin sponges as alternative bone grafting substitutes has many advantages, including the ability to swell, high porosity, tailorable degradation, and versatility to incorporate multiple components such as growth factors and nanofillers. The purpose of this study was to mineralize (M and further characterize 1-Ethyl-3-[3-dimethylaminopropyl]carbodiimide hydrochloride (EDC cross-linked gelatin sponges enhanced with preparations rich in growth factors, hydroxyapatite, and chitin whiskers (PHCE. Sponges were characterized for their swelling and in vitro mineralization potential, surface characteristics, protein release, mechanical properties, and MG-63 cell attachment and infiltration. All sponges swelled up to 50% of their original volume upon hydration. Scanning electron microscopy showed sparse mineral deposition for gelatin-M scaffolds while PHCE-M scaffolds exhibited more uniform mineral nucleation. Over 21 days, PHCE-M scaffolds cumulatively released significantly more (30% of its initial protein content than all other scaffolds. PHCE-M scaffolds reported lower modulus values (1.3–1.6 MPa when compared to gelatin control scaffolds (1.6–3.2 MPa. Increased cell attachment and infiltration was noticed on PHCE and PHCE-M scaffolds. The results of the study demonstrate the enhanced performance of PHCE and PHCE-M scaffolds to serve as bone healing scaffolds. Their potential to release incorporated factors, comparable composition/mechanical properties to tissues developed in the early stages of bone healing, and enhanced initial cellular response make them suitable for further studies evaluating more complex cellular interactions.

  9. Efficacy of Platelet-Rich-Plasma (PRP) and Highly Purified Bovine Xenograft (Laddec®) Combination in Bone Regeneration after Cyst Enucleation: Radiological and Histological Evaluation

    OpenAIRE

    Sabrina Pappalardo; Renzo Guarnieri

    2013-01-01

    Objectives: The purpose of the present study was to evaluate the efficacy of adding platelet-rich plasma (PRP) to a new highly purified bovine allograft (Laddec®) in the bone regeneration of cystic bony defects augmented following cystectomy.Material and Methods: Study sample included 20 patients undergoing cystectomy in which the bone defect was filled with PRP and Laddec®. All patients were examined with periapical radiographs before operation and at follow-up. After 3 months, at re-entry s...

  10. Bone regeneration with active angiogenesis by basic fibroblast growth factor gene transfected mesenchymal stem cells seeded on porous β-TCP ceramic scaffolds

    International Nuclear Information System (INIS)

    Large segmental bone defect repair remains a clinical and scientific challenge with increasing interest focused on combining gene transfer with tissue engineering techniques. Basic fibroblast growth factor (bFGF) is one of the most prominent osteogenic growth factors that has the potential to accelerate bone healing by promoting the proliferation and differentiation of mesenchymal stem cells (MSCs) and the regeneration of capillary vasculature. However, the short biological half-lives of growth factors may impose severe restraints on their clinical usefulness. Gene-based delivery systems provide a better way of achieving a sustained high concentration of growth factors locally in the defect and delivering a more biologically active product than that achieved by exogenous application of recombinant proteins. The objective of this experimental study was to investigate whether the bFGF gene modified MSCs could enhance the repair of large segmental bone defects. The pcDNA3-bFGF gene transfected MSCs were seeded on biodegradable porous β tricalcium phosphate (β-TCP) ceramics and allografted into the 15 mm critical-sized segmental bone defects in the radius of 18 New Zealand White rabbits. The pcDNA3 vector gene transfected MSCs were taken as the control. The follow-up times were 2, 4, 6, 8, 10 and 12 weeks. Scanning electron microscopic, roentgenographic, histologic and immunohistological studies were used to assess angiogenesis and bone regeneration. In vitro, the proliferation and differentiation of bFGF gene transfected MSCs were more active than that of the control groups. In vivo, significantly more new bone formation accompanied by abundant active capillary regeneration was observed in pores of the ceramics loaded with bFGF gene transfected MSCs, compared with control groups. Transfer of gene encoding bFGF to MSCs increases their osteogenic properties by enhancing capillary regeneration, thus providing a rich blood supply for new bone formation. This new b

  11. Effects of rhBMP-2 on Sandblasted and Acid Etched Titanium Implant Surfaces on Bone Regeneration and Osseointegration: Spilt-Mouth Designed Pilot Study

    OpenAIRE

    Nam-Ho Kim; So-Hyoun Lee; Jae-Jun Ryu; Kyung-Hee Choi; Jung-Bo Huh

    2015-01-01

    This study was conducted to evaluate effects of rhBMP-2 applied at different concentrations to sandblasted and acid etched (SLA) implants on osseointegration and bone regeneration in a bone defect of beagle dogs as pilot study using split-mouth design. Methods. For experimental groups, SLA implants were coated with different concentrations of rhBMP-2 (0.1, 0.5, and 1 mg/mL). After assessment of surface characteristics and rhBMP-2 releasing profile, the experimental groups and untreated contro...

  12. Perovskite ceramic nanoparticles in polymer composites for augmenting bone tissue regeneration

    International Nuclear Information System (INIS)

    There is increasing interest in the use of nanoparticles as fillers in polymer matrices to develop biomaterials which mimic the mechanical, chemical and electrical properties of bone tissue for orthopaedic applications. The objective of this study was to prepare poly(ϵ-caprolactone) (PCL) nanocomposites incorporating three different perovskite ceramic nanoparticles, namely, calcium titanate (CT), strontium titanate (ST) and barium titanate (BT). The tensile strength and modulus of the composites increased with the addition of nanoparticles. Scanning electron microscopy indicated that dispersion of the nanoparticles scaled with the density of the ceramics, which in turn played an important role in determining the enhancement in mechanical properties of the composite. Dielectric spectroscopy revealed improved permittivity and reduced losses in the composites when compared to neat PCL. Nanofibrous scaffolds were fabricated via electrospinning. Induction coupled plasma-optical emission spectroscopy indicated the release of small quantities of Ca+2, Sr+2, Ba+2 ions from the scaffolds. Piezo-force microscopy revealed that BT nanoparticles imparted piezoelectric properties to the scaffolds. In vitro studies revealed that all composites support osteoblast proliferation. Expression of osteogenic genes was enhanced on the nanocomposites in the following order: PCL/CT > PCL/ST > PCL/BT > PCL. This study demonstrates that the use of perovskite nanoparticles could be a promising technique to engineer better polymeric scaffolds for bone tissue engineering. (paper)

  13. Potential Osteoporosis Recovery by Deep Sea Water through Bone Regeneration in SAMP8 Mice

    Directory of Open Access Journals (Sweden)

    Hen-Yu Liu

    2013-01-01

    Full Text Available The aim of this study is to examine the therapeutic potential of deep sea water (DSW on osteoporosis. Previously, we have established the ovariectomized senescence-accelerated mice (OVX-SAMP8 and demonstrated strong recovery of osteoporosis by stem cell and platelet-rich plasma (PRP. Deep sea water at hardness (HD 1000 showed significant increase in proliferation of osteoblastic cell (MC3T3 by MTT assay. For in vivo animal study, bone mineral density (BMD was strongly enhanced followed by the significantly increased trabecular numbers through micro-CT examination after a 4-month deep sea water treatment, and biochemistry analysis showed that serum alkaline phosphatase (ALP activity was decreased. For stage-specific osteogenesis, bone marrow-derived stromal cells (BMSCs were harvested and examined. Deep sea water-treated BMSCs showed stronger osteogenic differentiation such as BMP2, RUNX2, OPN, and OCN, and enhanced colony forming abilities, compared to the control group. Interestingly, most untreated OVX-SAMP8 mice died around 10 months; however, approximately 57% of DSW-treated groups lived up to 16.6 months, a life expectancy similar to the previously reported life expectancy for SAMR1 24 months. The results demonstrated the regenerative potentials of deep sea water on osteogenesis, showing that deep sea water could potentially be applied in osteoporosis therapy as a complementary and alternative medicine (CAM.

  14. Preparation of collagen/hydroxyapatite/alendronate hybrid hydrogels as potential scaffolds for bone regeneration.

    Science.gov (United States)

    Ma, Xin; He, Zhiwei; Han, Fengxuan; Zhong, Zhiyuan; Chen, Liang; Li, Bin

    2016-07-01

    Development of biomimetic scaffolds represents a promising direction in bone tissue engineering. In this study, we designed a two-step process to prepare a type of biomimetic hybrid hydrogels that were composed of collagen, hydroxyapatite (HAP) and alendronate (ALN), an anti-osteoporosis drug. First, water-soluble ALN-conjugated HAP (HAP-ALN) containing 4.0wt.% of ALN was synthesized by treating HAP particles with ALN. Hydrogels were then formed from HAP-ALN conjugate and collagen under physiological conditions using genipin (GNP) as the crosslinker. Depending on the ALN/collagen molar ratio and GNP concentration, the gelation time of hydrogels ranged from 5 to 37min. Notably, these hybrid hydrogels exhibited markedly improved mechanical property (storage modulus G'=38-187kPa), higher gel contents, and lower swelling ratios compared to the hydrogels prepared from collagen alone under similar conditions. Moreover, they showed tunable degradation behaviors against collagenase. The collagen/HAP-ALN hybrid hydrogels supported the adhesion and growth of murine MC3T3-E1 osteoblastic cells well. Such tough yet enzymatically degradable hybrid hydrogels hold potential as scaffolds for bone tissue engineering. PMID:26998869

  15. Poly(lactide-co-glycolide/Hydroxyapatite Porous Scaffold with Microchannels for Bone Regeneration

    Directory of Open Access Journals (Sweden)

    Ning Zhang

    2016-06-01

    Full Text Available Mass transfer restrictions of scaffolds are currently hindering the development of three-dimensional (3D, clinically viable, and tissue-engineered constructs. For this situation, a 3D poly(lactide-co-glycolide/hydroxyapatite porous scaffold, which was very favorable for the transfer of nutrients to and waste products from the cells in the pores, was developed in this study. The 3D scaffold had an innovative structure, including macropores with diameters of 300–450 μm for cell ingrowth and microchannels with diameters of 2–4 μm for nutrition and waste exchange. The mechanical strength in wet state was strong enough to offer structural support. The typical structure was more beneficial for the attachment, proliferation, and differentiation of rabbit bone marrow mesenchymal stem cells (rBMSCs. The alkaline phosphatase (ALP activity and calcium (Ca deposition were evaluated on the differentiation of rBMSCs, and the results indicated that the microchannel structure was very favorable for differentiating rBMSCs into maturing osteoblasts. For repairing rabbit radius defects in vivo, there was rapid healing in the defects treated with the 3D porous scaffold with microchannels, where the bridging by a large bony callus was observed at 12 weeks post-surgery. Based on the results, the 3D porous scaffold with microchannels was a promising candidate for bone defect repair.

  16. Undifferentiated Human Adipose-derived Stromal/Stem Cells loaded onto Wet-Spun Starch-polycaprolactone Scaffolds Enhance Bone Regeneration: Nude Mice Calvarial Defect in vivo Study

    OpenAIRE

    Carvalho, Pedro P.; Leonor, Isabel B.; Smith, Brenda J.; Dias, Isabel R.; Reis, Rui L.; Jeffrey M Gimble; Gomes, Manuela E.

    2013-01-01

    The repair of large bony defects remains challenging in the clinical setting. Human adipose-derived stromal/stem cells (hASCs) have been reported to differentiate along different cell lineages, including the osteogenic. The objective of the present study was to assess the bone regeneration potential of undifferentiated hASCs loaded in starch-polycaprolactone (SPCL) scaffolds, in a critical-sized nude mice calvarial defect.

  17. Biodegradable mesoporous bioactive glass nanospheres for drug delivery and bone tissue regeneration

    Science.gov (United States)

    Wang, Xiaojian; Li, Wei

    2016-06-01

    Bioactive inorganic materials are attractive for hard tissue regeneration, and they are used as delivery vehicles for pharmaceutical molecules, scaffolds and components for bio-composites. We demonstrated mesoporous bioactive glass (BG) nanospheres that exhibited the capacity to deliver pharmaceutical molecules. Mesoporous BG nanospheres with variable Ca to Si ratios were synthesized using sol–gel chemistry. By controlling the hydrolysis and condensation conditions, the diameter of the mesoporous BG nanospheres was changed from 300 nm to 1500 nm. The porous structure and surface area of the BG nanospheres were shown to be dependent on their composition. The surface area of the BG nanospheres decreased from 400 ± 2 m2 g‑1 to 56 ± 0.1 m2 g‑1 when the Ca/Si ratio increased from 5 to 50 at.%. When the mesoporous BG nanospheres were loaded with ibuprofen (IBU), they exhibited a sustained release profile in simulated body fluid (SBF). In the meantime, the IBU-loaded BG nanospheres degraded in SBF, and induced apatite layer formation on the surface as a result of their good bioactivity. When the BG nanospheres were used as a composite filler to poly (ε-caprolactone) (PCL), they were shown to be effective at improving the in vitro bioactivity of PCL microspheres.

  18. Can the material properties of regenerate bone be predicted with non-invasive methods of assessment? Exploring the correlation between dual X-ray absorptiometry and compression testing to failure in an animal model of distraction osteogenesis

    OpenAIRE

    Monsell, Fergal; Hughes, Andrew William; Turner, James; Bellemore, Michael C.; Bilston, Lynne

    2014-01-01

    Evaluation of the material properties of regenerate bone is of fundamental importance to a successful outcome following distraction osteogenesis using an external fixator. Plain radiographs are in widespread use for assessment of alignment and the distraction gap but are unable to detect bone formation in the early stages of distraction osteogenesis and do not quantify accurately the structural properties of the regenerate. Dual X-ray absorptiometry (DXA) is a widely available non-invasive im...

  19. Efficacy of Mucograft vs Conventional Resorbable Collagen Membranes in Guided Bone Regeneration Around Standardized Calvarial Defects in Rats: An In Vivo Microcomputed Tomographic Analysis.

    Science.gov (United States)

    Babay, Nadir; Ramalingam, Sundar; Basudan, Amani; Nooh, Nasser; AlKindi, Mohammed; Al-Rasheed, Abdulaziz; Al-Hezaimi, Khalid

    2016-01-01

    The aim of this in vivo microcomputed tomographic (μCT) study was to compare the efficacy of Mucograft (MG) vs resorbable collagen membranes (RCMs) in facilitating guided bone regeneration (GBR) around standardized calvarial defects in rats. Forty female Wistar albino rats with a mean age and weight of 6 to 9 weeks and 250 to 300 g, respectively, were used. With the rats under general anesthesia, the skin over the calvaria was exposed using a full-thickness flap. A standardized calvarial defect with a 4.6-mm diameter was created in the left parietal bone. For treatment, the rats were randomly divided into four groups (n = 10 per group): (1) defects covered with MG (MG group); (2) defects covered with an RCM (RCM group); (3) defects filled with xenograft bone particles and covered by MG (MG + bone group); and (4) defects filled with xenograft bone particles and covered by an RCM (RCM + bone group). Primary closure was achieved using interrupted resorbable sutures. The animals underwent high-resolution, three-dimensional μCT scans at baseline and at 2, 4, 6, and 8 weeks after the surgical procedures. Data regarding volume and bone mineral density (BMD) of newly formed bone (NFB) and bone particles revealed an increase in the volume of NFB in all the groups from baseline to 8 weeks. The MG group had the lowest volume of NFB (mean ± standard deviation [SD], 1.32 ± 0.22 mm(3)). No significant differences in mean ± SD values for volume of NFB were observed between the RCM (3.50 ± 0.24 mm(3)) and MG + bone (3.87 ± 0.36 mm(3)) groups, but their values were significantly lower than that of the RCM + bone group (2.95 ± 0.15 mm(3), F = 131.91, dfN = 2, dfD = 27, P RCM group having the highest mean ± SD BMD of NFB (0.42 ± 0.05 g/mm(3)). Significant differences in the bone particle volume between the RCM + bone and MG + bone groups (F = 91.04, dfN = 1, dfD = 18, P RCM + bone group displaying greater reduction in both volume (36.8%) and BMD (19.7%) of bone particles

  20. In vitro bioactivity assessment of composite membrane containing antimicrobial lauric acid for guided bone regeneration in dental application

    Science.gov (United States)

    Suleiman, Muhammad Jabir; Kalitheertha, Jamuna Thevi; Sabri, Siti Noorzidah

    2015-07-01

    The manuscript reflect research work in fabrication of a triple layered composite membrane and to perform an in vitro bioactivity evaluation on composite membrane containing antimicrobial lauric acid. Poly(lactic-co-glycolic acid) (PLGA) matrix was incorporated with various amounts of nanoapatite (NAp) and lauric acid (LA) to form a triple-layered composite membrane. This membrane was prepared using a single step fabrication technique comprising of solvent casting, thermally induced phase separation and solvent leaching processes. Apatite mineralization was detected on the composite membranes within 30 days of exposure to simulated body fluid (SBF) and showed increased apatite formation at 30-60wt% of NAp content in the PLGA matrix on layer 3 (L3), that has the highest amount of NAp compared with layer 1 (L1) and layer 2 (L2) of the membrane. However, apatite mineralization was not detected on pure PLGA membrane. In addition, incorporation of LA on L1 and L2 has no influence on apatite mineral formation as none detected on these surfaces. The presence of NAp determines the formation of apatite crystals on the composite membrane. These membranes with triple layered design and bioactive properties showed potential use for guided bone regeneration purposes in dental application.

  1. PLGA/nHA hybrid nanofiber scaffold as a nanocargo carrier of insulin for accelerating bone tissue regeneration

    Science.gov (United States)

    Haider, Adnan; Gupta, Kailash Chandra; Kang, Inn-Kyu

    2014-06-01

    The development of tissue engineering in the field of orthopedic surgery is booming. Two fields of research in particular have emerged: approaches for tailoring the surface properties of implantable materials with osteoinductive factors as well as evaluation of the response of osteogenic cells to these fabricated implanted materials (hybrid material). In the present study, we chemically grafted insulin onto the surface of hydroxyapatite nanorods (nHA). The insulin-grafted nHAs (nHA-I) were dispersed into poly(lactide-co-glycolide) (PLGA) polymer solution, which was electrospun to prepare PLGA/nHA-I composite nanofiber scaffolds. The morphology of the electrospun nanofiber scaffolds was assessed by field emission scanning electron microscopy (FESEM). After extensive characterization of the PLGA/nHA-I and PLGA/nHA composite nanofiber scaffolds by Fourier transform infrared spectroscopy (FTIR), X-ray diffraction spectroscopy (XRD), X-ray photoelectron spectroscopy (XPS), energy-dispersive X-ray spectrometry (EDS), and transmission electron microscopy (TEM), the PLGA/nHA-I and PLGA/nHA (used as control) composite nanofiber scaffolds were subjected to cell studies. The results obtained from cell adhesion, alizarin red staining, and Von Kossa assay suggested that the PLGA/nHA-I composite nanofiber scaffold has enhanced osteoblastic cell growth, as more cells were proliferated and differentiated. The fact that insulin enhanced osteoblastic cell proliferation will open new possibilities for the development of artificial scaffolds for bone tissue regeneration.

  2. Bioactive membranes for bone regeneration applications: effect of physical and biomolecular signals on mesenchymal stem cell behavior.

    Science.gov (United States)

    Tejeda-Montes, Esther; Smith, Katherine H; Rebollo, Elena; Gómez, Raúl; Alonso, Matilde; Rodriguez-Cabello, J Carlos; Engel, Elisabeth; Mata, Alvaro

    2014-01-01

    This study focuses on the in vitro characterization of bioactive elastin-like recombinamer (ELR) membranes for bone regeneration applications. Four bioactive ELRs exhibiting epitopes designed to promote mesenchymal stem cell adhesion (RGDS), endothelial cell adhesion (REDV), mineralization (HAP), and both cell adhesion and mineralization (HAP-RGDS) were synthesized using standard recombinant protein techniques. The materials were then used to fabricate ELR membranes incorporating a variety of topographical micropatterns including channels, holes and posts. Primary rat mesenchymal stem cells (rMSCs) were cultured on the different membranes and the effects of biomolecular and physical signals on cell adhesion, morphology, proliferation, and differentiation were evaluated. All results were analyzed using a custom-made MATLAB program for high throughput image analysis. Effects on cell morphology were mostly dependent on surface topography, while cell proliferation and cell differentiation were largely dependent on the biomolecular signaling from the ELR membranes. In particular, osteogenic differentiation (evaluated by staining for the osteoblastic marker osterix) was significantly enhanced on cells cultured on HAP membranes. Remarkably, cells growing on membranes containing the HAP sequence in non-osteogenic differentiation media exhibited significant up-regulation of the osteogenic marker as early as day 5, while those growing on fibronectin-coated glass in osteogenic differentiation media did not. These results are part of our ongoing effort to develop an optimized molecularly designed periosteal graft. PMID:24035887

  3. Preparation and osteogenic properties of magnesium calcium phosphate biocement scaffolds for bone regeneration

    International Nuclear Information System (INIS)

    The regenerative treatment of large osseous defects remains a formidable challenge in today. In the present study, we have synthesized biodegradable magnesium calcium phosphate biocement (MCPB) scaffolds with interconnected macroporous structure (100–600 μm), as well as good bioactivity, biocompatibility and proper degradatibility. The results revealed that the porosity increased from 52% to 80% of MCPB scaffolds while the compressive strength decreased from 6.1 MPa to 1.2 MPa. We further assessed the effects of scaffolds on the rabbit femur cavity defect model in vivo by using synchrotron radiation X-ray microCT and microCT imaging, indicating that the MCPB scaffolds underwent gradually degradation and promoted the extensive neo-bone formation

  4. Investigation of mechanism of bone regeneration in a porous biodegradable calcium phosphate (CaP) scaffold by a combination of a multi-scale agent-based model and experimental optimization/validation

    Science.gov (United States)

    Zhang, Le; Qiao, Minna; Gao, Hongjie; Hu, Bin; Tan, Hua; Zhou, Xiaobo; Li, Chang Ming

    2016-08-01

    Herein, we have developed a novel approach to investigate the mechanism of bone regeneration in a porous biodegradable calcium phosphate (CaP) scaffold by a combination of a multi-scale agent-based model, experimental optimization of key parameters and experimental data validation of the predictive power of the model. The advantages of this study are that the impact of mechanical stimulation on bone regeneration in a porous biodegradable CaP scaffold is considered, experimental design is used to investigate the optimal combination of growth factors loaded on the porous biodegradable CaP scaffold to promote bone regeneration and the training, testing and analysis of the model are carried out by using experimental data, a data-mining algorithm and related sensitivity analysis. The results reveal that mechanical stimulation has a great impact on bone regeneration in a porous biodegradable CaP scaffold and the optimal combination of growth factors that are encapsulated in nanospheres and loaded into porous biodegradable CaP scaffolds layer-by-layer can effectively promote bone regeneration. Furthermore, the model is robust and able to predict the development of bone regeneration under specified conditions.

