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Sample records for bone regeneration molecular

  1. Guided bone regeneration using resorbable membrane and different bone substitutes: Early histological and molecular events.

    Science.gov (United States)

    Elgali, Ibrahim; Turri, Alberto; Xia, Wei; Norlindh, Birgitta; Johansson, Anna; Dahlin, Christer; Thomsen, Peter; Omar, Omar

    2016-01-01

    Bone insufficiency remains a major challenge for bone-anchored implants. The combination of guided bone regeneration (GBR) and bone augmentation is an established procedure to restore the bone. However, a proper understanding of the interactions between the bone substitute and GBR membrane materials and the bone-healing environment is lacking. This study aimed to investigate the early events of bone healing and the cellular activities in response to a combination of GBR membrane and different calcium phosphate (CaP) materials. Defects were created in the trabecular region of rat femurs, and filled with deproteinized bovine bone (DBB), hydroxyapatite (HA) or strontium-doped HA (SrHA) or left empty (sham). All the defects were covered with an extracellular matrix membrane. Defects were harvested after 12h, 3d and 6d for histology/histomorphometry, immunohistochemistry and gene expression analyses. Histology revealed new bone, at 6d, in all the defects. Larger amount of bone was observed in the SrHA-filled defect. This was in parallel with the reduced expression of osteoclastic genes (CR and CatK) and the osteoblast-osteoclast coupling gene (RANKL) in the SrHA defects. Immunohistochemistry indicated fewer osteoclasts in the SrHA defects. The observations of CD68 and periostin-expressing cells in the membrane per se indicated that the membrane may contribute to the healing process in the defect. It is concluded that the bone-promoting effects of Sr in vivo are mediated by a reduction in catabolic and osteoblast-osteoclast coupling processes. The combination of a bioactive membrane and CaP bone substitute material doped with Sr may produce early synergistic effects during GBR. The study provides novel molecular, cellular and structural evidence on the promotion of early bone regeneration in response to synthetic strontium-containing hydroxyapatite (SrHA) substitute, in combination with a resorbable, guided bone regeneration (GBR) membrane. The prevailing view, based

  2. Cell-to-cell communication in guided bone regeneration: molecular and cellular mechanisms.

    Science.gov (United States)

    Gruber, Reinhard; Stadlinger, Bernd; Terheyden, Hendrik

    2017-09-01

    This overview provides insights into the molecular and cellular mechanisms involved in guided bone regeneration, in particular focusing on aspects presented in the 3D movie, Cell-To-Cell Communication in Guided Bone Regeneration. The information presented here is based almost exclusively on genetic mouse models in which single genes can be deleted or overexpressed, even in a specific cell type. This information needs to be extrapolated to humans and related to aspects relevant to graft consolidation under the clinical parameters of guided bone regeneration. The overview follows the ground tenor of the Cell-To-Cell Communication series and focuses on aspects of cell-to-cell communication in bone regeneration and guided bone regeneration. Here, we discuss (1) the role of inflammation during bone regeneration, including (2) the importance of the fibrin matrix, and (3) the pleiotropic functions of macrophages. We highlight (4) the origin of bone-forming osteoblasts and bone-resorbing osteoclasts as well as (5) what causes a progenitor cell to mature into an effector cell. (6) We touch on the complex bone adaptation and maintenance after graft consolidation and (7) how osteocytes control this process. Finally, we speculate on (8) how barrier membranes and the augmentation material can modulate graft consolidation. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  3. Bone regeneration: molecular and cellular interactions with calcium phospate ceramics

    NARCIS (Netherlands)

    Barrère, F.; van Blitterswijk, Clemens; de Groot, K.

    2006-01-01

    Calcium phosphate bioceramics are widely used in orthopedic and dental applications and porous scaffolds made of them are serious candidates in the field of bone tissue engineering. They have superior properties for the stimulation of bone formation and bone bonding, both related to the specific

  4. Guided bone regeneration is promoted by the molecular events in the membrane compartment.

    Science.gov (United States)

    Turri, Alberto; Elgali, Ibrahim; Vazirisani, Forugh; Johansson, Anna; Emanuelsson, Lena; Dahlin, Christer; Thomsen, Peter; Omar, Omar

    2016-04-01

    The working hypothesis of guided bone regeneration (GBR) is that the membrane physically excludes non-osteogenic tissues from interfering with bone healing. However, the underlying mechanisms are insufficiently explained. This study aimed to investigate the molecular and structural pattern of bone healing in trabecular bone defects, with and without naturally derived resorbable membrane. Defects were created in rat femurs and treated with the membrane or left empty (sham). After 3d, 6d and 28d, the defect sites and membranes were harvested and analyzed with histology, histomorphometry, quantitative-polymerase chain reaction (qPCR), Western blot (WB) and immunohistochemistry (IHC). Histomorphometry demonstrated that the presence of the membrane promoted bone formation in early and late periods. This was in parallel with upregulation of cell recruitment and coupled bone remodeling genes in the defect. Cells recruited into the membrane expressed signals for bone regeneration (BMP-2, FGF-2, TGF-β1 and VEGF). Whereas the native membrane contained FGF-2 but not BMP-2, an accumulation of FGF-2 and BMP-2 proteins and immunoreactive cells were demonstrated by WB and IHC in the in vivo implanted membrane. The results provide cellular and molecular evidence suggesting a novel role for the membrane during GBR, by acting as a bioactive compartment rather than a passive barrier. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

  5. Bone regeneration and stem cells

    DEFF Research Database (Denmark)

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

    2011-01-01

    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....

  6. Bone regeneration in dentistry

    Science.gov (United States)

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

    2011-01-01

    Summary 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 principles of osteogenesis, osteoinduction and osteoconduction. Several techniques combine these principles with different results, due to the condition of the bone base on which we operate changes, the surgical technique that we use, and finally for the bone metabolic conditions of the patient who can be in a state of systemic osteopenia or osteoporosis; these can also affect the result of jaw bone reconstruction. PMID:22461825

  7. Nanocomposites for bone tissue regeneration.

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    Sahoo, Nanda Gopal; Pan, Yong Zheng; Li, Lin; He, Chao Bin

    2013-04-01

    Natural bone tissue possesses a nanocomposite structure that provides appropriate physical and biological properties. For bone tissue regeneration, it is crucial for the biomaterial to mimic living bone tissue. Since no single type of material is able to mimic the composition, structure and properties of native bone, nanocomposites are the best choice for bone tissue regeneration as they can provide the appropriate matrix environment, integrate desirable biological properties, and provide controlled, sequential delivery of multiple growth factors for the different stages of bone tissue regeneration. This article reviews the composition, structure and properties of advanced nanocomposites for bone tissue regeneration. It covers aspects of interest such as the biomimetic synthesis of bone-like nanocomposites, guided bone regeneration from inert biomaterials and bioactive nanocomposites, and nanocomposite scaffolds for bone tissue regeneration. The design, fabrication, and in vitro and in vivo characterization of such nanocomposites are reviewed.

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

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    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.

  9. Pigs are useful for the molecular study of bone inflammation and regeneration in humans

    DEFF Research Database (Denmark)

    Lüthje, Freja Lea; Skovgaard, Kerstin; Jensen, Henrik Elvang

    2018-01-01

    Pigs are used with increased frequency to model different kinds of orthopedic surgical conditions. In order to show the full potential of porcine models in orthopedic research, it is therefore required to examine the expression of bone regulatory genes in pigs affected by orthopedic surgery...... and compare it to the expression in humans and mice as mice, are one of the most applied animal species in orthopedics today. In the present study, the local molecular response to drilling of a tibial implant cavity, and the subsequent insertion of a steel implant was examined in a porcine model. Pigs were...... euthanized five days after drilling of the bone. The molecular response of 73 different genes was analyzed using a high-throughput quantitative polymerase chain reaction platform and compared to histopathology. Histologically, it was found that bone remodeling was initiated on day 5 after surgery...

  10. Bone regeneration during distraction osteogenesis

    NARCIS (Netherlands)

    Amir, L.R.; Everts, V.; Bronckers, A.L.J.J.

    2009-01-01

    Bone has the capacity to regenerate in response to injury. During distraction osteogenesis, the renewal of bone is enhanced by gradual stretching of the soft connec- tive tissues in the gap area between two separated bone segments. This procedure has received much clinical atten- tion as a way to

  11. Mechanisms of Guided Bone Regeneration: A Review

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    Liu, Jie; Kerns, David G

    2014-01-01

    Post-extraction crestal bone resorption is common and unavoidable which can lead to significant ridge dimensional changes. To regenerate enough bone for successful implant placement, Guided Bone Regeneration (GBR) is often required. GBR is a surgical procedure that uses barrier membranes with or without particulate bone grafts or/and bone substitutes. There are two approaches of GBR in implant therapy: GBR at implant placement (simultaneous approach) and GBR before implant placement to increase the alveolar ridge or improve ridge morphology (staged approach). Angiogenesis and ample blood supply play a critical role in promoting bone regeneration. PMID:24894890

  12. Guided bone regeneration using individualized ceramic sheets.

    Science.gov (United States)

    Malmström, J; Anderud, J; Abrahamsson, P; Wälivaara, D-Å; Isaksson, S G; Adolfsson, E

    2016-10-01

    Guided bone regeneration (GBR) describes the use of membranes to regenerate bony defects. A membrane for GBR needs to be biocompatible, cell-occlusive, non-toxic, and mouldable, and possess space-maintaining properties including stability. The purpose of this pilot study was to describe a new method of GBR using individualized ceramic sheets to perfect bone regeneration prior to implant placement; bone regeneration was assessed using traditional histology and three-dimensional (3D) volumetric changes in the bone and soft tissue. Three patients were included. After full-thickness flap reflection, the individualized ceramic sheets were fixed. The sites were left to heal for 7 months. All patients were evaluated preoperatively and at 7 months postoperative using cone beam computed tomography and 3D optical equipment. Samples of the regenerated bone and soft tissue were collected and analyzed. The bone regenerated in the entire interior volume of all sheets. Bone biopsies revealed newly formed trabecular bone with a lamellar structure. Soft tissue biopsies showed connective tissue with no signs of an inflammatory response. This was considered to be newly formed periosteum. Thus ceramic individualized sheets can be used to regenerate large volumes of bone in both vertical and horizontal directions independent of the bone defect and with good biological acceptance of the material. Copyright © 2016 International Association of Oral and Maxillofacial Surgeons. Published by Elsevier Ltd. All rights reserved.

  13. Horizontal bone augmentation by means of guided bone regeneration.

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    Benic, Goran I; Hämmerle, Christoph H F

    2014-10-01

    The development of bone augmentation procedures has allowed placement of dental implants into jaw bone areas lacking an amount of bone sufficient for standard implant placement. Thus, the indications for implants have broadened to include jaw regions with bone defects and those with a bone anatomy that is unfavorable for implant anchorage. Of the different techniques, the best documented and the most widely used method to augment bone in localized alveolar defects is guided bone regeneration. A large body of evidence has demonstrated the successful use of guided bone regeneration to regenerate missing bone at implant sites with insufficient bone volume and the long-term success of implants placed simultaneously with, or after, guided bone regeneration. However, the influence of guided bone regeneration on implant survival and success rates, and the long-term stability of the augmented bone, remain unknown. Many of the materials and techniques currently available for bone regeneration of alveolar ridge defects were developed many years ago. Recently, various new materials and techniques have been introduced. Many of them have, however, not been sufficiently documented in clinical studies. The aim of this review was to present the scientific basis of guided bone regeneration and the accepted clinical procedures. A classification of bone defects has been presented, aiming at simplifying the decision-making process regarding the choice of strategy for bone augmentation. Finally, an outlook into actual research and the possible future options related to bone augmentation has been provided. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  14. Microwave regeneration of molecular sieves

    International Nuclear Information System (INIS)

    Singh, V.P.

    1984-05-01

    Molecular sieve driers have been included in the design of tritium handling systems for fusion reactors. In these systems there is a need to maintain extremely low exit dew points from the driers as well as a capability to rapidly reduce tritium concentrations following an accident. The required capacity of the driers is very high. The conventional method of regenerating these sieves after a water adsorption cycle is with hot air. However, because water is rapidly heated by microwave energy, this technology may be suitable for decreasing the bed regeneration time and hence may allow reduced capital and operating costs associated with a smaller bed. The present study was conducted to obtain preliminary information on the technical feasibility of regenerating molecular sieves with microwave energy. The study concentrated on Type 4A molecular sieve with a few tests on Type 13X sieve and also a silica gel adsorbent

  15. Guided Bone Regeneration with Novel Bioabsorbable Membranes

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    Koyama, Yoshihisa; Kikuchi, Masanori; Yamada, Takeki; Kanaya, Tomohiro; Matsumoto, Hiroko N.; Takakuda, Kazuo; Miyairi, Hiroo; Tanaka, Junzo

    Guided Bone Regeneration (GBR) is a method for bone tissue regeneration. In this method, membranes are used to cover bone defects and to block the invasion of the surrounding soft tissues. It would provide sufficient time for the osteogenic cells from bone marrow to proliferate and form new bony tissues. In spite of the potential usefulness of this method, no appropriate materials for the GBR membrane have been developed. Here we design the ideal mechanical properties of the GBR membranes and created novel materials, which is the composite of β-tricalcium phosphate and block copolymer of L-lactide, glycolide and ɛ-caplolactone. In the animal experiments with the use of the trial products, we observed significant enhancement in the bone regeneration and proved the effectiveness of the materials.

  16. Bone regeneration: current concepts and future directions

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    McGonagle Dennis

    2011-05-01

    Full Text Available Abstract Bone regeneration is a complex, well-orchestrated physiological process of bone formation, which can be seen during normal fracture healing, and is involved in continuous remodelling throughout adult life. However, there are complex clinical conditions in which bone regeneration is required in large quantity, such as for skeletal reconstruction of large bone defects created by trauma, infection, tumour resection and skeletal abnormalities, or cases in which the regenerative process is compromised, including avascular necrosis, atrophic non-unions and osteoporosis. Currently, there is a plethora of different strategies to augment the impaired or 'insufficient' bone-regeneration process, including the 'gold standard' autologous bone graft, free fibula vascularised graft, allograft implantation, and use of growth factors, osteoconductive scaffolds, osteoprogenitor cells and distraction osteogenesis. Improved 'local' strategies in terms of tissue engineering and gene therapy, or even 'systemic' enhancement of bone repair, are under intense investigation, in an effort to overcome the limitations of the current methods, to produce bone-graft substitutes with biomechanical properties that are as identical to normal bone as possible, to accelerate the overall regeneration process, or even to address systemic conditions, such as skeletal disorders and osteoporosis.

  17. Autogenous tooth bone graft: Ingenious bone regeneration material

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    Chadalavada Sarala

    2018-01-01

    Full Text Available Tooth-derived bone graft material, which is proved to be rich in bone growth factors and bone morphogenic proteins (BMPs, have been becoming a practical substitute to bone grafting. It can also be used as a carrier for growth factors and stem cells as reported in many recent studies. Autogenous-tooth bone grafting technique is significant as this biomaterial has excellent bone regeneration capacity and also relatively non-existent chances of antigenicity, genetic diseases and disease transmission. In this article, a broad overview of the published findings with regard to the properties and uses of tooth-derived regenerative bone grafting is discussed.

  18. Osteoinduction of bone grafting materials for bone repair and regeneration.

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    García-Gareta, Elena; Coathup, Melanie J; Blunn, Gordon W

    2015-12-01

    Regeneration of bone defects caused by trauma, infection, tumours or inherent genetic disorders is a clinical challenge that usually necessitates bone grafting materials. Autologous bone or autograft is still considered the clinical "gold standard" and the most effective method for bone regeneration. However, limited bone supply and donor site morbidity are the most important disadvantages of autografting. Improved biomaterials are needed to match the performance of autograft as this is still superior to that of synthetic bone grafts. Osteoinductive materials would be the perfect candidates for achieving this task. The aim of this article is to review the different groups of bone substitutes in terms of their most recently reported osteoinductive properties. The different factors influencing osteoinductivity by biomaterials as well as the mechanisms behind this phenomenon are also presented, showing that it is very limited compared to osteoinductivity shown by bone morphogenetic proteins (BMPs). Therefore, a new term to describe osteoinductivity by biomaterials is proposed. Different strategies for adding osteoinductivity (BMPs, stem cells) to bone substitutes are also discussed. The overall objective of this paper is to gather the current knowledge on osteoinductivity of bone grafting materials for the effective development of new graft substitutes that enhance bone regeneration. Copyright © 2015 Elsevier Inc. All rights reserved.

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

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    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.

  20. 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.

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

    Science.gov (United States)

    Kasai, Takao; Matsumura, Sachiko; Iizuka, Tadashi; Shiba, Kiyotaka; Kanamori, Takeshi; Yudasaka, Masako; Iijima, Sumio; Yokoyama, Atsuro

    2011-02-01

    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.

  2. Guided bone regeneration : the influence of barrier membranes on bone grafts and bone defects

    NARCIS (Netherlands)

    Gielkens, Pepijn Frans Marie

    2008-01-01

    Guided bone regeneration (GBR) can be described as the use of a barrier membrane to provide a space available for new bone formation in a bony defect. The barrier membrane protects the defect from in-growth of soft tissue cells and allows bone progenitor cells to develop bone within a blood clot

  3. Indirect rapid prototyping of sol-gel hybrid glass scaffolds for bone regeneration - Effects of organic crosslinker valence, content and molecular weight on mechanical properties.

    Science.gov (United States)

    Hendrikx, Stephan; Kascholke, Christian; Flath, Tobias; Schumann, Dirk; Gressenbuch, Mathias; Schulze, F Peter; Hacker, Michael C; Schulz-Siegmund, Michaela

    2016-04-15

    We present a series of organic/inorganic hybrid sol-gel derived glasses, made from a tetraethoxysilane-derived silica sol (100% SiO2) and oligovalent organic crosslinkers functionalized with 3-isocyanatopropyltriethoxysilane. The material was susceptible to heat sterilization. The hybrids were processed into pore-interconnected scaffolds by an indirect rapid prototyping method, described here for the first time for sol-gel glass materials. A large panel of polyethylene oxide-derived 2- to 4-armed crosslinkers of molecular weights ranging between 170 and 8000Da were incorporated and their effect on scaffold mechanical properties was investigated. By multiple linear regression, 'organic content' and the 'content of ethylene oxide units in the hybrid' were identified as the main factors that determined compressive strength and modulus, respectively. In general, 3- and 4-armed crosslinkers performed better than linear molecules. Compression tests and cell culture experiments with osteoblast-like SaOS-2 cells showed that macroporous scaffolds can be produced with compressive strengths of up to 33±2MPa and with a pore structure that allows cells to grow deep into the scaffolds and form mineral deposits. Compressive moduli between 27±7MPa and 568±98MPa were obtained depending on the hybrid composition and problems associated with the inherent brittleness of sol-gel glass materials could be overcome. SaOS-2 cells showed cytocompatibility on hybrid glass scaffolds and mineral accumulation started as early as day 7. On day 14, we also found mineral accumulation on control hybrid glass scaffolds without cells, indicating a positive effect of the hybrid glass on mineral accumulation. We produced a hybrid sol-gel glass material with significantly improved mechanical properties towards an application in bone regeneration and processed the material into macroporous scaffolds of controlled architecture by indirect rapid prototyping. We were able to produce macroporous materials

  4. Bone-Inspired Spatially Specific Piezoelectricity Induces Bone Regeneration.

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    Yu, Peng; Ning, Chengyun; Zhang, Yu; Tan, Guoxin; Lin, Zefeng; Liu, Shaoxiang; Wang, Xiaolan; Yang, Haoqi; Li, Kang; Yi, Xin; Zhu, Ye; Mao, Chuanbin

    2017-01-01

    The extracellular matrix of bone can be pictured as a material made of parallel interspersed domains of fibrous piezoelectric collagenous materials and non-piezoelectric non-collagenous materials. To mimic this feature for enhanced bone regeneration, a material made of two parallel interspersed domains, with higher and lower piezoelectricity, respectively, is constructed to form microscale piezoelectric zones (MPZs). The MPZs are produced using a versatile and effective laser-irradiation technique in which K 0.5 Na 0.5 NbO 3 (KNN) ceramics are selectively irradiated to achieve microzone phase transitions. The phase structure of the laser-irradiated microzones is changed from a mixture of orthorhombic and tetragonal phases (with higher piezoelectricity) to a tetragonal dominant phase (with lower piezoelectricity). The microzoned piezoelectricity distribution results in spatially specific surface charge distribution, enabling the MPZs to bear bone-like microscale electric cues. Hence, the MPZs induce osteogenic differentiation of stem cells in vitro and bone regeneration in vivo even without being seeded with stem cells. The concept of mimicking the spatially specific piezoelectricity in bone will facilitate future research on the rational design of tissue regenerative materials.

  5. The role of vasculature in bone development, regeneration and proper systemic functioning.

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    Filipowska, Joanna; Tomaszewski, Krzysztof A; Niedźwiedzki, Łukasz; Walocha, Jerzy A; Niedźwiedzki, Tadeusz

    2017-08-01

    Bone is a richly vascularized connective tissue. As the main source of oxygen, nutrients, hormones, neurotransmitters and growth factors delivered to the bone cells, vasculature is indispensable for appropriate bone development, regeneration and remodeling. Bone vasculature also orchestrates the process of hematopoiesis. Blood supply to the skeletal system is provided by the networks of arteries and arterioles, having distinct molecular characteristics and localizations within the bone structures. Blood vessels of the bone develop through the process of angiogenesis, taking place through different, bone-specific mechanisms. Impaired functioning of the bone blood vessels may be associated with the occurrence of some skeletal and systemic diseases, i.e., osteonecrosis, osteoporosis, atherosclerosis or diabetes mellitus. When a disease or trauma-related large bone defects appear, bone grafting or bone tissue engineering-based strategies are required. However, a successful bone regeneration in both approaches largely depends on a proper blood supply. In this paper, we review the most recent data on the functions, molecular characteristics and significance of the bone blood vessels, with a particular emphasis on the role of angiogenesis and blood vessel functioning in bone development and regeneration, as well as the consequences of its impairment in the course of different skeletal and systemic diseases.