  5. Fabrication and in vitro characterization of bioactive glass composite scaffolds for bone regeneration

    International Nuclear Information System (INIS)

    Here we fabricate and characterize bioactive composite scaffolds for bone tissue engineering applications. 45S5 Bioglass® (45S5) or strontium-substituted bioactive glass (SrBG) were incorporated into polycaprolactone (PCL) and fabricated into 3D bioactive composite scaffolds utilizing additive manufacturing technology. We show that composite scaffolds (PCL/45S5 and PCL/SrBG) can be reproducibly manufactured with a scaffold morphology highly resembling that of PCL scaffolds. Additionally, micro-CT analysis reveals BG particles were homogeneously distributed throughout the scaffolds. Mechanical data suggested that PCL/45S5 and PCL/SrBG composite scaffolds have higher compressive Young's modulus compared to PCL scaffolds at similar porosity (∼75%). After 1 day in accelerated degradation conditions using 5M NaOH, PCL/SrBG, PCL/45S5 and PCL lost 48.6 ± 3.8%, 12.1 ± 1% and 1.6 ± 1% of the original mass, respectively. In vitro studies were conducted using MC3T3 cells under normal and osteogenic conditions. All scaffolds were shown to be non-cytotoxic, and supported cell attachment and proliferation. Our results also indicate that the inclusion of bioactive glass (BG) promotes precipitation of calcium phosphate on the scaffold surfaces which leads to earlier cell differentiation and matrix mineralization when compared to PCL scaffolds. However, as indicated by alkaline phosphatase activity, no significant difference in osteoblast differentiation was found between PCL/45S5 and PCL/SrBG scaffolds. These results suggest that PCL/45S5 and PCL/SrBG composite scaffolds show potential as next generation bone scaffolds. (paper)

  6. Mac-1low early myeloid cells in the bone marrow-derived SP fraction migrate into injured skeletal muscle and participate in muscle regeneration

    International Nuclear Information System (INIS)

    Recent studies have shown that bone marrow (BM) cells, including the BM side population (BM-SP) cells that enrich hematopoietic stem cells (HSCs), are incorporated into skeletal muscle during regeneration, but it is not clear how and what kinds of BM cells contribute to muscle fiber regeneration. We found that a large number of SP cells migrated from BM to muscles following injury in BM-transplanted mice. These BM-derived SP cells in regenerating muscles expressed different surface markers from those of HSCs and could not reconstitute the mouse blood system. BM-derived SP/Mac-1low cells increased in number in regenerating muscles following injury. Importantly, our co-culture studies with activated satellite cells revealed that this fraction carried significant potential for myogenic differentiation. By contrast, mature inflammatory (Mac-1high) cells showed negligible myogenic activities. Further, these BM-derived SP/Mac-1low cells gave rise to mononucleate myocytes, indicating that their myogenesis was not caused by stochastic fusion with host myogenic cells, although they required cell-to-cell contact with myogenic cells for muscle differentiation. Taken together, our data suggest that neither HSCs nor mature inflammatory cells, but Mac-1low early myeloid cells in the BM-derived SP fraction, play an important role in regenerating skeletal muscles

  7. Genipin-Crosslinked Chitosan Gels and Scaffolds for Tissue Engineering and Regeneration of Cartilage and Bone.

    Science.gov (United States)

    Muzzarelli, Riccardo A A; El Mehtedi, Mohamad; Bottegoni, Carlo; Aquili, Alberto; Gigante, Antonio

    2015-12-01

    The present review article intends to direct attention to the technological advances made since 2009 in the area of genipin-crosslinked chitosan (GEN-chitosan) hydrogels. After a concise introduction on the well recognized characteristics of medical grade chitosan and food grade genipin, the properties of GEN-chitosan obtained with a safe, spontaneous and irreversible chemical reaction, and the quality assessment of the gels are reviewed. The antibacterial activity of GEN-chitosan has been well assessed in the treatment of gastric infections supported by Helicobacter pylori. Therapies based on chitosan alginate crosslinked with genipin include stem cell transplantation, and development of contraction free biomaterials suitable for cartilage engineering. Collagen, gelatin and other proteins have been associated to said hydrogels in view of the regeneration of the cartilage. Viability and proliferation of fibroblasts were impressively enhanced upon addition of poly-l-lysine. The modulation of the osteocytes has been achieved in various ways by applying advanced technologies such as 3D-plotting and electrospinning of biomimetic scaffolds, with optional addition of nano hydroxyapatite to the formulations. A wealth of biotechnological advances and know-how has permitted reaching outstanding results in crucial areas such as cranio-facial surgery, orthopedics and dentistry. It is mandatory to use scaffolds fully characterized in terms of porosity, pore size, swelling, wettability, compressive strength, and degree of acetylation, if the osteogenic differentiation of human mesenchymal stem cells is sought: in fact, the novel characteristics imparted by GEN-chitosan must be simultaneously of physico-chemical and cytological nature. Owing to their high standard, the scientific publications dated 2010-2015 have met the expectations of an interdisciplinary audience. PMID:26690453

  8. Genipin-Crosslinked Chitosan Gels and Scaffolds for Tissue Engineering and Regeneration of Cartilage and Bone

    Directory of Open Access Journals (Sweden)

    Riccardo A. A. Muzzarelli

    2015-12-01

    Full Text Available The present review article intends to direct attention to the technological advances made since 2009 in the area of genipin-crosslinked chitosan (GEN-chitosan hydrogels. After a concise introduction on the well recognized characteristics of medical grade chitosan and food grade genipin, the properties of GEN-chitosan obtained with a safe, spontaneous and irreversible chemical reaction, and the quality assessment of the gels are reviewed. The antibacterial activity of GEN-chitosan has been well assessed in the treatment of gastric infections supported by Helicobacter pylori. Therapies based on chitosan alginate crosslinked with genipin include stem cell transplantation, and development of contraction free biomaterials suitable for cartilage engineering. Collagen, gelatin and other proteins have been associated to said hydrogels in view of the regeneration of the cartilage. Viability and proliferation of fibroblasts were impressively enhanced upon addition of poly-l-lysine. The modulation of the osteocytes has been achieved in various ways by applying advanced technologies such as 3D-plotting and electrospinning of biomimetic scaffolds, with optional addition of nano hydroxyapatite to the formulations. A wealth of biotechnological advances and know-how has permitted reaching outstanding results in crucial areas such as cranio-facial surgery, orthopedics and dentistry. It is mandatory to use scaffolds fully characterized in terms of porosity, pore size, swelling, wettability, compressive strength, and degree of acetylation, if the osteogenic differentiation of human mesenchymal stem cells is sought: in fact, the novel characteristics imparted by GEN-chitosan must be simultaneously of physico-chemical and cytological nature. Owing to their high standard, the scientific publications dated 2010–2015 have met the expectations of an interdisciplinary audience.

  9. Local delivery of parathyroid hormone-related protein-derived peptides coated onto a hydroxyapatite-based implant enhances bone regeneration in old and diabetic rats.

    Science.gov (United States)

    Ardura, Juan A; Portal-Núñez, Sergio; Lozano, Daniel; Gutiérrez-Rojas, Irene; Sánchez-Salcedo, Sandra; López-Herradón, Ana; Mulero, Francisca; Villanueva-Peñacarrillo, María L; Vallet-Regí, María; Esbrit, Pedro

    2016-08-01

    Diabetes mellitus (DM) and aging are associated with bone fragility and increased fracture risk. Both (1-37) N- and (107-111) C-terminal parathyroid hormone-related protein (PTHrP) exhibit osteogenic properties. We here aimed to evaluate and compare the efficacy of either PTHrP (1-37) or PTHrP (107-111) loaded into gelatin-glutaraldehyde-coated hydroxyapatite (HA-Gel) foams to improve bone repair of a transcortical tibial defect in aging rats with or without DM, induced by streptozotocin injection at birth. Diabetic old rats showed bone structural deterioration compared to their age-matched controls. Histological and μ-computerized tomography studies showed incomplete bone repair at 4 weeks after implantation of unloaded Ha-Gel foams in the transcortical tibial defects, mainly in old rats with DM. However, enhanced defect healing, as shown by an increase of bone volume/tissue volume and trabecular and cortical thickness and decreased trabecular separation, occurred in the presence of either PTHrP peptide in the implants in old rats with or without DM. This was accompanied by newly formed bone tissue around the osteointegrated HA-Gel implant and increased gene expression of osteocalcin and vascular endothelial growth factor (bone formation and angiogenic markers, respectively), and decreased expression of Sost gene, a negative regulator of bone formation, in the healing bone area. Our findings suggest that local delivery of PTHrP (1-37) or PTHrP (107-111) from a degradable implant is an attractive strategy to improve bone regeneration in aged and diabetic subjects. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 104A: 2060-2070, 2016. PMID:27086979

  10. Novel cerium doped glass-reinforced hydroxyapatite with antibacterial and osteoconductive properties for bone tissue regeneration.

    Science.gov (United States)

    Morais, D S; Fernandes, S; Gomes, P S; Fernandes, M H; Sampaio, P; Ferraz, M P; Santos, J D; Lopes, M A; Sooraj Hussain, N

    2015-09-01

    The aim of this work was to develop a bioactive bone substitute with an effective antibacterial ability based on a cerium (Ce) doped glass-reinforced hydroxyapatite (GR-HA) composite. Developed composites were physicochemically characterized, using x-ray diffraction (XRD) analysis, SEM, energy dispersive x-ray spectroscopy (EDS), and flexural bending strength (FBS) tests. X-ray photoelectron spectroscopy (XPS) analysis was performed to analyze the oxidation state of Ce in the prepared doped glass. The antimicrobial activity of the composites was evaluated against Staphylococcus aureus, Staphylococcus epidermidis and Pseudomonas aeruginosa; whether the cytocompatibility profile was assayed with human osteoblastic-like cells (Mg-63 cell line). The results revealed that the Ce inclusion in the GR-HA matrix induced the antimicrobial ability of the composite. In addition, Ce-doped materials reported an adequate biological behavior following seeding of osteoblastic populations, by inducing cell adhesion and proliferation. Developed materials were also found to enhance the expression of osteoblastic-related genes. Overall, the developed GR-HA_Ce composite is a prospective candidate to be used within the clinical scenario with a successful performance due to the effective antibacterial properties and capability of enhancing the osteoblastic cell response. PMID:26391473

  11. Stem cell homing using local delivery of plerixafor and stromal derived growth factor-1alpha for improved bone regeneration around Ti-implants.

    Science.gov (United States)

    Karlsson, Johan; Harmankaya, Necati; Palmquist, Anders; Atefyekta, Saba; Omar, Omar; Tengvall, Pentti; Andersson, Martin

    2016-10-01

    Triggering of the early healing events, including the recruitment of progenitor cells, has been suggested to promote bone regeneration. In implantology, local drug release technologies could provide an attractive approach to promote tissue regeneration. In this study, we targeted the chemotactic SDF-1α/CXCR4 axis that is responsible e.g. for the homing of stem cells to trauma sites. This was achieved by local delivery of plerixafor, an antagonist to CXCR4, and/or SDF-1α, from titanium implants coated with mesoporous titania thin films with a pore size of 7.5 nm. In vitro drug delivery experiments demonstrated that the mesoporous coating provided a high drug loading capacity and controlled release. The subsequent in vivo study in rat tibia showed beneficial effects with respect to bone-implant anchorage and bone-formation along the surface of the implants when plerixafor and SDF-1α were delivered locally. The effect was most prominent by the finding that the combination of the drugs significantly improved the mechanical bone anchorage. These observations suggest that titanium implants with local delivery of drugs for enhanced local recruitment of progenitor cells have the ability to promote osseointegration. This approach may provide a potential strategy for the development of novel implant treatments. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 104A: 2466-2475, 2016. PMID:27213764

  12. Biological Evaluation (In Vitro and In Vivo) of Bilayered Collagenous Coated (Nano Electrospun and Solid Wall) Chitosan Membrane for Periodontal Guided Bone Regeneration.

    Science.gov (United States)

    Lotfi, Ghogha; Shokrgozar, Mohammad Ali; Mofid, Rasoul; Abbas, Fatemeh Mashhadi; Ghanavati, Farzin; Baghban, Alireza Akbarzadeh; Yavari, Seyedeh Kimia; Pajoumshariati, Seyedramin

    2016-07-01

    The application of barrier membranes in guided bone regeneration (GBR) has become a commonly used surgical technique in periodontal research. The objectives of this study were to evaluate the in vitro biocompatibility and osteogenic differentiation of mesenchymal stem cells (MSCs) on two different collagenous coatings (nano electrospun fibrous vs. solid wall) of bilayered collagen/chitosan membrane and their histological evaluation on bone regeneration in rabbit calvarial defects. It was found that chitosan-nano electrospun collagen (CNC) membranes had higher proliferation/metabolic activity compared to the chitosan-collagen (CC) and pristine chitosan membranes. The qRT-PCR analysis demonstrated the CNC membranes induced significant expression of osteogenic genes (Osteocalcin, RUNX2 and Col-α1) in MSCs. Moreover, higher calcium content and alkaline phosphatase activity of MSCs were observed compared to the other groups. Histologic and histomorphometric evaluations were performed on the uncovered (negative control) as well as covered calvarial defects of ten adult white rabbits with different membranes (CNC, CC, BioGide (BG, positive control)) at 1 and 2 months after surgery. More bone formation was detected in the defects covered with CNC and BG membranes than those covered by CC and the negative control. No inflammation and residual biomaterial particles were observed on the membrane surface or in the surrounding tissues in the surgical areas. These results suggest that bilayer CNC membrane can have the potential for use as a GBR membrane material facilitating bone formation. PMID:26586588

  13. Graphene Oxide-Copper Nanocomposite-Coated Porous CaP Scaffold for Vascularized Bone Regeneration via Activation of Hif-1α.

    Science.gov (United States)

    Zhang, Wenjie; Chang, Qing; Xu, Ling; Li, Guanglong; Yang, Guangzheng; Ding, Xun; Wang, Xiansong; Cui, Daxiang; Jiang, Xinquan

    2016-06-01

    Graphene has been studied for its in vitro osteoinductive capacity. However, the in vivo bone repair effects of graphene-based scaffolds remain unknown. The aqueous soluble graphene oxide-copper nanocomposites (GO-Cu) are fabricated, which are used to coat porous calcium phosphate (CaP) scaffolds for vascularized bone regeneration. The GO-Cu nanocomposites, containing crystallized CuO/Cu2 O nanoparticles of ≈30 nm diameters, distribute uniformly on the surfaces of the porous scaffolds and maintain a long-term release of Cu ions. In vitro, the GO-Cu coating enhances the adhesion and osteogenic differentiation of rat bone marrow stem cells (BMSCs). It is also found that by activating the Erk1/2 signaling pathway, the GO-Cu nanocomposites upregulate the expression of Hif-1α in BMSCs, resulting in the secretion of VEGF and BMP-2 proteins. When transplanted into rat with critical-sized calvarial defects, the GO-Cu-coated calcium phosphate cement (CPC) scaffolds (CPC/GO-Cu) significantly promote angiogenesis and osteogenesis. Moreover, it is observed via histological sections that the GO-Cu nanocomposites are phagocytosed by multinucleated giant cells. The results suggest that GO-Cu nanocomposite coatings can be utilized as an attractive strategy for vascularized bone regeneration. PMID:26945787

  14. Injectable porous nano-hydroxyapatite/chitosan/tripolyphosphate scaffolds with improved compressive strength for bone regeneration.

    Science.gov (United States)

    Uswatta, Suren P; Okeke, Israel U; Jayasuriya, Ambalangodage C

    2016-12-01

    In this study we have fabricated porous injectable spherical scaffolds using chitosan biopolymer, sodium tripolyphosphate (TPP) and nano-hydroxyapatite (nHA). TPP was primarily used as an ionic crosslinker to crosslink nHA/chitosan droplets. We hypothesized that incorporating nHA into chitosan could support osteoconduction by emulating the mineralized cortical bone structure, and improve the Ultimate Compressive Strength (UCS) of the scaffolds. We prepared chitosan solutions with 0.5%, 1% and 2% (w/v) nHA concentration and used simple coacervation and lyophilization techniques to obtain spherical scaffolds. Lyophilized spherical scaffolds had a mean diameter of 1.33mm (n=25). Further, portion from each group lyophilized scaffolds were soaked and dried to obtain Lyophilized Soaked and Dried (LSD) scaffolds. LSD scaffolds had a mean diameter of 0.93mm (n=25) which is promising property for the injectability. Scanning Electron Microscopy images showed porous surface morphology and interconnected pore structures inside the scaffolds. Lyophilized and LSD scaffolds had surface pores lyophilized scaffolds at 3.93MPa. Standardize UCS values were 79.98MPa and 357MPa for 2% nHA/chitosan lyophilized and LSD particles respectively. One-way ANOVA results showed a significant increase (plyophilized scaffolds compared to 0% and 0.5% nHA/chitosan lyophilized scaffolds. Moreover, 2% nHA LSD scaffolds had significantly increased (plyophilized scaffolds. In a drawback, all scaffolds have lost their mechanical properties by 95% on the 2nd day when fully immersed in phosphate buffered saline. Additionally live and dead cell assay showed no cytotoxicity and excellent osteoblast attachment to both lyophilized and LSD scaffolds at the end of 14th day of in vitro studies. 2% nHA/chitosan scaffolds showed higher osteoblast attachment than 0% nHA/chitosan scaffolds. PMID:27612741

  15. Surface modification of electrospun fibre meshes by oxygen plasma for bone regeneration

    International Nuclear Information System (INIS)

    Plasma treatment is a method to modify the physicochemical properties of biomaterials, which consequently may affect interactions with cells. Based on the rationale that physical cues on the surface of culture substrates and implants, such as surface roughness, have proven to alter cell behaviour, we used electrospinning to fabricate fibrous three-dimensional scaffolds made of a poly (ethylene oxide terephthalate)/poly (butylene terephthalate) copolymer to mimic the physical microenvironment of extracellular matrix and applied radio-frequency oxygen plasma treatment to create nanoscale roughness. Scanning electron microscopy (SEM) analysis revealed a fibre diameter of 5.49 ± 0.96 µm for as-spun meshes. Atomic force microscopy (AFM) measurements determined an exponential increase of surface roughness with plasma treatment time. An increase in hydrophilicity after plasma treatment was observed, which was associated with higher oxygen content in plasma treated scaffolds compared to untreated ones. A more pronounced adsorption of bovine serum albumin occurred on scaffolds treated with plasma for 15 and 30 min compared to untreated fibres. Clinically relevant human mesenchymal stromal cells (hMSCs) were cultured on untreated, 15 and 30 min treated scaffolds. SEM analysis confirmed cell attachment and a pronounced spindle-like morphology on all scaffolds. No significant differences were observed between different scaffolds regarding the amount of DNA, metabolic activity and alkaline phosphatase (ALP) activity after 7 days of culture. The amount of ALP positive cells increased between 7 and 21 days of culture on both untreated and 30 min treated meshes. In addition, ALP staining of cells on plasma treated meshes appeared more pronounced than on untreated meshes after 21 days of culture. Quantitative polymerase chain reaction showed significant upregulation of bone sialoprotein and osteonectin expression on oxygen plasma treated fibres compared to untreated fibres in

  16. Magnetic biodegradable Fe{sub 3}O{sub 4}/CS/PVA nanofibrous membranes for bone regeneration

    Energy Technology Data Exchange (ETDEWEB)

    Wei Yan; Zhang Xuehui; Hu Xiaoyang; Deng Xuliang [Department of Geriatric Dentistry, School and Hospital of Stomatology, Peking University, Beijing, 100081 (China); Song Yu; Lin Yuanhua [State Key Laboratory of New Ceramics and Fine Processing, Department of Materials Science and Engineering, Tsinghua University, Beijing, 100084 (China); Han Bing [Department of Orthodontics, School and Hospital of Stomatology, Peking University, Beijing, 100081 (China); Wang Xinzhi, E-mail: kqdengxuliang@bjmu.edu.cn [Department of Prosthodontics, School and Hospital of Stomatology, Peking University, Beijing, 100081 (China)

    2011-10-15

    In recent years, interest in magnetic biomimetic scaffolds for tissue engineering has increased considerably. The aim of this study is to develop magnetic biodegradable fibrous materials with potential use in bone regeneration. Magnetic biodegradable Fe{sub 3}O{sub 4}/chitosan (CS)/poly vinyl alcohol (PVA) nanofibrous membranes were achieved by electrospinning with average fiber diameters ranging from 230 to 380 nm and porosity of 83.9-85.1%. The influences of polymer concentration, applied voltage and Fe{sub 3}O{sub 4} nanoparticles loading on the fabrication of nanofibers were investigated. The polymer concentration of 4.5 wt%, applied voltage of 20 kV and Fe{sub 3}O{sub 4} nanoparticles loading of lower than 5 wt% could produce homogeneous, smooth and continuous Fe{sub 3}O{sub 4}/CS/PVA nanofibrous membranes. X-ray diffraction (XRD) data confirmed that the crystalline structure of the Fe{sub 3}O{sub 4}, CS and PVA were maintained during electrospinning process. Fourier transform infrared spectroscopy (FT-IR) demonstrated that the Fe{sub 3}O{sub 4} loading up to 5 wt% did not change the functional groups of CS/PVA greatly. Transmission electron microscopy (TEM) showed islets of Fe{sub 3}O{sub 4} nanoparticles evenly distributed in the fibers. Weak ferrimagnetic behaviors of membranes were revealed by vibrating sample magnetometer (VSM) test. Tensile test exhibited Young's modulus of membranes that were gradually enhanced with the increase of Fe{sub 3}O{sub 4} nanoparticles loading, while ultimate tensile stress and ultimate strain were slightly reduced by Fe{sub 3}O{sub 4} nanoparticles loading of 5%. Additionally, MG63 human osteoblast-like cells were seeded on the magnetic nanofibrous membranes to evaluate their bone biocompatibility. Cell growth dynamics according to MTT assay and scanning electron microscopy (SEM) observation exhibited good cell adhesion and proliferation, suggesting that this magnetic biodegradable Fe{sub 3}O{sub 4}/CS/PVA nanofibrous

  17. Layer-by-layer paper-stacking nanofibrous membranes to deliver adipose-derived stem cells for bone regeneration

    Directory of Open Access Journals (Sweden)

    Wan W

    2015-02-01

    Full Text Available Wenbing Wan,1–3,* Shiwen Zhang,2–4,* Liangpeng Ge,2,3,5 Qingtao Li,1 Xingxing Fang,1 Quan Yuan,4 Wen Zhong,6 Jun Ouyang,1 Malcolm Xing1,2,7 1Department of Anatomy, Guangdong Provincial Medical Biomechanical Key Laboratory, Southern Medical University, Guangzhou, People’s Republic of China; 2Department of Mechanical Engineering, University of Manitoba, Winnipeg, MB, Canada; 3Manitoba Institute of Child Health, Winnipeg, MB, Canada; 4Sichuan University, Chengdu, People’s Republic of China; 5Chongqing Academy of Animal Sciences, Chongqing, People’s Republic of China; 6Department of Textile Sciences, University of Manitoba, Winnipeg, MB, Canada; 7Department of Biochemistry and Medical Genetics, University of Manitoba, Winnipeg, MB, Canada *These authors contributed equally to this work Abstract: Bone tissue engineering through seeding of stem cells in three-dimensional scaffolds has greatly improved bone regeneration technology, which historically has been a constant challenge. In this study, we researched the use of adipose-derived stem cell (ADSC-laden layer-by-layer paper-stacking polycaprolactone/gelatin electrospinning nanofibrous membranes for bone regeneration. Using this novel paper-stacking method makes oxygen distribution, nutrition, and waste transportation work more efficiently. ADSCs can also secrete multiple growth factors required for osteogenesis. After the characterization of ADSC surface markers CD29, CD90, and CD49d using flow cytometry, we seeded ADSCs on the membranes and found cells differentiated, with significant expression of the osteogenic-related proteins osteopontin, osteocalcin, and osteoprotegerin. During 4 weeks in vitro, the ADSCs cultured on the paper-stacking membranes in the osteogenic medium exhibited the highest osteogenic-related gene expressions. In vivo, the paper-stacking scaffolds were implanted into the rat calvarial defects (5 mm diameter, one defect per parietal bone for 12 weeks. Investigating

  18. Acceleration of segmental bone regeneration in a rabbit model by strontium-doped calcium polyphosphate scaffold through stimulating VEGF and bFGF secretion from osteoblasts

    Energy Technology Data Exchange (ETDEWEB)

    Gu, Zhipeng [College of Polymer Science and Engineering, Sichuan University, Chengdu 610065 (China); Suzhou Institute of Sichuan University, Suzhou 215123 (China); Zhang, Xu [College of Polymer Science and Engineering, Sichuan University, Chengdu 610065 (China); Li, Li [Department of Oncology, the 452 Hospital of Chinese PLA, Chengdu, Sichuan Province 610021 (China); Wang, Qiguang [College of Polymer Science and Engineering, Sichuan University, Chengdu 610065 (China); Yu, Xixun, E-mail: yuxixun@163.com [College of Polymer Science and Engineering, Sichuan University, Chengdu 610065 (China); Suzhou Institute of Sichuan University, Suzhou 215123 (China); Feng, Ting [The Joint Research Center of West China Second University Hospital of Sichuan University and University of Hong Kong, Chengdu 610041 (China)

    2013-01-01

    The development of suitable bioactive three-dimensional scaffold for the promotion of bone regeneration is critical in bone tissue engineering. The purpose of this study was to investigate in vivo osteogenesis of the porous strontium-doped calcium polyphosphate (SCPP) scaffolds for bone repair, as well as the relationship between osteogenic properties of SCPP scaffolds and the secretion of bFGF and VEGF from osteoblasts stimulated by SCPP. Besides, the advantages of scaffolds seeded with mesenchymal stem cells (MSCs) for bone repair were also studied. Firstly, the bone repair evaluation of scaffolds was performed on a rabbit segmental bony defects model over a period of 16 weeks by histology combined with X-ray microradiography. And then, in order to avoid the influence from the other factors such as hypoxia which emerge in vivo study and affect the secretion of VEGF and bFGF from host cells, human osteoblast-like cells (MG63) were seeded to SCPP, CPP and HA scaffolds in vitro to determine the ability of these scaffolds to stimulate the secretion of angiogenic growth factors (VEGF and bFGF) from MG63 and further explore the reason for the better osteogenic properties of SCPP scaffolds. The histological and X-ray microradiographic results showed that the SCPP scaffolds presented better osteogenic potential than CPP and HA scaffolds, when combined with MSCs, the SCPP scaffolds could further accelerate the bone repair. And the amounts of VEGF measured by ELISA assay in SCPP, CPP and HA groups after cultured for 7 days were about 364.989 pg/mL, 244.035 pg/mL and 232.785 pg/mL, respectively. Accordingly, the amounts of bFGF were about 27.085 pg/mL, 15.727 pg/mL and 8.326 pg/mL. The results revealed that the SCPP scaffolds significantly enhanced the bFGF and VEGF secretion compared with other scaffolds. The results presented in vivo and in vitro study demonstrated that the SCPP could accelerate bone formation through stimulating the secretion of VEGF and bFGF from

  19. Tooth Movement out of the Bony Wall Using Augmented Corticotomy with Nonautogenous Graft Materials for Bone Regeneration

    OpenAIRE

    Kye-Bok Lee; Dong-Yeol Lee; Hyo-Won Ahn; Seong-Hun Kim; Eun-Cheol Kim; Igor Roitman

    2014-01-01

    This prospective randomized split-mouth study was performed to compare the effects of augmented corticotomy with those of different nonautogenous bone graft materials combined with orthodontic tooth movement in dogs. Decortication was performed on the buccal bone surface of 6 male beagle dogs that were randomly assigned to receive grafts of deproteinized bovine bone mineral, irradiated cortical bone, or synthetic bone. Immediate orthodontic force was applied to the second and third premolars ...