  6. Bone morphogenetic proteins in periodontal tissue regeneration

    Directory of Open Access Journals (Sweden)

    Suryakanth Malgikar

    2017-01-01

    Full Text Available Progress in understanding the role of bone morphogenetic proteins (BMPs in craniofacial and tooth development, the demonstration of stem cells in dental pulp, and accumulating knowledge on biomaterial scaffolds have set the stage for tissue engineering and regenerative therapy of the craniofacial complex. Furthermore, the recent approval by the US Food and Drug Administration (FDA; Rockville, MD, USA 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 dental applications. In the near term, these advances are likely to be applied to endodontics and periodontal surgery; ultimately, they may facilitate approaches to regenerating whole teeth for use in tooth replacement. Early on, scientists focused on creating a suitable environment that favored the innate potential for regeneration. However, complex clinical protocols and extended treatments, in addition to inconsistent results, often brought treatment protocols out of favor. Predictable outcomes and minimally invasive protocols have become fundamental to clinicians and patients. Thus, novel regenerative concepts with improved or superior outcomes, predictability, and minimally invasive protocols are being developed and considered.

  7. Osseointegration of dental implants placed into canine mandibular bone regenerated by bone transport distraction osteogenesis.

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

    2013-01-01

    The purpose of this study was to compare the osseointegration of dental implants placed in canine mandibular bone and in regenerated bone produced by bone transport distraction osteogenesis. Ten adult foxhounds were divided into two groups of five animals each. In all animals, a 40-mm defect was created on one side of the mandible. A bone transport reconstruction plate was used to stabilize the mandible and regenerate bone. Six weeks after the distraction period was finished, dental implants were placed in regenerated and native mandibular bone. The animals were sacrificed after another 6 and 12 weeks of healing, respectively. Microcomputed tomographic evaluation showed that bone volume fraction (BV/TV) was greater at the coronal regions of the implants and decreased toward the apical regions. There was an increase in BV/TV around implants placed in regenerated bone from 6 to 12 weeks of healing. The regenerated group showed lower BV/TV at 6 weeks versus implants placed in native bone but had reached the same levels as the native bone at 12 weeks. Histology showed that direct bone-to-implant contact was greater for implants placed in native bone than for those placed in regenerated bone for both time periods. The removal torque of the implants placed in native bone was higher at 6 weeks than that of implants placed in regenerated bone. At 12 weeks, there were no statistically significant differences in removal torque between the groups. Bone was successfully regenerated in all animals. The implants placed entirely in regenerated bone were osseointegrated. The regenerated bone around the implants became denser over time. This finding suggests that implants placed entirely in regenerated bone will be as well integrated as implants in native mandibular bone by 12 weeks after placement.

  8. Enhanced bioactive scaffolds for bone tissue regeneration

    Science.gov (United States)

    Karnik, Sonali

    Bone injuries are commonly termed as fractures and they vary in their severity and causes. If the fracture is severe and there is loss of bone, implant surgery is prescribed. The response to the implant depends on the patient's physiology and implant material. Sometimes, the compromised physiology and undesired implant reactions lead to post-surgical complications. [4, 5, 20, 28] Efforts have been directed towards the development of efficient implant materials to tackle the problem of post-surgical implant failure. [ 15, 19, 24, 28, 32]. The field of tissue engineering and regenerative medicine involves the use of cells to form a new tissue on bio-absorbable or inert scaffolds. [2, 32] One of the applications of this field is to regenerate the damaged or lost bone by using stem cells or osteoprogenitor cells on scaffolds that can integrate in the host tissue without causing any harmful side effects. [2, 32] A variety of natural, synthetic materials and their combinations have been used to regenerate the damaged bone tissue. [2, 19, 30, 32, 43]. Growth factors have been supplied to progenitor cells to trigger a sequence of metabolic pathways leading to cellular proliferation, differentiation and to enhance their functionality. [56, 57] The challenge persists to supply these proteins, in the range of nano or even picograms, and in a sustained fashion over a period of time. A delivery system has yet to be developed that would mimic the body's inherent mechanism of delivering the growth factor molecules in the required amount to the target organ or tissue. Titanium is the most preferred metal for orthopedic and orthodontic implants. [28, 46, 48] Even though it has better osteogenic properties as compared to other metals and alloys, it still has drawbacks like poor integration into the surrounding host tissue leading to bone resorption and implant failure. [20, 28, 35] It also faces the problem of postsurgical infections that contributes to the implant failure. [26, 37

  9. Recent advances in bone regeneration using adult stem cells.

    Science.gov (United States)

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

    2015-04-26

    Bone is a highly vascularized tissue reliant on the close spatial and temporal association between blood vessels and bone cells. Therefore, cells that participate in vasculogenesis and osteogenesis play a pivotal role in bone formation during prenatal and postnatal periods. Nevertheless, spontaneous healing of bone fracture is occasionally impaired due to insufficient blood and cellular supply to the site of injury. In these cases, bone regeneration process is interrupted, which might result in delayed union or even nonunion of the fracture. Nonunion fracture is difficult to treat and have a high financial impact. In the last decade, numerous technological advancements in bone tissue engineering and cell-therapy opened new horizon in the field of bone regeneration. This review starts with presentation of the biological processes involved in bone development, bone remodeling, fracture healing process and the microenvironment at bone healing sites. Then, we discuss the rationale for using adult stem cells and listed the characteristics of the available cells for bone regeneration. The mechanism of action and epigenetic regulations for osteogenic differentiation are also described. Finally, we review the literature for translational and clinical trials that investigated the use of adult stem cells (mesenchymal stem cells, endothelial progenitor cells and CD34(+) blood progenitors) for bone regeneration.

  10. ALVEOLAR BONE REGENERATION AFTER DEMINERALIZED FREEZE DRIED BONE ALOGRAFT (DFDBA BONE GRAFTING

    Directory of Open Access Journals (Sweden)

    Sri Oktawati

    2006-04-01

    Full Text Available Periodontal treatment by conventional way will result in healing repair, which easily cause recurrence. Modification of treatment should be done to get an effective result, that is the regeneration of alveolar bone and to reduce inflammation. The objective of this study is to determine the alveolar bone regeneration after using DFDBA (Demineralized Freeze Dried Bone Allograft. Quasi experimental designs with pre and post test method was used in this study. From 13 patients, 26 defects got conventional or regenerative treatment. The indicator of alveolar bone regenaration in bone height in radiographic appearance and level of osteocalsin in gingival crevicular fluid (GCF were checked before and after the treatment, then the changes that occurred were analyzed. The result of the research showed that alveolar bone regeneration only occurred to the group of regenerative treatment using DFDBA. The conclusion is the effective periodontal tissue regeneration occurred at regenerative treatment by using DFDBA, and the osteocalsin in GCF can be used as indicator of bone growth.

  11. 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.

  12. Bone regenerates via dedifferentiation of osteoblasts in the zebrafish fin

    NARCIS (Netherlands)

    Knopf, F.; Hammond, C.J.; Chekuru, A.; Kurth, T.; Hans, S.; Weber, C.W.; Mahatma, G.; Fisher, S.; Brand, M.; Schulte-Merker, S.; Weidinger, G.

    2011-01-01

    While mammals have a limited capacity to repair bone defects, zebrafish can completely regenerate amputated bony structures of their fins. Fin regeneration is dependent on formation of a blastema, a progenitor cell pool accumulating at the amputation plane. It is unclear which cells the blastema is

  13. Guided bone regeneration associated with L-PRF vertical bone gain: a case report

    OpenAIRE

    Brilhante, Felipe Vilhena; de Araújo, Rodolfo José Gomes; Tavares, Ana Catarina Nunes; de Andrade, Wagner Almeida; de Andrade, Cícero Almeida; Mauad, Bruno Albuquerque; Bastos Neto, Fabio Valverde Rodrigues; Damasceno, Jessica Mendes; Miranda, João Evandro da Silva

    2017-01-01

    Every day have been increased the number of patients in the dental office looking for oral reabilitações, many of them being a challenge to the dentist surgeon. Currently, implants are installed on guided bone regeneration, the use of membranes, titanium threads and bone substitutes are key parts for correcting bone defects and to support the implant. Thereunto, the aim of this study was the description of a case addressing the methods and materials used for guided bone regeneration with the ...

  14. PREDICTION OF THE DURATION OF DISTRACTION REGENERATED BONE MATURATION

    Directory of Open Access Journals (Sweden)

    N. V. Tushina

    2012-01-01

    Full Text Available Aim of the study the characteristics of changes of serum biochemical parameters in dogs with delayed maturation of the distraction regenerate after surgical lengthening the leg bones by Ilizarov. The comparative analysis of biochemical changes in blood serum of animals with delayed regenerated bone osteogenesis after surgical leg bone lengthening according to Ilizarov has been made in the work. The development of persistent and marked hypocalcemia, significant accumulation of blood serum nonoxidized degradation products during limb bone surgical lengthening according to Ilizarov have been revealed to be adverse signs evidencing of the high probability of the disorder of further formation of the regenerated bone and its subsequent maturation at the stage of fixation.

  15. Pharmacokinetics of gentamicin eluted from a regenerating bone graft substitute

    DEFF Research Database (Denmark)

    Stravinskas, M; Horstmann, P; Ferguson, J

    2016-01-01

    in combination with bone regeneration. Gentamicin release was measured in four setups: 1) in vitro elution in Ringer's solution; 2) local elution in patients treated for trochanteric hip fractures or uncemented hip revisions; 3) local elution in patients treated with a bone tumour resection; and 4) local elution...

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

    DEFF Research Database (Denmark)

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

    1998-01-01

    of the membrane. The calvarial defects of 2 groups were covered by an outer expanded polytetrafluoroethylene (ePTFE) membrane respectively by a Polyglactin 910 membrane. Bicortical ePTFE membranes or Polyglactin 910 membranes were used in 2 other groups. The defects were not covered by membranes in the control...... herniation into the defects. Subsequently, bone regeneration was impaired. The cellular reactions due to degradation of the material were minor and did not interfere with bone healing. Defects covered bicortically by ePTFE membranes revealed the largest amount of regenerated bone. The ePTFE membrane induced...

  17. Nanomechanical mapping of bone tissue regenerated by magnetic scaffolds.

    Science.gov (United States)

    Bianchi, Michele; Boi, Marco; Sartori, Maria; Giavaresi, Gianluca; Lopomo, Nicola; Fini, Milena; Dediu, Alek; Tampieri, Anna; Marcacci, Maurilio; Russo, Alessandro

    2015-01-01

    Nanoindentation can provide new insights on the maturity stage of regenerating bone. The aim of the present study was the evaluation of the nanomechanical properties of newly-formed bone tissue at 4 weeks from the implantation of permanent magnets and magnetic scaffolds in the trabecular bone of rabbit femoral condyles. Three different groups have been investigated: MAG-A (NdFeB magnet + apatite/collagen scaffold with magnetic nanoparticles directly nucleated on the collagen fibers during scaffold synthesis); MAG-B (NdFeB magnet + apatite/collagen scaffold later infiltrated with magnetic nanoparticles) and MAG (NdFeB magnet). The mechanical properties of different-maturity bone tissues, i.e. newly-formed immature, newly-formed mature and native trabecular bone have been evaluated for the three groups. Contingent correlations between elastic modulus and hardness of immature, mature and native bone have been examined and discussed, as well as the efficacy of the adopted regeneration method in terms of "mechanical gap" between newly-formed and native bone tissue. The results showed that MAG-B group provided regenerated bone tissue with mechanical properties closer to that of native bone compared to MAG-A or MAG groups after 4 weeks from implantation. Further, whereas the mechanical properties of newly-formed immature and mature bone were found to be fairly good correlated, no correlation was detected between immature or mature bone and native bone. The reported results evidence the efficacy of nanoindentation tests for the investigation of the maturity of newly-formed bone not accessible through conventional analyses.

  18. Current understanding of osteoconduction in bone regeneration.

    Science.gov (United States)

    Cornell, C N; Lane, J M

    1998-10-01

    Bone tissue is osteoconductive. In particular, cancellous bone with its porous and highly interconnected trabecular architecture allows easy ingrowth of surrounding tissues. When placed in an osseous environment, living tissue for the host bed migrates into the cancellous structure, which results in new bone formation and incorporation of that structure. This is the process of osteoconduction. The mineral and collagenous components of bone are osteoconductive. Osteoconduction also is observed in fabricated materials that have porosity similar to that of bone structure. Corallin ceramics, hydroxyapatite beads, and combinations of hydroxyapatite and collagen all have osteoconductive properties, and porous metals and biodegradable polymers. Osteoconduction appears to be optimized in devices that mimic not only bone structure, but also bone chemistry. The incorporation of calcium salts and collagen by osteoconductive matrices leads to more complete ingrowth with new bone formation.

  19. Salmon DNA Accelerates Bone Regeneration by Inducing Osteoblast Migration

    Science.gov (United States)

    Sato, Ayako; Kajiya, Hiroshi; Mori, Nana; Sato, Hironobu; Fukushima, Tadao; Kido, Hirofumi

    2017-01-01

    The initial step of bone regeneration requires the migration of osteogenic cells to defective sites. Our previous studies suggest that a salmon DNA-based scaffold can promote the bone regeneration of calvarial defects in rats. We speculate that the salmon DNA may possess osteoinductive properties, including the homing of migrating osteogenic cells. In the present study, we investigated the influence of the salmon DNA on osteoblastic differentiation and induction of osteoblast migration using MG63 cells (human preosteoblasts) in vitro. Moreover, we analyzed the bone regeneration of a critical-sized in vivo calvarial bone defect (CSD) model in rats. The salmon DNA enhanced both mRNA and protein expression of the osteogenesis-related factors, runt-related transcription factor 2 (Runx2), alkaline phosphatase, and osterix (OSX) in the MG63 cells, compared with the cultivation using osteogenic induction medium alone. From the histochemical and immunohistochemical assays using frozen sections of the bone defects from animals that were implanted with DNA disks, many cells were found to express aldehyde dehydrogenase 1, one of the markers for mesenchymal stem cells. In addition, OSX was observed in the replaced connective tissue of the bone defects. These findings indicate that the DNA induced the migration and accumulation of osteogenic cells to the regenerative tissue. Furthermore, an in vitro transwell migration assay showed that the addition of DNA enhanced an induction of osteoblast migration, compared with the medium alone. The implantation of the DNA disks promoted bone regeneration in the CSD of rats, compared with that of collagen disks. These results indicate that the salmon DNA enhanced osteoblastic differentiation and induction of migration, resulting in the facilitation of bone regeneration. PMID:28060874

  20. 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...

  1. Osteostatin-coated porous titanium can improve early bone regeneration of cortical bone defects in rats

    NARCIS (Netherlands)

    Van Der Stok, Johan; Lozano, Daniel; Chai, Yoke Chin; Amin Yavari, Saber; Bastidas Coral, Angela P.; Verhaar, Jan A N; Gómez-Barrena, Enrique; Schrooten, Jan; Jahr, Holger; Zadpoor, Amir A.; Esbrit, Pedro; Weinans, Harrie

    2015-01-01

    A promising bone graft substitute is porous titanium. Porous titanium, produced by selective laser melting (SLM), can be made as a completely open porous and load-bearing scaffold that facilitates bone regeneration through osteoconduction. In this study, the bone regenerative capacity of porous

  2. Stem Cells and Calcium Phosphate Cement Scaffolds for Bone Regeneration.

    Science.gov (United States)

    Wang, P; Zhao, L; Chen, W; Liu, X; Weir, M D; Xu, H H K

    2014-07-01

    Calcium phosphate cements (CPCs) have excellent biocompatibility and osteoconductivity for dental, craniofacial, and orthopedic applications. This article reviews recent developments in stem cell delivery via CPC for bone regeneration. This includes: (1) biofunctionalization of the CPC scaffold, (2) co-culturing of osteoblasts/endothelial cells and prevascularization of CPC, (3) seeding of CPC with different stem cell species, (4) human umbilical cord mesenchymal stem cell (hUCMSC) and bone marrow MSC (hBMSC) seeding on CPC for bone regeneration, and (5) human embryonic stem cell (hESC) and induced pluripotent stem cell (hiPSC) seeding with CPC for bone regeneration. Cells exhibited good attachment/proliferation in CPC scaffolds. Stem-cell-CPC constructs generated more new bone and blood vessels in vivo than did the CPC control without cells. hUCMSCs, hESC-MSCs, and hiPSC-MSCs in CPC generated new bone and blood vessels similar to those of hBMSCs; hence, they were viable cell sources for bone engineering. CPC with hESC-MSCs and hiPSC-MSCs generated new bone two- to three-fold that of the CPC control. Therefore, this article demonstrates that: (1) CPC scaffolds are suitable for delivering cells; (2) hUCMSCs, hESCs, and hiPSCs are promising alternatives to hBMSCs, which require invasive procedures to harvest with limited cell quantity; and (3) stem-cell-CPC constructs are highly promising for bone regeneration in dental, craniofacial, and orthopedic applications. © International & American Associations for Dental Research.

  3. Histologic evaluation of chitosan as an accelerator of bone regeneration in microdrilled rat tibias

    Directory of Open Access Journals (Sweden)

    Fatemeh Ezoddini-Ardakani

    2012-01-01

    Conclusion: Chitosan significantly accelerated the bone regeneration process in rat tibias. Regarding its biocompatibility and osteoinductivity, it can be studied as a biomaterial in human bone healing.

  4. Guided bone regeneration using demineralized allogenic bone matrix with calcium sulfate: case series.

    Science.gov (United States)

    Kim, Young-Kyun; Lee, Ji-Young; Kim, Su-Gwan; Lim, Seung-Chul

    2013-05-01

    The purpose of this case series was to evaluate the effect of guided bone regeneration using demineralized allogenic bone matrix with calcium sulfate. Guided bone regeneration using Demineralized Allogenic Bone Matrix with Calcium Sulfate (AlloMatrix™, Wright. USA) was performed at the time of implant placement from February 2010 to April 2010. At the time of the second surgery, clinical evaluation of bone healing and histologic evaluation were performed. The study included 10 patients, and 23 implants were placed. The extent of bony defects around implants was determined by measuring the horizontal and vertical bone defects using a periodontal probe from the mesial, distal, buccal, and lingual sides and calculating the mean and standard deviation of these measurements. Wedge-shaped tissue samples were obtained from 3 patients and histologic examination was performed. In clinical evaluation, it was observed that horizontal bone defects were completely healed with new bones, and in the vertical bone defect area, 15.1% of the original defect area remained. In 3 patients, histological tests were performed, and 16.7-41.7% new bone formation was confirmed. Bone graft materials slowly underwent resorption over time. AlloMatrix™ is an allograft material that can be readily manipulated. It does not require the use of barrier membranes, and good bone regeneration can be achieved with time.

  5. Biomechanical, microvascular, and cellular factors promote muscle and bone regeneration.

    Science.gov (United States)

    Duda, Georg N; Taylor, William R; Winkler, Tobias; Matziolis, Georg; Heller, Markus O; Haas, Norbert P; Perka, Carsten; Schaser, Klaus-D

    2008-04-01

    It is becoming clear that the long-term outcome of complex bone injuries benefits from approaches that selectively target biomechanical, vascular, and cellular pathways. The typically held view of either biological or mechanical aspects of healing is oversimplified and does not correspond to clinical reality. The fundamental mechanisms of soft tissue regeneration most likely hold the key to understanding healing response.

  6. The Molecular and Cellular Choreography of Appendage Regeneration.

    Science.gov (United States)

    Tanaka, Elly M

    2016-06-16

    Recent advances in limb regeneration are revealing the molecular events that integrate growth control, cell fate programming, and positional information to yield the exquisite replacement of the amputated limb. Parallel progress in several invertebrate and vertebrate models has provided a broader context for understanding the mechanisms and the evolution of regeneration. Together, these discoveries provide a foundation for describing the principles underlying regeneration of complex, multi-tissue structures. As such these findings should provide a wealth of ideas for engineers seeking to reconstitute regeneration from constituent parts or to elicit full regeneration from partial regeneration events. Copyright © 2016 Elsevier Inc. All rights reserved.

  7. 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

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

    Science.gov (United States)

    Gu, Wenyi; Wu, Chengtie; Chen, Jiezhong; Xiao, Yin

    2013-01-01

    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.

  9. Manufacture of degradable polymeric scaffolds for bone regeneration.

    Science.gov (United States)

    Ge, Zigang; Jin, Zhaoxia; Cao, Tong

    2008-06-01

    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.

  10. Manufacture of degradable polymeric scaffolds for bone regeneration

    International Nuclear Information System (INIS)

    Ge Zigang; Jin Zhaoxia; Cao Tong

    2008-01-01

    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)

  11. Mechanotransduction in musculoskeletal tissue regeneration: effects of fluid flow, loading, and cellular-molecular pathways.

    Science.gov (United States)

    Qin, Yi-Xian; Hu, Minyi

    2014-01-01

    While mechanotransductive signal is proven essential for tissue regeneration, it is critical to determine specific cellular responses to such mechanical signals and the underlying mechanism. Dynamic fluid flow induced by mechanical loading has been shown to have the potential to regulate bone adaptation and mitigate bone loss. Mechanotransduction pathways are of great interests in elucidating how mechanical signals produce such observed effects, including reduced bone loss, increased bone formation, and osteogenic cell differentiation. The objective of this review is to develop a molecular understanding of the mechanotransduction processes in tissue regeneration, which may provide new insights into bone physiology. We discussed the potential for mechanical loading to induce dynamic bone fluid flow, regulation of bone adaptation, and optimization of stimulation parameters in various loading regimens. The potential for mechanical loading to regulate microcirculation is also discussed. Particularly, attention is allotted to the potential cellular and molecular pathways in response to loading, including osteocytes associated with Wnt signaling, elevation of marrow stem cells, and suppression of adipotic cells, as well as the roles of LRP5 and microRNA. These data and discussions highlight the complex yet highly coordinated process of mechanotransduction in bone tissue regeneration.

  12. 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.

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

    International Nuclear Information System (INIS)

    Cabrejos-Azama, Jatsue; Alkhraisat, Mohammad Hamdan; Rueda, Carmen; Torres, Jesús; Blanco, Luis; López-Cabarcos, Enrique

    2014-01-01

    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

  14. A novel osteogenesis technique: The expansible guided bone regeneration

    Directory of Open Access Journals (Sweden)

    Osama Zakaria

    2012-12-01

    Full Text Available Guided bone regeneration is a unique osteogenesis technique that requires a barrier membrane under periosteum to create space for bone regeneration. However, creating sizeable spaces is clinically not commonly feasible. A titanium plate and a thin silicone membrane were surgically layered on each calvaria of eight rabbits. Then, the periphery of the silicone membrane was fixed by a plastic ring to the underlying bone using titanium micro screws. After 1 week, a 5-mm-length titanium screw was used to elevate the titanium plate, which in turn elevated the silicone membrane together with overlying soft tissue in a rate of 1 mm/day for 5 days to create a secluded space. Animals were killed at 2 months (n = 4, group 1 and 4 months (n = 4, group 2 after the elevation. Histological and microradiographical analyses demonstrated creation of an amount of de novo bone formation (68.2 ± 22 mm3 in group 1 and 70.3 ± 14 mm3 in group 2 in the sizeable created spaces (207.1 ± 31 mm3 in group 1 and 202 ± 21 mm3 in group 2 without exposure of the device. This novel osteogenesis technique, “expansible guided bone regeneration,” created a substantial in vivo incubator without applying growth factors or osteoprogenitor cells. Creating a growing space over the secluded surface allowed the development of normal biological healing process occurring on the bone surface into a regenerative process, generating bone outside the genetically determined skeletal bone. This technique is a new tissue engineering approach stimulating endogenous tissue repair without applying cells or factors exogenously.