  20. Nanoparticulate mineralized collagen scaffolds induce in vivo bone regeneration independent of progenitor cell loading or exogenous growth factor stimulation.

    Science.gov (United States)

    Ren, Xiaoyan; Tu, Victor; Bischoff, David; Weisgerber, Daniel W; Lewis, Michael S; Yamaguchi, Dean T; Miller, Timothy A; Harley, Brendan A C; Lee, Justine C

    2016-05-01

    Current strategies for skeletal regeneration often require co-delivery of scaffold technologies, growth factors, and cellular material. However, isolation and expansion of stem cells can be time consuming, costly, and requires an additional procedure for harvest. Further, the introduction of supraphysiologic doses of growth factors may result in untoward clinical side effects, warranting pursuit of alternative methods for stimulating osteogenesis. In this work, we describe a nanoparticulate mineralized collagen glycosaminoglycan scaffold that induces healing of critical-sized rabbit cranial defects without addition of expanded stem cells or exogenous growth factors. We demonstrate that the mechanism of osteogenic induction corresponds to an increase in canonical BMP receptor signalling secondary to autogenous production of BMP-2 and -9 early and BMP-4 later during differentiation. Thus, nanoparticulate mineralized collagen glycosaminoglycan scaffolds may provide a novel growth factor-free and ex vivo progenitor cell culture-free implantable method for bone regeneration. PMID:26950166

  1. Hybrid Macro-Porous Titanium Ornamented by Degradable 3D Gel/nHA Micro-Scaffolds for Bone Tissue Regeneration

    Science.gov (United States)

    Yin, Bo; Ma, Pei; Chen, Jun; Wang, Hai; Wu, Gui; Li, Bo; Li, Qiang; Huang, Zhifeng; Qiu, Guixing; Wu, Zhihong

    2016-01-01

    Porous titanium is a kind of promising material for bone substitution, while its bio-inert property results in demand of modifications to improve the osteointegration capacity. In this study, gelatin (Gel) and nano-hydroxyapatite (nHA) were used to construct 3D micro-scaffolds in the pores of porous titanium in the ratios of Gel:nHA = 1:0, Gel:nHA = 1:1, and Gel:nHA = 1:3, respectively. Cell attachment and proliferation, and gene and protein expression levels of osteogenic markers were evaluated in MC3T3-E1 cells, followed by bone regeneration assessment in a rabbit radius defect model. All hybrid scaffolds with different composition ratio were found to have significant promotional effects in cell adhesion, proliferation and differentiation, in which the group with Gel:nHA = 1:1 showed the best performance in vitro, as well as the most bone regeneration volume in vivo. This 3D micro-scaffolds modification may be an innovative method for porous titanium ornamentation and shows potential application values in clinic. PMID:27092492

  2. Degradability, biocompatibility, and osteogenesis of biocomposite scaffolds containing nano magnesium phosphate and wheat protein both in vitro and in vivo for bone regeneration.

    Science.gov (United States)

    Xia, Yan; Zhou, Panyu; Wang, Fei; Qiu, Chao; Wang, Panfeng; Zhang, Yuntong; Zhao, Liming; Xu, Shuogui

    2016-01-01

    In this study, bioactive scaffold of nano magnesium phosphate (nMP)/wheat protein (WP) composite (MWC) was fabricated. The results revealed that the MWC scaffolds had interconnected not only macropores (sized 400-600 μm) but also micropores (sized 10-20 μm) on the walls of macropores. The MWC scaffolds containing 40 w% nMP had an appropriate degradability in phosphate-buffered saline and produced a weak alkaline microenvironment. In cell culture experiments, the results revealed that the MWC scaffolds significantly promoted the MC3T3-E1 cell proliferation, differentiation, and growth into the scaffolds. The results of synchrotron radiation microcomputed tomography and analysis of the histological sections of the in vivo implantation revealed that the MWC scaffolds evidently improved the new bone formation and bone defects repair as compared with WP scaffolds. Moreover, it was found that newly formed bone tissue continued to increase with the gradual reduction of materials residual in the MWC scaffolds. Furthermore, the immunohistochemical analysis further offered the evidence of the stimulatory effects of MWC scaffolds on osteogenic-related cell differentiation and new bone regeneration. The results indicated that MWC scaffolds with good biocompability and degradability could promote osteogenesis in vivo, which would have potential for bone tissue repair. PMID:27555766

  3. Degradability, biocompatibility, and osteogenesis of biocomposite scaffolds containing nano magnesium phosphate and wheat protein both in vitro and in vivo for bone regeneration

    Science.gov (United States)

    Xia, Yan; Zhou, Panyu; Wang, Fei; Qiu, Chao; Wang, Panfeng; Zhang, Yuntong; Zhao, Liming; Xu, Shuogui

    2016-01-01

    In this study, bioactive scaffold of nano magnesium phosphate (nMP)/wheat protein (WP) composite (MWC) was fabricated. The results revealed that the MWC scaffolds had interconnected not only macropores (sized 400–600 μm) but also micropores (sized 10–20 μm) on the walls of macropores. The MWC scaffolds containing 40 w% nMP had an appropriate degradability in phosphate-buffered saline and produced a weak alkaline microenvironment. In cell culture experiments, the results revealed that the MWC scaffolds significantly promoted the MC3T3-E1 cell proliferation, differentiation, and growth into the scaffolds. The results of synchrotron radiation microcomputed tomography and analysis of the histological sections of the in vivo implantation revealed that the MWC scaffolds evidently improved the new bone formation and bone defects repair as compared with WP scaffolds. Moreover, it was found that newly formed bone tissue continued to increase with the gradual reduction of materials residual in the MWC scaffolds. Furthermore, the immunohistochemical analysis further offered the evidence of the stimulatory effects of MWC scaffolds on osteogenic-related cell differentiation and new bone regeneration. The results indicated that MWC scaffolds with good biocompability and degradability could promote osteogenesis in vivo, which would have potential for bone tissue repair. PMID:27555766

  4. Development of tissue engineered strategies combining stem cells and scaffolds aimed to regenerate bone and osteochondral interfaces

    OpenAIRE

    Márcia T Rodrigues

    2011-01-01

    Bone is a specialized tissue characterized by its rigidity and hardness, yet light weighed to fulfill diverse functions as mineral storage, organ protection or body support and locomotion. Despite its extraordinary healing ability, bone response may be unsuccessful to repair severe damage caused by injury or degenerative diseases. Furthermore, when bone is affected, other tissues and interfaces might be quite distressed as well. Cartilage and bone interface of the joints (osteo...

  5. The effect of SDF-1α on low dose BMP-2 mediated bone regeneration by release from heparinized mineralized collagen type I matrix scaffolds in a murine critical size bone defect model.

    Science.gov (United States)

    Zwingenberger, Stefan; Langanke, Robert; Vater, Corina; Lee, Geoffrey; Niederlohmann, Eik; Sensenschmidt, Markus; Jacobi, Angela; Bernhardt, Ricardo; Muders, Michael; Rammelt, Stefan; Knaack, Sven; Gelinsky, Michael; Günther, Klaus-Peter; Goodman, Stuart B; Stiehler, Maik

    2016-09-01

    The treatment of critical size bone defects represents a challenge. The growth factor bone morphogenetic protein 2 (BMP-2) is clinically established but has potentially adverse effects when used at high doses. The aim of this study was to evaluate if stromal derived factor-1 alpha (SDF-1α) and BMP-2 released from heparinized mineralized collagen type I matrix (MCM) scaffolds have a cumulative effect on bone regeneration. MCM scaffolds were functionalized with heparin, loaded with BMP-2 and/or SDF-1α and implanted into a murine critical size femoral bone defect (control group, low dose BMP-2 group, low dose BMP-2 + SDF-1α group, and high dose BMP-2 group). After 6 weeks, both the low dose BMP-2 + SDF-1α group (5.8 ± 0.6 mm³, p = 0.0479) and the high dose BMP-2 group (6.5 ± 0.7 mm³, p = 0.008) had a significantly increased regenerated bone volume compared to the control group (4.2 ± 0.5 mm³). There was a higher healing score in the low dose BMP-2 + SDF-1α group (median grade 8; Q1-Q3 7-9; p = 0.0357) than in the low dose BMP-2 group (7; Q1-Q3 5-9) histologically. This study showed that release of BMP-2 and SDF-1α from heparinized MCM scaffolds allows for the reduction of the applied BMP-2 concentration since SDF-1α seems to enhance the osteoinductive potential of BMP-2. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 104A: 2126-2134, 2016. PMID:27060915

  6. Efficacy of Mucograft vs Conventional Resorbable Collagen Membranes in Guided Bone Regeneration Around Standardized Calvarial Defects in Rats: A Histologic and Biomechanical Assessment.

    Science.gov (United States)

    Ramalingam, Sundar; Babay, Nadir; Al-Rasheed, Abdulaziz; Nooh, Nasser; Naghshbandi, Jafar; Aldahmash, Abdullah; Atteya, Muhammad; Al-Hezaimi, Khalid

    2016-01-01

    Guided bone regeneration (GBR) using a porcine-derived collagen matrix (Mucograft [MG], Geistlich) has not yet been reported. The aim of this histologic and biomechanical study was to compare the efficacy of MG versus resorbable collagen membranes (RCMs) in facilitating GBR around standardized rat calvarial defects. Forty female Wistar albino rats with a mean age and weight of 6 to 9 weeks and 250 to 300 g, respectively, were used. With the rats under general anesthesia, the skin over the calvaria was exposed using a full-thickness flap. A 4.6-mm-diameter standardized calvarial defect was created in the left parietal bone. For treatment, the rats were randomly divided into four groups (n = 10 per group): (1) MG group: the defect was covered with MG; (2) RCM group: the defect was covered with an RCM; (3) MG + bone group: the defect was filled with bone graft particles and covered by MG; and (4) RCM + bone group: the defect was filled with bone graft particles and covered by an RCM. Primary closure was achieved using interrupted resorbable sutures. The animals were sacrificed at 8 weeks after the surgical procedures. Qualitative histologic analysis and biomechanical assessment to identify hardness and elastic modulus of newly formed bone (NFB) were performed. Collected data were statistically analyzed using one-way analysis of variance. Histologic findings revealed NFB with fibrous connective tissue in all groups. The quantity of NFB was highest in the RCM + bone group. Statistically significant differences in the hardness (F = 567.69, dfN = 3, dfD = 36, P RCM + bone group had the highest mean ± standard deviation (SD) hardness of NFB (531.4 ± 24.9 MPa), the RCM group had the highest mean ± SD elastic modulus of NFB (18.63 ± 1.89 GPa). The present study demonstrated that RCMs are better than MG at enhancing new bone formation in standardized rat calvarial defects when used along with mineralized particulate graft material. PMID:27031638

  7. Tooth Movement out of the Bony Wall Using Augmented Corticotomy with Nonautogenous Graft Materials for Bone Regeneration

    Directory of Open Access Journals (Sweden)

    Kye-Bok Lee

    2014-01-01

    Full Text Available This prospective randomized split-mouth study was performed to compare the effects of augmented corticotomy with those of different nonautogenous bone graft materials combined with orthodontic tooth movement in dogs. Decortication was performed on the buccal bone surface of 6 male beagle dogs that were randomly assigned to receive grafts of deproteinized bovine bone mineral, irradiated cortical bone, or synthetic bone. Immediate orthodontic force was applied to the second and third premolars for buccal tipping for 6 weeks. The pocket depth and width of keratinized tissue (WKT were measured. Histologic and histomorphometric analyses were performed. The probing depth, WKT, and ratio of the area of new bone to that of total bone on the buccal side were not significantly different between groups. All groups had considerable new bone formation on the pressure side. New bone formation on the buccal side and buccal plate formation in the coronal direction along the root surfaces were induced by the bone-derived and PDL-derived mesenchymal matrix, respectively. The angular change between groups was significantly different (P < 0.001. Augmented corticotomy using nonautogenous graft materials facilitated tooth movement without fenestrations and accelerated new bone formation on the pressure side.

  8. Tooth movement out of the bony wall using augmented corticotomy with nonautogenous graft materials for bone regeneration.

    Science.gov (United States)

    Lee, Kye-Bok; Lee, Dong-Yeol; Ahn, Hyo-Won; Kim, Seong-Hun; Kim, Eun-Cheol; Roitman, Igor

    2014-01-01

    This prospective randomized split-mouth study was performed to compare the effects of augmented corticotomy with those of different nonautogenous bone graft materials combined with orthodontic tooth movement in dogs. Decortication was performed on the buccal bone surface of 6 male beagle dogs that were randomly assigned to receive grafts of deproteinized bovine bone mineral, irradiated cortical bone, or synthetic bone. Immediate orthodontic force was applied to the second and third premolars for buccal tipping for 6 weeks. The pocket depth and width of keratinized tissue (WKT) were measured. Histologic and histomorphometric analyses were performed. The probing depth, WKT, and ratio of the area of new bone to that of total bone on the buccal side were not significantly different between groups. All groups had considerable new bone formation on the pressure side. New bone formation on the buccal side and buccal plate formation in the coronal direction along the root surfaces were induced by the bone-derived and PDL-derived mesenchymal matrix, respectively. The angular change between groups was significantly different (P corticotomy using nonautogenous graft materials facilitated tooth movement without fenestrations and accelerated new bone formation on the pressure side. PMID:25247172

  9. Testing stem cell therapy in a rat model of inflammatory bowel disease: role of bone marrow stem cells and stem cell factor in mucosal regeneration.

    Directory of Open Access Journals (Sweden)

    Bo Qu

    Full Text Available BACKGROUND: The gastrointestinal (GI mucosal cells turnover regularly under physiological conditions, which may be stimulated in various pathological situations including inflammation. Local epithelial stem cells appear to play a major role in such mucosal renewal or pathological regeneration. Less is clear about the involvement of multipotent stem cells from blood in GI repair. We attempted to explore a role of bone marrow mesenchymal stromal cells (BMMSCs and soluble stem cell factor (SCF in GI mucosa regeneration in a rat model of inflammatory bowel diseases (IBD. METHODS: BMMSCs labelled with the fluorescent dye PKH26 from donor rats were transfused into rats suffering indomethacin-induced GI injury. Experimental effects by BMMSCs transplant and SCF were determined by morphometry of intestinal mucosa, double labeling of PKH26 positive BMMSCs with endogenous proliferative and intestinal cell markers, and western blot and PCR analyses of the above molecular markers in the recipient rats relative to controls. RESULTS: PKH26 positive BMMSCs were found in the recipient mucosa, partially colocalizing with the proliferating cell nuclear antigen (PCNA, Lgr5, Musashi-1 and ephrin-B3. mRNA and protein levels of PCNA, Lgr5, Musashi-1 and ephrin-B3 were elevated in the intestine in BMMSCs-treated rats, most prominent in the BMMSCs-SCF co-treatment group. The mucosal layer and the crypt layer of the small intestine were thicker in BMMSCs-treated rats, more evident in the BMMSCs-SCF co-treatment group. CONCLUSION: BMMSCs and SCF participate in but may play a synergistic role in mucosal cell regeneration following experimentally induced intestinal injury. Bone marrow stem cell therapy and SCF administration may be of therapeutic value in IBD.

  10. Regeneration of human bones in hip osteonecrosis and human cartilage in knee osteoarthritis with autologous adipose-tissue-derived stem cells: a case series

    Directory of Open Access Journals (Sweden)

    Pak Jaewoo

    2011-07-01

    Full Text Available Abstract Introduction This is a series of clinical case reports demonstrating that a combination of percutaneously injected autologous adipose-tissue-derived stem cells, hyaluronic acid, platelet rich plasma and calcium chloride may be able to regenerate bones in human osteonecrosis, and with addition of a very low dose of dexamethasone, cartilage in human knee osteoarthritis. Case reports Stem cells were obtained from adipose tissue of abdominal origin by digesting lipoaspirate tissue with collagenase. These stem cells, along with hyaluronic acid, platelet rich plasma and calcium chloride, were injected into the right hip of a 29-year-old Korean woman and a 47-year-old Korean man. They both had a history of right hip osteonecrosis of the femoral head. For cartilage regeneration, a 70-year-old Korean woman and a 79-year-old Korean woman, both with a long history of knee pain due to osteoarthritis, were injected with stem cells along with hyaluronic acid, platelet rich plasma, calcium chloride and a nanogram dose of dexamethasone. Pre-treatment and post-treatment MRI scans, physical therapy, and pain score data were then analyzed. Conclusions The MRI data for all the patients in this series showed significant positive changes. Probable bone formation was clear in the patients with osteonecrosis, and cartilage regeneration in the patients with osteoarthritis. Along with MRI evidence, the measured physical therapy outcomes, subjective pain, and functional status all improved. Autologous mesenchymal stem cell injection, in conjunction with hyaluronic acid, platelet rich plasma and calcium chloride, is a promising minimally invasive therapy for osteonecrosis of femoral head and, with low-dose dexamethasone, for osteoarthritis of human knees.

  11. Testing Stem Cell Therapy in a Rat Model of Inflammatory Bowel Disease: Role of Bone Marrow Stem Cells and Stem Cell Factor in Mucosal Regeneration

    Science.gov (United States)

    Qu, Bo; Xin, Guo-Rong; Zhao, Li-Xia; Xing, Hui; Lian, Li-Ying; Jiang, Hai-Yan; Tong, Jia-Zhao; Wang, Bei-Bei; Jin, Shi-Zhu

    2014-01-01

    Background The gastrointestinal (GI) mucosal cells turnover regularly under physiological conditions, which may be stimulated in various pathological situations including inflammation. Local epithelial stem cells appear to play a major role in such mucosal renewal or pathological regeneration. Less is clear about the involvement of multipotent stem cells from blood in GI repair. We attempted to explore a role of bone marrow mesenchymal stromal cells (BMMSCs) and soluble stem cell factor (SCF) in GI mucosa regeneration in a rat model of inflammatory bowel diseases (IBD). Methods BMMSCs labelled with the fluorescent dye PKH26 from donor rats were transfused into rats suffering indomethacin-induced GI injury. Experimental effects by BMMSCs transplant and SCF were determined by morphometry of intestinal mucosa, double labeling of PKH26 positive BMMSCs with endogenous proliferative and intestinal cell markers, and western blot and PCR analyses of the above molecular markers in the recipient rats relative to controls. Results PKH26 positive BMMSCs were found in the recipient mucosa, partially colocalizing with the proliferating cell nuclear antigen (PCNA), Lgr5, Musashi-1 and ephrin-B3. mRNA and protein levels of PCNA, Lgr5, Musashi-1 and ephrin-B3 were elevated in the intestine in BMMSCs-treated rats, most prominent in the BMMSCs-SCF co-treatment group. The mucosal layer and the crypt layer of the small intestine were thicker in BMMSCs-treated rats, more evident in the BMMSCs-SCF co-treatment group. Conclusion BMMSCs and SCF participate in but may play a synergistic role in mucosal cell regeneration following experimentally induced intestinal injury. Bone marrow stem cell therapy and SCF administration may be of therapeutic value in IBD. PMID:25309991

  12. Integration of a Novel Injectable Nano Calcium Sulfate/Alginate Scaffold and BMP2 Gene-Modified Mesenchymal Stem Cells for Bone Regeneration

    Science.gov (United States)

    He, Xiaoning; Dziak, Rosemary; Mao, Keya; Genco, Robert; Swithart, Mark; Li, Chunyi

    2013-01-01

    The repair of craniofacial bone defects is surgically challenging due to the complex anatomical structure of the craniofacial skeleton. Current strategies for bone tissue engineering using a preformed scaffold have not resulted in the expected clinical regeneration due to difficulty in seeding cells into the deep internal space of scaffold, and the inability to inject them in minimally invasive surgeries. In this study, we used the osteoconductive and mechanical properties of nano-scale calcium sulfate (nCS) and the biocompatibility of alginate to develop the injectable nCS/alginate (nCS/A) paste, and characterized the effect of this nCS/A paste loaded with bone morphogenetic protein 2 (BMP2) gene-modified rat mesenchymal stem cells (MSCs) on bone and blood vessel growth. Our results showed that the nCS/A paste was injectable under small injection forces. The mechanical properties of the nCS/A paste were increased with an increased proportion of alginate. MSCs maintained their viability after the injection, and MSCs and BMP2 gene-modified MSCs in the injectable pastes remained viable, osteodifferentiated, and yielded high alkaline phosphatase activity. By testing the ability of this injectable paste and BMP2-gene-modified MSCs for the repair of critical-sized calvarial bone defects in a rat model, we found that BMP2-gene-modified MSCs in nCS/A (nCS/A+M/B2) showed robust osteogenic activity, which resulted in consistent bone bridging of the bone defects. The vessel density in nCS/A+M/B2 was significantly higher than that in the groups of blank control, nCS/A alone, and nCS/A mixed with MSCs (nCS/A+M). These results indicate that BMP2 promotes MSCs-mediated bone formation and vascularization in nCS/A paste. Overall, the results demonstrated that the combination of injectable nCS/A paste and BMP2-gene-modified MSCs is a new and effective strategy for the repair of bone defects. PMID:22994418

  13. Can the material properties of regenerate bone be predicted with non-invasive methods of assessment? Exploring the correlation between dual X-ray absorptiometry and compression testing to failure in an animal model of distraction osteogenesis.

    Science.gov (United States)

    Monsell, Fergal; Hughes, Andrew William; Turner, James; Bellemore, Michael C; Bilston, Lynne

    2014-04-01

    Evaluation of the material properties of regenerate bone is of fundamental importance to a successful outcome following distraction osteogenesis using an external fixator. Plain radiographs are in widespread use for assessment of alignment and the distraction gap but are unable to detect bone formation in the early stages of distraction osteogenesis and do not quantify accurately the structural properties of the regenerate. Dual X-ray absorptiometry (DXA) is a widely available non-invasive imaging modality that, unlike X-ray, can be used to measure bone mineral content (BMC) and density quantitatively. In order to be useful as a clinical investigation; however, the structural two-dimensional geometry and density distributions assessed by DXA should reflect material properties such as modulus and also predict the structural mechanical properties of the regenerate bone formed. We explored the hypothesis that there is a relationship between DXA assessment of regenerate bone and structural mechanical properties in an animal model of distraction osteogenesis. Distraction osteogenesis was carried out on the tibial diaphysis of 41 male, 12 week old, New Zealand white rabbits as part of a larger study. Distraction started after a latent period of 24 h at a rate of 0.375 mm every 12 h and continued for 10-days, achieving average lengthening of 7.1 mm. Following an 18-day period of consolidation, the regenerate bone was subject to bone density measurements using a total body dual-energy X-ray densitometer. This produced measurement of BMC, bone mineral density (BMD) and volumetric bone mineral density (vBMD). The tibiae were then disarticulated and cleaned of soft tissue before loading in compression to failure using an Instron mechanical testing machine (Instron Corporation, Massachusetts USA). Using Spearman rank correlation and linear regression, there was a significant correlation between vBMD and the Modulus of Elasticity, Yield Stress and Failure Stress of the

  14. Validity of T2 mapping in characterization of the regeneration tissue by bone marrow derived cell transplantation in osteochondral lesions of the ankle

    International Nuclear Information System (INIS)

    Objective: Bone marrow derived cell transplantation (BMDCT) has been recently suggested as a possible surgical technique to repair osteochondral lesions. To date, no qualitative MRI studies have evaluated its efficacy. The aim of our study is to investigate the validity of MRI T2-mapping sequence in characterizing the reparative tissue obtained and its ability to correlate with clinical results. Methods and materials: 20 patients with an osteochondral lesion of the talus underwent BMDCT and were evaluated at 2 years follow up using MRI T2-mapping sequence. 20 healthy volunteers were recruited as controls. MRI images were acquired using a protocol suggested by the International Cartilage Repair Society, MOCART scoring system and T2 mapping. Results were then correlated with AOFAS clinical score. Results: AOFAS score increased from 66.8 ± 14.5 pre-operatively to 91.2 ± 8.3 (p < 0.0005) at 2 years follow-up. T2-relaxation time value of 35-45 ms was derived from healthy ankles evaluation and assumed as normal hyaline cartilage value and used as a control. Regenerated tissue with a T2-relaxation time value comparable to hyaline cartilage was found in all the cases treated, covering a mean of 78% of the repaired lesion area. A high clinical score was related directly to isointense signal in DPFSE fat sat (p = 0.05), and percentage of regenerated hyaline cartilage (p = 0.05), inversely to the percentage of regenerated fibrocartilage. Lesion's depth negatively related to the integrity of the repaired tissue's surface (tau = -0.523, p = 0.007), and to the percentage of regenerated hyaline cartilage (rho = -0.546, p = 0.013). Conclusions: Because of its ability to detect cartilage's quality and to correlate to the clinical score, MRI T2-mapping sequence integrated with Mocart score represent a valid, non-invasive technique for qualitative cartilage assessment after regenerative surgical procedures.

  15. Validity of T2 mapping in characterization of the regeneration tissue by bone marrow derived cell transplantation in osteochondral lesions of the ankle

    Energy Technology Data Exchange (ETDEWEB)

    Battaglia, M., E-mail: milva.battaglia@ior.it [Service of Ecography and Radiology, Rizzoli Orthopaedic Institute, via Pupilli n. 1, 40136 Bologna (Italy); Rimondi, E. [Service of Ecography and Radiology, Rizzoli Orthopaedic Institute, via Pupilli n. 1, 40136 Bologna (Italy); Monti, C. [Service of CT and MRI, Casa di Cura Madre Fortunata Toniolo, Bologna (Italy); Guaraldi, F. [Department of Pathology, The Johns Hopkins University, School of Medicine, Baltimore, MD (United States); Sant' Andrea, A. [Service of CT and MRI, Casa di Cura Madre Fortunata Toniolo, Bologna (Italy); Buda, R.; Cavallo, M.; Giannini, S.; Vannini, F. [Clinical Orthopaedic and Traumatology Unit II, Rizzoli Orthopaedic Institute, Bologna (Italy)

    2011-11-15

    Objective: Bone marrow derived cell transplantation (BMDCT) has been recently suggested as a possible surgical technique to repair osteochondral lesions. To date, no qualitative MRI studies have evaluated its efficacy. The aim of our study is to investigate the validity of MRI T2-mapping sequence in characterizing the reparative tissue obtained and its ability to correlate with clinical results. Methods and materials: 20 patients with an osteochondral lesion of the talus underwent BMDCT and were evaluated at 2 years follow up using MRI T2-mapping sequence. 20 healthy volunteers were recruited as controls. MRI images were acquired using a protocol suggested by the International Cartilage Repair Society, MOCART scoring system and T2 mapping. Results were then correlated with AOFAS clinical score. Results: AOFAS score increased from 66.8 {+-} 14.5 pre-operatively to 91.2 {+-} 8.3 (p < 0.0005) at 2 years follow-up. T2-relaxation time value of 35-45 ms was derived from healthy ankles evaluation and assumed as normal hyaline cartilage value and used as a control. Regenerated tissue with a T2-relaxation time value comparable to hyaline cartilage was found in all the cases treated, covering a mean of 78% of the repaired lesion area. A high clinical score was related directly to isointense signal in DPFSE fat sat (p = 0.05), and percentage of regenerated hyaline cartilage (p = 0.05), inversely to the percentage of regenerated fibrocartilage. Lesion's depth negatively related to the integrity of the repaired tissue's surface (tau = -0.523, p = 0.007), and to the percentage of regenerated hyaline cartilage (rho = -0.546, p = 0.013). Conclusions: Because of its ability to detect cartilage's quality and to correlate to the clinical score, MRI T2-mapping sequence integrated with Mocart score represent a valid, non-invasive technique for qualitative cartilage assessment after regenerative surgical procedures.

  16. Phenotypic and functional properties of murine thymocytes. II. Quantitation of host- and donor-derived cytolytic T lymphocyte precursors in regenerating radiation bone marrow chimeras

    International Nuclear Information System (INIS)

    Thymocytes from radiation bone marrow chimeras, in which donor bone marrow and irradiated recipient differed at the Thy-1 locus, were stained by indirect immunofluorescence with monoclonal anti-Thy-1 antibodies and analyzed by flow microfluorometry (FMF). Kinetic studies indicated an early appearance of host-derived (CBA, Thy-1.2+) thymocytes, which reaches maximum number of 10 to 20 x 106 cells at 12 to 16 days after bone marrow reconstitution. Donor-derived (AKR, Thy-1.1+) cells were not detectable until 10 to 12 days after reconstitution; subsequently, they increased exponentially in number until 28 days, when they accounted for essentially all cells in the thymus (50 x 106). Concomitant with the appearance and disappearance of host-derived cells was a change in their Thy-1 surface phenotype. In particular, the proportion of host cells having a ''mature'' phenotype (weakly Thy-1.2 staining) increased progressively with time after irradiation. Functional studies using a sensitive mixed leukocyte microculture system to quantitate cytolytic T lymphocyte precursors (CTL-P) were also carried out in regenerating chimeric thymuses. Initially, the regenerating thymus contained few CTL-P, but by 4 wk after reconstitution, frequencies similar to control adult thymuses were obtained. Analysis of the CTL-P content of host and donor-derived subpopulations, separated either by appropriate anti-Thy-1 antibody plus complement or by direct cell sorting, indicated that both host- and donor-derived cells contained appreciable numbers of CTL-P. Furthermore, increases in CTL-P frequency of both host and donor subpopulations correlated with changes in their surface Thy-1 phenotype

  17. Real-Time Assessment of Guided Bone Regeneration in Standardized Calvarial Defects Using a Combination of Bone Graft and Platelet-Derived Growth Factor With and Without Collagen Membrane: An In Vivo Microcomputed Tomographic and Histologic Experiment in Rats.

    Science.gov (United States)

    Alrasheed, Abdulaziz; Al-Ahmari, Fatemah; Ramalingam, Sundar; Nooh, Nasser; Wang, Cun-Yu; Al-Hezaimi, Khalid

    2016-01-01

    The aim of the present in vivo microcomputed tomography (μCT) and histologic experiment was to assess the efficacy of guided bone regeneration (GBR) around standardized calvarial defects using recombinant human platelet-derived growth factor (rhPDGF) with and without resorbable collagen membrane (RCM). A total of 50 female Wistar albino rats with a mean age of 7.5 months and mean weight of 275 g were used. The calvarium was exposed following midsagittal scalp incision and flap reflection. A full-thickness standardized calvarial defect (4.6 mm diameter) was created. Study animals were randomly divided into five groups based on biomaterials used for GBR within the defect: (1) no treatment (negative control), (2) bone graft alone (BG), (3) bone graft covered by RCM (BG + RCM), (4) bone graft soaked in rhPDGF (BG + rhPDGF), and (5) bone graft soaked in rhPDGF and covered with RCM (BG + rhPDGF + RCM). In vivo μCT for determination of newly formed bone volume (NFBV) and mineral density (NFBMD) and remnant bone particles volume (RBPV) and mineral density (RBPMD) was done at baseline and at 2, 4, 6, and 8 weeks postoperatively. Eight weeks following surgery, the animals were sacrificed and harvested calvarial specimens were subjected to histologic and biomechanical analysis. There was an increase in NFBV and NFBMD associated with a corresponding decrease in RBPV and RBPMD in all the study groups. Two-way analysis of variance revealed significant differences in the measured values within and between the groups across the timelines examined during the study period (P RCM, and BG + rhPDGF + RCM groups, the NFBMD was similar in all the groups except negative control. The greatest decreases in RBPV and RBPMD were observed in the BG + rhPDGF + RCM group in comparison to the other groups. Similarly, BG + rhPDGF + RCM groups had hardness and elastic modulus similar to that of natural bone. The in vivo μCT results were validated by the qualitative histologic findings. In real

  18. Estrogen enhances the bone regeneration potential of periodontal ligament stem cells derived from osteoporotic rats and seeded on nano-hydroxyapatite/collagen/poly(L-lactide).

    Science.gov (United States)

    E, Ling-Ling; Xu, Wen-Huan; Feng, Lin; Liu, Yi; Cai, Dong-Qing; Wen, Ning; Zheng, Wen-Jie

    2016-06-01

    This study investigated the effects of estrogen on the bone regeneration potential of periodontal ligament stem cells (PDLSCs) derived from osteoporotic rats and seeded on a collagen-based composite scaffold [nano-hydroxyapatite/collagen/poly(L-lactide) (nHAC/PLA)]. For this purpose, 48 healthy 3‑month-old Sprague-Dawley female rats were divided into 2 groups as follows: the bilaterally ovariectomized (OVX) rats and sham‑operated rats. The PDLSCs were isolated at 3 months after surgery (by which time postmenopausal osteoporosis had developed). The effects of estrogen on the characteristics of these cells seeded in a culture plate and of the cells seeded on nHAC/PLA were then investigated. The PDLSC + nHAC/PLA constructs were implanted subcutaneously into the backs of severe combined immunodeficient (SCID) mice for 12 weeks in order to examine the role of estrogen in the bone formation ability of PDLSCs derived from osteoporotic rats. The results from methyl thiazolyl tetrazolium (MTT) assay revealed that the proliferation of the cells derived from the rats in the OVX group was significantly higher than that of the cells derived from the rats in the sham-operated group at the stage of logarithmic growth. The staining intensity of alkaline phosphatase (ALP) and the mineralization of the cells derived from the rats in the OVX group was significantly weaker than that of the cells from the rats in the sham-operated group. When the PDLSCs were seeded on nHAC/PLA, ALP activity, osteocalcin (OCN) secretion, mineral formation and the mRNA expression levels of ALP, OCN, estrogen receptor (ER)α and ERβ in the cells derived from the rats in the OVX group were markedly decreased. Treatment with 17β-estradiol (E2) significantly weakened the proliferative ability of the cells derived from the OVX group rats, and enhanced their osteogenic differentiation ability and the mRNA expression levels of ALP, OCN, ERα and ERβ. When the constructs were implanted

  19. Bone marrow stromal cells cultured on poly (lactide-co-glycolide)/nano-hydroxyapatite composites with chemical immobilization of Arg-Gly-Asp peptide and preliminary bone regeneration of mandibular defect thereof.

    Science.gov (United States)

    Huang, Yanxia; Ren, Jie; Ren, Tianbin; Gu, Shuying; Tan, Qinggang; Zhang, Lihong; Lv, Kaige; Pan, Kefeng; Jiang, Xinquan

    2010-12-15

    Polyethyleneimine (PEI) was used to create active groups on the poly (lactide-co-glycolide)/nano-hydroxyapatite (PLGA/NHA) surface and Arg-Gly-Asp (RGD) was grafted on the active groups and novel PLGA/NHA 2-D membranes and 3D scaffolds modified with RGD were obtained. X-ray photoelectron spectrum (XPS) results show that sulfur displays only on the modified surface. The RGD-modified PLGA/NHA materials also have much lower static water contact angle and much higher water-absorption ability, which shows that after chemical treatment, the modified materials show better hydrophilic properties. Atomic force microscope (AFM) shows that after surface modification, the surface morphology of PLGA is greatly changed. All these results indicate that RGD peptide has successfully grafted on the surface of PLGA. Rabbit bone marrow stromal cells (MSCs) were seeded in the 2D membranes and 3D scaffolds materials. The influences of the RGD on the cell attachment, growth and differentiation, and proliferation on the different materials were studied. The modified scaffolds were implanted into rabbits to observe preliminary application in regeneration of mandibular defect. The PLGA/NHA-RGD presents better results in bone regeneration in rabbit mandibular defect. PMID:20872750

  20. The application of bone morphogenetic proteins to periodontal and peri-implant tissue regeneration: A literature review

    OpenAIRE

    Sasikumar, Karuppanan P.; Sugumari Elavarasu; Jayaprakash S Gadagi

    2012-01-01

    Progress in understanding the role of bone morphogenetic proteins (BMPs) in craniofacial and tooth development and the demonstration of stem cells in periodontal ligament have set the stage for periodontal regenerative therapy and tissue engineering. Furthermore, recent approval by the Food and Drug Administration of recombinant human BMPs for accelerating bone fusion in slow-healing fractures indicates that this protein family may prove useful in designing regenerative treatments in periodon...

  1. Fabrication and characterization of polycaprolactone cross- linked and highly-aligned 3-D artificial scaffolds for bone tissue regeneration via electrospinning technology

    Science.gov (United States)

    Gorodzha, S. N.; Surmeneva, M. A.; Surmenev, R. A.

    2015-11-01

    Novel technologies allowed the scientific community to develop scaffolds for regeneration of bone tissue. A successful scaffold should possess specific macroscopic geometry and internal architecture to perform biological and biophysical functions. In this study the process of polycaprolactone microfibrous development with either cross-linked or highly-aligned three-dimensional artificial mats via electrospinning technology for potential application in tissue engineering is described. The morphology and size of electrospun fibers were assessed systematically by varying the rotation speed of grounded collector. It was found that the diameter of the fibers decreased by increasing the rotation speed of collector. The morphology of the fibers changed from cross-linked to highly-aligned at appr. 1000-1100 rpm.

  2. Three-Dimensional Bone Regeneration of Alveolar Ridge Defects Using Corticocancellous Allogeneic Block Grafts: Histologic and Immunohistochemical Analysis.

    Science.gov (United States)

    Jun, Choong-Man; Yun, Jeong-Ho

    2016-01-01

    In this study, the effectiveness of a corticocancellous block allograft for restoring alveolar ridge defects in preparation for the placement of dental implants was assessed. Significant ridge defects in four partially edentulous patients were reconstructed using an irradiated corticocancellous allogeneic block soaked in platelet-rich plasma, which was also covered with a resorbable collagen membrane. After 5 or 6 months, the sites were reentered and a trephine bone core specimen was obtained from each augmented site for histologic, histomorphometric, and immunohistochemical assessment. In all four cases, histologic evaluation of the augmented site showed areas of new vital bone formation around the graft material (mean newly formed bone fraction, 23.7%; mean total mineralized tissue fraction, 40.1%), in which osteocytes were frequently observed within the lacunae. Immunohistochemical analysis showed the presence of biomarkers commonly related to active bone formation (alkaline phosphatase, osteocalcin, and bone morphogenetic protein-2), confirming that the biochemical environment was conducive to new bone formation. The findings of this study demonstrate that the use of allogeneic block grafts for restoring alveolar ridge defects prior to the placement of dental implants may be an effective and advantageous alternative to autograft procedures. PMID:26697555

  3. Functional Self-Assembled Peptide Nanofibers for Bone Marrow Mesenchymal Stem Cell Encapsulation and Regeneration in Nucleus Pulposus.

    Science.gov (United States)

    Wu, Yaohong; Jia, Zhiwei; Liu, Longgang; Zhao, Yachao; Li, Hao; Wang, Chaofeng; Tao, Hui; Tang, Yong; He, Qing; Ruan, Dike

    2016-06-01

    Low back pain (LBP) is mainly caused by intervertebral disc degeneration (IDD). Recent studies have demonstrated that the transplantation of mesenchymal stem cells (MSCs) can regenerate regions that have undergone degeneration, and the regenerative effect can be enhanced by using a hydrogel carrier. This article describes an injectable functional hydrogel system manufactured by combining RADA16-I and RADA-KPSS (RADA-KPSS was manufactured by conjugating a bioactive motif derived from BMP-7 [KPSS] onto the C terminal of RADA16-I) at a volume ratio of 1:1. This hydrogel system can enhance the proliferation, differentiation, and chemotactic migration of BMSCs. In addition, the encapsulation of BMSCs with this system maintains cell viability for a long period after transplantation into an ex vivo cultured disc model. In conclusion, KPSS-conjugated RADKPS is an ideal encapsulation system for BMSCs in intervertebral disc (IVD) regeneration. PMID:27153338

  4. Clinical comparison of guided tissue regeneration, with collagen membrane and bone graft, versus connective tissue graft in the treatment of gingival recessions

    Directory of Open Access Journals (Sweden)

    Haghighati F

    2006-06-01

    Full Text Available Background and Aim: Increasing patient demands for esthetic, put the root coverage procedures in particular attention. Periodontal regeneration with GTR based root coverage methods is the most common treatment used. The purpose of this study was to compare guided tissue regeneration (GTR with collagen membrane and a bone graft, with sub-epithelial connective tissue graft (SCTG, in treatment of gingival recession. Materials and Methods: In this randomized clinical trial study, eleven healthy patients with no systemic diseases who had miller’s class I or II recession defects (gingival recession  2mm were treated with SCTG or GTR using a collagen membrane and a bone graft. Clinical measurements were obtained at baseline and 6 months after surgery. These clinical measurements included recession depth (RD, recession width (RW, probing depth (PD, and clinical attachment level (CAL. Data were analyzed using independent t test with p<0.05 as the limit of significance. Results: Both treatment methods resulted in a statistically significant reduction of recession depth (SCTG=2.3mm, GTR=2.1mm; P<0.0001. CAL gain after 6 months was also improved in both groups (SCG= 2.5mm, GTR=2.1mm, compared to baseline (P<0.0001. No statistical differences were observed in RD, RW, CAL between test and control groups. Root coverage was similar in both methods (SCTG= 74.2%, GTR= 62.6%, P=0.87. Conclusion: Based on the results of this study, the two techniques are clinically comparable. Therefore the use of collagen membrane and a bovine derived xenograft may alleviate the need for connective tissue graft.

  5. Influence of chondroitin sulfate and hyaluronic acid presence in nanofibers and its alignment on the bone marrow stromal cells: cartilage regeneration.

    Science.gov (United States)

    Lee, Paul; Tran, Katelyn; Chang, Wei; Shelke, Namdev B; Kumbar, Sangamesh G; Yu, Xiaojun

    2014-08-01

    Cartilage degeneration is the major cause of disability and poses several challenges to repair and regenerate. Conventional surgical treatments often induce fibrous tissues and compromise its function. Alternative tissue engineering strategies utilized scaffolds, factors and cells alone or in combination with some degree of success. This study reports the use of nanostructured biomimetic scaffold system in regulating the rat bone marrow stem cells (rBMSCs) differentiation into chondrogenic lineage in vitro. The biometric scaffold is essentially a micro-porous polycaprolactone (PCL) spiral structure decorated with sparsely spaced bioactive PCL nanofibers. The bioactivity stems from the use of two major components of hyaline cartilage extracellular matrix (ECM) namely chondroitin sulfate (CS) and hyaluronic acid (HYA). The PCL spiral structure was surface functionalized with PCL nanofibers encapsulated with CS (20% (w/w)) and HYA (0.2% (w/w)). In order to retain and sustain the release of CS and HYA nanofibers were cross-linked using carbodiimide chemistry. This study also evaluated the effect of nanofiber alignment on rBMSCs differentiation and evaluated the production of characteristic hyaline cartilage proteins namely collagen type II and aggrecan in vitro up to 28 days. Rat bone marrow derived stem cells cultured on the aligned nanofibers expressed significantly elevated levels of collagen type II and aggrecan secretions (western blots) as compared to scaffolds decorated with random fibers and tissue culture polystyrene (TCPS). This fiber alignment dependent expression of collagen type II and aggrecan secretion were further confirmed through immunofluorescence staining. This biomimetic and bioactive scaffold may serve as a serve as an efficient scaffold system for cartilage regeneration. PMID:25016647

  6. Bone regenerating effect of surface-functionalized titanium implants with sustained-release characteristics of strontium in ovariectomized rats

    Science.gov (United States)

    Offermanns, Vincent; Andersen, Ole Zoffmann; Riede, Gregor; Andersen, Inge Hald; Almtoft, Klaus Pagh; Sørensen, Søren; Sillassen, Michael; Jeppesen, Christian Sloth; Rasse, Michael; Foss, Morten; Kloss, Frank

    2016-01-01

    Since strontium (Sr) is known for its anabolic and anticatabolic effect on bone, research has been focused on its potential impact on osseointegration. The objective of this study was to investigate the performance of nanotopographic implants with a Sr-functionalized titanium (Ti) coating (Ti–Sr–O) with respect to osseointegration in osteoporotic bone. The trial was designed to examine the effect of sustained-release characteristics of Sr in poor-quality bone. Three Ti–Sr–O groups, which differed from each other in coating thickness, Sr contents, and Sr release, were examined. These were prepared by a magnetron sputtering process and compared to uncoated grade 4 Ti. Composition, morphology, and mechanical stability of the coatings were analyzed, and Sr release data were gained from in vitro washout experiments. In vivo investigation was carried out in an osteoporotic rat model and analyzed histologically, 6 weeks and 12 weeks after implantation. Median values of bone-to-implant contact and new bone formation after 6 weeks were found to be 84.7% and 54.9% (best performing Sr group) as compared to 65.2% and 23.8% (grade 4 Ti reference), respectively. The 12-week observation period revealed 84.3% and 56.5% (best performing Sr group) and 81.3% and 39.4% (grade 4 Ti reference), respectively, for the same measurements. The increase in new bone formation was found to correlate with the amount of Sr released in vitro. The results indicate that sputtered nanostructured Ti–Sr–O coatings showed sustained release of Sr and accelerate osseointegration even in poor-quality bone, and thus, may have impact on practical applications for medical implants. PMID:27313456

  7. Biomechanical Stability of Dental Implants in Augmented Maxillary Sites: Results of a Randomized Clinical Study with Four Different Biomaterials and PRF and a Biological View on Guided Bone Regeneration

    Directory of Open Access Journals (Sweden)

    Troedhan Angelo

    2015-01-01

    Full Text Available Introduction. Bone regenerates mainly by periosteal and endosteal humoral and cellular activity, which is given only little concern in surgical techniques and choice of bone grafts for guided bone regeneration. This study investigates on a clinical level the biomechanical stability of augmented sites in maxillary bone when a new class of moldable, self-hardening calcium-phosphate biomaterials (SHB is used with and without the addition of Platelet Rich Fibrin (aPRF in the Piezotome-enhanced subperiosteal tunnel-technique (PeSPTT. Material and Methods. 82 patients with horizontal atrophy of anterior maxillary crest were treated with PeSPTT and randomly assigned biphasic (60% HA/40% bTCP or monophasic (100% bTCP SHB without or with addition of aPRF. 109 implants were inserted into the augmented sites after 8.3 months and the insertion-torque-value (ITV measured as clinical expression of the (biomechanical stability of the augmented bone and compared to ITVs of a prior study in sinus lifting. Results. Significant better results of (biomechanical stability almost by two-fold, expressed by higher ITVs compared to native bone, were achieved with the used biomaterials and more constant results with the addition of aPRF. Conclusion. The use of SHB alone or combined with aPRF seems to be favourable to achieve a superior (biomechanical stable restored alveolar bone.

  8. Carbon nanotubes play an important role in the spatial arrangement of calcium deposits in hydrogels for bone regeneration.