  15. Regeneration of damaged osteoporotic bone tissue with synthetic biomaterials

    Directory of Open Access Journals (Sweden)

    Petrović Nenad D.

    2014-01-01

    Full Text Available In some cases in oral and maxillofacial surgery, bone regeneration is required in large quantities. One of these cases is osteoporosis. This paper aims to show the new approach to solving this problem of impaired healing of bone defects in the jaw, as well as in other bones, with the use of synthetic biomaterials whose properties resemble the natural bone. Latest development in this area present an effort to create local drug-delivery systems for BMPs and growth factors, direct delivery of MSCs, as well as scaffolds for osteoconduction and also to utilize nanotechnology to synthesize composite biomaterials, predominantly based on HAp and polymers, that would mimic the natural bone nanocomposite architecture. There is also a tendency to create injectable biomaterials for simplified application.

  16. Perkembangan Terkini Membran Guided Tissue Regeneration/Guided Bone Regeneration sebagai Terapi Regenerasi Jaringan Periodontal

    Directory of Open Access Journals (Sweden)

    Cindy Cahaya

    2015-06-01

    kombinasi prosedur-prosedur di atas, termasuk prosedur bedah restoratif yang berhubungan dengan rehabilitasi oral dengan penempatan dental implan. Pada tingkat selular, regenerasi periodontal adalah proses kompleks yang membutuhkan proliferasi yang terorganisasi, differensiasi dan pengembangan berbagai tipe sel untuk membentuk perlekatan periodontal. Rasionalisasi penggunaan guided tissue regeneration sebagai membran pembatas adalah menahan epitel dan gingiva jaringan pendukung, sebagai barrier membrane mempertahankan ruang dan gigi serta menstabilkan bekuan darah. Pada makalah ini akan dibahas sekilas mengenai 1. Proses penyembuhan terapi periodontal meliputi regenerasi, repair ataupun pembentukan perlekatan baru. 2. Periodontal spesific tissue engineering. 3. Berbagai jenis membran/guided tissue regeneration yang beredar di pasaran dengan keuntungan dan kerugian sekaligus karakteristik masing-masing membran. 4. Perkembangan membran terbaru sebagai terapi regenerasi penyakit periodontal. Tujuan penulisan untuk memberi gambaran masa depan mengenai terapi regenerasi yang menjanjikan sebagai perkembangan terapi penyakit periodontal.   Latest Development of Guided Tissue Regeneration and Guided Bone Regeneration Membrane as Regenerative Therapy on Periodontal Tissue. Periodontitis is a patological state which influences the integrity of periodontal system that could lead to the destruction of the periodontal tissue and end up with tooth loss. Currently, there are so many researches and efforts to regenerate periodontal tissue, not only to stop the process of the disease but also to reconstruct the periodontal tissue. Periodontal regenerative therapy aims at directing the growth of new bone, cementum and periodontal ligament on the affected teeth. Regenerative procedures consist of soft tissue graft, bone graft, roots biomodification, guided tissue regeneration and combination of the procedures, including restorative surgical procedure that is

  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. Instructive function of surface structure of calcium phosphate ceramics in bone regeneration

    NARCIS (Netherlands)

    Zhang, Jingwei

    2016-01-01

    The incidence of patients which require spinal fusion or bone regeneration in large bone defects caused by trauma, tumors, tumor resection, infections or abnormal skeletal development, is on the rise. Traditionally, in both spinal fusion surgery and other bone regeneration approaches, bone grafts

  19. APIOS - Bioactive films for bone regeneration

    OpenAIRE

    Crouzier, Thomas

    2014-01-01

    APIOS technology brings the osteoinduction power of Bone Morphogenetic Proteins (BMP) to all types of orthopedic implants. A thin film deposited on the implant immobilizes large quantities of BMP in its active form. This results in effective osteoinduction, low cost BMP treatement and a controlled BMP delivery. Technology delvelopped by Dr. Thomas Crouzier and Prof. Catherine Picart at INP in Grenoble (France). http://www.lmgp.grenoble-inp.fr/research/catherine-picart-261416.kjsp

  20. Pullulan microcarriers for bone tissue regeneration

    Energy Technology Data Exchange (ETDEWEB)

    Aydogdu, Hazal [Middle East Technical University, Department of Biomedical Engineering, Ankara 06800 (Turkey); Keskin, Dilek [Middle East Technical University, Department of Biomedical Engineering, Ankara 06800 (Turkey); Middle East Technical University, Department of Engineering Sciences, Ankara 06800 (Turkey); METU BIOMATEN Center of Excellence in Biomaterials and Tissue Engineering, Ankara 06800 (Turkey); Baran, Erkan Turker, E-mail: erkanturkerbaran@gmail.com [METU BIOMATEN Center of Excellence in Biomaterials and Tissue Engineering, Ankara 06800 (Turkey); Tezcaner, Aysen, E-mail: tezcaner@metu.edu.tr [Middle East Technical University, Department of Biomedical Engineering, Ankara 06800 (Turkey); Middle East Technical University, Department of Engineering Sciences, Ankara 06800 (Turkey); METU BIOMATEN Center of Excellence in Biomaterials and Tissue Engineering, Ankara 06800 (Turkey)

    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. - Highlights: • Porous PULL microspheres were prepared as cell carrier for the first time. • Mineralization on the microspheres improved their mechanical properties. • Mineralization and SF coating enhanced cell proliferation on PULL microspheres.

  1. Pullulan microcarriers for bone tissue regeneration

    International Nuclear Information System (INIS)

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

    2016-01-01

    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. - Highlights: • Porous PULL microspheres were prepared as cell carrier for the first time. • Mineralization on the microspheres improved their mechanical properties. • Mineralization and SF coating enhanced cell proliferation on PULL microspheres.

  2. 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.

  3. 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.

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

    Science.gov (United States)

    Pavan Mateus, Christiano; Orivaldo Chierice, Gilberto; Okamoto, Tetuo

    2011-09-01

    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.

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

    International Nuclear Information System (INIS)

    Mateus, Christiano Pavan; Chierice, Gilberto Orivaldo; Okamoto, Tetuo

    2011-01-01

    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.

  6. 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.

  7. Mathematical Model of Bone Regeneration in a Porous Implant

    Science.gov (United States)

    Maslov, L. B.

    2017-07-01

    A mathematical model of the reparative regeneration of bone tissue governed by the law of cell differentiation and action of an external periodic mechanical loading is presented. The model allows one to study the recovery processes of injured human locomotor system elements under a dynamic loading and to theoretically substantiate the choice of an optimum periodic impact on the defective tissues for their fastest and steady healing.

  8. Administration of RANKL boosts thymic regeneration upon bone marrow transplantation.

    Science.gov (United States)

    Lopes, Noella; Vachon, Hortense; Marie, Julien; Irla, Magali

    2017-06-01

    Cytoablative treatments lead to severe damages on thymic epithelial cells (TECs), which result in delayed de novo thymopoiesis and a prolonged period of T-cell immunodeficiency. Understanding the mechanisms that govern thymic regeneration is of paramount interest for the recovery of a functional immune system notably after bone marrow transplantation (BMT). Here, we show that RANK ligand (RANKL) is upregulated in CD4 + thymocytes and lymphoid tissue inducer (LTi) cells during the early phase of thymic regeneration. Importantly, whereas RANKL neutralization alters TEC recovery after irradiation, ex vivo RANKL administration during BMT boosts the regeneration of TEC subsets including thymic epithelial progenitor-enriched cells, thymus homing of lymphoid progenitors, and de novo thymopoiesis. RANKL increases specifically in LTi cells, lymphotoxin α, which is critical for thymic regeneration. RANKL treatment, dependent on lymphotoxin α, is beneficial upon BMT in young and aged individuals. This study thus indicates that RANKL may be clinically useful to improve T-cell function recovery after BMT by controlling multiple facets of thymic regeneration. © 2017 The Authors. Published under the terms of the CC BY 4.0 license.

  9. Role of mesenchymal stem cells in bone regeneration and fracture repair: a review.

    Science.gov (United States)

    Wang, Xin; Wang, Yu; Gou, Wenlong; Lu, Qiang; Peng, Jiang; Lu, Shibi

    2013-12-01

    Mesenchymal stem cells (MSCs) are non-haematopoietic stromal stem cells that have many sources, such as bone marrow, periosteum, vessel walls, adipose, muscle, tendon, peripheral circulation, umbilical cord blood, skin and dental tissues. They are capable of self-replication and of differentiating into, and contributing to the regeneration of, mesenchymal tissues, such as bone, cartilage, ligament, tendon, muscle and adipose tissue. The homing of MSCs may play an important role in the repair of bone fractures. As a composite material, the formation and growth of bone tissue is a complex process, including molecular, cell and biochemical metabolic changes. The recruitment of factors with an adequate number of MSCs and the micro-environment around the fracture are effective for fracture repair. Several studies have investigated the functional expression of various chemokine receptors, trophic factors and adhesion molecules in human MSCs. Many external factors affect MSC homing. MSCs have been used as seed cells in building tissue-engineered bone grafts. Scaffolds seeded with MSCs are most often used in tissue engineering and include biotic and abiotic materials. This knowledge provides a platform for the development of novel therapies for bone regeneration with endogenous MSCs.

  10. Novel bioresorbable strontium hydroxyapatite membrane for guided bone regeneration.

    Science.gov (United States)

    Hao, J; Acharya, A; Chen, K; Chou, J; Kasugai, S; Lang, N P

    2015-01-01

    Membrane materials have been widely used for guided bone regeneration (GBR). However, due to bio-functional limitation of the current membranes, the ideal resorbable membrane that can stimulate bone regeneration has yet to be developed. This study seeks to investigate the effects of a strontium hydroxyapatite (SrHA)-containing membrane for GBR. Strontium hydroxyapatite powder was synthesized and mixed with gelatin solution to the final concentration of 10 mg/ml (Sr10) and 20 mg/ml (Sr20). Approximately 100-μm-thick membranes were fabricated, and the mechanical properties and strontium ion release pattern were analyzed. Rat bone marrow stromal cell (BMSC) responses were investigated in vitro. Bilaterial rat calvarial defects were used in vivo to compare the SrHA membranes against commercially available collagen membranes and evaluated radiologically and histologically. Strontium hydroxyapatite membranes exhibited higher elasticity and strength than the collagen membrane, and slow strontium ion release was also confirmed. No BMSC cytotoxicity was found on the SrHA membranes, and the alkaline phosphatase positively stained area was significantly greater than the collagen membrane at earlier time point. At 4 weeks, both micro-CT and histological analyses revealed that the Sr20 group yielded significantly greater bone formation. The SrHA-containing membrane developed in this study was found to be a biocompatible material that can stimulate BMSC differentiation as well as bone regeneration and maturation in rat calvarial defects at early time point compared with collagen membrane. The best result was observed in Sr20 group, which can be potentially effective for GBR. © 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  11. Advances in electrospun nanofibers for bone and cartilage regeneration.

    Science.gov (United States)

    Ghasemi-Mobarakeh, Laleh; Prabhakaran, Molamma P; Balasubramanian, Preethi; Jin, Guorui; Valipouri, Afsaneh; Ramakrishna, Seeram

    2013-07-01

    Regeneration of bone and cartilage tissues has been an important issue for biological repair in the field of regenerative medicine. The rapidly emerging field of tissue engineering holds great promise for repair and generation of functional bone and cartilage substitutes with a combination of biomaterials, cells, drugs and growth factors. Scaffolds play a pivotal role in tissue engineering as they mimic the natural extracellular matrix (ECM) and play an important role in guiding cell adhesion and proliferation, and maintaining the normal phenotype of the tissues. The use of tissue-engineered grafts based on scaffolds has found to be a more effective method than conventional implantations of autograft, allograft, xenograft. In recent years much attention has been given to electrospinning as a feasible and versatile technique for fabrication of nanofibrous scaffolds, with large surface area to volume ratio, high porosity, mechanical properties and physical dimension similar to the ECM of natural tissues. Extensive research has been carried out for fabrication polymeric nanofibrous substrates with incorporation of hydroxyapatite nanoparticles or bone morphogenetic protein molecules for efficient tissue repair. Here we review on the literature of electrospun nanofibrous scaffolds, their modifications, and advances aimed towards the rapid regeneration of bone and cartilage.

  12. Effect of Low-Level Laser Therapy on Bone Regeneration During Osseointegration and Bone Graft.

    Science.gov (United States)

    Zein, Randa; Selting, Wayne; Benedicenti, Stefano

    2017-12-01

    The effect of low-level laser therapy (LLLT) on bone regeneration during osseointegration and bone graft is very controversial. Despite many positive reports of in vitro and in vivo studies and more than 50 randomized clinical trials claiming a positive effect of photobiomodulation (PBM), many reports found no significant effect of lasers. The aim of this study was to evaluate studies correlating PBM and bone regeneration and to assesses parameters that produce positive results based on dose and output power used. Four electronic databases were used: PubMed, Springer, Google Scholar, and Cochrane. The research yielded 230 articles. The full texts of all articles were evaluated and scored using eligibility criteria adapted from Cericato et al. After evaluation, only 19 articles met the inclusion criteria. A positive effect of low-level laser energy on bone regeneration within a certain relationship between dose and output power was found. LLLT stimulates cellular metabolism, increasing protein synthesis and subsequent bone regeneration. A high dose combined with low power or a low dose combined with high power appears to produce a positive effect.

  13. Bioinspired, biomimetic, double-enzymatic mineralization of hydrogels for bone regeneration with calcium carbonate

    DEFF Research Database (Denmark)

    Lopez-Heredia, Marco A.; Łapa, Agata; Mendes, Ana Carina Loureiro

    2017-01-01

    Hydrogels are popular materials for tissue regeneration. Incorporation of biologically active substances, e.g. enzymes, is straightforward. Hydrogel mineralization is desirable for bone regeneration. Here, hydrogels of Gellan Gum (GG), a biocompatible polysaccharide, were mineralized biomimetically...

  14. Calcium-containing scaffolds induce bone regeneration by regulating mesenchymal stem cell differentiation and migration

    Directory of Open Access Journals (Sweden)

    Rubén Aquino-Martínez

    2017-11-01

    Full Text Available Abstract Background Osteoinduction and subsequent bone formation rely on efficient mesenchymal stem cell (MSC recruitment. It is also known that migration is induced by gradients of growth factors and cytokines. Degradation of Ca2+-containing biomaterials mimics the bone remodeling compartment producing a localized calcium-rich osteoinductive microenvironment. The aim of our study was to determine the effect of calcium sulfate (CaSO4 on MSC migration. In addition, to evaluate the influence of CaSO4 on MSC differentiation and the potential molecular mechanisms involved. Methods A circular calvarial bone defect (5 mm diameter was created in the parietal bone of 35 Balb-C mice. We prepared and implanted a cell-free agarose/gelatin scaffold alone or in combination with different CaSO4 concentrations into the bone defects. After 7 weeks, we determined the new bone regenerated by micro-CT and histological analysis. In vitro, we evaluated the CaSO4 effects on MSC migration by both wound healing and agarose spot assays. Osteoblastic gene expression after BMP-2 and CaSO4 treatment was also evaluated by qPCR. Results CaSO4 increased MSC migration and bone formation in a concentration-dependent manner. Micro-CT analysis showed that the addition of CaSO4 significantly enhanced bone regeneration compared to the scaffold alone. The histological evaluation confirmed an increased number of endogenous cells recruited into the cell-free CaSO4-containing scaffolds. Furthermore, MSC migration in vitro and active AKT levels were attenuated when CaSO4 and BMP-2 were in combination. Addition of LY294002 and Wortmannin abrogated the CaSO4 effects on MSC migration. Conclusions Specific CaSO4 concentrations induce bone regeneration of calvarial defects in part by acting on the host’s undifferentiated MSCs and promoting their migration. Progenitor cell recruitment is followed by a gradual increment in osteoblast gene expression. Moreover, CaSO4 regulates BMP-2-induced

  15. Calcium-containing scaffolds induce bone regeneration by regulating mesenchymal stem cell differentiation and migration.

    Science.gov (United States)

    Aquino-Martínez, Rubén; Angelo, Alcira P; Pujol, Francesc Ventura

    2017-11-16

    Osteoinduction and subsequent bone formation rely on efficient mesenchymal stem cell (MSC) recruitment. It is also known that migration is induced by gradients of growth factors and cytokines. Degradation of Ca 2+ -containing biomaterials mimics the bone remodeling compartment producing a localized calcium-rich osteoinductive microenvironment. The aim of our study was to determine the effect of calcium sulfate (CaSO 4 ) on MSC migration. In addition, to evaluate the influence of CaSO 4 on MSC differentiation and the potential molecular mechanisms involved. A circular calvarial bone defect (5 mm diameter) was created in the parietal bone of 35 Balb-C mice. We prepared and implanted a cell-free agarose/gelatin scaffold alone or in combination with different CaSO 4 concentrations into the bone defects. After 7 weeks, we determined the new bone regenerated by micro-CT and histological analysis. In vitro, we evaluated the CaSO 4 effects on MSC migration by both wound healing and agarose spot assays. Osteoblastic gene expression after BMP-2 and CaSO 4 treatment was also evaluated by qPCR. CaSO 4 increased MSC migration and bone formation in a concentration-dependent manner. Micro-CT analysis showed that the addition of CaSO 4 significantly enhanced bone regeneration compared to the scaffold alone. The histological evaluation confirmed an increased number of endogenous cells recruited into the cell-free CaSO 4 -containing scaffolds. Furthermore, MSC migration in vitro and active AKT levels were attenuated when CaSO 4 and BMP-2 were in combination. Addition of LY294002 and Wortmannin abrogated the CaSO 4 effects on MSC migration. Specific CaSO 4 concentrations induce bone regeneration of calvarial defects in part by acting on the host's undifferentiated MSCs and promoting their migration. Progenitor cell recruitment is followed by a gradual increment in osteoblast gene expression. Moreover, CaSO 4 regulates BMP-2-induced MSC migration by differentially activating the PI3

  16. Plant regeneration: cellular origins and molecular mechanisms.

    Science.gov (United States)

    Ikeuchi, Momoko; Ogawa, Yoichi; Iwase, Akira; Sugimoto, Keiko

    2016-05-01

    Compared with animals, plants generally possess a high degree of developmental plasticity and display various types of tissue or organ regeneration. This regenerative capacity can be enhanced by exogenously supplied plant hormones in vitro, wherein the balance between auxin and cytokinin determines the developmental fate of regenerating organs. Accumulating evidence suggests that some forms of plant regeneration involve reprogramming of differentiated somatic cells, whereas others are induced through the activation of relatively undifferentiated cells in somatic tissues. We summarize the current understanding of how plants control various types of regeneration and discuss how developmental and environmental constraints influence these regulatory mechanisms. © 2016. Published by The Company of Biologists Ltd.

  17. The Hypoxia-Inducible Factor Pathway, Prolyl Hydroxylase Domain Protein Inhibitors, and Their Roles in Bone Repair and Regeneration

    Directory of Open Access Journals (Sweden)

    Lihong Fan

    2014-01-01

    Full Text Available Hypoxia-inducible factors (HIFs are oxygen-dependent transcriptional activators that play crucial roles in angiogenesis, erythropoiesis, energy metabolism, and cell fate decisions. The group of enzymes that can catalyse the hydroxylation reaction of HIF-1 is prolyl hydroxylase domain proteins (PHDs. PHD inhibitors (PHIs activate the HIF pathway by preventing degradation of HIF-α via inhibiting PHDs. Osteogenesis and angiogenesis are tightly coupled during bone repair and regeneration. Numerous studies suggest that HIFs and their target gene, vascular endothelial growth factor (VEGF, are critical regulators of angiogenic-osteogenic coupling. In this brief perspective, we review current studies about the HIF pathway and its role in bone repair and regeneration, as well as the cellular and molecular mechanisms involved. Additionally, we briefly discuss the therapeutic manipulation of HIFs and VEGF in bone repair and bone tumours. This review will expand our knowledge of biology of HIFs, PHDs, PHD inhibitors, and bone regeneration, and it may also aid the design of novel therapies for accelerating bone repair and regeneration or inhibiting bone tumours.

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

    Science.gov (United States)

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

    2015-09-01

    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. The immature rabbit tibial DO model (20 mm length-gain) was used. Twenty-eight animals received DBM 100 mg percutaneously at the end of distraction. Another 22 animals were left without further procedure (control). Plain radiographs were taken every week. Postmortem bone dual-energy X-ray absorptiometry and micro-computed tomography (micro-CT) studies were performed at the third and sixth weeks of the consolidation period and histological analysis was performed. The regenerate bone mineral density was higher in the DBM group when compared with that in the saline injection control group at the third week postdistraction. Quantitative analysis using micro-CT revealed larger trabecular bone volume, higher trabecular number, and less trabecular separation in the DBM group than in the saline injection control group. Cross-sectional area and cortical thickness at the sixth week postdistraction, assessed using micro-CT, were greater in the regenerates of the DBM group compared with the control group. Histological evaluation revealed higher trabecular bone volume and trabecular number in the regenerate of the DBM group. New bone formation was apparently enhanced, via endochondral ossification, at the site and in the vicinity of the injected DBM. DBM was absorbed slowly, but it remained until the sixth postoperative week after injection. DBM administration into the distraction gap at the end of the distraction period resulted in a significantly greater regenerate bone area, trabecular number, and cortical thickness in the rabbit tibial DO model. These data suggest

  19. Pulsed Electromagnetic Fields Enhance Bone Morphogenetic Protein-2 Dependent-Bone Regeneration.

    Science.gov (United States)

    Yang, Hoon Joo; Kim, Ri Youn; Hwang, Soon Jung

    2015-10-01

    The use of recombinant human bone morphogenetic protein-2 (rhBMP-2) for the purpose of promoting bone regeneration is emerging; however, the high dose of rhBMP-2 required in humans is accompanied by several limitations, including bone resorption and swelling. To reduce the dose of rhBMP-2 required, the applicability of pulsed electromagnetic fields (PEMF) was evaluated using a rat calvarial defect model. After creating an 8-mm-diameter calvarial bone defect, a collagen sponge soaked in different concentrations (0, 2.5, 5, 10 μg) of rhBMP-2 was implanted at the defect area. One week after surgery, PEMF was applied for 8 h/day over 5 days in an experimental group of animals (n = 28) using a width of 12 μs, a pulse frequency of 60 Hz, and a magnetic intensity of 10 G. Animals were sacrificed 4 weeks after surgery and assessed by microcomputed tomography and histological and immunohistochemical analyses. In the absence of application of PEMF, bone volume, bone mineral density, trabecular thickness, trabecular number, and trabecular separation, all showed statistically significant differences, depending on the concentration of rhBMP-2 utilized (p PEMF accelerated bone regeneration in the groups that received 0, 2.5, and 5 μg rhBMP-2 (p PEMF. Groups receiving no rhBMP-2 showed distinct bone regeneration in the central zone of the bone defect when treated with PEMF, whereas they failed to bridge the defect space without PEMF. Among the groups without PEMF, soft tissue infiltrations from the outer surface on the skin side were common. Among groups with PEMF, the groups receiving 5 and 10 μg rhBMP-2 displayed denser bone with significantly reduced dead spaces. The application of PEMF did not result in an accelerated effect on bone regeneration in groups treated with 10 μg rhBMP-2. Therefore, our data demonstrate that PEMF can promote bone regeneration in animals treated with a low concentration of rhBMP-2.

  20. 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. Copyright © 2016 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

  1. 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...... and 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 defects covered by 2 Polyglactin 910 membranes. Defects covered by 1 ePTFE or 1 Polyglactin 910 membranes revealed 10% or 18% bone regeneration, respectively. The control group regenerated 14%. The major difference of the estimates was caused by real difference between specimens, i.e. biologic variation...

  2. A Novel Porcine Graft for Regeneration of Bone Defects

    Directory of Open Access Journals (Sweden)

    Eisner Salamanca

    2015-05-01

    Full Text Available Bone regeneration procedures require alternative graft biomaterials to those for autogenous bone. Therefore, we developed a novel porcine graft using particle sizes of 250–500 μm and 500–1000 μm in rabbit calvarial bone defects and compared the graft properties with those of commercial hydroxyapatite (HA/beta-tricalcium phosphate (β-TCP over eight weeks. Surgery was performed in 20 adult male New Zealand white rabbits. During a standardized surgical procedure, four calvarial critical-size defects of 5 mm diameter and 3 mm depth were prepared. The defects were filled with HA/β-TCP, 250–500 μm or 500–1000 μm porcine graft, and control defects were not filled. The animals were grouped for sacrifice at 1, 2, 4, and 8 weeks post-surgery. Subsequently, sample blocks were prepared for micro-computed tomography (micro-CT scanning and histological sectioning. Similar bone formations were observed in all three treatment groups, although the 250–500 μm porcine graft performed slightly better. Rabbit calvarial bone tissue positively responded to porcine grafts and commercial HA/β-TCP, structural analyses showed similar crystallinity and porosity of the porcine and HA/β-TCP grafts, which facilitated bone formation through osteoconduction. These porcine grafts can be considered as graft substitutes, although further development is required for clinical applications.

  3. Endochondral Priming: A Developmental Engineering Strategy for Bone Tissue Regeneration.

    Science.gov (United States)

    Freeman, Fiona E; McNamara, Laoise M

    2017-04-01

    Tissue engineering and regenerative medicine have significant potential to treat bone pathologies by exploiting the capacity for bone progenitors to grow and produce tissue constituents under specific biochemical and physical conditions. However, conventional tissue engineering approaches, which combine stem cells with biomaterial scaffolds, are limited as the constructs often degrade, due to a lack of vascularization, and lack the mechanical integrity to fulfill load bearing functions, and as such are not yet widely used for clinical treatment of large bone defects. Recent studies have proposed that in vitro tissue engineering approaches should strive to simulate in vivo bone developmental processes and, thereby, imitate natural factors governing cell differentiation and matrix production, following the paradigm recently defined as "developmental engineering." Although developmental engineering strategies have been recently developed that mimic specific aspects of the endochondral ossification bone formation process, these findings are not widely understood. Moreover, a critical comparison of these approaches to standard biomaterial-based bone tissue engineering has not yet been undertaken. For that reason, this article presents noteworthy experimental findings from researchers focusing on developing an endochondral-based developmental engineering strategy for bone tissue regeneration. These studies have established that in vitro approaches, which mimic certain aspects of the endochondral ossification process, namely the formation of the cartilage template and the vascularization of the cartilage template, can promote mineralization and vascularization to a certain extent both in vitro and in vivo. Finally, this article outlines specific experimental challenges that must be overcome to further exploit the biology of endochondral ossification and provide a tissue engineering construct for clinical treatment of large bone/nonunion defects and obviate the need for

  4. Salicylic Acid-Based Polymers for Guided Bone Regeneration Using Bone Morphogenetic Protein-2.

    Science.gov (United States)

    Subramanian, Sangeeta; Mitchell, Ashley; Yu, Weiling; Snyder, Sabrina; Uhrich, Kathryn; O'Connor, J Patrick

    2015-07-01

    Bone morphogenetic protein-2 (BMP-2) is used clinically to promote spinal fusion, treat complex tibia fractures, and to promote bone formation in craniomaxillofacial surgery. Excessive bone formation at sites where BMP-2 has been applied is an established complication and one that could be corrected by guided tissue regeneration methods. In this study, anti-inflammatory polymers containing salicylic acid [salicylic acid-based poly(anhydride-ester), SAPAE] were electrospun with polycaprolactone (PCL) to create thin flexible matrices for use as guided bone regeneration membranes. SAPAE polymers hydrolyze to release salicylic acid, which is a nonsteroidal anti-inflammatory drug. PCL was used to enhance the mechanical integrity of the matrices. Two different SAPAE-containing membranes were produced and compared: fast-degrading (FD-SAPAE) and slow-degrading (SD-SAPAE) membranes that release salicylic acid at a faster and slower rate, respectively. Rat femur defects were treated with BMP-2 and wrapped with FD-SAPAE, SD-SAPAE, or PCL membrane or were left unwrapped. The effects of different membranes on bone formation within and outside of the femur defects were measured by histomorphometry and microcomputed tomography. Bone formation within the defect was not affected by membrane wrapping at BMP-2 doses of 12 μg or more. In contrast, the FD-SAPAE membrane significantly reduced bone formation outside the defect compared with all other treatments. The rapid release of salicylic acid from the FD-SAPAE membrane suggests that localized salicylic acid treatment during the first few days of BMP-2 treatment can limit ectopic bone formation. The data support development of SAPAE polymer membranes for guided bone regeneration applications as well as barriers to excessive bone formation.

  5. Nano-Hydroxyapatite Bone Substitute Functionalized with Bone Active Molecules for Enhanced Cranial Bone Regeneration.

    Science.gov (United States)

    Teotia, Arun Kumar; Raina, Deepak Bushan; Singh, Chandan; Sinha, Neeraj; Isaksson, Hanna; Tägil, Magnus; Lidgren, Lars; Kumar, Ashok

    2017-03-01

    The aim of this study was to synthesize and characterize a nano-hydroxyapatite (nHAP) and calcium sulfate bone substitute (NC) for cranioplasty. The NC was functionalized with low concentrations of bone morphogenetic protein-2 (BMP-2) and zoledronic acid (ZA) and characterized both in vitro and in vivo. In vitro studies included MTT, ALP assays, and fluorescent staining of Saos-2 (human osteoblasts) and MC3T3-E1 (murine preosteoblasts) cells cultured on NC. An in vivo study divided 20 male Wistar rats into four groups: control (defect only), NC, NC + ZA, and NC + ZA + rhBMP-2. The materials were implanted in an 8.5 mm critical size defect in the calvarium for 12 weeks. Micro-CT quantitative analysis was carried out in vivo at 8 weeks and ex vivo after 12 weeks. Mineralization was highest in the NC + ZA + rhBMP-2 group (13.0 ± 2.8 mm 3 ) compared to the NC + ZA group (9.0 ± 3.2 mm 3 ), NC group (6.4 ± 1.9 mm 3 ), and control group (3.4 ± 1.0 mm 3 ) after 12 weeks. Histological and spectroscopic analysis of the defect site provided a qualitative confirmation of neo-bone, which was in agreement with the micro-CT results. In conclusion, NC can be used as a carrier for bioactive molecules, and functionalization with rhBMP-2 and ZA in low doses enhances bone regeneration.

  6. Histomorphometric evaluation of bone regeneration using autogenous bone and beta-tricalcium phosphate in diabetic rabbits

    Directory of Open Access Journals (Sweden)

    Živadinović Milka

    2016-01-01

    Full Text Available Background/Aim. The mechanism of impaired bone healing in diabetes mellitus includes different tissue and cellular level activities due to micro- and macrovascular changes. As a chronic metabolic disease with vascular complications, diabetes affects a process of bone regeneration as well. The therapeutic approach in bone regeneration is based on the use of osteoinductive autogenous grafts as well as osteoconductive synthetic material, like a β-tricalcium phosphate. The aim of the study was to determine the quality and quantity of new bone formation after the use of autogenous bone and β-tricalcium phosphate in the model of calvarial critical-sized defect in rabbits with induced diabetes mellitus type I. Methods. The study included eight 4-month-old Chincilla rabbits with alloxan-induced diabetes mellitus type I. In all animals, there were surgically created two calvarial bilateral defects (diameter 12 mm, which were grafted with autogenous bone and β-tricalcium phosphate (n = 4 or served as unfilled controls (n = 4. After 4 weeks of healing, animals were sacrificed and calvarial bone blocks were taken for histologic and histomorphometric analysis. Beside descriptive histologic evaluation, the percentage of new bone formation, connective tissue and residual graft were calculated. All parameters were statistically evaluated by Friedman Test and post hock Wilcoxon Singed Ranks Test with a significance of p < 0.05. Results. Histology revealed active new bone formation peripherally with centrally located connective tissue, newly formed woven bone and well incorporated residual grafts in all treated defects. Control samples showed no bone bridging of defects. There was a significantly more new bone in autogeonous graft (53% compared with β-tricalcium phosphate (30%, (p < 0.030 and control (7%, (p < 0.000 groups. A significant difference was also recorded between β-tricalcium phosphate and control groups (p < 0.008. Conclusion. In the present

  7. Strontium borate glass: potential biomaterial for bone regeneration.

    Science.gov (United States)

    Pan, H B; Zhao, X L; Zhang, X; Zhang, K B; Li, L C; Li, Z Y; Lam, W M; Lu, W W; Wang, D P; Huang, W H; Lin, K L; Chang, J

    2010-07-06

    Boron plays important roles in many life processes including embryogenesis, bone growth and maintenance, immune function and psychomotor skills. Thus, the delivery of boron by the degradation of borate glass is of special interest in biomedical applications. However, the cytotoxicity of borate glass which arises with the rapid release of boron has to be carefully considered. In this study, it was found that the incorporation of strontium into borate glass can not only moderate the rapid release of boron, but also induce the adhesion of osteoblast-like cells, SaOS-2, thus significantly increasing the cyto-compatibility of borate glass. The formation of multilayers of apatite with porous structure indicates that complete degradation is optimistic, and the spread of SaOS-2 covered by apatite to form a sandwich structure may induce bone-like tissue formation at earlier stages. Therefore, such novel strontium-incorporated borosilicate may act as a new generation of biomaterial for bone regeneration, which not only renders boron as a nutritious element for bone health, but also delivers strontium to stimulate formation of new bones.

  8. A Therapeutic Potential for Marine Skeletal Proteins in Bone Regeneration

    Directory of Open Access Journals (Sweden)

    Bruce Milthorpe

    2013-04-01

    Full Text Available A vital ingredient for engineering bone tissue, in the culture dish, is the use of recombinant matrix and growth proteins to help accelerate the growth of cultivated tissues into clinically acceptable quantities. The skeletal organic matrices of calcifying marine invertebrates are an untouched potential source of such growth inducing proteins. They have the advantage of being ready-made and retain the native state of the original protein. Striking evidence shows that skeleton building bone morphogenic protein-2/4 (BMP and transforming growth factor beta (TGF-β exist within various marine invertebrates such as, corals. Best practice mariculture and the latest innovations in long-term marine invertebrate cell cultivation can be implemented to ensure that these proteins are produced sustainably and supplied continuously. This also guarantees that coral reef habitats are not damaged during the collection of specimens. Potential proteins for bone repair, either extracted from the skeleton or derived from cultivated tissues, can be identified, evaluated and retrieved using chromatography, cell assays and proteomic methods. Due to the current evidence for bone matrix protein analogues in marine invertebrates, together with the methods established for their production and retrieval there is a genuine prospect that they can be used to regenerate living bone for potential clinical use.

  9. Application of VEGFA and FGF-9 Enhances Angiogenesis, Osteogenesis and Bone Remodeling in Type 2 Diabetic Long Bone Regeneration

    Science.gov (United States)

    Wallner, Christoph; Schira, Jessica; Wagner, Johannes Maximilian; Schulte, Matthias; Fischer, Sebastian; Hirsch, Tobias; Richter, Wiltrud; Abraham, Stephanie; Kneser, Ulrich; Lehnhardt, Marcus; Behr, Björn

    2015-01-01

    Although bone regeneration is typically a reliable process, type 2 diabetes is associated with impaired or delayed healing processes. In addition, angiogenesis, a crucial step in bone regeneration, is often altered in the diabetic state. In this study, different stages of bone regeneration were characterized in an unicortical bone defect model comparing transgenic type 2 diabetic (db-/db-) and wild type (WT) mice in vivo. We investigated angiogenesis, callus formation and bone remodeling at early, intermediate and late time points by means of histomorphometry as well as protein level analyses. In order to enhance bone regeneration, defects were locally treated with recombinant FGF-9 or VEGFA. Histomorphometry of aniline blue stained sections indicated that bone regeneration is significantly decreased in db-/db- as opposed to WT mice at intermediate (5 days post operation) and late stages (7 days post operation) of bone regeneration. Moreover, immunohistochemical analysis revealed significantly decreased levels of RUNX-2, PCNA, Osteocalcin and PECAM-1 in db-/db- defects. In addition, osteoclastogenesis is impaired in db-/db- indicating altered bone remodeling. These results indicate significant impairments in angiogenesis and osteogenesis in type 2 diabetic bones. Importantly, angiogenesis, osteogenesis and bone remodeling could be reconstituted by application of recombinant FGF-9 and, in part, by VEGFA application. In conclusion, our study demonstrates that type 2 diabetes affects angiogenesis, osteogenesis and subsequently bone remodeling, which in turn leads to decreased bone regeneration. These effects could be reversed by local application of FGF-9 and to a lesser degree VEGFA. These data could serve as a basis for future therapeutic applications aiming at improving bone regeneration in the type 2 diabetic patient population. PMID:25742620

  10. Mechanical regulation of bone regeneration: theories, models, and experiments.

    Science.gov (United States)

    Betts, Duncan Colin; Müller, Ralph

    2014-01-01

    How mechanical forces influence the regeneration of bone remains an open question. Their effect has been demonstrated experimentally, which has allowed mathematical theories of mechanically driven tissue differentiation to be developed. Many simulations driven by these theories have been presented, however, validation of these models has remained difficult due to the number of independent parameters considered. An overview of these theories and models is presented along with a review of experimental studies and the factors they consider. Finally limitations of current experimental data and how this influences modeling are discussed and potential solutions are proposed.

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

    Science.gov (United States)

    Gu, Wenyi; Wu, Chengtie; Chen, Jiezhong; Xiao, Yin

    2013-01-01

    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. PMID:23836972

  12. Silk fibroin membrane used for guided bone tissue regeneration.

    Science.gov (United States)

    Cai, Yurong; Guo, Junmao; Chen, Cen; Yao, Chenxue; Chung, Sung-Min; Yao, Juming; Lee, In-Seop; Kong, Xiangdong

    2017-01-01

    With the aim to develop a novel membrane with an appropriate mechanical property and degradation rate for guided bone tissue regeneration, lyophilized and densified silk fibroin membrane was fabricated and its mechanical behavior as well as biodegradation property were investigated. The osteoconductive potency of the silk fibroin membranes were evaluated in a defect rabbit calvarial model. Silk fibroin membrane showed the modulated biodegradable and mechanical properties via ethanol treatment with different concentration. The membrane could prevent soft tissue invasion from normal tissue healing, and the amounts of new bone and defect closure with silk fibroin membrane were similar to those of commercially available collagen membrane. Copyright © 2016 Elsevier B.V. All rights reserved.

  13. Bone as a source of organism vitality and regeneration

    Directory of Open Access Journals (Sweden)

    Jolanta Kowalewska

    2012-01-01

    Full Text Available The most important features that determine the vital role of bone include: a a continuous supply of calcium, which is indispensible for every cell of the entire organism at all times, and b the delivery of circulating blood cells and some adult stem cells to keep the body vigorous, ready for self-reparation, and continuously rebuilding throughout life. These functions of bones are no less important than protecting the body cavities, serving as mechanical levers connected to the muscles, and determining the shape and dimensions of the entire organism. The aim of this review was to address some basic cellular and molecular knowledge to better understand the complex interactions of bone structural components. The apprehension of osteoblast differentiation and its local regulation has substantially increased in recent years. It has been suggested that osteocytes, cells within the bone matrix, act as regulatory mechanosensors. Therefore immobility as well as limited activity has a dramatic effect on bone structure and influences a broad spectrum of bone physiology-related functions as well as the functions of many other organs. Lifelong bone rebuilding is modulated through several pathways, including the Wnt pathway that regulates bone formation and resorption. In the adult skeleton, bone is continuously renewed in response to a variety of stimuli, such as the specific process of remodeling dependent on RANK/ /RANKL/OPG interactions. Better understanding of bone biology provides opportunities for the development of more effective prevention and treatment modalities for a variety of bone diseases, including new approaches to adult stem cell-based therapies. (Folia Histochemica et Cytobiologica 2011; Vol. 49, No. 4, pp. 558–569

  14. Enhancing dermal and bone regeneration in calvarial defect surgery

    Directory of Open Access Journals (Sweden)

    Bruno Zanotti

    2014-01-01

    Full Text Available Introduction: To optimize the functional and esthetic result of cranioplasty, it is necessary to choose appropriate materials and take steps to preserve and support tissue vitality. As far as materials are concerned, custom-made porous hydroxyapatite implants are biomimetic, and therefore, provide good biological interaction and biointegration. However, before it is fully integrated, this material has relatively low mechanical resistance. Therefore, to reduce the risk of postoperative implant fracture, it would be desirable to accelerate regeneration of the tissues around and within the graft. Objectives: The objective was to determine whether integrating growth-factor-rich platelet gel or supportive dermal matrix into hydroxyapatite implant cranioplasty can accelerate bone remodeling and promote soft tissue regeneration, respectively. Materials and Methods: The investigation was performed on cranioplasty patients fitted with hydroxyapatite cranial implants between 2004 and 2010. In 7 patients, platelet gel was applied to the bone/prosthesis interface during surgery, and in a further 5 patients, characterized by thin, hypotrophic skin coverage of the cranial lacuna, a sheet of dermal matrix was applied between the prosthesis and the overlying soft tissue. In several of the former groups, platelet gel mixed with hydroxyapatite granules was used to fill small gaps between the skull and the implant. To confirm osteointegration, cranial computed tomography (CT scans were taken at 3-6 month intervals for 1-year, and magnetic resonance imaging (MRI was used to confirm dermal integrity. Results: Clinical examination performed a few weeks after surgery revealed good dermal regeneration, with thicker, healthier skin, apparently with a better blood supply, which was confirmed by MRI at 3-6 months. Furthermore, at 3-6 months, CT showed good biomimetism of the porous hydroxyapatite scaffold. Locations at which platelet gel and hydroxyapatite granules were

  15. Enhancing dermal and bone regeneration in calvarial defect surgery.

    Science.gov (United States)

    Zanotti, Bruno; Zingaretti, Nicola; Almesberger, Daria; Verlicchi, Angela; Stefini, Roberto; Ragonese, Mauro; Guarneri, Gianni Franco; Parodi, Pier Camillo

    2014-01-01

    To optimize the functional and esthetic result of cranioplasty, it is necessary to choose appropriate materials and take steps to preserve and support tissue vitality. As far as materials are concerned, custom-made porous hydroxyapatite implants are biomimetic, and therefore, provide good biological interaction and biointegration. However, before it is fully integrated, this material has relatively low mechanical resistance. Therefore, to reduce the risk of postoperative implant fracture, it would be desirable to accelerate regeneration of the tissues around and within the graft. The objective was to determine whether integrating growth-factor-rich platelet gel or supportive dermal matrix into hydroxyapatite implant cranioplasty can accelerate bone remodeling and promote soft tissue regeneration, respectively. The investigation was performed on cranioplasty patients fitted with hydroxyapatite cranial implants between 2004 and 2010. In 7 patients, platelet gel was applied to the bone/prosthesis interface during surgery, and in a further 5 patients, characterized by thin, hypotrophic skin coverage of the cranial lacuna, a sheet of dermal matrix was applied between the prosthesis and the overlying soft tissue. In several of the former groups, platelet gel mixed with hydroxyapatite granules was used to fill small gaps between the skull and the implant. To confirm osteointegration, cranial computed tomography (CT) scans were taken at 3-6 month intervals for 1-year, and magnetic resonance imaging (MRI) was used to confirm dermal integrity. Clinical examination performed a few weeks after surgery revealed good dermal regeneration, with thicker, healthier skin, apparently with a better blood supply, which was confirmed by MRI at 3-6 months. Furthermore, at 3-6 months, CT showed good biomimetism of the porous hydroxyapatite scaffold. Locations at which platelet gel and hydroxyapatite granules were used to fill gaps between the implant and skull appeared to show more rapid

  16. Bone regeneration using the pouch-and-tunnel technique.

    Science.gov (United States)

    Azzi, Robert; Etienne, Daniel; Takei, Henry; Carranza, Fermin

    2009-10-01

    Several surgical techniques, such as the papilla preservation flap, the modified papilla preservation flap, and the sulcular incision flap, have attempted to achieve clot stabilization and graft coverage in an attempt to regenerate lost tissue due to periodontal disease. This case report focuses on soft tissue root coverage and bone regeneration in a one-wall osseous defect using the pouch-and-tunnel surgical procedure. The pouch-and-tunnel surgical technique is a minimally invasive periodontal plastic surgical procedure that uses subepithelial connective tissue as a free graft in a pouch beneath the gingival margin, created by sulcular incisions around the involved teeth. The autogenous bone graft placed in this one-wall osseous defect through a sulcular incision after root planing is protected in a stable pouch-like recipient site with an abundant blood supply. The free connective tissue graft also prevents epithelial migration into the recipient site. The use of Emdogain may help with cementogenesis around the planed root surface. This technique warrants further evaluation of cases with similar defects using this surgical procedure. (Int J Periodontics Restorative Dent 2009;29:515-521.).