    Science.gov (United States)

    Cancian, Giulia; Tozzi, Gianluca; Hussain, Amirul Ashraf Bin; De Mori, Arianna; Roldo, Marta

    2016-08-01

    Age related bone diseases such as osteoporosis are considered among the main causes of reduced bone mechanical stability and bone fractures. In order to restore both biological and mechanical function of diseased/fractured bones, novel bioactive scaffolds that mimic the bone structure are constantly under development in tissue engineering applications. Among the possible candidates, chitosan-based thermosensitive hydrogel scaffolds represent ideal systems due to their biocompatibility, biodegradability, enhanced antibacterial properties, promotion of osteoblast formation and ease of injection, which makes them suitable for less invasive surgical procedures. As a main drawback, these chitosan systems present poor mechanical performance that could not support load-bearing applications. In order to produce more mechanically-competent biomaterials, the combined addition of hydroxyapatite and carbon nanotubes (CNTs) is proposed in this study. Specifically, the aim of this work is to develop thermosensitive chitosan hydrogels containing stabilised single-walled and multi-walled CNTs, where their effect on the mechanical/physiochemical properties, calcium deposition patterns and ability to provide a platform for the controlled release of protein drugs was investigated. It was found that the addition of CNTs had a significant effect on the sol-gel transition time and significantly increased the resistance to compression for the hydrogels. Moreover, in vitro calcification studies revealed that CNTs played a major role in the spatial arrangements of newly formed calcium deposits in the composite materials studied, suggesting that they may have a role in the way the repair of fragile and/or fractured bones occurs in vivo. PMID:27324780

  9. Histologic and histomorphometric study on the effects of lactoferrin and porous bovine bone mineral (Bio-Oss on the regeneration of bone defects made on rabbit calvarium

    Directory of Open Access Journals (Sweden)

    Paknejad M

    2010-12-01

    Full Text Available "nBackground and Aims: Nowadays reconstruction of alveolar defects has become one of dentists' problems especially in areas which are going to get dental implants. Inorganic bovine bone mineral (Bio-Oss is one of the most popular graft materials that acts as a structure for migration of osteoblasts. If migration, proliferation, and differentiation of osteoblasts can be promoted by a material, it would be possible to reconstruct more amount of bone in a shorter period of time. Milk contains vital proteins that regulate bone growth. One of these important proteins is lactoferrin. The aim of this study was to examine the effect of added bovine lactoferrin to Bio-Oss on osteogenesis."nMaterials and Methods: Two doses of 50 and 500 µg/ml of lactoferrin were prepared. Ten New Zealand white rabbits were selected for this study. Four 6-mm symmetrical detects were created in each rabbit's calvarium. Two of these sites were filled with Bio-Oss that was wetted with two doses of lactoferrin. Third detect was filled with Bio-Oss alone and the forth one was left empty as control group. After 4 weeks histologic and histomorphometric analysis was performed."nResult: There was no sign of obvious inflammation in any of four groups. Also there was no difference among four groups in terms of vitality, type of new bone, and foreign body reaction. However, amount of bone formation in control group was significantly lower compared with the other 3 groups. Although lactoferrin containing groups showed little increase in bone formation especially in higher concentration, there was not statistically significant difference among the three test groups. Amount of remaining biomaterial also was lower in lactoferrin containing groups compared with the Bio-Oss group but the differences were not significant."nConclusion: Although there was no significant difference among the test groups, it seems that the added lactoferrin increases bone formation. Considering the

  10. Delivery of RANKL-Binding Peptide OP3-4 Promotes BMP-2-Induced Maxillary Bone Regeneration.

    Science.gov (United States)

    Uehara, T; Mise-Omata, S; Matsui, M; Tabata, Y; Murali, R; Miyashin, M; Aoki, K

    2016-06-01

    Although bone morphogenetic protein 2 (BMP-2) is known to stimulate osteogenesis, there is evidence that high doses of BMP-2 can lead to side effects, including inflammation and carcinogenesis. The supplementation of other bone-augmenting agents is considered helpful in preventing such side effects by reducing the amount of BMP-2 required to obtain a sufficient amount of bone. We recently showed that a receptor activator of nuclear factor κB ligand (RANKL)-binding peptide promotes osteoblast differentiation. In the present study, we aimed to investigate whether OP3-4, a RANKL-binding peptide, promotes BMP-2-induced bone formation in the murine maxilla using an injectable gelatin hydrogel (GH) carrier. A GH carrier containing OP3-4 with BMP-2 was subperiosteally injected into the murine maxillary right diastema between the incisor and the first molar. The mice were sacrificed 28 d after the injections. The local bone formation in the OP3-4-BMP-2-injected group was analyzed in comparison to the carrier-injected, BMP-2-injected, and control-peptide-BMP-2-injected groups. The GH carrier containing OP3-4 with BMP-2 enlarged the radio-opaque area and increased the bone mineral content and density in the radiological analyses in comparison to the other experimental groups. Interestingly, fluorescence-based histological analyses revealed that the mineralization had started from the outside, then proceeded inward, suggesting that the size of the newly formed bone had already been set before calcification started and that the effects of OP3-4 might be involved in accelerating the early steps of osteogenesis. Actually, OP3-4 enhanced the BMP-2-induced 5-bromo-2'-deoxyuridine (BrdU)-positive cell numbers at the injected site on day 7 and the expression of Runx2 and Col1a1, which are early osteogenic cell markers, on day 10 after the subperiosteal injections. In summary, we demonstrated, for the first time, that the application of OP3-4 by subperiosteal injection promoted BMP

  11. Bone

    International Nuclear Information System (INIS)

    Bone scanning provides information on the extent of primary bone tumors, on possible metastatic disease, on the presence of osteomyelitis prior to observation of roentgenographic changes so that earlier therapy is possible, on the presence of collagen diseases, on the presence of fractures not disclosed by x-ray films, and on the evaluation of aseptic necrosis. However, the total effect and contribution of bone scanning to the diagnosis, treatment, and ultimate prognosis of pediatric skeletal diseases is, as yet, unknown. (auth)

  12. Towards the Design of 3D Fiber-Deposited Poly(ε-caprolactone)/lron-Doped Hydroxyapatite Nanocomposite Magnetic Scaffolds for Bone Regeneration.

    Science.gov (United States)

    De Santis, Roberta; Russo, Alessandro; Gloria, Antonio; D'Amora, Ugo; Russo, Teresa; Panseri, Silvia; Sandri, Monica; Tampieri, Anna; Marcacci, Maurilio; Dediu, Valentin A; Wilde, Colin J; Ambrosio, Luigi

    2015-07-01

    In the past few years, researchers have focused on the design and development of three-dimensional (3D) advanced scaffolds, which offer significant advantages in terms of cell performance. The introduction of magnetic features into scaffold technology could offer innovative opportunities to control cell populations within 3D microenvironments, with the potential to enhance their use in tissue regeneration or in cell-based analysis. In the present study, 3D fully biodegradable and magnetic nanocomposite scaffolds for bone tissue engineering, consisting of a poly(ε-caprolactone) (PCL) matrix reinforced with iron-doped hydroxyapatite (FeHA) nanoparticles, were designed and manufactured using a rapid prototyping technique. The performances of these novel 3D PCL/FeHA scaffolds were assessed through a combination of theoretical evaluation, experimental in vitro analyses and in vivo testing in a rabbit animal model. The results from mechanical com- pression tests were consistent with FEM simulations. The in vitro results showed that the cell growth in the magnetized scaffolds was 2.2-fold greater than that in non-magnetized ones. In vivo experiments further suggested that, after only 4 weeks, the PCL/FeHA scaffolds were completely filled with newly formed bone, proving a good level of histocompatibility. All of the results suggest that the introduction of magnetic features into biocompatible materials may confer significant advantages in terms of 3D cell assembly. PMID:26307846

  13. The use of beta-tricalcium phosphate and bovine bone matrix in the guided tissue regeneration treatment of deep infra-bony defects

    Directory of Open Access Journals (Sweden)

    Luković Natalija

    2009-01-01

    Full Text Available Introduction. The primary goal of bone regeneration procedures with application of various regenerative biologic agents and biomaterials is to facilitate the formation of periodontal tissues lost as a result of periodontitis. Objective. The aim of the study was to compare clinical outcome of the guided tissue regeneration (GTR treatment with the use of β-tricalcium phosphate and with bovine bone matrix in human deep intra-osseous defects. Methods. Twenty-one systemically healthy subjects with moderate to advanced periodontitis, between 30 and 56 years of age, 11 females and 10 males, were selected. Patients having two similar inter-proximal defects with pocket probing depths following initial therapy greater than 5 mm were recruited for the study. Experimental sites were grafted with pure β-tricalcium phosphate biomaterial (Cerasorb® and a biomembrane, while control sites were treated with bovine-bone hydroxiapatite xenograft (Bio-oss® and a biomembrane. Immediately before surgery and 12 months after surgery, pocket probing depth (PPD, epithelial attachment level (EAL and gingival recession (GR were evaluated. Results. In the experimental group PPD amounted to 6.76±0.83 mm before surgery, and decreased significantly to 2.67±0.48 mm 12 months following surgery, while in the control group PPD significantly decreased from 7.14±0.65 mm presurgically to 2.85±0.57 mm postsurgically. After one year, EAL gain was 2.76±0.99 mm in the experimental group, and 3.24±0.16 mm in the control group. After twelve months postoperatively GR amounted to 1.33±0.79 mm in the experimental group and to 1.05±0.80 mm in the control group. No statistically significant differences for PPD reduction, EAL gain and GR increase were detected between the groups. Conclusion. Results from the present study indicate that GTR treatment of deep intra-osseous defects with Bio-oss® and Cerasorb® resulted in clinically and statistically significant improvement of EAL gain

  14. Bone regenerating effect of surface-functionalized titanium implants with sustained-release characteristics of strontium in ovariectomized rats

    Directory of Open Access Journals (Sweden)

    Offermanns V

    2016-05-01

    Full Text Available Vincent Offermanns,1 Ole Zoffmann Andersen,2 Gregor Riede,1 Inge Hald Andersen,3 Klaus Pagh Almtoft,3 Søren Sørensen,3 Michael Sillassen,2 Christian Sloth Jeppesen,3 Michael Rasse,1 Morten Foss,2 Frank Kloss1 1Department of Cranio-, Maxillofacial and Oral Surgery, Medical University Innsbruck, Innsbruck, Austria; 2Interdisciplinary Nanoscience Center (iNANO, Faculty of Science and Technology, Aarhus University, Aarhus, Denmark; 3Tribology Centre, Danish Technological Institute, Aarhus, Denmark Abstract: Since strontium (Sr is known for its anabolic and anticatabolic effect on bone, research has been focused on its potential impact on osseointegration. The objective of this study was to investigate the performance of nanotopographic implants with a Sr-functionalized titanium (Ti coating (Ti–Sr–O with respect to osseointegration in osteoporotic bone. The trial was designed to examine the effect of sustained-release characteristics of Sr in poor-quality bone. Three Ti–Sr–O groups, which differed from each other in coating thickness, Sr contents, and Sr release, were examined. These were prepared by a magnetron sputtering process and compared to uncoated grade 4 Ti. Composition, morphology, and mechanical stability of the coatings were analyzed, and Sr release data were gained from in vitro washout experiments. In vivo investigation was carried out in an osteoporotic rat model and analyzed histologically, 6 weeks and 12 weeks after implantation. Median values of bone-to-implant contact and new bone formation after 6 weeks were found to be 84.7% and 54.9% (best performing Sr group as compared to 65.2% and 23.8% (grade 4 Ti reference, respectively. The 12-week observation period revealed 84.3% and 56.5% (best performing Sr group and 81.3% and 39.4% (grade 4 Ti reference, respectively, for the same measurements. The increase in new bone formation was found to correlate with the amount of Sr released in vitro. The results indicate that

  15. Effects of LED phototherapy on bone defects grafted with MTA, bone morphogenetic proteins, and guided bone regeneration in a rodent model: a description of the bone repair by light microscopy

    Science.gov (United States)

    Pinheiro, Antonio Luiz B.; Aciole, Gilberth T. S.; Soares, Luiz G. P.; Correia, Neandder A.; N. dos Santos, Jean

    2011-03-01

    We carried out a histological analysis on surgical bone defects grafted or not with MTA, treated or not with LED, BMPs and GBR. We have used several models to assess the effects of laser on bone. Benefits of the isolated or combined use them on bone healing has been suggested. There is no previous report on their association with LED light. 90 rats were divided into 10 groups. On Groups II and I the defect were filled with the clot. On Group II, were further irradiated. On groups III-VI, defect was filled with MTA + Collagen gel (III); animals of group IV were further irradiated. On groups V and VI, the defects filled with the MTA were covered with a membrane. Animals of Group VI were further irradiated. On Groups VII and VIII a pool of BMPs was added to the MTA and was further irradiated. On groups IX and X, the MTA + BMP graft was covered with a membrane. On group X, the defect was further irradiated. LED (λ850 +/- 10nm, 150mW, A= 0.5cm2, 54s, 0.3W/cm2, 16 J/cm2) was applied at 48 h intervals during 15 days. Specimens were taken, processed, cut and stained with H&E and Sirius red and underwent histological analysis. The results showed that MTA seemed not being affected by LED light. However, its use positively affected healing around the graft. It is concluded that MTA is not affected by the LED light due to it characteristics, but beneficial results with LED usage was found.

  16. Pharmacologic targeting of a stem/progenitor population in vivo is associated with enhanced bone regeneration in mice

    OpenAIRE

    Mukherjee, Siddhartha; Raje, Noopur; Schoonmaker, Jesse A.; Liu, Julie C.; Hideshima, Teru; Wein, Marc N.; Jones, Dallas C; Vallet, Sonia; Bouxsein, Mary L.; Pozzi, Samantha; Chhetri, Shweta; Seo, Y. David; Aronson, Joshua P.; Patel, Chirayu; Fulciniti, Mariateresa

    2008-01-01

    Drug targeting of adult stem cells has been proposed as a strategy for regenerative medicine, but very few drugs are known to target stem cell populations in vivo. Mesenchymal stem/progenitor cells (MSCs) are a multipotent population of cells that can differentiate into muscle, bone, fat, and other cell types in context-specific manners. Bortezomib (Bzb) is a clinically available proteasome inhibitor used in the treatment of multiple myeloma. Here, we show that Bzb induces MSCs to preferentia...

  17. Derivation of Schwann cell precursors from neural crest cells resident in bone marrow for cell therapy to improve peripheral nerve regeneration.

    Science.gov (United States)

    Shi, Haiyan; Gong, Yanpei; Qiang, Liang; Li, Xiaoli; Zhang, Shibo; Gao, Jiawen; Li, Kai; Ji, Ximeng; Tian, Ling; Gu, Xiaosong; Ding, Fei

    2016-05-01

    We have previously successfully enriched post-migratory neural crest cells (NCCs) from postnatal rat bone marrow (BM). These BM-NCCs possess glial and neuronal differentiating potential. Based on the neural crest origin of Schwann cells (SCs), in this study, we aimed at using a straightforward protocol to derive Schwann cell precursors (SCPs) from BM-NCCs. Several clonal subpopulations were isolated from BM-NCCs, displaying long-term proliferative capacity and maintaining the NCC identity. The BM-NCC clones could be induced to differentiate into SCs. In particular, clone N1 gave rise to a large and pure population of SCs. Clone N1-derived SCs demonstrated the myelinating capacity in their co-culture with primary dorsal root ganglion (DRG) neurons. The decreased expression of NCC-markers and increased expression of SC-markers were related to the differentiation state of clone N1-derived SCs. To investigate the repair-promoting effects of clone N1 on injured peripheral neurons in vitro and in vivo, on one hand, the oxygen glucose deprivation-injured DRG neurons were treated with clone N1-conditioned medium, improving the cell survival and axon growth of neurons; on the other hand, clone N1 or clone N1-derived SCs were respectively implanted to the crush sciatic nerve of rats, and clone N1 yielded the better outcome of nerve regeneration and function restoration than clone N1-derived SCs. Taken together, all the results collectively showed that clone N1 could be identified as SCPs, which might hold promise for cell therapy to improve peripheral nerve regeneration. PMID:26946403

  18. On-Demand Guided Bone Regeneration with Microbial Protection of Ornamented SPU Scaffold with Bismuth-Doped Single Crystalline Hydroxyapatite: Augmentation and Cartilage Formation.

    Science.gov (United States)

    Selvakumar, M; Srivastava, Priyanka; Pawar, Harpreet Singh; Francis, Nimmy K; Das, Bodhisatwa; Sathishkumar, G; Subramanian, Bhuvaneshwaran; Jaganathan, Saravana Kumar; George, Gibin; Anandhan, S; Dhara, Santanu; Nando, Golok B; Chattopadhyay, Santanu

    2016-02-17

    Guided bone regeneration (GBR) scaffolds are futile in many clinical applications due to infection problems. In this work, we fabricated GBR with an anti-infective scaffold by ornamenting 2D single crystalline bismuth-doped nanohydroxyapatite (Bi-nHA) rods onto segmented polyurethane (SPU). Bi-nHA with high aspect ratio was prepared without any templates. Subsequently, it was introduced into an unprecedented synthesized SPU matrix based on dual soft segments (PCL-b-PDMS) of poly(ε-caprolactone) (PCL) and poly(dimethylsiloxane) (PDMS), by an in situ technique followed by electrospinning to fabricate scaffolds. For comparison, undoped pristine nHA rods were also ornamented into it. The enzymatic ring-opening polymerization technique was adapted to synthesize soft segments of PCL-b-PDMS copolymers of SPU. Structure elucidation of the synthesized polymers is done by nuclear magnetic resonance spectroscopy. Sparingly, Bi-nHA ornamented scaffolds exhibit tremendous improvement (155%) in the mechanical properties with excellent antimicrobial activity against various human pathogens. After confirmation of high osteoconductivity, improved biodegradation, and excellent biocompatibility against osteoblast cells (in vitro), the scaffolds were implanted in rabbits by subcutaneous and intraosseous (tibial) sites. Various histological sections reveal the signatures of early cartilage formation, endochondral ossification, and rapid bone healing at 4 weeks of the critical defects filled with ornamented scaffold compared to SPU scaffold. This implies osteogenic potential and ability to provide an adequate biomimetic microenvironment for mineralization for GBR of the scaffolds. Organ toxicity studies further confirm that no tissue architecture abnormalities were observed in hepatic, cardiac, and renal tissue sections. This finding manifests the feasibility of fabricating a mechanically adequate nanofibrous SPU scaffold by a biomimetic strategy and the advantages of Bi

  19. Fabrication of novel Si-doped hydroxyapatite/gelatine scaffolds by rapid prototyping for drug delivery and bone regeneration.

    Science.gov (United States)

    Martínez-Vázquez, F J; Cabañas, M V; Paris, J L; Lozano, D; Vallet-Regí, M

    2015-03-01

    Porous 3-D scaffolds consisting of gelatine and Si-doped hydroxyapatite were fabricated at room temperature by rapid prototyping. Microscopic characterization revealed a highly homogeneous structure, showing the pre-designed porosity (macroporosity) and a lesser in-rod porosity (microporosity). The mechanical properties of such scaffolds are close to those of trabecular bone of the same density. The biological behavior of these hybrid scaffolds is greater than that of pure ceramic scaffolds without gelatine, increasing pre-osteoblastic MC3T3-E1 cell differentiation (matrix mineralization and gene expression). Since the fabrication process of these structures was carried out at mild conditions, an antibiotic (vancomycin) was incorporated in the slurry before the extrusion of the structures. The release profile of this antibiotic was measured in phosphate-buffered saline solution by high-performance liquid chromatography and was adjusted to a first-order release kinetics. Vancomycin released from the material was also shown to inhibit bacterial growth in vitro. The implications of these results for bone tissue engineering applications are discussed. PMID:25560614

  20. A novel simple strategy for in situ deposition of apatite layer on AZ31B magnesium alloy for bone tissue regeneration

    Energy Technology Data Exchange (ETDEWEB)

    Mousa, Hamouda M. [Department of Bionanosystem Engineering, Chonbuk National University, Jeonju, Jeonbuk 561-756 (Korea, Republic of); Department of Engineering Materials and Mechanical Design, Faculty of Engineering, South Valley University, Qena 83523 (Egypt); Lee, Do Hee [Department of Bionanosystem Engineering, Chonbuk National University, Jeonju, Jeonbuk 561-756 (Korea, Republic of); Park, Chan Hee, E-mail: biochan@jbnu.ac.kr [Department of Bionanosystem Engineering, Chonbuk National University, Jeonju, Jeonbuk 561-756 (Korea, Republic of); Division of Mechanical Design Engineering, Chonbuk National University, Jeonju, Jeonbuk 561-756 (Korea, Republic of); Kim, Cheol Sang, E-mail: chskim@jbnu.ac.kr [Department of Bionanosystem Engineering, Chonbuk National University, Jeonju, Jeonbuk 561-756 (Korea, Republic of); Division of Mechanical Design Engineering, Chonbuk National University, Jeonju, Jeonbuk 561-756 (Korea, Republic of)

    2015-10-01

    Graphical abstract: - Highlights: • Anodizing process was used for the surface modification of AZ31B magnesium alloy. • An appetite-like film was deposited on the surface of AZ31B magnesium alloy. • Ceramic film was investigated by XRD and XPS. • Nano-plates growth are observed though the implemented experimental design. • Significant increase in the substrate hardness and surface roughness was observed. - Abstract: In this study, for the first time, the degradation performance of AZ31B Mg alloy was tuned by an in situ deposition of apatite thin layer within a short time in one step. Using Taguchi method for experimental design, anodization process was designed under control conditions (time and voltage), and simulated body fluid (SBF) was used as the electrolyte to nucleate apatite-like compounds. The coated alloy was characterized through field emission scanning electron microscopy (FE-SEM), EDS, X-ray diffraction and XPS analysis. The results show that the applied voltage has a significant effect on the formation of apatite-like layers. Compared to the uncoated samples, microhardness and surface roughness of the coated samples showed remarkably different values. The potentiodynamic polarization results demonstrate that the polarization resistance of the anodized samples is higher than the substrate polarization resistance, thus improving the alloy corrosion resistant. Based on the experimental results, the proposed nanostructure apatite-like coating can offer a promising way to improve the biocompatibility and degradability properties of the Mg alloy for bone tissue regeneration.

  1. A novel simple strategy for in situ deposition of apatite layer on AZ31B magnesium alloy for bone tissue regeneration

    International Nuclear Information System (INIS)

    Graphical abstract: - Highlights: • Anodizing process was used for the surface modification of AZ31B magnesium alloy. • An appetite-like film was deposited on the surface of AZ31B magnesium alloy. • Ceramic film was investigated by XRD and XPS. • Nano-plates growth are observed though the implemented experimental design. • Significant increase in the substrate hardness and surface roughness was observed. - Abstract: In this study, for the first time, the degradation performance of AZ31B Mg alloy was tuned by an in situ deposition of apatite thin layer within a short time in one step. Using Taguchi method for experimental design, anodization process was designed under control conditions (time and voltage), and simulated body fluid (SBF) was used as the electrolyte to nucleate apatite-like compounds. The coated alloy was characterized through field emission scanning electron microscopy (FE-SEM), EDS, X-ray diffraction and XPS analysis. The results show that the applied voltage has a significant effect on the formation of apatite-like layers. Compared to the uncoated samples, microhardness and surface roughness of the coated samples showed remarkably different values. The potentiodynamic polarization results demonstrate that the polarization resistance of the anodized samples is higher than the substrate polarization resistance, thus improving the alloy corrosion resistant. Based on the experimental results, the proposed nanostructure apatite-like coating can offer a promising way to improve the biocompatibility and degradability properties of the Mg alloy for bone tissue regeneration

  2. Immediate placement and provisionalization of maxillary anterior single implant with guided bone regeneration, connective tissue graft, and coronally positioned flap procedures.

    Science.gov (United States)

    Waki, Tomonori; Kan, Joseph Y K

    2016-01-01

    Immediate implant placement and provisionalization in the esthetic zone have been documented with success. The benefit of immediate implant placement and provisionalization is the preservation of papillary mucosa. However, in cases with osseous defects presenting on the facial bony plate, immediate implant placement procedures have resulted in facial gingival recession. Subepithelial connective tissue grafts for immediate implant placement and provisionalization procedures have been reported with a good esthetic outcome. Biotype conversion around implants with subepithelial connective tissue grafts have been advocated, and the resulting tissues appear to be more resistant to recession. The dimensions of peri-implant mucosa in a thick biotype were significantly greater than in a thin biotype. Connective tissue graft with coronally positioned flap procedures on natural teeth has also been documented with success. This article describes a technique combining immediate implant placement, provisionalization, guided bone regeneration (GBR), connective tissue graft, and a coronally positioned flap in order to achieve more stable peri-implant tissue in facial osseous defect situations. PMID:27092345

  3. Cellular compatibility of a gamma-irradiated modified siloxane-poly(lactic acid)-calcium carbonate hybrid membrane for guided bone regeneration.

    Science.gov (United States)

    Takeuchi, Naoshi; Machigashira, Miho; Yamashita, Daisuke; Shirakata, Yoshinori; Kasuga, Toshihiro; Noguchi, Kazuyuki; Ban, Seiji

    2011-01-01

    A bi-layered silicon-releasable membrane consisting of a siloxane-poly(lactic acid) (PLA)-vaterite hybrid material (Si-PVH) microfiber mesh and a PLA microfiber mesh has been developed by an electrospinning method for guided bone regeneration (GBR) application. The bi-layered membrane was modified to a three-laminar structure by sandwiching an additional PLA microfiber mesh between the Si-PVH and PLA microfiber meshes (Si-PVH/PLA membrane). In this study, the influence of gamma irradiation, used for sterilization, on biological properties of the Si-PVH/PLA membrane was evaluated with osteoblasts and fibroblasts. After gamma irradiation, while the average molecular weight of the Si-PVH/PLA membrane decreased, the Si-PVH/PLA membrane promoted cell proliferation and differentiation (alkaline phosphatase activity and calcification) of osteoblasts, compared with the poly(lactide-co-glycolide) membrane. These results suggest that the gamma-irradiated Si-PVH/PLA membrane is biocompatible with both fibroblasts and osteoblasts, and may have an application for GBR. PMID:21946495

  4. Possible Involvement of Smad Signaling Pathways in Induction of Odontoblastic Properties in KN-3 Cells by Bone Morphogenetic Protein-2: A Growth Factor to Induce Dentin Regeneration

    Directory of Open Access Journals (Sweden)

    Ayako Washio

    2012-01-01

    Full Text Available We examined the effects of bone morphogenetic protein-2 (BMP-2 on growth, differentiation, and intracellular signaling pathways of odontoblast-like cells, KN-3 cells, to clarify molecular mechanisms of odontoblast differentiation during pulp regeneration process. After treatment with BMP-2, the cell morphology, growth, alkaline phosphatase (ALP activity, and the activation and expression of BMP-induced intracellular signaling molecules, such as Smad1/5/8 and Smad6/7, as well as activities of dentin sialoprotein (DSP and dentin matrix protein 1 (DMP1, were examined. BMP-2 had no effects on the morphology, growth, or ALP activity of KN-3 cells, whereas it induced the phosphorylation of Smad1/5/8 and expression of Smad6/7. BMP-2 also induced the expressions of DSP and DMP-1. Our results suggest that KN-3 cells may express an odontoblastic phenotype with the addition of BMP-2 through the activation of Smad signaling pathways.