  17. Strontium-rich injectable hybrid system for bone regeneration

    Energy Technology Data Exchange (ETDEWEB)

    Neves, Nuno, E-mail: nsmneves@gmail.com [Instituto de Investigação e Inovação em Saúde, Universidade do Porto (Portugal); INEB — Instituto de Engenharia Biomédica, Universidade do Porto, Rua do Campo Alegre 823, 4150-180 Porto (Portugal); FMUP — Faculdade de Medicina da Universidade do Porto, Departamento de Cirurgia, Serviço de Ortopedia, Alameda Prof. Hernâni Monteiro, 4200-319 Porto (Portugal); Campos, Bruno B. [FCUP — Faculdade de Ciências da Universidade do Porto, Centro de Investigação em Química, Departamento de Química e Bioquímica, Rua do Campo Alegre 1021/1055, 4169-007 Porto (Portugal); Almeida, Isabel F.; Costa, Paulo C. [FFUP — Faculdade de Farmácia da Universidade do Porto, Laboratório de Tecnologia Farmacêutica, Departamento de Ciências do Medicamento, Rua de Jorge Viterbo Ferreira 228, 4050-313 Porto (Portugal); Cabral, Abel Trigo [FMUP — Faculdade de Medicina da Universidade do Porto, Departamento de Cirurgia, Serviço de Ortopedia, Alameda Prof. Hernâni Monteiro, 4200-319 Porto (Portugal); and others

    2016-02-01

    Current challenges in the development of scaffolds for bone regeneration include the engineering of materials that can withstand normal dynamic physiological mechanical stresses exerted on the bone and provide a matrix capable of supporting cell migration and tissue ingrowth. The objective of the present work was to develop and characterize a hybrid polymer–ceramic injectable system that consists of an alginate matrix crosslinked in situ in the presence of strontium (Sr), incorporating a ceramic reinforcement in the form of Sr-rich microspheres. The incorporation of Sr in the microspheres and in the vehicle relies on the growing evidence that Sr has beneficial effects in bone remodeling and in the treatment of osteopenic disorders and osteoporosis. Sr-rich porous hydroxyapatite microspheres with a uniform size and a mean diameter of 555 μm were prepared, and their compression strength and friability tested. A 3.5% (w/v) ultrapure sodium alginate solution was used as the vehicle and its in situ gelation was promoted by the addition of calcium (Ca) or Sr carbonate and Glucone-δ-lactone. Gelation times varied with temperature and crosslinking agent, being slower for Sr than for Ca, but adequate for injection in both cases. Injectability was evaluated using a device employed in vertebroplasty surgical procedures, coupled to a texture analyzer in compression mode. Compositions with 35% w of microspheres presented the best compromise between injectability and compression strength of the system, the force required to extrude it being lower than 100 N. Micro CT analysis revealed a homogeneous distribution of the microspheres inside the vehicle, and a mean inter-microspheres space of 220 μm. DMA results showed that elastic behavior of the hybrid is dominant over the viscous one and that the higher storage modulus was obtained for the 3.5%Alg–35%Sr-HAp-Sr formulation. - Highlights: • We developed a Sr rich viscoelastic hybrid system (alginate matrix crosslinked in

  18. 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.

  19. Octacalcium phosphate collagen composite facilitates bone regeneration of large mandibular bone defect in humans.

    Science.gov (United States)

    Kawai, Tadashi; Suzuki, Osamu; Matsui, Keiko; Tanuma, Yuji; Takahashi, Tetsu; Kamakura, Shinji

    2017-05-01

    Recently it was reported that the implantation of octacalcium phosphate (OCP) and collagen composite (OCP-collagen) was effective at promoting bone healing in small bone defects after cystectomy in humans. In addition, OCP-collagen promoted bone regeneration in a critical-sized bone defect of a rodent or canine model. In this study, OCP-collagen was implanted into a human mandibular bone defect with a longer axis of approximately 40 mm, which was diagnosed as a residual cyst with apical periodontitis. The amount of OCP-collagen implanted was about five times greater than the amounts implanted in previous clinical cases. Postoperative wound healing was satisfactory and no infection or allergic reactions occurred. The OCP-collagen-treated lesion was gradually filled with radio-opaque figures, and the alveolar region occupied the whole of the bone defect 12 months after implantation. This study suggests that OCP-collagen could be a useful bone substitute material for repairing large bone defects in humans that might not heal spontaneously. Copyright © 2015 John Wiley & Sons, Ltd. Copyright © 2015 John Wiley & Sons, Ltd.

  20. Jaw bones regeneration using mesenchymal stem cells. A single-center experience.

    Science.gov (United States)

    Colangeli, Walter; Riccelli, Umberto; Giudice, Amerigo; Barca, Ida; Caruso, Davide; Novembre, Daniela; Tortosa, Claudio; Cordaro, Raffaella; Cristofaro, Maria Giulia

    2017-12-21

    Mesenchymal stem cells (MSC), which are multipotent stromal cells, are considered to be a promising resource in tissue engineering and tissue regeneration. MSCs have been used to generate new maxillary bone with clinically successful results. The aim of this study was to determine the role of MSC in bone regeneration procedures in patients with benign maxillary lesions. A study was conducted on five patients treated for maxillary bone defects resulting from biopsy of benign lesions at the University Hospital of Magna Græcia, Catanzaro, Italy from January 2015 to October 2016. MSC from autologous bone marrow were used for bone regeneration. The bone mineral density was compared, using the Hounsfield scale, before and after treatment. Follow-up was monthly for six months, and the patients underwent a computed tomography scan of the maxilla at 6 months. Five patients, who underwent biopsy of osteolytic odontogenic benign tumors, were included in the study. There were no intraoperative or postoperative complications. The mean volume of the newly formed bone was 2.44cm3 (range 2,0-3,1) and the mean bone density was 1137 Hounsfield Units (range 898-1355). Bone regeneration with MSC from autologous bone marrow appears to be a valid treatment option for maxillary bone defects. Bone regeneration, Mesenchymal stem cells, BM-MSC, Upper jaw, Mandible.

  1. Poly(glycerol sebacate) elastomer: a novel material for mechanically loaded bone regeneration.

    Science.gov (United States)

    Zaky, Samer Helal; Lee, Kee-Won; Gao, Jin; Jensen, Adrianna; Close, John; Wang, Yadong; Almarza, Alejandro J; Sfeir, Charles

    2014-01-01

    The selection criteria for potential bone engineering scaffolds are based chiefly on their relative mechanical comparability to mature bone. In this study, we challenge this notion by obtaining full regeneration of a rabbit ulna critical size defect by employing the elastomeric polymer, poly(glycerol sebacate) (PGS). We tested the regeneration facilitated by PGS alone, PGS in combination with hydroxyapatite particles, or PGS seeded with bone marrow stromal cells. We investigated the quantity and quality of the regenerated bone histologically, by microcomputed tomography and by four-point bending flexural mechanical testing at 8 weeks postimplantation. We conclude that the relatively lower stiffness of this biocompatible elastomer allows a load-transducing milieu in which osteogenesis, matrix deposition, and eventual bone maturation can take place. This study's results suggest that PGS elastomer is an auspicious osteoconductive material for the regeneration of bony defects. These results call for an innovative reassessment of the current art of selection for novel bone scaffold materials.

  2. Electrospun PVA-PCL-HAB scaffold for Craniofacial Bone Regeneration

    DEFF Research Database (Denmark)

    Prabha, R. D.; Kraft, D. C.; Melsen, B.

    2015-01-01

    body fluid immersed scaffold samples. Culturing human adult dental pulp stem cells (DPSC) and human bone marrow derived MSC seeded on PVA-PCL-HAB scaffold showed enhanced cell proliferation and in vitro osteoblastic differentiation. Cell-containing scaffolds were implanted subcutaneously in immune......-caprolactone (PCL)- triphasic bioceramic(HAB) scaffold to biomimic native tissue and we tested its ability to support osteogenic differentiation of stromal stem cells ( MSC) and its suitability for regeneration of craniofa- cial defects. Physiochemical characterizations of the scaffold, including con- tact angle...... deficient mice. Histologic ex- amination of retrieved implant sections stained with H&E, Col- lagenType I and Human Vimentin antibody demonstrated that the cells survived in vivo in the implants for at least 8 weeks with evidence of osteoblastic differentiation and angiogenesis within the implants. Our...

  3. Guided bone regeneration of peri-implant defects with particulated and block xenogenic bone substitutes.

    Science.gov (United States)

    Benic, Goran I; Thoma, Daniel S; Muñoz, Fernando; Sanz Martin, Ignacio; Jung, Ronald E; Hämmerle, Christoph H F

    2016-05-01

    To test whether an equine bone substitute block used for guided bone regeneration (GBR) of peri-implant defects renders different results from bovine block or particulated bone substitutes regarding the dimensions of the augmented ridge and the amount of new bone. Mandibular premolars and molars were extracted in eight dogs. After 4 months, four semi-saddle bone defects were created in each mandible and one titanium implant was inserted into every site. Bone augmentation by GBR was attempted using the following randomly assigned modalities: (i) particulated deproteinized bovine bone mineral (DBBM) + a collagen membrane (CM), (ii) block DBBM + CM, (iii) equine bone substitute block + CM, and (iv) empty controls. After 4 months, one central and two lateral sections of each site were prepared. Descriptive histological and histomorphometrical assessments were performed evaluating the augmented area (AA) within the former bone defect, the area of mineralized tissue (MT), non-mineralized tissue (NMT), and residual bone substitute (BS) within AA, the horizontal thicknesses of the augmented region (HTaugm ) and of the mucosa (HTmucosa ). At the central sections, AA measured 11.2 ± 3.3 mm(2) for the equine block, 9.5 ± 2.6 mm(2) for DBBM block, 7.9 ± 4.8 mm(2) for particulated DBBM, and 2.4 ± 2.1 mm(2) for the empty control. All GBR groups rendered significantly higher values of AA in comparison with control (P ≤ 0.05). The differences in AA between GBR groups did not reach statistical significance (P > 0.05). The equine block rendered the highest values in HTaugm , although only the differences between equine block and control as well as equine block and DBBM block were statistically significant (P ≤ 0.05). With respect to HTmucosa , all GBR groups reached significantly higher values compared to control (P ≤ 0.05). The equine block revealed the most pronounced signs of graft degradation. Guided bone regeneration lead to higher ridge dimensions and thicker

  4. Synthetic bone substitute engineered with amniotic epithelial cells enhances bone regeneration after maxillary sinus augmentation.

    Directory of Open Access Journals (Sweden)

    Barbara Barboni

    Full Text Available BACKGROUND: Evidence has been provided that a cell-based therapy combined with the use of bioactive materials may significantly improve bone regeneration prior to dental implant, although the identification of an ideal source of progenitor/stem cells remains to be determined. AIM: In the present research, the bone regenerative property of an emerging source of progenitor cells, the amniotic epithelial cells (AEC, loaded on a calcium-phosphate synthetic bone substitute, made by direct rapid prototyping (rPT technique, was evaluated in an animal study. MATERIAL AND METHODS: Two blocks of synthetic bone substitute (∼0.14 cm(3, alone or engineered with 1×10(6 ovine AEC (oAEC, were grafted bilaterally into maxillary sinuses of six adult sheep, an animal model chosen for its high translational value in dentistry. The sheep were then randomly divided into two groups and sacrificed at 45 and 90 days post implantation (p.i.. Tissue regeneration was evaluated in the sinus explants by micro-computer tomography (micro-CT, morphological, morphometric and biochemical analyses. RESULTS AND CONCLUSIONS: The obtained data suggest that scaffold integration and bone deposition are positively influenced by allotransplantated oAEC. Sinus explants derived from sheep grafted with oAEC engineered scaffolds displayed a reduced fibrotic reaction, a limited inflammatory response and an accelerated process of angiogenesis. In addition, the presence of oAEC significantly stimulated osteogenesis either by enhancing bone deposition or making more extent the foci of bone nucleation. Besides the modulatory role played by oAEC in the crucial events successfully guiding tissue regeneration (angiogenesis, vascular endothelial growth factor expression and inflammation, data provided herein show that oAEC were also able to directly participate in the process of bone deposition, as suggested by the presence of oAEC entrapped within the newly deposited osteoid matrix and by their

  5. 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.

  6. Local pulsatile PTH delivery regenerates bone defect via enhanced bone remodeling in a cell-free scaffold

    Science.gov (United States)

    Dang, Ming; Koh, Amy J.; Jin, Xiaobing; McCauley, Laurie K.; Ma, Peter X.

    2016-01-01

    Parathyroid hormone (PTH) is currently the only FDA-approved anabolic drug to treat osteoporosis, and is systemically administered through daily injections. A new local pulsatile PTH delivery device was developed from biodegradable polymers to expand PTH’s application from osteoporosis treatment to spatially controlled local bone defect regeneration in this work. This is the first time that local pulsatile PTH delivery has been demonstrated to promote bone regeneration via enhanced bone remodeling. The biodegradable delivery device was designed to locally deliver PTH in a preprogrammed pulsatile manner. The PTH delivery was utilized to facilitate the regeneration of a bone defect spatially defined with a cell-free biomimetic nanofibrous (NF) scaffold. The local pulsatile PTH delivery (daily pulse for 21 days) not only promoted the regeneration of a critical-sized bone defect with negligible systemic side effects in a mouse model, but also advantageously achieved higher quality regenerated bone than the standard systemic PTH injection. These results demonstrate a promising and novel pulsatile PTH delivery device for spatially defined local bone regeneration. PMID:27835763

  7. Local pulsatile PTH delivery regenerates bone defects via enhanced bone remodeling in a cell-free scaffold.

    Science.gov (United States)

    Dang, Ming; Koh, Amy J; Jin, Xiaobing; McCauley, Laurie K; Ma, Peter X

    2017-01-01

    Parathyroid hormone (PTH) is currently the only FDA-approved anabolic drug to treat osteoporosis, and is systemically administered through daily injections. A new local pulsatile PTH delivery device was developed from biodegradable polymers to expand the application of PTH from systemic treatment to spatially controlled local bone defect regeneration in this work. This is the first time that local pulsatile PTH delivery has been demonstrated to promote bone regeneration via enhanced bone remodeling. The biodegradable delivery device was designed to locally deliver PTH in a preprogrammed pulsatile manner. The PTH delivery was utilized to facilitate the regeneration of a bone defect spatially defined with a cell-free biomimetic nanofibrous (NF) scaffold. The local pulsatile PTH delivery (daily pulse for 21 days) not only promoted the regeneration of a critical-sized bone defect with negligible systemic side effects in a mouse model, but also advantageously achieved higher quality regenerated bone than the standard systemic PTH injection. These results demonstrate a promising and novel pulsatile PTH delivery device for spatially defined local bone regeneration. Copyright © 2016 Elsevier Ltd. All rights reserved.

  8. Osteoblast Production by Reserved Progenitor Cells in Zebrafish Bone Regeneration and Maintenance.

    Science.gov (United States)

    Ando, Kazunori; Shibata, Eri; Hans, Stefan; Brand, Michael; Kawakami, Atsushi

    2017-12-04

    Mammals cannot re-form heavily damaged bones as in large fracture gaps, whereas zebrafish efficiently regenerate bones even after amputation of appendages. However, the source of osteoblasts that mediate appendage regeneration is controversial. Several studies in zebrafish have shown that osteoblasts are generated by dedifferentiation of existing osteoblasts at injured sites, but other observations suggest that de novo production of osteoblasts also occurs. In this study, we found from cell-lineage tracing and ablation experiments that a group of cells reserved in niches serves as osteoblast progenitor cells (OPCs) and has a significant role in fin ray regeneration. Besides regeneration, OPCs also supply osteoblasts for normal bone maintenance. We further showed that OPCs are derived from embryonic somites, as is the case with embryonic osteoblasts, and are replenished from mesenchymal precursors in adult zebrafish. Our findings reveal that reserved progenitors are a significant and complementary source of osteoblasts for zebrafish bone regeneration. Copyright © 2017 Elsevier Inc. All rights reserved.

  9. Xerogel Interfaced Nanofibers Stimulate Bone Regeneration Through the Activation of Integrin and Bone Morphogenetic Protein Pathways.

    Science.gov (United States)

    Lee, Yoo-Mi; Yun, Hyung-Mun; Lee, Hye-Young; Lim, Hyun-Chang; Lee, Hae-Hyoung; Kim, Hae-Won; Kim, Eun-Cheol

    2017-02-01

    A xerogel was interfaced onto biopolymer nanofibers though a core–shell electrospinning design for bone regeneration. The xerogel-interfaced biopolymer nanofibrous matrix was bioactive and highly hydrophilic, with a significant decrease in the water contact angle. The matrix showed excellent in vitro responses of primary osteoblasts in terms of adhesion, proliferation, and migration. Furthermore, the osteoblastic differentiation of cells, including alkaline phosphatase activity, mineralization, and gene expression, was significantly upregulated by the xerogel interface. In vivo animal tests in a critical-sized calvarial defect confirmed the new bone formation ability of the xerogel-surfaced nanofiber matrices. The underlying signaling mechanisms of the stimulation were implied to be integrin and bone morphogenetic protein (BMP) pathways, as demonstrated by the activation of integrin (α2β1) and downstream signaling molecules (FAK, paxillin, RhoA, MAPK, and NF-κB), as well as the BMPs and the downstream transcription factor Smad1/5/8. Taking these findings together, the xerogel-surfaced biopolymer nanofibers are proposed to be a promising scaffold candidate for bone regeneration.

  10. The Mechanical Properties and Biometrical Effect of 3D Preformed Titanium Membrane for Guided Bone Regeneration on Alveolar Bone Defect

    Directory of Open Access Journals (Sweden)

    So-Hyoun Lee

    2017-01-01

    Full Text Available The purpose of this study is to evaluate the effect of three-dimensional preformed titanium membrane (3D-PFTM to enhance mechanical properties and ability of bone regeneration on the peri-implant bone defect. 3D-PFTMs by new mechanically compressive molding technology and manually shaped- (MS- PFTMs by hand manipulation were applied in artificial peri-implant bone defect model for static compressive load test and cyclic fatigue load test. In 12 implants installed in the mandibular of three beagle dogs, six 3D-PFTMs, and six collagen membranes (CM randomly were applied to 2.5 mm peri-implant buccal bone defect with particulate bone graft materials for guided bone regeneration (GBR. The 3D-PFTM group showed about 7.4 times higher mechanical stiffness and 5 times higher fatigue resistance than the MS-PFTM group. The levels of the new bone area (NBA, %, the bone-to-implant contact (BIC, %, distance from the new bone to the old bone (NB-OB, %, and distance from the osseointegration to the old bone (OI-OB, % were significantly higher in the 3D-PFTM group than the CM group (p<.001. It was verified that the 3D-PFTM increased mechanical properties which were effective in supporting the space maintenance ability and stabilizing the particulate bone grafts, which led to highly efficient bone regeneration.

  11. The Mechanical Properties and Biometrical Effect of 3D Preformed Titanium Membrane for Guided Bone Regeneration on Alveolar Bone Defect

    Science.gov (United States)

    Lee, So-Hyoun; Moon, Jong-Hoon; Jeong, Chang-Mo; Bae, Eun-Bin; Park, Chung-Eun; Jeon, Gye-Rok; Lee, Jin-Ju; Jeon, Young-Chan

    2017-01-01

    The purpose of this study is to evaluate the effect of three-dimensional preformed titanium membrane (3D-PFTM) to enhance mechanical properties and ability of bone regeneration on the peri-implant bone defect. 3D-PFTMs by new mechanically compressive molding technology and manually shaped- (MS-) PFTMs by hand manipulation were applied in artificial peri-implant bone defect model for static compressive load test and cyclic fatigue load test. In 12 implants installed in the mandibular of three beagle dogs, six 3D-PFTMs, and six collagen membranes (CM) randomly were applied to 2.5 mm peri-implant buccal bone defect with particulate bone graft materials for guided bone regeneration (GBR). The 3D-PFTM group showed about 7.4 times higher mechanical stiffness and 5 times higher fatigue resistance than the MS-PFTM group. The levels of the new bone area (NBA, %), the bone-to-implant contact (BIC, %), distance from the new bone to the old bone (NB-OB, %), and distance from the osseointegration to the old bone (OI-OB, %) were significantly higher in the 3D-PFTM group than the CM group (p bone grafts, which led to highly efficient bone regeneration. PMID:29018818

  12. Mathematical model for osteobstruction in bone regeneration mechanisms: a headway in skeletal tissue engineering.

    Science.gov (United States)

    Ogunsalu, C; Arunaye, F I; Ezeokoli, C; Gardner, M; Rohrer, M; Prasad, H

    2012-11-01

    In this paper, we formulate a mathematical model for the evaluation of parameters responsible for the retardation and eventual acceleration of bone regeneration on the contralateral side of the mandible of experimental animals, following the discovery of a new mechanism of bone regeneration called the osteobstruction mechanism (a negative mechanism of bone regeneration as opposed to the well established and extensively documented positive mechanisms such as osteogenesis, osteoinduction and osteoconduction). This osteobstructive mechanism was demonstrated by episodes of overtaking and reovertaking on single photon emission computed tomography (SPECT) following evaluation of osteoblastic activities in a sequential animal experiment to validate both the Ogunsalu sandwich technique (a double guided tissue technique; D-GTR) and the interceed membrane technique (a single guided tissue regeneration technique; S-GTR) utilizing SPECT, histological and histomorphometric evaluation. This work is now given special attention in terms of mathematical analysis because of limited experimental observations since experiments cannot be observed infinitely. Mathematical modelling is as such essential to generalize the results of this osteobstructive mechanism in bone regeneration. We utilize the Fisher's equation to describe bone cell mobilization during bone regeneration by two different techniques: the Ogunsalu sandwich bone regeneration technique (D-GTR) and the S-GTR.