  5. Compositional and in Vitro Evaluation of Nonwoven Type I Collagen/Poly-dl-lactic Acid Scaffolds for Bone Regeneration

    CERN Document Server

    Qiao, Xiangchen; Yang, Xuebin; Tronci, Giuseppe; Wood, David J

    2015-01-01

    Poly-dl-lactic acid (PDLLA) was blended with type I collagen to attempt to overcome the instantaneous gelation of electrospun collagen scaffolds in biological environments. Scaffolds based on blends of type I collagen and PDLLA were investigated for material stability in cell culture conditions (37 {\\deg}C; 5% CO2) in which post-electrospinning glutaraldehyde crosslinking was also applied. The resulting wet-stable webs were cultured with bone marrow stromal cells (HBMSC) for five weeks. Scanning electron microscopy (SEM), confocal laser scanning microscopy (CLSM), Fourier transform infra-red spectroscopy (FTIR) and biochemical assays were used to characterise the scaffolds and the consequent cell-scaffold constructs. To investigate any electrospinning-induced denaturation of collagen, identical PDLLA/collagen and PDLLA/gelatine blends were electrospun and their potential to promote osteogenic differentiation investigated. PDLLA/collagen blends with w/w ratios of 40/60, 60/40 and 80/20 resulted in satisfactory...

  6. How Can Nanotechnology Help to Repair the Body? Advances in Cardiac, Skin, Bone, Cartilage and Nerve Tissue Regeneration

    Directory of Open Access Journals (Sweden)

    Juan Antonio Marchal

    2013-03-01

    Full Text Available Nanotechnologists have become involved in regenerative medicine via creation of biomaterials and nanostructures with potential clinical implications. Their aim is to develop systems that can mimic, reinforce or even create in vivo tissue repair strategies. In fact, in the last decade, important advances in the field of tissue engineering, cell therapy and cell delivery have already been achieved. In this review, we will delve into the latest research advances and discuss whether cell and/or tissue repair devices are a possibility. Focusing on the application of nanotechnology in tissue engineering research, this review highlights recent advances in the application of nano-engineered scaffolds designed to replace or restore the followed tissues: (i skin; (ii cartilage; (iii bone; (iv nerve; and (v cardiac.

  7. Investigation of emulsified, acid and acid-alkali catalyzed mesoporous bioactive glass microspheres for bone regeneration and drug delivery

    Energy Technology Data Exchange (ETDEWEB)

    Miao, Guohou [School of Materials Science and Engineering, South China University of Technology, Guangzhou 510641 China (China); National Engineering Research Center for Tissue Restoration and Reconstruction, Guangzhou 510006 China (China); Guangdong Province Key Laboratory of Biomedical Engineering, South China University of Technology, Guangzhou 510006 China (China); Chen, Xiaofeng, E-mail: chenxf@scut.edu.cn [School of Materials Science and Engineering, South China University of Technology, Guangzhou 510641 China (China); National Engineering Research Center for Tissue Restoration and Reconstruction, Guangzhou 510006 China (China); Guangdong Province Key Laboratory of Biomedical Engineering, South China University of Technology, Guangzhou 510006 China (China); Dong, Hua [National Engineering Research Center for Tissue Restoration and Reconstruction, Guangzhou 510006 China (China); Guangdong Province Key Laboratory of Biomedical Engineering, South China University of Technology, Guangzhou 510006 China (China); School of Biological Science and Engineering, South China University of Technology, Guangzhou 510006 (China); Fang, Liming; Mao, Cong; Li, Yuli; Li, Zhengmao; Hu, Qing [School of Materials Science and Engineering, South China University of Technology, Guangzhou 510641 China (China); National Engineering Research Center for Tissue Restoration and Reconstruction, Guangzhou 510006 China (China); Guangdong Province Key Laboratory of Biomedical Engineering, South China University of Technology, Guangzhou 510006 China (China)

    2013-10-15

    Acid-catalyzed mesoporous bioactive glass microspheres (MBGMs-A) and acid-alkali co-catalyzed mesoporous bioactive glass microspheres (MBGMs-B) were successfully synthesized via combination of sol-gel and water-in-oil (W/O) micro-emulsion methods. The structural, morphological and textural properties of mesoporous bioactive glass microspheres (MBGMs) were characterized by various techniques. Results show that both MBGMs-A and MBGMs-B exhibit regularly spherical shape but with different internal porous structures, i.e., a dense microstructure for MBGMs-A and internally porous structure for MBGMs-B. {sup 29}Si NMR data reveal that MGBMs have low polymerization degree of silica network. The in vitro bioactivity tests indicate that the apatite formation rate of MBGMs-B was faster than that of MBGMs-A after soaking in simulated body fluid (SBF) solution. Furthermore, the two kinds of MBGMs have similar storage capacity of alendronate (AL), and the release behaviors of AL could be controlled due to their unique porous structure. In conclusion, the microspheres are shown to be promising candidates as bone-related drug carriers and filling materials of composite scaffold for bone repair. - Graphical abstract: The morphologies and microstructures of acid-catalyzed mesoporous bioactive glass microspheres (MBGMs-A) and acid-alkali co-catalyzed mesoporous bioactive glass microspheres (MBGMs-B) were observed by scanning electron microscope and transmission electron microscope. MBGMs-A exhibits a dense structure and a porous can be observed in MBGMs-B. The microspheres have a quick inducing-apatite formation ability and show a sustained release of alendronate (AL). Highlights: • A rapid method was reported to prepare mesoporous bioactive glass microspheres. • The addition of ammonia significantly shortens the preparation time. • Acid and acid-alkali co-catalyzed microspheres were studied for the first time. • The materials exhibited excellent in vitro bioactivity and

  8. Investigation of emulsified, acid and acid-alkali catalyzed mesoporous bioactive glass microspheres for bone regeneration and drug delivery

    International Nuclear Information System (INIS)

    Acid-catalyzed mesoporous bioactive glass microspheres (MBGMs-A) and acid-alkali co-catalyzed mesoporous bioactive glass microspheres (MBGMs-B) were successfully synthesized via combination of sol-gel and water-in-oil (W/O) micro-emulsion methods. The structural, morphological and textural properties of mesoporous bioactive glass microspheres (MBGMs) were characterized by various techniques. Results show that both MBGMs-A and MBGMs-B exhibit regularly spherical shape but with different internal porous structures, i.e., a dense microstructure for MBGMs-A and internally porous structure for MBGMs-B. 29Si NMR data reveal that MGBMs have low polymerization degree of silica network. The in vitro bioactivity tests indicate that the apatite formation rate of MBGMs-B was faster than that of MBGMs-A after soaking in simulated body fluid (SBF) solution. Furthermore, the two kinds of MBGMs have similar storage capacity of alendronate (AL), and the release behaviors of AL could be controlled due to their unique porous structure. In conclusion, the microspheres are shown to be promising candidates as bone-related drug carriers and filling materials of composite scaffold for bone repair. - Graphical abstract: The morphologies and microstructures of acid-catalyzed mesoporous bioactive glass microspheres (MBGMs-A) and acid-alkali co-catalyzed mesoporous bioactive glass microspheres (MBGMs-B) were observed by scanning electron microscope and transmission electron microscope. MBGMs-A exhibits a dense structure and a porous can be observed in MBGMs-B. The microspheres have a quick inducing-apatite formation ability and show a sustained release of alendronate (AL). Highlights: • A rapid method was reported to prepare mesoporous bioactive glass microspheres. • The addition of ammonia significantly shortens the preparation time. • Acid and acid-alkali co-catalyzed microspheres were studied for the first time. • The materials exhibited excellent in vitro bioactivity and drug

  9. Combined transplantation of bone marrow mesenchymal stem cells and pedicled greater omentum promotes locomotor function and regeneration of axons after spinal cord injury in rats

    Institute of Scientific and Technical Information of China (English)

    Liang Li; Zhiying Zhang; Haiyan Lin; Congli Ren; Chuansen Zhang

    2008-01-01

    BACKGROUND: According to previous studies, the neuroprotective effect of the pedicled greater omentum may be attributed to the secretion of neurotrophic factors and stimulation of angiogenesis. The neurotrophic factors released from the pedicled greater omentum, such as brain-derived neurotrophic factor and neurotrophin 3/4/5 could exert a neuroprotective effect on the damaged host neural and glial cells, and also could induce the transdifferentiation of transplanted bone marrow mesenchymal stem cells (BMSCs) into neural cells. OBJECTIVE: Based on the functions of the omentum of neuro-protection and vascularization, we hypothesize that the transplantation of BMSCs and pedicled greater omentum into injured rat spinal cord might improve the survival rate and neural differentiation of transplanted BMSCs and consequently gain a better functional outcome. DESIGN, TIME AND SETTING: A randomized, controlled animal experiment. The experiments were carried out at the Department of Anatomy, the Secondary Military Medical University of Chinese PLA between June 2005 and June 2007.MATERIALS: Fifteen male inbred Wistar rats, weighing (200±20) g, provided by the Experimental Animal Center of the Secondary Military Medical University of Chinese PLA were used and met the animal ethical standards. Mouse anti-BrdU and mouse anti-NF200 monoclonal antibody were purchased from Boster, China. METHODS: Cell culture: We used inbred Sprague-Dawley rats to harvest bone marrow for culture of BMSCs and transplantation to avoid possible immune rejection. BMSCs were cultured via total bone marrow adherence. Experimental grouping and intervention: The rats were randomly divided into a control group, cell group and combined group, five rats per group. Rats in the control group underwent spinal cord injury (SCI) only, during which an artery clamp with pressure force of 30 g was employed to compress the spinal cord at the T10 level for 30 seconds to produce the SCI model. 5 μL PBS containing 105

  10. Compositional and in Vitro Evaluation of Nonwoven Type I Collagen/Poly-dl-lactic Acid Scaffolds for Bone Regeneration

    Directory of Open Access Journals (Sweden)

    Xiangchen Qiao

    2015-08-01

    Full Text Available Poly-dl-lactic acid (PDLLA was blended with type I collagen to attempt to overcome the instantaneous gelation of electrospun collagen scaffolds in biological environments. Scaffolds based on blends of type I collagen and PDLLA were investigated for material stability in cell culture conditions (37 °C; 5% CO2 in which post-electrospinning glutaraldehyde crosslinking was also applied. The resulting wet-stable webs were cultured with bone marrow stromal cells (HBMSC for five weeks. Scanning electron microscopy (SEM, confocal laser scanning microscopy (CLSM, Fourier transform infra-red spectroscopy (FTIR and biochemical assays were used to characterise the scaffolds and the consequent cell-scaffold constructs. To investigate any electrospinning-induced denaturation of collagen, identical PDLLA/collagen and PDLLA/gelatine blends were electrospun and their potential to promote osteogenic differentiation investigated. PDLLA/collagen blends with w/w ratios of 40/60, 60/40 and 80/20 resulted in satisfactory wet stabilities in a humid environment, although chemical crosslinking was essential to ensure long term material cell culture. Scaffolds of PDLLA/collagen at a 60:40 weight ratio provided the greatest stability over a five-week culture period. The PDLLA/collagen scaffolds promoted greater cell proliferation and osteogenic differentiation compared to HMBSCs seeded on the corresponding PDLLA/gelatine scaffolds, suggesting that any electrospinning-induced collagen denaturation did not affect material biofunctionality within 5 weeks in vitro.

  11. Natural Killer Cells-Produced IFN-γ Improves Bone Marrow-Derived Hepatocytes Regeneration in Murine Liver Failure Model.

    Science.gov (United States)

    Li, Lu; Zeng, Zhutian; Qi, Ziping; Wang, Xin; Gao, Xiang; Wei, Haiming; Sun, Rui; Tian, Zhigang

    2015-01-01

    Bone-marrow transplantation (BMT) can repopulate the liver through BM-derived hepatocyte (BMDH) generation, although the underlying mechanism remains unclear. Using fumarylacetoacetate hydrolase-deficient (Fah(-/-)) mice as a liver-failure model, we confirmed that BMDHs were generated by fusion of BM-derived CD11b(+)F4/80(+)myelomonocytes with resident Fah(-/-) hepatocytes. Hepatic NK cells became activated during BMDH generation and were the major IFN-γ producers. Indeed, both NK cells and IFN-γ were required for BMDH generation since WT, but not NK-, IFN-γ-, or IFN-γR1-deficient BM transplantation successfully generated BMDHs and rescued survival in Fah(-/-) hosts. BM-derived myelomonocytes were determined to be the IFN-γ-responding cells. The IFN-γ-IFN-γR interaction contributed to the myelomonocyte-hepatocyte fusion process, as most of the CD11b(+) BMDHs in mixed BM chimeric Fah(-/-) hosts transplanted with a 1:1 ratio of CD45.1(+) WT and CD45.2(+) Ifngr1(-/-) BM cells were of CD45.1(+) WT origin. Confirming these findings in vitro, IFN-γ dose-dependently promoted the fusion of GFP(+) myelomonocytes with Fah(-/-) hepatocytes due to a direct effect on myelomonocytes; similar results were observed using activated NK cells. In conclusion, BMDH generation requires NK cells to facilitate myelomonocyte-hepatocyte fusion in an IFN-γ-dependent manner, providing new insights for treating severe liver failure. PMID:26345133

  12. Efficacy of rhBMP-2 loaded PCL/PLGA/β-TCP guided bone regeneration membrane fabricated by 3D printing technology for reconstruction of calvaria defects in rabbit

    International Nuclear Information System (INIS)

    We successfully fabricated a three-dimensional (3D) printing-based PCL/PLGA/β-TCP guided bone regeneration (GBR) membrane that slowly released rhBMP-2. To impregnate the GBR membrane with intact rhBMP-2, collagen solution encapsulating rhBMP-2 (5 µg ml−1) was infused into pores of a PCL/PLGA/β-TCP membrane constructed using a 3D printing system with four dispensing heads. In a release profile test, sustained release of rhBMP-2 was observed for up to 28 d. To investigate the efficacy of the GBR membrane on bone regeneration, PCL/PLGA/β-TCP membranes with or without rhBMP-2 were implanted in an 8 mm calvaria defect of rabbits. Bone formation was evaluated at weeks 4 and 8 histologically and histomorphometrically. A space making ability of the GBR membrane was successfully maintained in both groups, and significantly more new bone was formed at post-implantation weeks 4 and 8 by rhBMP-2 loaded GBR membranes. Interestingly, implantation with rhBMP-2 loaded GBR membranes led to almost entire healing of calvaria defects within 8 weeks. (paper)

  13. Excavating the Role of Aloe Vera Wrapped Mesoporous Hydroxyapatite Frame Ornamentation in Newly Architectured Polyurethane Scaffolds for Osteogenesis and Guided Bone Regeneration with Microbial Protection.

    Science.gov (United States)

    Selvakumar, M; Pawar, Harpreet Singh; Francis, Nimmy K; Das, Bodhisatwa; Dhara, Santanu; Chattopadhyay, Santanu

    2016-03-01

    Guided bone regeneration (GBR) scaffolds are unsuccessful in many clinical applications due to a high incidence of postoperative infection. The objective of this work is to fabricate GBR with an anti-infective electrospun scaffold by ornamenting segmented polyurethane (SPU) with two-dimensional Aloe vera wrapped mesoporous hydroxyapatite (Al-mHA) nanorods. The antimicrobial characteristic of the scaffold has been retrieved from the prepared Al-mHA frame with high aspect ratio (∼14.2) via biosynthesis route using Aloe vera (Aloe barbadensis miller) extract. The Al-mHA frame was introduced into an unprecedented SPU matrix (solution polymerized) based on combinatorial soft segments of poly(ε-caprolactone) (PCL), poly(ethylene carbonate) (PEC), and poly(dimethylsiloxane) (PDMS), by an in situ technique followed by electrospinning to fabricate scaffolds. For comparison, pristine mHA nanorods are also ornamented into it. An enzymatic ring-opening polymerization technique was adapted to synthesize soft segment of (PCL-PEC-b-PDMS). Structure elucidation of the synthesized polymers is established by nuclear magnetic resonance spectroscopy. Sparingly, Al-mHA ornamented scaffolds exhibit tremendous improvement (175%) in the mechanical properties with promising antimicrobial activity against various human pathogens. After confirmation of high osteoconductivity, improved biodegradation, and excellent biocompatibility against osteoblast-like MG63 cells (in vitro), the scaffolds were implanted in rabbits as an animal model by subcutaneous and intraosseous (tibial) sites. Improved in vivo biocompatibilities, biodegradation, osteoconductivity, and the ability to provide an adequate biomimetic environment for biomineralization for GBR of the scaffolds (SPU and ornamented SPUs) have been found from the various histological sections. Early cartilage formation, endochondral ossification, and rapid bone healing at 4 weeks were found in the defects filled with Al-mHA ornamented

  14. Biomedical potential of chitosan/HA and chitosan/β-1,3-glucan/HA biomaterials as scaffolds for bone regeneration--A comparative study.

    Science.gov (United States)

    Przekora, Agata; Palka, Krzysztof; Ginalska, Grazyna

    2016-01-01

    The aim of this work was to compare biomedical potential of chitosan/hydroxyapatite (chit/HA) and novel chitosan/β-1,3-glucan/hydroxyapatite (chit/glu/HA) materials as scaffolds for bone regeneration via characterization of their biocompatibility, porosity, mechanical properties, and water uptake behaviour. Biocompatibility of the scaffolds was assessed in direct-contact with the materials using normal human foetal osteoblast cell line. Cytotoxicity and osteoblast proliferation rate were evaluated. Porosity was assessed using computed microtomography analysis and mechanical properties were determined by compression testing. Obtained results demonstrated that chit/HA scaffold possessed significantly better mechanical properties (compressive strength: 1.23 MPa, Young's modulus: 0.46 MPa) than chit/glu/HA material (compressive strength: 0.26 MPa, Young's modulus: 0.25 MPa). However, addition of bacterial β-1,3-glucan to the chit/HA scaffold improved its flexibility and porosity. Moreover, chit/glu/HA scaffold revealed significantly higher water uptake capability (52.6% after 24h of soaking) compared to the chit/HA (30.7%) and thus can serve as a very good drug delivery carrier. Chit/glu/HA scaffold was also more favourable to osteoblast survival (near 100% viability after 24-h culture), proliferation, and spreading compared to the chit/HA (63% viability). The chit/glu/HA possesses better biomedical potential than chit/HA scaffold. Nevertheless, poor mechanical properties of the chit/glu/HA limit its application to non-load bearing implantation area. PMID:26478384

  15. Evaluation of autologous bone marrow-derived mesenchymal stem cells on renal regeneration after experimentally induced acute kidney injury in dogs.

    Science.gov (United States)

    Lim, Chae-Young; Han, Jae-Ik; Kim, Seung-Gon; Lee, Chang-Min; Park, Hee-Myung

    2016-02-01

    OBJECTIVE To evaluate the usefulness of autologous bone marrow-derived mesenchymal stem cell (BM-MSC) therapy for the treatment of dogs with experimentally induced acute kidney injury. ANIMALS 6 healthy dogs. PROCEDURES After induction of kidney injury (day 0) with cisplatin (5 mg/kg, IV), dogs immediately received saline (0.9% NaCl) solution (10 mL; n = 3) or BM-MSCs (1 × 10(6) cells/kg in 10 mL of saline solution; 3) IV. A CBC, serum biochemical analysis, and urinalysis were performed for each dog before administration of cisplatin and on days 1 through 4. Glomerular filtration rate was determined for all dogs on days -7 and 2; BM-MSC tracking by MRI was performed on BM-MSC-treated dogs on days -14 and 4. After sample collection and BM-MSC tracking on day 4, all dogs were euthanized; kidney tissue samples underwent histologic evaluation, immunohistochemical analysis, and cytokine profiling via reverse transcriptase PCR assays. RESULTS Kidney tissue from both groups had mononuclear inflammatory cell infiltration, tubular necrosis, dilated tubules, and glomerular damage. However, there was less fibrotic change and increased proliferation of renal tubular epithelial cells in the BM-MSC-treated dogs, compared with findings for the control dogs. Expressions of tumor necrosis factor-α and transforming growth factor-β were lower in the BM-MSC-treated group, compared with findings for the control group. Laboratory data revealed no improvement in the renal function in BM-MSC-treated dogs. CONCLUSIONS AND CLINICAL RELEVANCE Results of this study suggested that autologous BM-MSCs may accelerate renal regeneration after experimentally induced acute kidney injury in dogs. (Am J Vet Res 2016;77:208-217). PMID:27027716

  16. Heart Regeneration

    OpenAIRE

    Laflamme, Michael A.; Charles E. Murry

    2011-01-01

    Heart failure plagues industrialized nations, killing more people than any other disease. Heart failure usually results from a deficiency of cardiomyocytes, and a robust therapy to regenerate lost myocardium could help millions of patients a year. Heart regeneration is well documented in lower vertebrates and in developing mammals. After we are born, however, human heart regeneration becomes limited. In this article, Laflamme and Murry review the innate barriers to heart regeneration, the evi...

  17. Cryogenic regenerators

    International Nuclear Information System (INIS)

    Importance of regenerators in cryogenic refrigerators is highlighted. Design aspects of regenerator are reviewed and the factors involved in the selection of regenerator material are enumerated. Various methods used to calculate the heat transfer coefficient and regenerator effectiveness are mentioned. Variation of effectiveness with various parameters is calculated by a computer programme using the ideal, Ackermann and Tipler formulae. Results are presented in graphical form. Listing of the computer programme is given in the Appendix. (author)

  18. Guided bone regeneration in standardized calvarial defects using beta-tricalcium phosphate and collagen membrane: a real-time in vivo micro-computed tomographic experiment in rats.

    Science.gov (United States)

    Ramalingam, Sundar; Al-Rasheed, Abdulaziz; ArRejaie, Aws; Nooh, Nasser; Al-Kindi, Mohammed; Al-Hezaimi, Khalid

    2016-05-01

    Guided bone regeneration (GBR) procedures using graft materials have been used for reconstruction of osseous defects. The aim of the present in vivo micro-computed tomographic (µCT) and histologic study was to assess in real time the bone regeneration at GBR sites in standardized experimental calvarial defects (diameter 3.3 mm) using β-tricalcium phosphate (β-TCP) with and without collagen membrane (CM). A single full-thickness calvarial defect was created on the left parietal bone in young female Wistar albino rats (n = 30) weighing approximately 300 g and aged about 6 weeks. The animals were randomly divided into three groups for treatment, based on calvarial defect filling material: (1) control group (n = 10); (2) β-TCP + CM group (n = 10); (3) β-TCP group (n = 10). Real-time in vivo µCT analyses were performed immediately after surgery and at 2, 4, 6 and 10 weeks to determine the volume and mineral density of the newly formed bone (BVNFB, MDNFB) and remaining β-TCP particles (VRBP, MDRBP). The animals were killed at 10 weeks and calvarial specimens were evaluated histologically. In the control group, MDNFB increased significantly at 6 weeks (0.32 ± 0.002 g/mm(3), P < 0.01) compared to that at baseline. In β-TCP + CM group, BVNFB (1.10 ± 0.12 mm(3), P < 0.01) and MDNFB (0.13 ± 0.02 g/mm(3), P < 0.01) significantly increased at the 4th week than baseline. In the β-TCP group, BVNFB (1.13 ± 0.12 mm(3), P < 0.01) and MDNFB (0.14 ± 0.01 g/mm(3), P < 0.01) significantly increased at 6 weeks compared to that at baseline. Significant reduction in VRBP was neither seen in the β-TCP + CM group nor in the β-TCP group. While in the β-TCP + CM group MDRBP was reduced significantly at 6 weeks (0.44 ± 0.9 g/mm(3), P < 0.01) from baseline (0.98 ± 0.03 g/mm(3)), similar significant reduction in MDRBP from baseline (0.92 ± 0.07 g/mm(3)) was seen only at 10 weeks (0.45 ± 0.06 g/mm(3), P < 0

  19. Prunetin signals via G-protein-coupled receptor, GPR30(GPER1): Stimulation of adenylyl cyclase and cAMP-mediated activation of MAPK signaling induces Runx2 expression in osteoblasts to promote bone regeneration.