  13. The Components of Bone and What They Can Teach Us about Regeneration

    Directory of Open Access Journals (Sweden)

    Bach Quang Le

    2017-12-01

    Full Text Available The problem of bone regeneration has engaged both physicians and scientists since the beginning of medicine. Not only can bone heal itself following most injuries, but when it does, the regenerated tissue is often indistinguishable from healthy bone. Problems arise, however, when bone does not heal properly, or when new tissue is needed, such as when two vertebrae are required to fuse to stabilize adjacent spine segments. Despite centuries of research, such procedures still require improved therapeutic methods to be devised. Autologous bone harvesting and grafting is currently still the accepted benchmark, despite drawbacks for clinicians and patients that include limited amounts, donor site morbidity, and variable quality. The necessity for an alternative to this “gold standard” has given rise to a bone-graft and substitute industry, with its central conundrum: what is the best way to regenerate bone? In this review, we dissect bone anatomy to summarize our current understanding of its constituents. We then look at how various components have been employed to improve bone regeneration. Evolving strategies for bone regeneration are then considered.

  14. Stem cells applications in bone and tooth repair and regeneration: New insights, tools, and hopes.

    Science.gov (United States)

    Abdel Meguid, Eiman; Ke, Yuehai; Ji, Junfeng; El-Hashash, Ahmed H K

    2018-03-01

    The exploration of stem and progenitor cells holds promise for advancing our understanding of the biology of tissue repair and regeneration mechanisms after injury. This will also help in the future use of stem cell therapy for the development of regenerative medicine approaches for the treatment of different tissue-species defects or disorders such as bone, cartilages, and tooth defects or disorders. Bone is a specialized connective tissue, with mineralized extracellular components that provide bones with both strength and rigidity, and thus enable bones to function in body mechanical supports and necessary locomotion process. New insights have been added to the use of different types of stem cells in bone and tooth defects over the last few years. In this concise review, we briefly describe bone structure as well as summarize recent research progress and accumulated information regarding the osteogenic differentiation of stem cells, as well as stem cell contributions to bone repair/regeneration, bone defects or disorders, and both restoration and regeneration of bones and cartilages. We also discuss advances in the osteogenic differentiation and bone regeneration of dental and periodontal stem cells as well as in stem cell contributions to dentine regeneration and tooth engineering. © 2017 Wiley Periodicals, Inc.

  15. 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

    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

  16. 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

    and 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 defects covered by 2 Polyglactin 910 membranes. Defects covered by 1 ePTFE or 1 Polyglactin 910 membranes revealed 10% or 18% bone regeneration, respectively. The control group regenerated 14%. The major difference of the estimates was caused by real difference between specimens, i.e. biologic variation...

  17. Network-Based Method for Identifying Co- Regeneration Genes in Bone, Dentin, Nerve and Vessel Tissues.

    Science.gov (United States)

    Chen, Lei; Pan, Hongying; Zhang, Yu-Hang; Feng, Kaiyan; Kong, XiangYin; Huang, Tao; Cai, Yu-Dong

    2017-10-02

    Bone and dental diseases are serious public health problems. Most current clinical treatments for these diseases can produce side effects. Regeneration is a promising therapy for bone and dental diseases, yielding natural tissue recovery with few side effects. Because soft tissues inside the bone and dentin are densely populated with nerves and vessels, the study of bone and dentin regeneration should also consider the co-regeneration of nerves and vessels. In this study, a network-based method to identify co-regeneration genes for bone, dentin, nerve and vessel was constructed based on an extensive network of protein-protein interactions. Three procedures were applied in the network-based method. The first procedure, searching, sought the shortest paths connecting regeneration genes of one tissue type with regeneration genes of other tissues, thereby extracting possible co-regeneration genes. The second procedure, testing, employed a permutation test to evaluate whether possible genes were false discoveries; these genes were excluded by the testing procedure. The last procedure, screening, employed two rules, the betweenness ratio rule and interaction score rule, to select the most essential genes. A total of seventeen genes were inferred by the method, which were deemed to contribute to co-regeneration of at least two tissues. All these seventeen genes were extensively discussed to validate the utility of the method.

  18. Development of a Novel Degradation-Controlled Magnesium-Based Regeneration Membrane for Future Guided Bone Regeneration (GBR Therapy

    Directory of Open Access Journals (Sweden)

    Da-Jun Lin

    2017-11-01

    Full Text Available This study aimed to develop and evaluate the ECO-friendly Mg-5Zn-0.5Zr (ECO505 alloy for application in dental-guided bone regeneration (GBR. The microstructure and surface properties of biomedical Mg materials greatly influence anti-corrosion performance and biocompatibility. Accordingly, for the purpose of microstructure and surface modification, heat treatments and surface coatings were chosen to provide varied functional characteristics. We developed and integrated both an optimized solution heat-treatment condition and surface fluoride coating technique to fabricate a Mg-based regeneration membrane. The heat-treated Mg regeneration membrane (ARRm-H380 and duplex-treated regeneration membrane group (ARRm-H380-F24 h were thoroughly investigated to characterize the mechanical properties, as well as the in vitro corrosion and in vivo degradation behaviors. Significant enhancement in ductility and corrosion resistance for the ARRm-H380 was obtained through the optimized solid-solution heat treatment; meanwhile, the corrosion resistance of ARRm-H380-F24 h showed further improvement, resulting in superior substrate integrity. In addition, the ARRm-H380 provided the proper amount of Mg-ion concentration to accelerate bone growth in the early stage (more than 80% new bone formation. From a specific biomedical application point of view, these research results point out a successful manufacturing route and suggest that the heat treatment and duplex treatment could be employed to offer custom functional regeneration membranes for different clinical patients.

  19. Alkali-free bioactive glasses for bone regeneration =

    Science.gov (United States)

    Kapoor, Saurabh

    Bioactive glasses and glass-ceramics are a class of third generation biomaterials which elicit a special response on their surface when in contact with biological fluids, leading to strong bonding to living tissues. The purpose of the present study was to develop diopside based alkali-free bioactive glasses in order to achieve good sintering behaviour, high bioactivity, and a dissolution/ degradation rates compatible with the target applications in bone regeneration and tissue engineering. Another aim was to understand the structure-property relationships in the investigated bioactive glasses. In this quest, various glass compositions within the Diopside (CaMgSi2O6) - Fluorapatite (Ca5(PO4)3F) - Tricalcium phosphate (3CaO•P2O5) system have been investigated. All the glasses were prepared by melt-quenching technique and characterized by a wide array of complementary characterization techniques. The glass-ceramics were produced by sintering of glass powders compacts followed by a suitable heat treatment to promote the nucleation and crystallization phenomena. Furthermore, selected parent glass compositions were doped with several functional ions and an attempt to understand their effects on the glass structure, sintering ability and on the in vitro bio-degradation and biomineralization behaviours of the glasses was made. The effects of the same variables on the devitrification (nucleation and crystallization) behaviour of glasses to form bioactive glass-ceramics were also investigated. Some of the glasses exhibited high bio-mineralization rates, expressed by the formation of a surface hydroxyapatite layer within 1-12 h of immersion in a simulated body fluid (SBF) solution. All the glasses showed relatively lower degradation rates in comparison to that of 45S5 Bioglass. Some of the glasses showed very good in vitro behaviour and the glasses co-doped with zinc and strontium showed an in vitro dose dependent behaviour. The as-designed bioactive glasses and glass

  20. Decellularization and Delipidation Protocols of Bovine Bone and Pericardium for Bone Grafting and Guided Bone Regeneration Procedures.

    Directory of Open Access Journals (Sweden)

    Chiara Gardin

    Full Text Available The combination of bone grafting materials with guided bone regeneration (GBR membranes seems to provide promising results to restore bone defects in dental clinical practice. In the first part of this work, a novel protocol for decellularization and delipidation of bovine bone, based on multiple steps of thermal shock, washes with detergent and dehydration with alcohol, is described. This protocol is more effective in removal of cellular materials, and shows superior biocompatibility compared to other three methods tested in this study. Furthermore, histological and morphological analyses confirm the maintenance of an intact bone extracellular matrix (ECM. In vitro and in vivo experiments evidence osteoinductive and osteoconductive properties of the produced scaffold, respectively. In the second part of this study, two methods of bovine pericardium decellularization are compared. The osmotic shock-based protocol gives better results in terms of removal of cell components, biocompatibility, maintenance of native ECM structure, and host tissue reaction, in respect to the freeze/thaw method. Overall, the results of this study demonstrate the characterization of a novel protocol for the decellularization of bovine bone to be used as bone graft, and the acquisition of a method to produce a pericardium membrane suitable for GBR applications.

  1. Guided bone regeneration with tripolyphosphate cross-linked asymmetric chitosan membrane.

    Science.gov (United States)

    Ma, Shiqing; Chen, Zhen; Qiao, Feng; Sun, Yingchun; Yang, Xiaoping; Deng, Xuliang; Cen, Lian; Cai, Qing; Wu, Mingyao; Zhang, Xu; Gao, Ping

    2014-12-01

    The objective of this study was to prepare a novel asymmetric chitosan guided bone regeneration (GBR) membrane, which is composed of a dense layer isolating the bone defect from the invasion of surrounding connective fibrous tissue and a loose layer which can improve cell adhesion and stabilize blood clots, thus guided bone regeneration. The chitosan membrane was fabricated through liquid nitrogen quencher combined with lyophilization and cross-linked by sodium tripolyphosphate (TPP). The physical properties of asymmetric chitosan membrane were measured by scanning electron microscope (SEM), Fourier-transform infrared (FTIR), x-ray diffraction (XRD) and tensile test machine. MTT assay and Live/Dead cell staining for MC3T3-E1 osteoblasts cultured on the membrane were used to characterize the biocompatibility of the membrane. In animal experiments, full-thickness and critical sized skull defects were made to evaluate the effect of the membrane on bone regeneration. The results of this study indicate that the asymmetric chitosan membrane can be built and cross-linked by TPP to enhance the tensile strength of the membrane. In vitro experiment showed that no significant numbers of dead cells were detected on the chitosan membrane, indicating that the membrane had good biocompatibility. In animal experiments, the chitosan membrane had faster new bone formation, showing the capability to enhance bone regeneration. The chitosan membrane prepared in this study has an asymmetric structure; its tensile strength, biodegradation and biocompatibility fulfil the requirements of guided bone regeneration. Therefore, the asymmetric chitosan membrane is a promising GBR membrane for bone regeneration. Guided bone regeneration (GBR) is an effective method for healing bone defects caused by periodontitis and implantitis, in which GBR membrane is a key biomaterial. Copyright © 2014 Elsevier Ltd. All rights reserved.

  2. The application of nanomaterials in controlled drug delivery for bone regeneration.

    Science.gov (United States)

    Shi, Shuo; Jiang, Wenbao; Zhao, Tianxiao; Aifantis, Katerina E; Wang, Hui; Lin, Lei; Fan, Yubo; Feng, Qingling; Cui, Fu-zhai; Li, Xiaoming

    2015-12-01

    Bone regeneration is a complicated process that involves a series of biological events, such as cellular recruitment, proliferation and differentiation, and so forth, which have been found to be significantly affected by controlled drug delivery. Recently, a lot of research studies have been launched on the application of nanomaterials in controlled drug delivery for bone regeneration. In this article, the latest research progress in this area regarding the use of bioceramics-based, polymer-based, metallic oxide-based and other types of nanomaterials in controlled drug delivery for bone regeneration are reviewed and discussed, which indicates that the controlling drug delivery with nanomaterials should be a very promising treatment in orthopedics. Furthermore, some new challenges about the future research on the application of nanomaterials in controlled drug delivery for bone regeneration are described in the conclusion and perspectives part. Copyright © 2015 Wiley Periodicals, Inc.

  3. The zebrafish as a model for tissue regeneration and bone remodelling

    NARCIS (Netherlands)

    Sharif, Faiza

    2011-01-01

    The aim of this thesis was to investigate the expression, and function of genes associated with remodelling and regeneration in the zebrafish model species. Here, we studied the role of cell populations, defined by their expression of markers, in bone regeneration and remodelling in zebrafish

  4. Delivery of bone morphogenetic protein-2 and substance P using graphene oxide for bone regeneration

    Directory of Open Access Journals (Sweden)

    La WG

    2014-05-01

    Full Text Available Wan-Geun La,1 Min Jin,1 Saibom Park,1,2 Hee-Hun Yoon,1 Gun-Jae Jeong,1 Suk Ho Bhang,1 Hoyoung Park,1,2 Kookheon Char,1,2 Byung-Soo Kim1,31School of Chemical and Biological Engineering, Seoul National University, Seoul, Republic of Korea; 2The National Creative Research Initiative Center for Intelligent Hybrids, Seoul National University, Seoul, Republic of Korea; 3Institute of Bioengineering, Institute of Chemical Processes, Engineering Research Institute, Seoul National University, Seoul, Republic of KoreaAbstract: In this study, we demonstrate that graphene oxide (GO can be used for the delivery of bone morphogenetic protein-2 (BMP-2 and substance P (SP, and that this delivery promotes bone formation on titanium (Ti implants that are coated with GO. GO coating on Ti substrate enabled a sustained release of BMP-2. BMP-2 delivery using GO-coated Ti exhibited a higher alkaline phosphatase activity in bone-forming cells in vitro compared with bare Ti. SP, which is known to recruit mesenchymal stem cells (MSCs, was co-delivered using Ti or GO-coated Ti to further promote bone formation. SP induced the migration of MSCs in vitro. The dual delivery of BMP-2 and SP using GO-coated Ti showed the greatest new bone formation on Ti implanted in the mouse calvaria compared with other groups. This approach may be useful to improve osteointegration of Ti in dental or orthopedic implants.Keywords: bone morphogenetic protein-2, bone regeneration, graphene oxides, stem cell recruitment, substance P

  5. The use of titanium plates for bone regeneration with root form implants: a case report.

    Science.gov (United States)

    Maksoud, M A

    1999-01-01

    In reconstruction of the partially and totally edentulous ridges that have bony defects due to old trauma or longstanding atrophy, it is necessary to reconstruct both the width and height of the alveolar ridge. This clinical case report covers bone regeneration prior to implant placement to achieve an aesthetic and functional base for prosthetic restoration. The focus of this report will be on bone regeneration, which does not depend on the utilization of a barrier membrane.

  6. 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.

  7. 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.

  8. Demineralized Freeze-Dried Bovine Cortical Bone: Its Potential for Guided Bone Regeneration Membrane

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    David B. Kamadjaja

    2017-01-01

    Full Text Available Background. Bovine pericardium collagen membrane (BPCM had been widely used in guided bone regeneration (GBR whose manufacturing process usually required chemical cross-linking to prolong its biodegradation. However, cross-linking of collagen fibrils was associated with poorer tissue integration and delayed vascular invasion. Objective. This study evaluated the potential of bovine cortical bone collagen membrane for GBR by evaluating its antigenicity potential, cytotoxicity, immune and tissue response, and biodegradation behaviors. Material and Methods. Antigenicity potential of demineralized freeze-dried bovine cortical bone membrane (DFDBCBM was done with histology-based anticellularity evaluation, while cytotoxicity was analyzed using MTT Assay. Evaluation of immune response, tissue response, and biodegradation was done by randomly implanting DFDBCBM and BPCM in rat’s subcutaneous dorsum. Samples were collected at 2, 5, and 7 days and 7, 14, 21, and 28 days for biocompatibility and tissue response-biodegradation study, respectively. Result. DFDBCBM, histologically, showed no retained cells; however, it showed some level of in vitro cytotoxicity. In vivo study exhibited increased immune response to DFDBCBM in early healing phase; however, normal tissue response and degradation rate were observed up to 4 weeks after DFDBCBM implantation. Conclusion. Demineralized freeze-dried bovine cortical bone membrane showed potential for clinical application; however, it needs to be optimized in its biocompatibility to fulfill all requirements for GBR membrane.

  9. Effects of directly autotransplanted tibial bone marrow aspirates on bone regeneration and osseointegration of dental implants.

    Science.gov (United States)

    Payer, Michael; Lohberger, Birgit; Strunk, Dirk; Reich, Karoline M; Acham, Stephan; Jakse, Norbert

    2014-04-01

    Aim of the pilot trial was to evaluate applicability and effects of directly autotransplanted tibial bone marrow (BM) aspirates on the incorporation of porous bovine bone mineral in a sinus lift model and on the osseointegration of dental implants. Six edentulous patients with bilaterally severely resorbed maxillae requiring sinus augmentation and implant treatment were included. During surgery, tibial BM was harvested and added to bone substitute material (Bio-Oss(®) ) at the randomly selected test site. At control sites, augmentation was performed with Bio-Oss(®) alone. The cellular content of each BM aspirate was checked for multipotency and surface antigen expression as quality control. Histomorphometric analysis of biopsies from the augmented sites after 3 and 6 months (during implantation) was used to evaluate effects on bone regeneration. Osseointegration of implants was evaluated with Periotest(®) and radiographic means. Multipotent cellular content in tibial BM aspirates was comparable to that in punctures from the iliac crest. No significant difference in amount of new bone formation and the integration of bone substitute particles was detected histomorphometrically. Periotest(®) values and radiographs showed successful osseointegration of inserted implants at all sites. Directly autotransplanted tibial BM aspirates did not show beneficial regenerative effects in the small study population (N = 6) of the present pilot trial. However, the proximal tibia proved to be a potential donor site for small quantities of BM. Future trials should clarify whether concentration of tibial BM aspirates could effect higher regenerative potency. © 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

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

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    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.

  11. The role of rhFGF-2 soaked polymer membrane for enhancement of guided bone regeneration.

    Science.gov (United States)

    Lee, Sang-Hoon; Park, Young-Bum; Moon, Hong-Seok; Shim, June-Sung; Jung, Han-Sung; Kim, Hyung Jun; Chung, Moon-Kyu

    2017-08-02

    The purposes of this study are to confirm the role of Fibroblast Growth Factor-2 (FGF-2) in bone regeneration by adding various concentrations of FGF-2 to the collagen membrane and applying it to the Biphasic Calcium Phosphate (BCP) bone graft site for guided bone regeneration, to explore the potential of collagen membrane as FGF-2 carrier, and to determine the optimum FGF concentration for enhancement of bone regeneration. Four bone defects of 8 mm in diameter were created in 18 New Zealand rabbit calvaria. After BCP bone graft, graft material was covered with collagen membranes adding various concentration of FGF-2. The concentration of FGF-2 was set at 1.0, 0.5, 0.1 mg/ml, and same amount of saline was used in the control group. To confirm the bone regeneration over time, six New Zealand rabbits were sacrificed each at 2, 4, and 12 weeks, and the amounts of new bone and residual bone graft material were analyzed by histologic and histomorphometric analysis. Qualitative analyses are also conducted through immunohistochemistry, Tetrate-resistant acid phosphatase (TRAP) stain and Russell-Movat pentachrome stain. As the healing period increased, the formation of new bone increased and the amount of residual graft material decreased in all experimental groups. Immunohistochemistry, TRAP staining and pentachrome staining further showed that the addition of FGF-2 promoted bone regeneration in all experimental groups. It was also confirmed that polymer collagen membrane can be used as a useful carrier of FGF-2 when enhanced early stage of new bone formation is required.

  12. Molecular cues for development and regeneration of salivary glands

    Science.gov (United States)

    Liu, Fei; Wang, Songlin

    2015-01-01

    The hypofunction of salivary glands caused by Sjögren’s Syndrome or radiotherapy for head and neck cancer significantly compromises the quality of life of millions patients. Currently no curative treatment is available for the irreversible hyposalivation, whereas regenerative strategies targeting salivary stem/progenitor cells are promising. However, the success of these strategies is constrained by the lack of insights on the molecular cues of salivary gland regeneration. Recent advances in the molecular controls of salivary gland morphogenesis provided valuable clues for identifying potential regenerative cues. A complicated network of signaling molecules between epithelia, mesenchyme, endothelia, extracellular matrix and innervating nerves orchestrate the salivary gland organogenesis. Here we discuss the roles of several cross-talking intercellular signaling pathways, i.e., FGF, Wnt, Hedgehog, Eda, Notch, Chrm1/HB-EGF and Laminin/Integrin pathways, in the development of salivary glands and their potentials to promote salivary regeneration. PMID:24189993

  13. Nanoparticles of cobalt-substituted hydroxyapatite in regeneration of mandibular osteoporotic bones.

    Science.gov (United States)

    Ignjatović, Nenad; Ajduković, Zorica; Savić, Vojin; Najman, Stevo; Mihailović, Dragan; Vasiljević, Perica; Stojanović, Zoran; Uskoković, Vuk; Uskoković, Dragan

    2013-02-01

    Indications exist that paramagnetic calcium phosphates may be able to promote regeneration of bone faster than their regular, diamagnetic counterparts. In this study, analyzed was the influence of paramagnetic cobalt-substituted hydroxyapatite nanoparticles on osteoporotic alveolar bone regeneration in rats. Simultaneously, biocompatibility of the material was tested in vitro, on osteoblastic MC3T3-E1 and epithelial Caco-2 cells in culture. The material was shown to be biocompatible and nontoxic when added to epithelial monolayers in vitro, while it caused a substantial decrease in the cell viability as well as deformation of the cytoskeleton and cell morphology when incubated with the osteoblastic cells. In the course of 6 months after the implantation of the material containing different amounts of cobalt, ranging from 5 to 12 wt%, in the osteoporotic alveolar bone of the lower jaw, the following parameters were investigated: histopathological parameters, alkaline phosphatase and alveolar bone density. The best result in terms of osteoporotic bone tissue regeneration was observed for hydroxyapatite nanoparticles with the largest content of cobalt ions. The histological analysis showed a high level of reparatory ability of the nanoparticulate material implanted in the bone defect, paralleled by a corresponding increase in the alveolar bone density. The combined effect of growth factors from autologous plasma admixed to cobalt-substituted hydroxyapatite was furthermore shown to have a crucial effect on the augmented osteoporotic bone regeneration upon the implantation of the biomaterial investigated in this study.

  14. Survival and regeneration of deep-freeze preserved autologous cranial bones after cranioplasty.

    Science.gov (United States)

    Lu, Yi; Hui, Guozhen; Liu, Fengqiang; Wang, Zhengan; Tang, Yuming; Gao, Shuxing

    2012-04-01

    After decompressive craniectomy, a deep-freeze-preserved autologous cranial bone graft can be used for cranioplasty to avoid immunoreaction against an artificial patch material. Autologous cranial bone grafts not only have better physical properties, such as heat conduction, compared to artificial patch materials, but they also have the advantages of a lower medical cost and satisfactory physical flexibility. The discussion over (99)Tc(m)-MDP SPECT static cranial bone tomography in the diagnosis of survival and regeneration in deep-freeze preservation autologous cranial bones after cranioplasty is valuable. Objective. To investigate whether deep-freeze-preserved autologous cranial bone grafts could survive and regenerate after autologous reimplantation. The method of cranial bone preservation involved removing the cranial graft and sealing it in a double-layer sterile plastic bag under sterile surgical conditions. On the day of the cranioplasty operation, the cranial bone graft was disinfected by immersing it in 3% povidone-iodine for 30 minutes. At short-term (2 weeks), medium-term (3 months), and long-term (12 months) postoperative follow-up visits, (99)Tc(m)-MDP SPECT static cranial bone tomography was used to examine the reimplanted cranial bone. Results. There were no postoperative infections or seromas in all 16 cases. Two weeks following cranial bone graft reimplantation, the SPECT tomography showed some radioactivity uptake in the reimplanted cranial bone graft, which was lower than that in the cranial bone on the healthy side. At 3 months and 12 months after the operation, the radioactivity uptake in the reimplanted cranial bone graft was the same as that in the cranial bone on the healthy side. X-ray films showed blurred sutures in the reimplanted cranial bone graft at 12 months after surgery. Reimplanted deep-freeze-preserved autologous cranial bone can survive in the short term and regenerate in the medium and long terms.

  15. New nano-hydroxyapatite in bone defect regeneration: A histological study in rats.

    Science.gov (United States)

    Kubasiewicz-Ross, Paweł; Hadzik, Jakub; Seeliger, Julia; Kozak, Karol; Jurczyszyn, Kamil; Gerber, Hanna; Dominiak, Marzena; Kunert-Keil, Christiane

    2017-09-01

    Many types of bone substitute materials are available on the market. Researchers are refining new bone substitutes to make them comparable to autologous grafting materials in treatment of bone defects. The purpose of the study was to evaluate the osseoconductive potential and bone defect regeneration in rat calvaria bone defects treated with new synthetic nano-hydroxyapatite. The study was performed on 30 rats divided into 5 equal groups. New preproduction of experimental nano-hydroxyapatite material by NanoSynHap (Poznań, Poland) was tested and compared with commercially available materials. Five mm critical size defects were created and filled with the following bone grafting materials: 1) Geistlich Bio-Oss ® ; 2) nano-hydroxyapatite+β-TCP; 3) nano-hydroxyapatite; 4) nano-hydroxyapatite+collagen membrane. The last group served as controls without any augmentation. Bone samples from calvaria were harvested for histological and micro-ct evaluation after 8 weeks. New bone formation was observed in all groups. Histomorphometric analysis revealed an amount of regenerated bone between 34.2 and 44.4% in treated bone defects, whereas only 13.0% regenerated bone was found in controls. Interestingly, in group 3, no significant particles of the nano-HA material were found. In contrast, residual bone substitute material could be detected in all other test groups. Micro-CT study confirmed the results of the histological examinations. The new nano-hydroxyapatite provides comparable results to other grafts in the field of bone regeneration. Copyright © 2017 Elsevier GmbH. All rights reserved.

  16. Self-fitting shape memory polymer foam inducing bone regeneration: A rabbit femoral defect study.

    Science.gov (United States)

    Xie, Ruiqi; Hu, Jinlian; Hoffmann, Oskar; Zhang, Yuanchi; Ng, Frankie; Qin, Tingwu; Guo, Xia

    2018-04-01

    Although tissue engineering has been attracted greatly for healing of critical-sized bone defects, great efforts for improvement are still being made in scaffold design. In particular, bone regeneration would be enhanced if a scaffold precisely matches the contour of bone defects, especially if it could be implanted into the human body conveniently and safely. In this study, polyurethane/hydroxyapatite-based shape memory polymer (SMP) foam was fabricated as a scaffold substrate to facilitate bone regeneration. The minimally invasive delivery and the self-fitting behavior of the SMP foam were systematically evaluated to demonstrate its feasibility in the treatment of bone defects in vivo. Results showed that the SMP foam could be conveniently implanted into bone defects with a compact shape. Subsequently, it self-matched the boundary of bone defects upon shape-recovery activation in vivo. Micro-computed tomography determined that bone ingrowth initiated at the periphery of the SMP foam with a constant decrease towards the inside. Successful vascularization and bone remodeling were also demonstrated by histological analysis. Thus, our results indicate that the SMP foam demonstrated great potential for bone regeneration. Copyright © 2018 Elsevier B.V. All rights reserved.

  17. Antibacterial Membrane with a Bone-Like Structure for Guided Bone Regeneration

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    YuYuan Zhang

    2015-01-01

    Full Text Available An antibacterial membrane with a bone-like structure was developed for guided bone regeneration (GBR by mineralising acellular bovine pericardium (ABP and loading it with the antibiotic minocycline. The bovine pericardium (BP membrane was processed using physical and chemical methods to remove the cellular components and obtain ABP membranes. Then, the ABP membranes were biomimetically mineralised using a calcium phosphate-loaded agarose hydrogel system aided by electrophoresis. Minocycline was adsorbed to the mineralised ABP membrane, and the release profile in vitro was studied. The membranes were characterised through scanning electron microscopy, diffuse reflectance-Fourier transform infrared spectroscopy, and X-ray diffraction. Results showed that the ABP membrane had an asymmetric structure with a layer of densely arranged and irregularly aligned collagen fibrils. Collagen fibrils were calcified with the formation of intrafibrillar and interfibrillar hydroxyapatites similar to the bone structure. Minocycline was incorporated into the mineralised collagen membrane and could be released in vitro. This process endowed the membrane with an antibacterial property. This novel composite membrane offers promising applications in bioactive GBR.

  18. Production of new 3D scaffolds for bone tissue regeneration by rapid prototyping.

    Science.gov (United States)

    Fradique, R; Correia, T R; Miguel, S P; de Sá, K D; Figueira, D R; Mendonça, A G; Correia, I J

    2016-04-01

    The incidence of bone disorders, whether due to trauma or pathology, has been trending upward with the aging of the worldwide population. The currently available treatments for bone injuries are rather limited, involving mainly bone grafts and implants. A particularly promising approach for bone regeneration uses rapid prototyping (RP) technologies to produce 3D scaffolds with highly controlled structure and orientation, based on computer-aided design models or medical data. Herein, tricalcium phosphate (TCP)/alginate scaffolds were produced using RP and subsequently their physicochemical, mechanical and biological properties were characterized. The results showed that 60/40 of TCP and alginate formulation was able to match the compression and present a similar Young modulus to that of trabecular bone while presenting an adequate biocompatibility. Moreover, the biomineralization ability, roughness and macro and microporosity of scaffolds allowed cell anchoring and proliferation at their surface, as well as cell migration to its interior, processes that are fundamental for osteointegration and bone regeneration.

  19. Demineralized Bone Matrix Scaffolds Modified by CBD-SDF-1α Promote Bone Regeneration via Recruiting Endogenous Stem Cells.

    Science.gov (United States)

    Shi, Jiajia; Sun, Jie; Zhang, Wen; Liang, Hui; Shi, Qin; Li, Xiaoran; Chen, Yanyan; Zhuang, Yan; Dai, Jianwu

    2016-10-07

    The reconstruction of bone usually depends on substitute transplantation, which has drawbacks including the limited bone substitutes available, comorbidity, immune rejection, and limited endogenous bone regeneration. Here, we constructed a functionalized bone substitute by combining application of the demineralized bone matrix (DBM) and collagen-binding stromal-cell-derived factor-1α (CBD-SDF-1α). DBM was a poriferous and biodegradable bone substitute, derived from bovine bone and consisting mainly of collagen. CBD-SDF-1α could bind to collagen and be controllably released from the DBM to mobilize stem cells. In a rat femur defect model, CBD-SDF-1α-modified DBM scaffolds could efficiently mobilize CD34 + and c-kit + endogenous stem cells homing to the injured site at 3 days after implantation. According to the data from micro-CT, CBD-SDF-1α-modified DBM scaffolds could help the bone defects rejoin with mineralization accumulated and bone volume expanded. Interestingly, osteoprotegerin (OPG) and osteopontin (OPN) were highly expressed in CBD-SDF-1α group at an early time after implantation, while osteocalcin (OCN) was more expanded. H&E and Masson's trichrome staining showed that the CBD-SDF-1α-modified DBM scaffold group had more osteoblasts and that the bone defect rejoined earlier. The ultimate strength of the regenerated bone was investigated by three-point bending, showing that the CBD-SDF-1α group had superior strength. In conclusion, CBD-SDF-1α-modified DBM scaffolds could promote bone regeneration by recruiting endogenous stem cells.

  20. Histochemical examination of systemic administration of eldecalcitol combined with guided bone regeneration for bone defect restoration in rats.

    Science.gov (United States)

    Han, Xiuchun; Du, Juan; Liu, Di; Liu, Hongrui; Amizuka, Norio; Li, Minqi

    2017-02-01

    The aim of this experiment was to elucidate the histological alterations after systemic administration of eldecalcitol (ELD) combined with guided bone regeneration during the restoration of bone defect healing in rats. The femurs of 8-week-old Wister rats were used to generate bone defect models. The defect was covered with a collagen membrane, and ELD group was administrated with eldecalcitol (50 ng/kg body weight) intragastrically once every other day. Femora were harvested at 1, 2, 4 and 8 weeks post-surgery. Decalcify tissue slices were made and used for histological and immunohistochemical examination. Bone biomarkers of RANKL, OPG and osteocalcin (OCN) were detected by western blot. The results revealed that the system administration of ELD could improve new bone formation demonstrated by the increased bone volume/tissue volume ratio and accelerated mineralization. ELD suppressed osteoclastic bone resorption by reducing the number of osteoclasts, decreasing the expression of cathepsin-K and the ratio of RANKL/OPG at the early stage of bone defect restoration (1 and 2 weeks) and upregulating OCN expression at the later stage of bone defect healing (4 and 8 weeks). These data suggested that systemic administration of eldecalcitol accelerated bone formation and promoted bone maturation by decreasing bone resorption and promoting bone mineralization during bone defect restoration.

  1. Combination of BMP-2-releasing gelatin/β-TCP sponges with autologous bone marrow for bone regeneration of X-ray-irradiated rabbit ulnar defects.

    Science.gov (United States)

    Yamamoto, Masaya; Hokugo, Akishige; Takahashi, Yoshitake; Nakano, Takayoshi; Hiraoka, Masahiro; Tabata, Yasuhiko

    2015-07-01

    The objective of this study is to evaluate the feasibility of gelatin sponges incorporating β-tricalcium phosphate (β-TCP) granules (gelatin/β-TCP sponges) to enhance bone regeneration at a segmental ulnar defect of rabbits with X-ray irradiation. After X-ray irradiation of the ulnar bone, segmental critical-sized defects of 20-mm length were created, and bone morphogenetic protein-2 (BMP-2)-releasing gelatin/β-TCP sponges with or without autologous bone marrow were applied to the defects to evaluate bone regeneration. Both gelatin/β-TCP sponges containing autologous bone marrow and BMP-2-releasing sponges enhanced bone regeneration at the ulna defect to a significantly greater extent than the empty sponges (control). However, in the X-ray-irradiated bone, the bone regeneration either by autologous bone marrow or BMP-2 was inhibited. When combined with autologous bone marrow, the BMP-2 exhibited significantly high osteoinductivity, irrespective of the X-ray irradiation. The bone mineral content at the ulna defect was similar to that of the intact bone. It is concluded that the combination of bone marrow with the BMP-2-releasing gelatin/β-TCP sponge is a promising technique to induce bone regeneration at segmental bone defects after X-ray irradiation. Copyright © 2015 Elsevier Ltd. All rights reserved.

  2. 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.

  3. Magnetic forces and magnetized biomaterials provide dynamic flux information during bone regeneration.

    Science.gov (United States)

    Russo, Alessandro; Bianchi, Michele; Sartori, Maria; Parrilli, Annapaola; Panseri, Silvia; Ortolani, Alessandro; Sandri, Monica; Boi, Marco; Salter, Donald M; Maltarello, Maria Cristina; Giavaresi, Gianluca; Fini, Milena; Dediu, Valentin; Tampieri, Anna; Marcacci, Maurilio

    2016-03-01

    The fascinating prospect to direct tissue regeneration by magnetic activation has been recently explored. In this study we investigate the possibility to boost bone regeneration in an experimental defect in rabbit femoral condyle by combining static magnetic fields and magnetic biomaterials. NdFeB permanent magnets are implanted close to biomimetic collagen/hydroxyapatite resorbable scaffolds magnetized according to two different protocols . Permanent magnet only or non-magnetic scaffolds are used as controls. Bone tissue regeneration is evaluated at 12 weeks from surgery from a histological, histomorphometric and biomechanical point of view. The reorganization of the magnetized collagen fibers under the effect of the static magnetic field generated by the permanent magnet produces a highly-peculiar bone pattern, with highly-interconnected trabeculae orthogonally oriented with respect to the magnetic field lines. In contrast, only partial defect healing is achieved within the control groups. We ascribe the peculiar bone regeneration to the transfer of micro-environmental information, mediated by collagen fibrils magnetized by magnetic nanoparticles, under the effect of the static magnetic field. These results open new perspectives on the possibility to improve implant fixation and control the morphology and maturity of regenerated bone providing "in site" forces by synergically combining static magnetic fields and biomaterials.

  4. Enhanced guided bone regeneration by asymmetrically porous PCL/pluronic F127 membrane and ultrasound stimulation.

    Science.gov (United States)

    Oh, Se Heang; Kim, Tae Ho; Chun, So Young; Park, Eui Kyun; Lee, Jin Ho

    2012-01-01

    Recently, we developed a novel method for fabricating a guided bone regeneration (GBR) membrane with an asymmetrical pore structure and hydrophilicity by an immersion precipitation method. Results from an animal study, in a cranial defect model in rats, indicated that the unique asymmetrically porous GBR membrane would provide a good environment for bone regeneration. In the present study, we applied low intensity pulsed ultrasound as a simple and non-invasive stimulus to an asymmetrically porous polycaprolactone (PCL)/Pluronic F127 GBR membrane-implanted site transcutaneously in rats to investigate the feasibility of using ultrasound to stimulate enhanced bone regeneration through the membrane. It was observed that the ultrasound-stimulated PCL/F127 GBR membrane group had much faster bone regeneration behavior than a PCL/F127 membrane group w/o ultrasound or a control group (w/o membrane and ultrasound). The greater bone regeneration behavior in the GBR membrane/ultrasound group may be caused by a synergistic effect of the asymmetrically porous PCL/F127 membrane with unique properties (selective permeability, hydrophilicity and osteoconductivity), and the stimulatory effect of ultrasound (induction of angiogenesis and osteogenesis of cells).

  5. [Low intensity pulsed ultrasound irradiating combined with guided bone regeneration for promoting the repair effect of periodontal bone defect].

    Science.gov (United States)

    Jiang, Xinyi; Yang, Ji; Chai, Zhaowu; Song, Jinlin; Deng, Feng; Wang, Zhibiao

    2012-10-01

    To study the repair effect of low intensity pulsed ultrasound (LIPUS) irradiating combined with guided bone regeneration (GBR) on the defect of Beagle dog canines periodontal bone. Four canine teeth of every beagle dog (8 beagle dogs) were randomly distributed: Group 1 (LIPUS disposal + GBR+ autogenous bone graft group), group 2 (LIPUS disposal + autogenous bone graft group), group 3 (GBR + autogenous bone graft group), blank control group. The model of periodontal bone defect was established in the 1/3 part of the root buccal area. According to the group division, autogenous bone were grafted, group 1 and group 2 were disposed by LIPUS 20 min x d(-1). The intensity of ultrasound were 30 mW x cm(-2). Group 1 and group 3 were injected with Bio-Gide collagen membrane. The beagle dogs were executed at 6 and 8 weeks of the disposal of LIPUS and then Micro-CT test and analysis were conducted to periodontal bone defect area of each group. By clinical observation, there were different degrees of shrinkages of the area of periodontal bone defect in each group. The Micro-CT test analysis indicated that there was a statistical difference among the number, the thickness as well as the size of bone trabecula of each group (P 0.05) in terms of bone issue measurement index between 6 to B weeks of each group. Group 1 had the most new bone. LIPUS has the potential to promote the repair of periodontal bone defect. Therefore the combination of LIPUS and GBR may be more conducive to the repair and regeneration of periodontal bone defect.

  6. Maxillary Bone Regeneration Based on Nanoreservoirs Functionalized ε-Polycaprolactone Biomembranes in a Mouse Model of Jaw Bone Lesion

    Directory of Open Access Journals (Sweden)

    Marion Strub

    2018-01-01

    Full Text Available Current approaches of regenerative therapies constitute strategies for bone tissue reparation and engineering, especially in the context of genetical diseases with skeletal defects. Bone regeneration using electrospun nanofibers’ implant has the following objectives: bone neoformation induction with rapid healing, reduced postoperative complications, and improvement of bone tissue quality. In vivo implantation of polycaprolactone (PCL biomembrane functionalized with BMP-2/Ibuprofen in mouse maxillary defects was followed by bone neoformation kinetics evaluation using microcomputed tomography. Wild-Type (WT and Tabby (Ta mice were used to compare effects on a normal phenotype and on a mutant model of ectodermal dysplasia (ED. After 21 days, no effect on bone neoformation was observed in Ta treated lesion (4% neoformation compared to 13% in the control lesion. Between the 21st and the 30th days, the use of biomembrane functionalized with BMP-2/Ibuprofen in maxillary bone lesions allowed a significant increase in bone neoformation peaks (resp., +8% in mutant Ta and +13% in WT. Histological analyses revealed a neoformed bone with regular trabecular structure, areas of mineralized bone inside the membrane, and an improved neovascularization in the treated lesion with bifunctionalized membrane. In conclusion, PCL functionalized biomembrane promoted bone neoformation, this effect being modulated by the Ta bone phenotype responsible for an alteration of bone response.

  7. Optimized Bone Regeneration in Calvarial Bone Defect Based on Biodegradation-Tailoring Dual-shell Biphasic Bioactive Ceramic Microspheres.

    Science.gov (United States)

    Xu, Antian; Zhuang, Chen; Xu, Shuxin; He, Fuming; Xie, Lijun; Yang, Xianyan; Gou, Zhongru

    2018-02-21

    Bioceramic particulates capable of filling bone defects have gained considerable interest over the last decade. Herein, dual-shell bioceramic microspheres (CaP@CaSi@CaP, CaSi@CaP@CaSi) with adjustable beta-tricalcium phosphate (CaP) and beta-calcium silicate (CaSi) distribution were fabricated using a co-concentric capillary system enabling bone repair via a tailorable biodegradation process. The in vitro results showed the optimal concentration (1/16 of 200 mg/ml) of extracts of dual-shell microspheres could promote bone marrow mesenchymal cell (BMSC) proliferation and enhance the level of ALP activity and Alizarin Red staining. The in vivo bone repair and microsphere biodegradation in calvarial bone defects were compared using micro-computed tomography and histological evaluations. The results indicated the pure CaP microspheres were minimally resorbed at 18 weeks post-operatively and new bone tissue was limited; however, the dual-shell microspheres were appreciably biodegraded with time in accordance with the priority from CaSi to CaP in specific layers. The CaSi@CaP@CaSi group showed a significantly higher ability to promote bone regeneration than the CaP@CaSi@CaP group. This study indicates that the biphasic microspheres with adjustable composition distribution are promising for tailoring material degradation and bone regeneration rate, and such versatile design strategy is thought to fabricate various advanced biomaterials with tailorable biological performances for bone reconstruction.

  8. Comparative Efficacies of Collagen-Based 3D Printed PCL/PLGA/β-TCP Composite Block Bone Grafts and Biphasic Calcium Phosphate Bone Substitute for Bone Regeneration.

    Science.gov (United States)

    Hwang, Kyoung-Sub; Choi, Jae-Won; Kim, Jae-Hun; Chung, Ho Yun; Jin, Songwan; Shim, Jin-Hyung; Yun, Won-Soo; Jeong, Chang-Mo; Huh, Jung-Bo

    2017-04-17

    The purpose of this study was to compare bone regeneration and space maintaining ability of three-dimensional (3D) printed bone grafts with conventional biphasic calcium phosphate (BCP). After mixing polycaprolactone (PCL), poly (lactic-co-glycolic acid) (PLGA), and β-tricalcium phosphate (β-TCP) in a 4:4:2 ratio, PCL/PLGA/β-TCP particulate bone grafts were fabricated using 3D printing technology. Fabricated particulate bone grafts were mixed with atelocollagen to produce collagen-based PCL/PLGA/β-TCP composite block bone grafts. After formation of calvarial defects 8 mm in diameter, PCL/PLGA/β-TCP composite block bone grafts and BCP were implanted into bone defects of 32 rats. Although PCL/PLGA/β-TCP composite block bone grafts were not superior in bone regeneration ability compared to BCP, the results showed relatively similar performance. Furthermore, PCL/PLGA/β-TCP composite block bone grafts showed better ability to maintain bone defects and to support barrier membranes than BCP. Therefore, within the limitations of this study, PCL/PLGA/β-TCP composite block bone grafts could be considered as an alternative to synthetic bone grafts available for clinical use.

  9. Si-doping bone composite based on protein template-mediated assembly for enhancing bone regeneration

    Science.gov (United States)

    Yang, Qin; Du, Yingying; Wang, Yifan; Wang, Zhiying; Ma, Jun; Wang, Jianglin; Zhang, Shengmin

    2017-06-01

    Bio-inspired hybrid materials that contain organic and inorganic networks interpenetration at the molecular level have been a particular focus of interest on designing novel nanoscale composites. Here we firstly synthesized a series of hybrid bone composites, silicon-hydroxyapatites/silk fibroin/collagen, based on a specific molecular assembled strategy. Results of material characterization confirmed that silicate had been successfully doped into nano-hydroxyapatite lattice. In vitro evaluation at the cellular level clearly showed that these Si-doped composites were capable of promoting the adhesion and proliferation of rat mesenchymal stem cells (rMSCs), extremely enhancing osteoblastic differentiation of rMSCs compared with silicon-free composite. More interestingly, we found there was a critical point of silicon content in the composition on regulating multiple cell behaviors. In vivo animal evaluation further demonstrated that Si-doped composites enabled to significantly improve the repair of cranial bone defect. Consequently, our current work not only suggests fabricating a potential bone repair materials by integrating element-doping and molecular assembled strategy in one system, but also paves a new way for constructing multi-functional composite materials in the future.