    Science.gov (United States)

    Khan, Kainat; Pal, Subhashis; Yadav, Manisha; Maurya, Rakesh; Trivedi, Arun Kumar; Sanyal, Sabyasachi; Chattopadhyay, Naibedya

    2015-12-01

    Prunetin is found in red clover and fruit of Prunus avium (red cherry). The effect of prunetin on osteoblast function, its mode of action and bone regeneration in vivo were investigated. Cultures of primary osteoblasts, osteoblastic cell line and HEK293T cells were used for various in vitro studies. Adult female rats received drill-hole injury at the femur diaphysis to assess the bone regenerative effect of prunetin. Prunetin at 10nM significantly (a) increased proliferation and differentiation of primary cultures of osteoblasts harvested from rats and (b) promoted formation of mineralized nodules by bone marrow stromal/osteoprogenitor cells. At this concentration, prunetin did not activate any of the two nuclear estrogen receptors (α and β). However, prunetin triggered signaling via a G-protein-coupled receptor, GPR30/GPER1, and enhanced cAMP levels in osteoblasts. G15, a selective GPR30 antagonist, abolished prunetin-induced increases in osteoblast proliferation, differentiation and intracellular cAMP. In osteoblasts, prunetin up-regulated runt-related transcription factor 2 (Runx2) protein through cAMP-dependent Erk/MAP kinase activation that ultimately resulted in the up-regulation of GPR30. Administration of prunetin at 0.25mg/kg given to rats stimulated bone regeneration at the site of drill hole and up-regulated Runx2 expression in the fractured callus and the effect was comparable to human parathyroid hormone, the only clinically used osteogenic therapy. We conclude that prunetin promotes osteoinduction in vivo and the mechanism is defined by signaling through GPR30 resulting in the up-regulation of the key osteogenic gene Runx2 that in turn up-regulates GPR30. PMID:26345541

  20. Real-time-guided bone regeneration around standardized critical size calvarial defects using bone marrow-derived mesenchymal stem cells and collagen membrane with and without using tricalcium phosphate: an in vivo micro-computed tomographic and histologic experiment in rats.

    Science.gov (United States)

    Al-Hezaimi, Khalid; Ramalingam, Sundar; Al-Askar, Mansour; ArRejaie, Aws S; Nooh, Nasser; Jawad, Fawad; Aldahmash, Abdullah; Atteya, Muhammad; Wang, Cun-Yu

    2016-01-01

    The aim of the present real time in vivo micro-computed tomography (µCT) and histologic experiment was to assess the efficacy of guided bone regeneration (GBR) around standardized calvarial critical size defects (CSD) using bone marrow-derived mesenchymal stem cells (BMSCs), and collagen membrane (CM) with and without tricalcium phosphate (TCP) graft material. In the calvaria of nine female Sprague-Dawley rats, full-thickness CSD (diameter 4.6 mm) were created under general anesthesia. Treatment-wise, rats were divided into three groups. In group 1, CSD was covered with a resorbable CM; in group 2, BMSCs were filled in CSD and covered with CM; and in group 3, TCP soaked in BMSCs was placed in CSD and covered with CM. All defects were closed using resorbable sutures. Bone volume and bone mineral density of newly formed bone (NFB) and remaining TCP particles and rate of new bone formation was determined at baseline, 2, 4, 6, and 10 weeks using in vivo µCT. At the 10th week, the rats were killed and calvarial segments were assessed histologically. The results showed that the hardness of NFB was similar to that of the native bone in groups 1 and 2 as compared to the NFB in group 3. Likewise, values for the modulus of elasticity were also significantly higher in group 3 compared to groups 1 and 2. This suggests that TCP when used in combination with BMSCs and without CM was unable to form bone of significant strength that could possibly provide mechanical "lock" between the natural bone and NFB. The use of BMSCs as adjuncts to conventional GBR initiated new bone formation as early as 2 weeks of treatment compared to when GBR is attempted without adjunct BMSC therapy. PMID:27025260

  1. Injertos sustitutos no óseos: Aportaciones del ácido poliláctico y poliglicólico Synthetic grafts materials: Polylactide and poliglycolide acid effects in bone regeneration

    Directory of Open Access Journals (Sweden)

    M. Marín Ruiz

    2009-04-01

    Full Text Available En el presente trabajo se realiza una revisión bibliográfica de los sustitutos no óseos disponibles en el mercado para mejorar y acelerar la regeneración ósea centrándonos en los polímeros de ácido poliláctico y poliglicólico por su relativa novedad para dicha aplicación. Los resultados obtenidos permiten confirmar la capacidad osteoconductora de dichos sustitutos en los procesos reparativos óseos pero a menudo también pueden actuar como barrera del proceso fisiológico de autorremodelación ósea al requerir un tiempo de reabsorción demasiado largo.The goal of the present study is to describe the nonbony sustitutes available to improve and to acelerate the bone regeneration pointing us polilactide and poliglycolide acid polymers by its relative newness for this application. The results confirm the osteoconductive capacity of this sustitutes in the bone regeneration even thought they can also be a barrier on the osseous autoremodelation of the physiological process as they need long time to be reabsorbed.

  2. Enhancement of a magnetic nanofibrous composite scaffold for bone regeneration%磁性纳米纤维复合材料原位诱导体内成骨的研究

    Institute of Scientific and Technical Information of China (English)

    许振; 孟洁; 张宇; 常晓; 边焱焱; 孔桦; 顾宁; 许海燕

    2011-01-01

    目的:研究一种新型顺磁性的纳米纤维复合支架γ-Fe2O3/nHAP/PDLLA在弱磁场下体内诱导新骨形成的功效.方法:纳米纤维复合材料支架通过电纺丝方法制成,支架内部的微观结构用扫描电镜(SEM)进行表征.将支架植入兔横突根部骨缺损处并在12周后处死动物,应用组织学方法研究支架在动物体内原位诱导新骨形成和胶原蛋白沉积的情况.结果:与对照的nHAP/PDLLA纳米纤维支架相比,磁性纳米纤维复合支架上有更多的Ⅰ型胶原沉积,新骨的生成量也明显增加.结论:磁性纳米纤维复合支架能够促进骨缺损部位的新骨生成,在引导骨组织再生与修复方面具有应用潜能.%Objective: To investigate the function of inducing bone regeneration of a novel paramagnetic nanofibrous composite scaffold of γ-Fe2O3/nHAP/PDLLA in vivo under a weak applied magnetic field.Methods: The scaffold was fabricated with the composite by electrospinning technique.The microstructure of the scaffold was characterized by scanning electron microscopy.The scaffold was implanted in defects at the root segment of the lumbar transverse process on a rabbit model.Bone tissue samples were collected after 12 weeks of implant surgery.New bone formation in the defects was assessed using histological analysis in reference to a control nanofibrous composite of nHAP/PDLLA.Deposition of type Ⅰ collagen fibers were examined by Sirius red staining.Results: There was new bone formation observed in the scaffold.Type Ⅰ collagen was deposited abundantly on the scaffold.Together all, the bone regeneration was enhanced obviously in comparison with that induced by control scaffold of nHAP/PDLLA.Conclusion: The scaffold of γ-Fe2O3/nHAP/PDLLA enhanced osteogenesis under a weak static magnetic field, and exhibited promising potential for use in bone repair.

  3. Stimulating endogenous cardiac regeneration

    Directory of Open Access Journals (Sweden)

    Amanda eFinan

    2015-09-01

    Full Text Available The healthy adult heart has a low turnover of cardiac myocytes. The renewal capacity, however, is augmented after cardiac injury. Participants in cardiac regeneration include cardiac myocytes themselves, cardiac progenitor cells, and peripheral stem cells, particularly from the bone marrow compartment. Cardiac progenitor cells and bone marrow stem cells are augmented after cardiac injury, migrate to the myocardium, and support regeneration. Depletion studies of these populations have demonstrated their necessary role in cardiac repair. However, the potential of these cells to completely regenerate the heart is limited. Efforts are now being focused on ways to augment these natural pathways to improve cardiac healing, primarily after ischemic injury but in other cardiac pathologies as well. Cell and gene therapy or pharmacological interventions are proposed mechanisms. Cell therapy has demonstrated modest results and has passed into clinical trials. However, the beneficial effects of cell therapy have primarily been their ability to produce paracrine effects on the cardiac tissue and recruit endogenous stem cell populations as opposed to direct cardiac regeneration. Gene therapy efforts have focused on prolonging or reactivating natural signaling pathways. Positive results have been demonstrated to activate the endogenous stem cell populations and are currently being tested in clinical trials. A potential new avenue may be to refine pharmacological treatments that are currently in place in the clinic. Evidence is mounting that drugs such as statins or beta blockers may alter endogenous stem cell activity. Understanding the effects of these drugs on stem cell repair while keeping in mind their primary function may strike a balance in myocardial healing. To maximize endogenous cardiac regeneration,a combination of these approaches couldameliorate the overall repair process to incorporate the participation ofmultiple cell players.

  4. PDGFRα-positive cells in bone marrow are mobilized by high mobility group box 1 (HMGB1) to regenerate injured epithelia

    OpenAIRE

    Tamai, Katsuto; Yamazaki, Takehiko; Chino, Takenao; Ishii, Masaru; Otsuru, Satoru; Kikuchi, Yasushi; Iinuma, Shin; Saga, Kotaro; Nimura, Keisuke; Shimbo, Takashi; Umegaki, Noriko; Katayama, Ichiro; Miyazaki, Jun-ichi; Takeda, Junji; McGrath, John A.

    2011-01-01

    The role of bone marrow cells in repairing ectodermal tissue, such as skin epidermis, is not clear. To explore this process further, this study examined a particular form of cutaneous repair, skin grafting. Grafting of full thickness wild-type mouse skin onto mice that had received a green fluorescent protein-bone marrow transplant after whole body irradiation led to an abundance of bone marrow-derived epithelial cells in follicular and interfollicular epidermis that persisted for at least 5 ...

  5. Cellular regeneration in bone marrow with synthesized semiconductor polymers by plasma; Regeneracion celular en medula espinal con polimeros semiconductores sintetizados por plasma

    Energy Technology Data Exchange (ETDEWEB)

    Morales, J.; Olayo, R. [UAM-I, 09340 Mexico D.F. (Mexico); Alvarez, L.; Mondragon, R.; Morales, A. [UPIITA-IPN, 07000 Mexico D.F. (Mexico); Diaz, A.; Rios, C. [INNN, Mexico D.F. (Mexico); Salgado, H. [IMSS y Proyecto Camina A.C. Mexico D.F. (Mexico); Cruz, G.; Olayo, M.G. [ININ, 52045 Ocoyoacac, Estado de Mexico (Mexico)

    2004-07-01

    In this work the intervention of polymers with capacity of conducting electric current for the regeneration of the spinal marrow in rats of laboratory is studied. It is a focus different from the one that up to now has taken in account since it involves medical, biological, physical and chemical sciences. Inside the properties of transporting electric charges, the polymers would have to respond before the biological media with ionic mechanisms of conduction, besides the electronic ones, to promote the regeneration of the spinal marrow. They should also be biocompatible to avoid the rejection of the media before the implantation. (Author)

  6. Effect of copper-doped silicate 13-93 bioactive glass scaffolds on the response of MC3T3-E1 cells in vitro and on bone regeneration and angiogenesis in rat calvarial defects in vivo.

    Science.gov (United States)

    Lin, Yinan; Xiao, Wei; Bal, B Sonny; Rahaman, Mohamed N

    2016-10-01

    The release of inorganic ions from biomaterials could provide an alternative approach to the use of growth factors for improving tissue healing. In the present study, the release of copper (Cu) ions from bioactive silicate (13-93) glass scaffolds on the response of cells in vitro and on bone regeneration and angiogenesis in vivo was studied. Scaffolds doped with varying concentrations of Cu (0-2.0wt.% CuO) were created with a grid-like microstructure by robotic deposition. When immersed in simulated body fluid in vitro, the Cu-doped scaffolds released Cu ions into the medium in a dose-dependent manner and converted partially to hydroxyapatite. The proliferation and alkaline phosphatase activity of pre-osteoblastic MC3T3-E1 cells cultured on the scaffolds were not affected by 0.4 and 0.8wt.% CuO in the glass but they were significantly reduced by 2.0wt.% CuO. The percent new bone that infiltrated the scaffolds implanted for 6weeks in rat calvarial defects (46±8%) was not significantly affected by 0.4 or 0.8wt.% CuO in the glass whereas it was significantly inhibited (0.8±0.7%) in the scaffolds doped with 2.0wt.% CuO. The area of new blood vessels in the fibrous tissue that infiltrated the scaffolds increased with CuO content of the glass and was significantly higher for the scaffolds doped with 2.0wt.% CuO. Loading the scaffolds with bone morphogenetic protein-2 (1μg/defect) significantly enhanced bone infiltration and reduced fibrous tissue in the scaffolds. These results showed that doping the 13-93 glass scaffolds with up to 0.8wt.% CuO did not affect their biocompatibility whereas 2.0wt.% CuO was toxic to cells and detrimental to bone regeneration. PMID:27287141

  7. Infection and Pulp Regeneration

    Directory of Open Access Journals (Sweden)

    Sahng G. Kim

    2016-03-01

    Full Text Available The regeneration of the pulp-dentin complex has been a great challenge to both scientists and clinicians. Previous work has shown that the presence of prior infection may influence the characteristics of tissues formed in the root canal space after regenerative endodontic treatment. The formation of ectopic tissues such as periodontal ligament, bone, and cementum has been observed in the root canal space of immature necrotic teeth with apical periodontitis, while the regeneration of dentin and pulp has been identified in previously non-infected teeth. The current regenerative endodontic therapy utilizes disinfection protocols, which heavily rely on chemical irrigation using conventional disinfectants. From a microbiological point of view, the current protocols may not allow a sufficiently clean root canal microenvironment, which is critical for dentin and pulp regeneration. In this article, the significance of root canal disinfection in regenerating the pulp-dentin complex, the limitations of the current regenerative endodontic disinfection protocols, and advanced disinfection techniques designed to reduce the microorganisms and biofilms in chronic infection are discussed.

  8. Regeneración ósea guiada con implante unitario con nanosuperficie y betafosfato tricálcico Guided bone regeneration with nanosurface single-tooth implant and beta-tricalcium phosphate

    Directory of Open Access Journals (Sweden)

    J. Pato Mourelo

    2010-12-01

    Full Text Available Introducción. El objetivo del presente caso clínico era mostrar los resultados del tratamiento con implantes dentales mediante regeneración ósea guiada. Caso clínico. Un varón de 32 años es valorado para tratamiento implantológico del incisivo central superior derecho perdido. El plan de tratamiento comprende la eliminación de un quiste periapical residual, inserción de forma sumergida de un implante unitario con nanosuperficie Galimplant® y regeneración ósea guiada con membrana de colágeno reabsorbible BioGide® y betafosfato tricálcico KeraOs® como material de injerto. Después de 8 meses se realiza una segunda cirugía con colocación de un tornillo de cicatrización. Después de 2 semanas, se realiza la carga funcional del implante con una corona unitaria cementada. Después de un periodo de carga funcional de 12 meses, no ha habido complicaciones. Conclusiones. Este caso clínico indica que el tratamiento con implantes dentales mediante la técnica de regeneración ósea guiada constituye una terapéutica implantológica con éxito.Introduction. The aim of this clinical case was to report the outcome of treatment with a dental implant by guided bone regeneration. Clinical case. A 32-year man is diagnosed for implant treatment of the upper central right incisive loss. Treatment planning including elimination of residual periapycal cyst, submerged insertion of a Galimplant® nanosurface implant and guided bone regeneration with BioGide® resorbable collagen membrane and betatricalcium phosphate KeraOs® grafting. After a time period of 8 months, a second surgical stage were realized with the healing screw. After two weeks, implant were loaded with a cemented fixed single-crown. Not complications were observed after a 12 months follow-up. Conclusions. This clinical case indicate that treatment with dental implant by guided bone regeneration constitute a successful treatment.

  9. Estudio experimental sobre la regeneración ósea mandibular de la rata con diferentes biomateriales Experimental study in rats of mandibular bone regeneration with different biomaterials

    Directory of Open Access Journals (Sweden)

    B. Peral Cagigal

    2008-10-01

    aim of this study was to compare new bone formation following application of a bioabsorbable membrane and two types of bone substitutes. Material and method. In the present study, 24 fourmonth- old male Wistar rats were used. Standardized round throughand-and-through bone defects (4 mm in diameter were made in both mandibles and the rats were divided into four groups: one control group and 3 experimental groups. Animals were killed 3 and 6 weeks after surgery. Bone defect healing was assessed by radiologic and histologic analysis. Results. The control defects showed no bone formation; holes were filled with fibrous connective tissue. Bone membrane alone was an efficient barrier, excluding nonosteogenic tissue. However, new bone formation underneath the membrane was incomplete. The Colloss® + membrane group showed complete healing after 6 weeks. The NovaBone® + membrane group showed no bone formation and particles appeared in the defect. Conclusions. The percentage bone regeneration was significantly better in the defects filled with Colloss® and covered with Lambone® than the other experimental groups.

  10. 引导性骨再生膜管治疗骨缺损:怎样更好的走向临床?%Membrane guided bone regeneration technology for treatment of bone defects:How better to be used in clinic?

    Institute of Scientific and Technical Information of China (English)

    王雷; 余德涛

    2013-01-01

    BACKGROUND:Membrane guided bone regeneration technology has become an important method in repairing bone defects. With the deepening of the research, related concept and the mechanism of membrane guided bone regeneration have been gradual y confirmed, but there are stil some unresolved issues. OBJECTIVE: To review the classification of membrane tubes, performance, disadvantages and advantages in membrane guided bone regeneration, as wel as some unresolved issues in application and research. METHODS:The first author searched PubMed and CNKI databases to retrieve articles about the discovery of membrane guided bone regeneration and the concepts, classification of membrane tubes, performance, disadvantages and advantages during bone defect treatment, which were published from 1963 to 2013. The key words were“guided bone regeneration, guided tissue regeneration, bone defect treatment”in English and Chinese, respectively. RESULTS AND CONCLUSION:Membrane guided bone regeneration technique is a most promising treatment for bone defects, but for the treatment of long tubular bone defects, it is stil in the experimental stage. Currently, there is no membrane tube for long-segment bone defects. According to the material sources, the membrane tubes can be divided into:non-biological material, such as polytetrafluoroethylene, polylactic acid, silica gel, titanium film;biological materials, such as col agen membrane, chitin membrane, polyhydroxybutyrate. The membrane tubes can also be classified into nondegradable materials and biodegradable materials. Biodegradable materials have good histocompatibility and no cytotoxicity, which can degrade in a certain period after implantation;part of the membrane can also al ow free exchange of tissue fluid and nutritional substances. But there are stil some shortcomings that the degradation time is difficult to control and the volume is difficultly maintained under the membrane tube. New bone formation in non-biodegradable materials

  11. Three-Dimensional Printing of rhBMP-2-Loaded Scaffolds with Long-Term Delivery for Enhanced Bone Regeneration in a Rabbit Diaphyseal Defect

    OpenAIRE

    Shim, Jin-Hyung; Kim, Se Eun; Park, Ju Young; Kundu, Joydip; Kim, Sung Won; Kang, Seong Soo; Cho, Dong-Woo

    2014-01-01

    In this study, recombinant human bone morphogenetic protein-2 (rhBMP-2) delivery system with slow mode was successfully developed in three-dimensional (3D) printing-based polycaprolactone (PCL)/poly(lactic-co-glycolic acid) (PLGA) scaffolds for bone formation of critical-sized rabbit segmental diaphyseal defect. To control the delivery of the rhBMP-2, collagen (for long-term delivery up to 28 days) and gelatin (for shor-term delivery within a week) solutions encapsulating rhBMP-2 were dispens...

  12. Multi-Composite Bioactive Osteogenic Sponges Featuring Mesenchymal Stem Cells, Platelet-Rich Plasma, Nanoporous Silicon Enclosures, and Peptide Amphiphiles for Rapid Bone Regeneration

    Directory of Open Access Journals (Sweden)

    Dongmei Fan

    2011-06-01

    Full Text Available A novel bioactive sponge was created with a composite of type I collagen sponges or porous poly(e-caprolactone (PCL scaffolds, platelet-rich plasma (PRP, BMP2-loaded nanoporous silicon enclosure (NSE microparticles, mineralizing peptide amphiphiles (PA, and mesenchymal stem cells (MSC. Primary MSC from cortical bone (CB  tissue proved to form more and larger colony units, as well as produce more mineral matrix under osteogenic differentiation, than MSC from bone marrow (BM. Coating pre-treatments were optimized for maximum cell adhesion and mineralization, while a PRP-based gel carrier was created to efficiently deliver and retain MSC and  microparticles within a porous scaffold while simultaneously promoting cell recruitment, proliferation, and angiogenesis. Components and composite sponges were evaluated for osteogenic differentiation in vitro. Osteogenic sponges were loaded with MSC, PRP, PA, and NSE and implanted subcutaneously in rats to evaluate the formation of bone tissue and angiogenesis in vivo. It was found that the combination of a collagen sponge with CB MSC, PRP, PA, and the BMP2-releasing NSE formed the most bone and was most vascularized by four weeks compared to analogous composites featuring BM MSC or PCL or lacking PRP, PA, and NSE. This study indicates that CB MSC should be considered as an alternative to marrow as a source of stem cells, while the PRP-PA cell and microparticle delivery system may be utilized for diverse tissue engineering applications.

  13. “Over-inlay” block graft and differential morphometry: a novel block graft model to study bone regeneration and host-to-graft interfaces in rats

    Science.gov (United States)

    2016-01-01

    Purpose The aim of this study was to present new a model that allows the study of the bone healing process, with an emphasis on the biological behavior of different graft-to-host interfaces. A standardized “over-inlay” surgical technique combined with a differential histomorphometric analysis is presented in order to optimize the use of critical-size calvarial defects in pre-clinical testing. Methods Critical-size defects were created into the parietal bone of 8 male Wistar rats. Deproteinized bovine bone (DBBM) blocks were inserted into the defects, so that part of the block was included within the calvarial thickness and part exceeded the calvarial height (an “over-inlay” graft). All animals were sacrificed at 1 or 3 months. Histomorphometric and immunohistochemical evaluation was carried out within distinct regions of interest (ROIs): the areas adjacent to the native bone (BA), the periosteal area (PA) and the central area (CA). Results The animals healed without complications. Differential morphometry allowed the examination of the tissue composition within distinct regions: the BA presented consistent amounts of new bone formation (NB), which increased over time (24.53%±1.26% at 1 month; 37.73%±0.39% at 3 months), thus suggesting that this area makes a substantial contribution toward NB. The PA was mainly composed of fibrous tissue (71.16%±8.06% and 78.30%±2.67%, respectively), while the CA showed high amounts of DBBM at both time points (78.30%±2.67% and 74.68%±1.07%, respectively), demonstrating a slow remodeling process. Blood vessels revealed a progressive migration from the interface with native bone toward the central area of the graft. Osterix-positive cells observed at 1 month within the PA suggested that the periosteum was a source of osteoprogenitor elements. Alkaline phosphatase data on matrix deposition confirmed this observation. Conclusions The present model allowed for a standardized investigation of distinct graft

  14. Computer-tomographic characteristics of tibial distraction regenerate

    International Nuclear Information System (INIS)

    Computer tomography (CT) potentialities in examinations of patients over the course of distraction osteosynthesis and in assessment of the bone regenerate structure of different sites in various periods of its formation and maturation were studied in 25 patients in periods from 24 days to 5 years. CT permitted a visual and densitometric assessment of the developing bone regenerate surrounded by metal constructions. CT helps follow up all the periods of bone regenerate formation and maturation and permits the detection of deviations in this process, if any

  15. Research progress in bone marrow mesenchymal stem cells for promotion of islet regeneration%骨髓间充质干细胞促进胰岛再生的作用与研究现状★

    Institute of Scientific and Technical Information of China (English)

    范子扬; 刘增亮; 白金宝; 王辉; 郄红征; 邓新生; 胡莹; 梁海生; 王龙飞; 王帅

    2013-01-01

      背景:研究发现,骨髓间充质干细胞移植入糖尿病大鼠后能够降低其血糖。目的:综述骨髓间充质干细胞在促进胰岛再生方面的作用与研究现状。方法:应用计算机检索2003年7月至2011年12月PubMed数据库相关文章,检索词为“bone marrow derive mesenchymal stem cel ,islet cel s”,并限定文章语言种类为English。同时计算机检索2003年7月至2011年12月万方数据库相关文章,检索词为“骨髓间充质干细胞,胰岛细胞”,并限定文章语言种类为中文。最终纳入符合标准的文献25篇。结果与结论:目前,移植胰岛治疗糖尿病已取得良好疗效,但由于胰岛来源匮乏和异种或异体来源的胰岛引起免疫排斥反应而难以使众多糖尿患者受益。骨髓间充质干细胞取材方便,容易进行体外分离、培养和纯化,且具有多向分化潜能。若将骨髓间充质干细胞诱导分化为胰岛细胞,可望解决胰岛细胞来源和免疫排斥问题。文章对骨髓间充质干细胞分化为胰岛细胞治疗糖尿病的研究进展进行综述,并指出了存在问题和今后的研究方向。%BACKGROUND:Bone marrow mesenchymal stem cel s transplanted into diabetes mel itus rats can decrease glucose level. OBJECTIVE:To summarize the research progress in bone marrow mesenchymal stem cel s for promotion of islet regeneration. METHODS:A computer-based online retrieval of PubMed and Wanfang databases was performed to search papers published during July 2003 to December 2011 with the key words bone marrow mesenchymal stem cel s, islet cel s in English and Chinese. Twenty-five papers were included in the final analysis. RESULTS AND CONCLUSION:At present, transplantation of islets has made great advance in treatment of diabetes mel itus. Many patients with diabetes mel itus hardly benefit from islet transplantation because of limited islet origins and the immunological rejections of

  16. Research progress in bone marrow mesenchymal stem cells for promotion of islet regeneration%骨髓间充质干细胞促进胰岛再生的作用与研究现状★

    Institute of Scientific and Technical Information of China (English)

    范子扬; 刘增亮; 白金宝; 王辉; 郄红征; 邓新生; 胡莹; 梁海生; 王龙飞; 王帅

    2013-01-01

    BACKGROUND:Bone marrow mesenchymal stem cel s transplanted into diabetes mel itus rats can decrease glucose level. OBJECTIVE:To summarize the research progress in bone marrow mesenchymal stem cel s for promotion of islet regeneration. METHODS:A computer-based online retrieval of PubMed and Wanfang databases was performed to search papers published during July 2003 to December 2011 with the key words bone marrow mesenchymal stem cel s, islet cel s in English and Chinese. Twenty-five papers were included in the final analysis. RESULTS AND CONCLUSION:At present, transplantation of islets has made great advance in treatment of diabetes mel itus. Many patients with diabetes mel itus hardly benefit from islet transplantation because of limited islet origins and the immunological rejections of heterogenous or xenogenous islets. Bone marrow mesenchymal stem cel s are characterized by easy to operate, easy in vitro isolation, culture and purification, and multipotential differentiation. Islets induce-differentiated by bone marrow mesenchymal stem cel s are expected to solve islet-related problems of the limited origin and immunological rejections. This paper summarizes the research progress in bone marrow mesenchymal stem cel s for treatment of diabetes mel itus and points out the existing problems and further study direction.%  背景:研究发现,骨髓间充质干细胞移植入糖尿病大鼠后能够降低其血糖。目的:综述骨髓间充质干细胞在促进胰岛再生方面的作用与研究现状。方法:应用计算机检索2003年7月至2011年12月PubMed数据库相关文章,检索词为“bone marrow derive mesenchymal stem cel ,islet cel s”,并限定文章语言种类为English。同时计算机检索2003年7月至2011年12月万方数据库相关文章,检索词为“骨髓间充质干细胞,胰岛细胞”,并限定文章语言种类为中文。最终纳入符合标准的文献25篇。结果与结论:目前,移植胰岛

  17. Bone marrow mesenchymal stem cells for epidermal and skin appendage regeneration%大鼠骨髓间充质干细胞重建表皮细胞及皮肤附件

    Institute of Scientific and Technical Information of China (English)

    李仙松; 杜娟; 宋振岚; 李伟平

    2014-01-01

    alone or combined with inducers for the repair of skin wound defect and epidermal reconstruction. METHODS:Under aseptic environment, rat bone marrow was harvested to culture adherent cells using low-glucose Dulbecco’s modified Eagle’s medium. Culture cells at passage 4 were confirmed as mesenchymal stem cells by flow cytometry. Bone marrow mesenchymal stem cells were induced by Dulbecco’s modified Eagle’s medium/Ham’s nutrient mixture F-12 containing 20%burned rat serum to differentiate into epidermal cells that were identified by immunohistochemistry. Wistar rat models of ful-thickness skin wounds were prepared and divided into three groups. The 5-bromo-2-deoxyuridine-labeled autologous bone marrow mesenchymal stem cells and induced bone marrow mesenchymal stem cells were coated singly onto a rat model of burn wounds, and rat models of burn wounds with no treatment served as controls. Wound contraction and regeneration of epidermal cells and skin appendages were observed. RESULTS AND CONCLUSION:After isolation and culture of cells for 24 hours, a few of adherent cells grew as fibroblast-like cells with fusiform shape. At 16 days, cells completely covered the bottom of bottle, exhibiting a fish or reticular arrangement. After detection by flow cytometry, cells were cultured in Dulbecco’s modified Eagle’s medium/Ham’s nutrient mixture F-12 containing 20%burned rat serum, and fusiform-shaped cells gradual y became round or oval cells. Flow cytometry analysis and immunocytochemistry results showed that cells expressed keratin, which were confirmed as epidermal cells. The results show that both the bone marrow mesenchymal stem cells transplantation alone or with necessary inductor is better for skin repair than natural healing, exhibiting a faster regeneration of skin and skin appendages. Bone marrow mesenchymal stem cells are deduced preliminarily to be involved in epidermis and hair fol icle regeneration, thereby improving skin healing.

  18. Use of Spongious Bone Chips and Fascia Temporalis in Alveolar Bone Defects

    OpenAIRE

    TÜZ, Hakan H.; AKAL, Ümit K.; CAMBAZOĞLU, Mine; KİŞNİŞCİ, Reha Ş.

    2004-01-01

    Graft materials are used for inducement of regeneration in bone defects. Organic and synthetic bone graft materials facilitate remodelation or healing of the bone and induce new bone formation in the area of bone resorption caused by pathological, traumatic, and physiological reasons. The aim of this study was to evaluate the effects of spongious allogenic bone graft and fascia temporalis membranous collagen tissue on the healing of bone defects clinically and radiologically. The study was c...

  19. Three-dimensional printing of rhBMP-2-loaded scaffolds with long-term delivery for enhanced bone regeneration in a rabbit diaphyseal defect.

    Science.gov (United States)

    Shim, Jin-Hyung; Kim, Se Eun; Park, Ju Young; Kundu, Joydip; Kim, Sung Won; Kang, Seong Soo; Cho, Dong-Woo

    2014-07-01

    In this study, recombinant human bone morphogenetic protein-2 (rhBMP-2) delivery system with slow mode was successfully developed in three-dimensional (3D) printing-based polycaprolactone (PCL)/poly(lactic-co-glycolic acid) (PLGA) scaffolds for bone formation of critical-sized rabbit segmental diaphyseal defect. To control the delivery of the rhBMP-2, collagen (for long-term delivery up to 28 days) and gelatin (for shor-term delivery within a week) solutions encapsulating rhBMP-2 were dispensed into a hollow cylinderical type of PCL/PLGA scaffold. An effective dose of 5μg/mL was determined by measuring the alkaline phosphatase and osteocalcin gene expression levels of human nasal inferior turbinate-derived mesenchymal stromal cells (hTMSCs) seeded on the PCL/PLGA/collagen scaffold in vitro. However, it was found that a burst release of rhBMP-2 from the PCL/PLGA/gelatin scaffold did not induce the osteogenic differentiation of hTMSCs in vitro at an equivalent dose. In the in vivo animal experiements, microcomputed tomography and histological analyses confirmed that PCL/PLGA/collagen/rhBMP-2 scaffolds (long-term delivery mode) showed the best bone healing quality at both weeks 4 and 8 after implantation without inflammatory response. On the other hand, a large number of macrophages indicating severe inflammation provoked by burst release of rhBMP-2 were observed in the vicinity of PCL/PLGA/gelatin/rhBMP-2 (short-term delivery mode) at week 4. PMID:24517081

  20. Designing the method for optical in vitro monitoring of the cell-mediated scaffold technology for bone regeneration based on laser-induced fluorescence spectroscopy

    Science.gov (United States)

    Larionov, P. M.; Maslov, N. A.; Papaeva, E. O.; Tereshchenko, V. P.; Khlestkin, V. K.; Bogachev, S. S.; Proskurina, A. S.; Titov, A. T.; Filipenko, M. L.; Pavlov, V. V.; Kudrov, G. A.; Orishich, A. M.

    2016-08-01

    One of the main unsolved problems in traumatology and orthopedics is reconstruction of critical-sized segmental bone defects. We believe that implementation of noninvasive monitoring of the bioengineering stages for cell-mediated bone scaffold by laser-induced fluorescence (LIF) can become a positive aspect in mastering this technique. An electrospun scaffold model (parameters: 10 wt. % polycaprolactone; 5% wt type A gelatin; mean fiber diameter 877.1 ± 169.1, and contact angle 45.3°) seeded with BHK IR cell culture (182 ± 38 cells/mm2) was used to show the principal possibility of differentiating between the scaffold seeded and unseeded with cells. First of all, the fluorescence spectra of the cell-seeded scaffold contain a peak at 305 nm for the excitation range of 230-290 nm, which can be used to differentiate between the samples. An increase in fluorescence intensity of the cell-seeded scaffold in the range of 400- 580 nm upon excitation at 230-340 nm is also noticeable. The wavelength of 250 nm is characterized by high signal intensity and is most suitable for differentiation between the samples.

  1. Porous hydroxyapatite for artificial bone applications

    OpenAIRE

    I. Sopyan et al

    2007-01-01

    Hydroxyapatite (HA) has been used clinically for many years. It has good biocompatibility in bone contact as its chemical composition is similar to that of bone material. Porous HA ceramics have found enormous use in biomedical applications including bone tissue regeneration, cell proliferation, and drug delivery. In bone tissue engineering it has been applied as filling material for bone defects and augmentation, artificial bone graft material, and prosthesis revision surgery. Its high surfa...

  2. RGD修饰的聚乳酸-羟基乙酸骨组织工程材料的研究进展%RGD-modified polylactide-co-glycolic acid tissue engineering scaffolds for bone regeneration: an advance

    Institute of Scientific and Technical Information of China (English)

    陶春; 陈琰; 钟延强

    2012-01-01

    Polylactide-co-glycolic acid (PLGA) tissue engineering scaffolds play an important role in the regeneration of bone and cartilage. Due to the poor hydrophilicity of PLGA, it is difficult for cells to attach to the scaffolds. Modification by RGD (Arg-Gly-Asp) peptides can effectively improve the cellular affinity of PLGA and adhesion and proliferation of the seed cells. This review summarizes the recent progress in PLGA tissue engineering scaffolds modified by RGD peptides.%聚乳酸-羟基乙酸(PLGA)骨组织工程支架在骨损伤修复和再造方面有着重要的应用,但由于PLGA亲水性差,不利于种子细胞在支架上的黏附和增殖.RGD(精氨酸-甘氨酸-天冬氨酸,Arg-Gly-Asp)肽修饰PLGA支架后,材料的细胞亲和性得到了有效改善,促进了种子细胞黏附和增殖.本文就近年来RGD修饰的PLGA骨组织工程材料的相关研究作一综述.

  3. Biocompatibility of plasma-treated poly(3-hydroxybutyrate-co-3-hydroxyvalerate) nanofiber mats modified by silk fibroin for bone tissue regeneration.

    Science.gov (United States)

    Unalan, Irem; Colpankan, Oylum; Albayrak, Aylin Ziylan; Gorgun, Cansu; Urkmez, Aylin Sendemir

    2016-11-01

    The objective of this study was to produce biocompatible plasma-treated and silk-fibroin (SF) modified poly(3-hydroxybutyrate-co-3-hydroxyvalerate) (PHBV) nanofiber mats. The mats were plasma-treated using O2 or N2 gas to increase their hydrophilicity followed by SF immobilization for the improvement of biocompatibility. Contact angle measurements and SEM showed increased hydrophilicity and no disturbed morphology, respectively. Cell proliferation assay revealed that SF modification together with N2 plasma (PS/N2) promoted higher osteoblastic (SaOs-2) cell viability. Although, O2 plasma triggered more mineral formation on the mats, it showed poor cell viability. Consequently, the PS/N2 nanofiber mats would be a potential candidate for bone tissue engineering applications. PMID:27524087

  4. Electrospun nanofibrous scaffolds of poly (L-lactic acid)-dicalcium silicate composite via ultrasonic-aging technique for bone regeneration

    Energy Technology Data Exchange (ETDEWEB)

    Dong, Shengjie [Department of Orthopaedics, The First Affiliated Hospital of Soochow University, 188 Shizi St, Suzhou, Jiangsu 215006 (China); Sun, Junying, E-mail: wodaoshi@sohu.com [Department of Orthopaedics, The First Affiliated Hospital of Soochow University, 188 Shizi St, Suzhou, Jiangsu 215006 (China); Li, Yadong [College of Chemistry, Chemical Engineering and Materials Science, Soochow University, Suzhou, Jiangsu 215123 (China); Li, Jun [Department of Orthopaedics, The First Affiliated Hospital of Soochow University, 188 Shizi St, Suzhou, Jiangsu 215006 (China); Cui, Wenguo [Orthopedic Institute, Soochow University, 708 Renmin Rd, Suzhou, Jiangsu 215007 (China); Li, Bin, E-mail: binli@suda.edu.cn [Department of Orthopaedics, The First Affiliated Hospital of Soochow University, 188 Shizi St, Suzhou, Jiangsu 215006 (China)

    2014-02-01

    Polymeric nanofibrous composite scaffolds incorporating bioglass and bioceramics have been increasingly promising for bone tissue engineering. In the present study, electrospun poly (L-lactic acid) (PLLA) scaffolds containing dicalcium silicate (C{sub 2}S) nanoparticles (approximately 300 nm) were fabricated. Using a novel ultrasonic dispersion and aging method, uniform C{sub 2}S nanoparticles were prepared and they were homogenously distributed in the PLLA nanofibers upon electrospinning. In vitro, the PLLA-C{sub 2}S fibers induced the formation of HAp on the surface when immersed in simulated body fluid (SBF). During culture, the osteoblastic MC3T3-E1 cells adhered well on PLLA-C{sub 2}S scaffolds, as evidenced by the well-defined actin stress fibers and well-spreading morphology. Further, compared to pure PLLA scaffolds without C{sub 2}S, PLLA-C{sub 2}S scaffolds markedly promoted the proliferation of MC3T3-E1 cells as well as their osteogenic differentiation, which was characterized by the enhanced alkaline phosphatase (ALP) activity. Together, findings from this study clearly demonstrated that PLLA-C{sub 2}S composite scaffold may function as an ideal candidate for bone tissue engineering. - Highlights: • Dicalcium silicate (C{sub 2}S) nanoparticles were prepared via a sol–gel process. • C{sub 2}S nanoparticles were stabilized using ultrasonic-aging technique. • PLLA-C{sub 2}S composite nanofibers were fabricated through electrospinning technique. • C{sub 2}S nanoparticles could be homogenously distributed in nanofibers. • The composite scaffolds enhanced proliferation and differentiation of osteoblasts.

  5. Bone tissue engineering in osteoporosis.

    Science.gov (United States)

    Jakob, Franz; Ebert, Regina; Ignatius, Anita; Matsushita, Takashi; Watanabe, Yoshinobu; Groll, Juergen; Walles, Heike

    2013-06-01

    Osteoporosis is a polygenetic, environmentally modifiable disease, which precipitates into fragility fractures of vertebrae, hip and radius and also confers a high risk of fractures in accidents and trauma. Aging and the genetic molecular background of osteoporosis cause delayed healing and impair regeneration. The worldwide burden of disease is huge and steadily increasing while the average life expectancy is also on the rise. The clinical need for bone regeneration applications, systemic or in situ guided bone regeneration and bone tissue engineering, will increase and become a challenge for health care systems. Apart from in situ guided tissue regeneration classical ex vivo tissue engineering of bone has not yet reached the level of routine clinical application although a wealth of scaffolds and growth factors has been developed. Engineering of complex bone constructs in vitro requires scaffolds, growth and differentiation factors, precursor cells for angiogenesis and osteogenesis and suitable bioreactors in various combinations. The development of applications for ex vivo tissue engineering of bone faces technical challenges concerning rapid vascularization for the survival of constructs in vivo. Recent new ideas and developments in the fields of bone biology, materials science and bioreactor technology will enable us to develop standard operating procedures for ex vivo tissue engineering of bone in the near future. Once prototyped such applications will rapidly be tailored for compromised conditions like vitamin D and sex hormone deficiencies, cellular deficits and high production of regeneration inhibitors, as they are prevalent in osteoporosis and in higher age. PMID:23562167

  6. Printing bone : the application of 3D fiber deposition for bone tissue engineering

    NARCIS (Netherlands)

    Fedorovich, N.E.

    2011-01-01

    Bone chips are used by orthopaedic surgeons for treating spinal trauma and to augment large bone defects. A potential alternative to autologous bone is regeneration of bone tissue in the lab by developing hybrid implants consisting of osteogenic (stem) cells seeded on supportive matrices. Applicatio

  7. GBR技术用于上颌前牙唇侧骨缺损的延期种植修复的效果观察%Clinical Effect of Guided Bone Regeneration in Delayed Implant Restoration of Bone Defects in the Maxillary Anterior Region

    Institute of Scientific and Technical Information of China (English)

    沈汉

    2015-01-01

    Objective To probe into the effect of double guided bone regeneration applied in delayed implant restoration of bone defects in the maxillary anterior region. Methods The selected study subjects, twelve outpatients from January 2012 to August 2013 in Stomatological Hospital of Yangzhou restored partial bone defects after the primary GBR treatment on the conditon of the alveolar bone resorption and serious bone implant thinning due to cyst of jaw, trauma, dental caries or periodontal disease after the removal of the anterior teeth. The implants were inserted and GBR technique was applied once again 4-6 months later after the healing. Stage II surgeries of dental implantion were done 4-6 months later and dental crown restoration was completed. All the cases in the repair were taken local dental and oral panoramic X-rays at post-operation simultaneously, 3 months later, 6 months later and 12 months later respectively. Follow-up comparisons in peri implant bone level, bone density and osseointergration degree were conducted. Results Two cases of patients with GBR technology and 12 cases of implant were used in the process of planting, and the results showed that the X film was closely related to the alveolar bone. Conclusion The results showed that in all cases with 6 months to 12 months loading the peri implant bone level was stable locating above the first thread and ideal osseointergration was achieved.%目的:观察两次运用引导骨再生技术(GBR)在上颌前牙唇侧区骨质严重缺损种植修复中的应用效果。方法选取2012年1月~2013年8月我院收治的因外伤或颌骨囊肿拔牙后导致牙槽骨严重缺损患者12例作为研究对象,在首次进行GBR恢复部分骨缺损,愈合4~6个月后,再进行种植体植入术,同时再次使用GBR技术。术后4~6月进行种植二期、牙冠修复完成,所有患者均在修复完成当天、3个月、6个月、12个月行局部牙片和口腔全景片,对比种植

  8. Bone Graft and Guided Tissue Regeneration in Treatment for Combined Periodontic-Endodontic Lesion%引导组织再生术治疗牙周牙髓联合病变的观察

    Institute of Scientific and Technical Information of China (English)

    刘琼; 孙江

    2011-01-01

    目的 观察应用Bio-Oss骨胶原与Bio-Gide 胶原膜联合进行引导组织再生术,对牙周牙髓联合病变治疗后3年疗效.方法 对16例患者20颗牙周牙髓联合病变患牙,先行根管治疗,牙周基础治疗后4周,联合使用Bio-Oss骨胶原与Bio-Gide胶原膜进行引导组织再生术,术后定期维护.术前和术后6、12、18、24、30、36个月,观测记录临床牙周指标,包括探诊深度(probing depth,PD)、附着丧失(attachment loss,AL)、牙龈退缩(gingival recession,GR),拍X线片,对所得数据进行统计学分析.结果 患牙行引导组织再生术术前PD、AL、GR分别为(4.81±1.37)mm、(5.48±1.76)mm、(0.64±0.62)mm,术后36个月PD、AL、GR分别为(2.09±0.66)mm、(3.90±1.11)mm、(1.86±0.83)mm.术后6、12、18、24、30、36个月PD、AL均较术前减少,差异有统计学意义(P<0.05);术后6、12、18、24、30、36个月GR较术前有所增加,差异有统计学意义(P<0.05).X线片显示治疗后随时间的延长,患牙周围骨密度不断增高,骨形成量不断增加.结论 Bio-Oss骨胶原与Bio-Gide胶原膜联合进行引导组织再生术,治疗牙周牙髓联合病变可获得良好稳定的临床疗效.%Objective To observe the effect of bone graft and guided tissue regeneration (GTR) in treatment for combined periodontic-endodontic lesion. Methods Sixteen patients (20 teeth) were investigated. Four weeks after root canal therapy and initial periodontal therapy, Bio-Oss collagen for bone graft and Bio-Gide collagen membrane for GTR were used in these teeth. Clinical examinations were performed, 6, 12, 18, 24, 30, 36 months after the surgery. Results Probing depth (PD) and attachment loss (AL) reduced 6, 12, 18, 24, 30, 36 months after the surgery. There was statistical significance. Gingival recession (GR) increased after the surgery, there was statistical significance. PD, AL, GR values at baseline were respectively (4.81 ± 1.37) mm, (5.48 ± 1.76) mm, (0.64 ± 0. 62 ) mm, and all

  9. Osteobiol (r) enhances osteogenic differentiation in bone marrow derived stem cells

    OpenAIRE

    D. Lauritano; Carinci, F.; Zollino, I; A. Hassanipour; Saggese, V; A. Palmieri; Girardi, A; Cura, F; A. Piras; Zamboni, P.; Brunelli, G

    2012-01-01

    OsteoBiol (R) (OsteoBiol, Tecnoss Dental, Turin, Italy) a cortical collagenated porcine bone is largely employed in oral implant techniques for bone regeneration thanks to its biocompatibility and osteoconductivity To study the mechanism by which cortical porcine bone promotes osteoblast differentiation and bone regeneration, changes in expression level of bone related genes were investigated by real time RT-PCR, in bone marrow derived stem cells and human osteoblasts cultivated with OsteoBio...

  10. Histological Observation of Autogenous Bone Dust Grafting and Membrane Guided Regeneration Technology to Repair Skull Defects%自体颅骨粉末移植和膜引导再生技术修复兔颅骨缺损的组织学研究

    Institute of Scientific and Technical Information of China (English)

    陈敏建; 陆婷; 陈平

    2013-01-01

    Objective To repair the skull defects by using autogenous skull bone dust grafting and membrane guided regeneration technology, and to investigate its histological evolution. Methods Fifty New Zealand white rabbits were selected. A whole thick defect with the diameter of 1 cm was created in the parietal bone of every rabbit. The defect was grafted with autogenous skull bone dust and two pieces of absorbable membrane on two side. After 2, 4, 6, 8, 12 weeks, the defects were harvested for histological observation. Results Two weeks after operation, a large number of bone meal was observed in the defect area. Inward infiltration of inflammatory cells, capillaries and fibroblasts were observed. Bone meal was swallowed in the central area, new bone was formed in the surrounding area and a clear boundary was observed between the two area. Four weeks after operation, the boundary had moved a lot to the central area. New woven bone was thickened, the connection between the woven bone became more closely. Tissue and cell components had no obvious change compared with 2 weeks after operation. Six weeks after operation, bone meal was almost absorbed, the woven bone became thicker and the connection was more closely. Eight weeks after operation, no bone dust could be observed, a monolayer new bone was formed in the central area. The woven bone in the surrounding area was relatively thick and closely connected with normal bone. The primary bone marrow cavity was formed. Twelve weeks after operation, double new bone was observed in the central area. New bone remodeling and mature bone marrow cavity were also observed. The morphology and composition of bone marrow cavity had no difference compared with normal bone. Conclusion Histological evolution of autogenous bone dust grafting and membrane guided regeneration technology to repair skull defects is guided and induced bone regeneration.%目的:应用自体颅骨粉末移植和膜引导再生技术修复兔颅骨缺损模型

  11. Bone defect animal models for testing efficacy of bone substitute biomaterials

    OpenAIRE

    Ye Li; Shu-Kui Chen; Long Li; Ling Qin; Xin-Luan Wang; Yu-Xiao Lai

    2015-01-01

    Large bone defects are serious complications that are most commonly caused by extensive trauma, tumour, infection, or congenital musculoskeletal disorders. If nonunion occurs, implantation for repairing bone defects with biomaterials developed as a defect filler, which can promote bone regeneration, is essential. In order to evaluate biomaterials to be developed as bone substitutes for bone defect repair, it is essential to establish clinically relevant in vitro and in vivo testing models for...

  12. Solid freeform fabrication of bone tissue engineering scaffolds

    Institute of Scientific and Technical Information of China (English)

    XIONG Zhuo; YAN Yongnian; ZHANG Renji; CHEN Lifeng; WANG Li

    2001-01-01

    @@ INTRODUCTIONTissue engineering is a promising approach to large segmental bone repair fortrauma, replacement surgery, skeletal deficiency or abnormal development. Thefabrication of bone regeneration scaffolds with appropriate bone conductive property,bone inductive property, biodegradation property and mechanical properties is thecrux of this approach.

  13. Novel phosphate glasses for bone