  10. A review of the effects of dietary silicon intake on bone homeostasis and regeneration.

    Science.gov (United States)

    Rodella, L F; Bonazza, V; Labanca, M; Lonati, C; Rezzani, R

    2014-11-01

    Increasing evidences suggest that dietary Silicon (Si) intake, is positively correlated with bone homeostasis and regeneration, representing a potential and valid support for the prevention and improvement of bone diseases, like osteoporosis. This review, aims to provide the state of art of the studies performed until today, in order to investigate and clarify the beneficial properties and effects of silicates, on bone metabolism. We conducted a systematic literature search up to March 2013, using two medical databases (Pubmed and the Cochrane Library), to review the studies about Si consumption and bone metabolism. We found 45 articles, but 38 were specifically focused on Si studies. RESULTS showed a positive relationship between dietary Si intake and bone regeneration.

  11. Extracellular matrix scaffolds for cartilage and bone regeneration

    NARCIS (Netherlands)

    Benders, K.E.M.; van Weeren, P.R.; Badylak, S.F.; Saris, Daniël B.F.; Dhert, W.J.A.; Malda, J.

    2013-01-01

    Regenerative medicine approaches based on decellularized extracellular matrix (ECM) scaffolds and tissues are rapidly expanding. The rationale for using ECM as a natural biomaterial is the presence of bioactive molecules that drive tissue homeostasis and regeneration. Moreover, appropriately

  12. 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.

  13. Cellular and molecular prerequisites for bone tissue engineering

    NARCIS (Netherlands)

    Siddappa, R.

    2007-01-01

    Recent advances in medicine and other biological disciplines have considerably enhanced the life expectancy of human and consequently, resulting in age related health problems including skeletal complications. In addition, bone substitute to regenerate fractures resulting from trauma, congenital and

  14. Bone regeneration assessment by optical coherence tomography and MicroCT synchrotron radiation

    Science.gov (United States)

    Negrutiu, Meda L.; Sinescu, Cosmin; Canjau, Silvana; Manescu, Adrian; Topalá, Florin I.; Hoinoiu, Bogdan; Romînu, Mihai; Márcáuteanu, Corina; Duma, Virgil; Bradu, Adrian; Podoleanu, Adrian G.

    2013-06-01

    Bone grafting is a commonly performed surgical procedure to augment bone regeneration in a variety of orthopaedic and maxillofacial procedures, with autologous bone being considered as the "gold standard" bone-grafting material, as it combines all properties required in a bone-graft material: osteoinduction (bone morphogenetic proteins - BMPs - and other growth factors), osteogenesis (osteoprogenitor cells) and osteoconduction (scaffold). The problematic elements of bone regenerative materials are represented by their quality control methods, the adjustment of the initial bone regenerative material, the monitoring (noninvasive, if possible) during their osteoconduction and osteointegration period and biomedical evaluation of the new regenerated bone. One of the research directions was the interface investigation of the regenerative bone materials and their behavior at different time periods on the normal femoral rat bone. 12 rat femurs were used for this investigation. In each ones a 1 mm diameter hole were drilled and a bone grafting material was inserted in the artificial defect. The femurs were removed after one, three and six months. The defects repaired by bone grafting material were evaluated by optical coherence tomography working in Time Domain Mode at 1300 nm. Three dimensional reconstructions of the interfaces were generated. The validations of the results were evaluated by microCT. Synchrotron Radiation allows achieving high spatial resolution images to be generated with high signal-to-noise ratio. In addition, Synchrotron Radiation allows acquisition of volumes at different energies and volume subtraction to enhance contrast. Evaluation of the bone grafting material/bone interface with noninvasive methods such as optical coherence tomography could act as a valuable procedure that can be use in the future in the usual clinical techniques. The results were confirmed by microCT. Optical coherence tomography can be performed in vivo and can provide a

  15. Synergistic effects of dimethyloxalylglycine and butyrate incorporated into α-calcium sulfate on bone regeneration.

    Science.gov (United States)

    Woo, Kyung Mi; Jung, Hong-Moon; Oh, Joung-Hwan; Rahman, Saeed Ur; Kim, Soung Min; Baek, Jeong-Hwa; Ryoo, Hyun-Mo

    2015-01-01

    Osteogenesis is closely related to angiogenesis, and the combined delivery of angiogenic and osteogenic factors has been suggested to enhance bone regeneration. Small molecules have been explored as alternatives to growth factors for tissue regeneration applications. In this study, we examined the effects of the combined application of angiogenic and osteogenic small molecules on bone regeneration using a prolyl hydroxylase, dimethyloxalylglycine (DMOG), and a histone deacetylase inhibitor, butyrate. In a critical size bone defect model in rats, DMOG and butyrate, which were incorporated into α calcium sulfate (αCS), resulted in synergistic enhancements in bone and blood vessel formation, eventually leading to bone healing, as confirmed by micro-CT and histological analyses. In MC4 pre-osteoblast cultures, DMOG and butyrate enhanced the pro-angiogenic responses and osteoblast differentiation, respectively, which were evaluated based on the levels of hypoxia inducible factor (HIF)-1α protein and the expression of pro-angiogenic molecules (VEGF, home oxidase-1, glucose transporter-1) and by alkaline phosphatase (ALP) activity and the expression of osteoblast phenotype marker molecules (ALP, α1(I)col, osteocalcin, and bone sialoprotein). DMOG combined with butyrate synergistically improved osteoblast differentiation and pro-angiogenic responses, the levels of which were drastically increased in the cultures on αCS disks. Furthermore, it was demonstrated that αCS increased the level of HIF-1α and as a consequence VEGF expression, and supported osteoblast differentiation through the release of calcium ions from the αCS. Altogether, the results of this study provide evidence that a combination treatment with the small molecules DMOG and butyrate can expedite the process of bone regeneration and that αCS can be an efficient delivery vehicle for the small molecules for bone regeneration. Copyright © 2014 Elsevier Ltd. All rights reserved.

  16. Degradation pattern of a porcine collagen membrane in an in vivo model of guided bone regeneration.

    Science.gov (United States)

    Calciolari, E; Ravanetti, F; Strange, A; Mardas, N; Bozec, L; Cacchioli, A; Kostomitsopoulos, N; Donos, N

    2018-02-15

    Although collagen membranes have been clinically applied for guided tissue/bone regeneration for more than 30 years, their in vivo degradation pattern has never been fully clarified. A better understanding of the different stages of in vivo degradation of collagen membranes is extremely important, considering that the biology of bone regeneration requires the presence of a stable and cell/tissue-occlusive barrier during the healing stages in order to ensure a predictable result. Therefore, the aim of this study was to investigate the degradation pattern of a porcine non-cross-linked collagen membrane in an in vivo model of guided bone regeneration (GBR). Decalcified and paraffin-embedded specimens from calvarial defects of 18, 10-month-old Wistar rats were used. The defects were treated with a double layer of collagen membrane and a deproteinized bovine bone mineral particulate graft. At 7, 14 and 30 days of healing, qualitative evaluation with scanning electron microscopy and atomic force microscopy, and histomorphometric measurements were performed. Markers of collagenase activity and bone formation were investigated using an immunofluorescence technique. A significant reduction of membrane thickness was observed from 7 to 30 days of healing, which was associated with progressive loss of collagen alignment, increased collagen remodeling and progressive invasion of woven bone inside the membranes. A limited inflammatory infiltrate was observed at all time points of healing. The collagen membrane investigated was biocompatible and able to promote bone regeneration. However, pronounced signs of degradation were observed starting from day 30. Since successful regeneration is obtained only when cell occlusion and space maintenance exist for the healing time needed by the bone progenitor cells to repopulate the defect, the suitability of collagen membranes in cases where long-lasting barriers are needed needs to be further reviewed. © 2018 John Wiley & Sons A

  17. Bone Regeneration Based on Tissue Engineering Conceptions — A 21st Century Perspective

    Science.gov (United States)

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

    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 osteoconductive but also osteoinductive, i.e. to stimulate regeneration of host tissues by combining tissue engineering 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. PMID:26273505

  18. Comparative analysis of guided bone regeneration using autogenous tooth bone graft material with and without resorbable membrane

    Directory of Open Access Journals (Sweden)

    Ji-Young Lee

    2013-09-01

    Conclusion: Both groups showed clinically acceptable bone regeneration without any eventful complications. Within the limitation of this study, we can carefully conclude that the use of resorbable membrane is not a critical factor in GBR when using AutoBT.

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

    International Nuclear Information System (INIS)

    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 colony-forming cells may explain the increased rate of leukopoietic regeneration in anabolic steroid-treated animals as compared to controls

  20. Guided bone regeneration following surgical treatment of a rare variant of Pindborg tumor: a case report.

    Science.gov (United States)

    Mariano, Ronaldo C; Oliveira, Marina R; Silva, Amanda C; Ferreira, Delano H; Almeida, Oslei P

    2014-03-01

    Calcifying epithelial odontogenic tumor is a benign neoplasm, but its local destructive potential may lead to the formation of major bone defects. Microscopically, there are some histological variants. Among them, we highlight the clear cell variant due to its more aggressive behavior and a higher incidence of relapse. In this context, it is pertinent to describe the clear cell variant of calcifying epithelial odontogenic tumor. Despite the large bone defect formed in the posterior region of the mandible, conservative treatment associated with guided bone regeneration assured complete bone formation and the absence of recurrence in an 8-year follow-up period.

  1. 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.

  2. Bone tissue modelling and remodelling following guided bone regeneration in combination with biphasic calcium phosphate materials presenting different microporosity.

    Science.gov (United States)

    Dahlin, Christer; Obrecht, Marcel; Dard, Michel; Donos, Nikos

    2015-07-01

    The aim of this study was to investigate bone regeneration following application of a novel biphasic calcium phosphate (BCP I) composed of microstructured granules of 90% β-tricalcium phosphate (β-TCP)/10% hydroxyapatite (HA) compared to BCP non-microstructured biphasic calcium phosphate with a composite of 60% hydroxyapatite/40% β-TCP (BCP II) and a deproteinized bovine bone mineral (DBBM) at surgically created defects in the mandible of minipigs in a combined approach with guided bone regeneration (GBR). Sixteen minipigs were used for the study. Lower premolars P2, P3, P4 and first molar M1 were extracted. Following 3 months of healing, two defects with a width and depth of 7 mm were created bilaterally in the mandible. The different grafting materials were randomly placed in the created defects and covered by means of a collagen membrane. After 3 and 8 weeks, biopsies were sampled. All specimens were evaluated with descriptive histology and histomorphometric evaluations complemented by micro-CT scan analysis. All three biomaterials presented with higher bone volume at 8 weeks compared to 3 weeks (P bone formation compared to BCP II at 8 weeks (P bone formation at 8 weeks. BCP I showed significant higher amounts of newly formed bone despite a higher remaining graft volume compared to the other groups. With regard to the regenerative outcome, all the three materials can be recommended for clinical use. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  3. Bone Regeneration of Hydroxyapatite with Granular Form or Porous Scaffold in Canine Alveolar Sockets

    Science.gov (United States)

    JANG, SEOK JIN; KIM, SE EUN; HAN, TAE SUNG; SON, JUN SIK; KANG, SEONG SOO; CHOI, SEOK HWA

    2017-01-01

    This study was undertaken to assess bone regeneration using hydroxyapatite (HA). The primary focus was comparison of bone regeneration between granular HA (gHA) forms and porous HA (pHA) scaffold. The extracted canine alveolar sockets were divided with three groups: control, gHA and pHA. Osteogenic effect in the gHA and pHA groups showed bone-specific surface and bone mineral density to be significantly higher than that of the control group (pBone volume fraction, bone mineral density, and amount of connective tissue related to disturbing osseointegration of the gHA group was higher than in the pHA group. Quantity of new bone formation of the pHA group was higher than that of the gHA group. This study demonstrated that gHA and pHA are potentially good bone substitutes for alveolar socket healing. For new bone formation during 8 weeks' post-implantation, HA with porous scaffold was superior to the granular form of HA. PMID:28438860

  4. Long-term evaluation of osseointegrated implants in regenerated and nonregenerated bone.

    Science.gov (United States)

    Corrente, G; Abundo, R; Cardaropoli, D; Cardaropoli, G; Martuscelli, G

    2000-08-01

    This investigation evaluated the predictability of dental implants subjected to bone regeneration procedures at the time of insertion. Fifty-two test implants were inserted into sites with periimplant bone defects. A calcium carbonate allograft material with or without a fibrin-fibronectin sealing system was used to fill the defects. Sixty control implants were inserted into an adequate volume of nonaugmented bone. Each of the 29 study patients received at least one test implant and one control implant. At the second-stage surgery, fill of the bone defect was assessed as complete or incomplete. The cumulative success rate was 91.7% (mean follow-up 55 mo) for the test implants and 93.2% (mean follow-up 59 mo) for the control implants. Within the test group, implants with complete bone fill achieved 97.6% success versus 59.1% success for implants with incomplete bone fill. These preliminary results suggest that implants placed with simultaneous bone regeneration procedures achieve long-term predictability that is comparable to that of implants placed in an adequate volume of bone, provided that complete bone fill of the periimplant defect is achieved. Long-term studies with other augmentation materials are needed to fully validate these findings.

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

    International Nuclear Information System (INIS)

    Torres, A.L.; Gaspar, V.M.; Serra, I.R.; Diogo, G.S.; Fradique, R.; Silva, A.P.; Correia, I.J.

    2013-01-01

    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

  6. Endogenous Bone Regeneration Is Dependent Upon a Dynamic Oxygen Event

    Science.gov (United States)

    2014-01-01

    exogenous induction. This makes P3 amputation an excellent model in which to study the effects of oxygen during regeneration. That oxygen tensions fluctuate...mechanisms to drug development. Antioxid Redox Signal. 2010; 13: 1593-616. 39. Ruiz JC, Walker SD, Anderson SA, Eisenstein RS and Bruick RK. F-box

  7. Bone regeneration potential of sub-microfibrous membranes with ...

    African Journals Online (AJOL)

    Conclusion: The results indicate that biodegradable PCL sub-microfibrous membrane produced by electrospinning process seems to have excellent biocompatibility, and may be used as a scaffold for bone tissue engineering. Keywords: Biocompatibility, Hard tissue, Biomaterial availability, Bone remodeling, Polylactic acid, ...

  8. Bioactive Nano-fibrous Scaffold for Vascularized Craniofacial Bone Regeneration

    DEFF Research Database (Denmark)

    Prabha, Rahul Damodaran; Kraft, David Christian Evar; Harkness, Linda

    2018-01-01

    There has been a growing demand for bone grafts for correction of bone defects in complicated fractures or tumors in the craniofacial region. Soft flexible membrane like material that could be inserted into defect by less invasive approaches; promote osteoconductivity and act as a barrier to soft...... tissue in growth while promoting bone formation is an attractive option for this region. Electrospinning has recently emerged as one of the most promising techniques for fabrication of extracellular matrix (ECM) like nano-fibrous scaffolds that can serve as a template for bone formation. To overcome...... and biocompatibility properties of the new scaffold material. Our results indicate PVA-PCL-HAB scaffolds support attachment and growth of stromal stem cells; (human bone marrow skeletal (mesenchymal) stem cells (hMSC) and dental pulp stem cells (DPSC)). In addition, the scaffold supported in vitro osteogenic...

  9. Bone regeneration in extraction sockets with autologous platelet rich fibrin gel.

    Science.gov (United States)

    Girish Rao, S; Bhat, Preethi; Nagesh, K S; Rao, Gundu H R; Mirle, Bharthi; Kharbhari, Lubna; Gangaprasad, B

    2013-03-01

    To evaluate the effects of autologous platelet rich fibrin gel (PRF gel) on bone regeneration following extraction. The study design was approved by the Institutional Ethical Committee. Study sample consisting of a total of 22 patients requiring bilateral transalveolar third molar extractions were included after written informed consent. One side was randomly chosen as case and the other side was the control. Autologous PRF gel was prepared from Fresh blood obtained from the patient. The PRF gel was placed in the extraction site and primary closure was obtained. The patient was called for a follow up on the first post op day, 1st week, one month, three month and six months post op. Regeneration of bone was measured using serial radiographs (RVG) at immediate post op, one, three and six months. This was then compared with the bone regeneration seen in the control group, with the radiographs taken at same intervals, to estimate the difference in bone regeneration if any. RVGs were assessed for amount of radiologic bone filling by the method described by Matteo Chiapasco et al. Higher mean pixels was recorded in cases compared to controls at all the time intervals viz., immediate post op, 1 month post op, 3 months post op and 6 months post op. However, the difference in the mean pixels recorded between the two groups was not statistically significant (P > 0.05). For complete analysis, further follow up of the present patients and a larger sample size is required to obtain a conclusive result of the Bone Regeneration in extraction sockets with PRF gel.

  10. Guided bone regeneration with asymmetric collagen-chitosan membranes containing aspirin-loaded chitosan nanoparticles.

    Science.gov (United States)

    Zhang, Jiayu; Ma, Shiqing; Liu, Zihao; Geng, Hongjuan; Lu, Xin; Zhang, Xi; Li, Hongjie; Gao, Chenyuan; Zhang, Xu; Gao, Ping

    2017-01-01

    Membranes allowing the sustained release of drugs that can achieve cell adhesion are very promising for guided bone regeneration. Previous studies have suggested that aspirin has the potential to promote bone regeneration. The purpose of this study was to prepare a local drug delivery system with aspirin-loaded chitosan nanoparticles (ACS) contained in an asymmetric collagen-chitosan membrane (CCM). In this study, the ACS were fabricated using different concentrations of aspirin (5 mg, 25 mg, 50 mg, and 75 mg). The drug release behavior of ACS was studied. Transmission electron microscopy (TEM) and scanning electron microscopy (SEM) were used to examine the micromorphology of ACS and aspirin-loaded chitosan nanoparticles contained in chitosan-collagen membranes (ACS-CCM). In vitro bone mesenchymal stem cells (BMSCs) were cultured and critical-sized cranial defects on Sprague-Dawley rats were made to evaluate the effect of the ACS-CCM on bone regeneration. Drug release behavior results of ACS showed that the nanoparticles fabricated in this study could successfully sustain the release of the drug. TEM showed the morphology of the nanoparticles. SEM images indicated that the asymmetric membrane comprised a loose collagen layer and a dense chitosan layer. In vitro studies showed that ACS-CCM could promote the proliferation of BMSCs, and that the degree of differentiated BMSCs seeded on CCMs containing 50 mg of ACS was higher than that of other membranes. Micro-computed tomography showed that 50 mg of ACS-CCM resulted in enhanced bone regeneration compared with the control group. This study shows that the ACS-CCM would allow the sustained release of aspirin and have further osteogenic potential. This membrane is a promising therapeutic approach to guiding bone regeneration.

  11. Interplay of thymus and bone marrow regeneration in x-irradiated mice

    International Nuclear Information System (INIS)

    Hiesche, K.-D.

    1975-01-01

    aim of the prepresent investigation was to study the modifying effects of bone marrow cells on regeneration, after X-irradiation, of thymus and bone marrow cell populations. Data are presented which indicate that the cellular composition of the thymus and, in particular, the frequency of the stem cells in the organ at the time of radiation exposure determines thymic regeneration for about two weeks after irradiation. After this period, regeneration depends on new precursors from the bone marrow which have previously seeded the thymus. In contrast to the thymus, cellular restoration of the bone marrow is already initially dependent on the number of protected or transplanted marrow cells. Two phases in the recovery of thymic PHA-reactivity after irradiation were observed: one initial phase which is independent on the number of the available bone marrow cells, and a subsequent phase during which PHA-reactivity is slightly increased in mice irradiated with partly protected bone marrow in comparison to in total body irradiated animals. During the entire observation period, PHA-reactivity remains at a low level not exeeding 50 % of that in untreated mice. In contrast the thymus is fully repopulated with regard to the number of nonreactive cells. Alternative pathways of thymocyte development within the thymus are discussed. Bone marrow X cells were shown to be as sensitive to in vitro treatment with a specific H-2 antiserum as were lymphocytes from normal bone marrow. This finding was teken to indicate that the X cells represent a particular lymphoid cell type. A xenogeneic rabbit-anti-mouse embryo antiserum was more toxic to pre-irradiated bone marrow, with high proportion of X cells, than to bone marrow from untreated mice, using in vitro cytotoxicity test. A possible embryonic character of the X cells is discussed. (author)

  12. Exploitation of a novel polysaccharide nanogel cross-linking membrane for guided bone regeneration (GBR).

    Science.gov (United States)

    Miyahara, Takayuki; Nyan, Myat; Shimoda, Asako; Yamamoto, Yuka; Kuroda, Shinji; Shiota, Makoto; Akiyoshi, Kazunari; Kasugai, Shohei

    2012-08-01

    Cholesterol-bearing pullulan (CHP) nanogel is a synthetic degradable biomaterial for drug delivery with high biocompatibility. Guided bone regeneration (GBR) is a bone augmentation technique in which a membrane is used to create and keep a secluded regenerative space. The purpose of the present study was to evaluate the effects of the novel CHP nanogel membrane in GBR. Thirty-six adult Wistar rats were used and bilaterally symmetrical full-thickness parietal bone defects of 5 mm diameter were created with a bone trephine burr. Each defect was covered with the collagen membrane or the CHP nanogel membrane or untreated without any membrane. The animals were sacrificed at 2, 4 and 8 weeks and analysed radiologically and histologically. Furthermore, after incubating human serum with CHP nanogel or collagen, the amount of PDGF in the serum was measured using ELISA. New bone formation in terms of bone volume was higher in the nanogel group than in the control or collagen groups at 2 and 4 weeks. At 8 weeks, both membrane groups showed higher bone volumes than the control group. Notably, the newly-formed bone in the bone defect in the nanogel group was uniform and histologically indistinguishable from the original bone, whereas in the collagen group the new bone showed an irregular structure that was completely different from the original bone. After incubating with CHP nanogel, the amount of PDGF in the serum decreased significantly. CHP nanogel GBR membrane favourably stimulated bone regeneration, in which a unique characteristic of CHP nanogel, the storage of endogenous growth factors, was likely implicated. Copyright © 2011 John Wiley & Sons, Ltd.

  13. In Vitro and In Vivo Study of a Novel Porcine Collagen Membrane for Guided Bone Regeneration

    Directory of Open Access Journals (Sweden)

    Eisner Salamanca

    2016-11-01

    Full Text Available For years, in order to improve bone regeneration and prevent the need of a second stage surgery to remove non-resorbable membranes, biological absorbable membranes have gradually been developed and applied in guided tissue regeneration (GTR. The present study’s main objective was to achieve space maintenance and bone regeneration using a new freeze-dried developed porcine collagen membrane, and compare it with an already commercial collagen membrane, when both were used with a bovine xenograft in prepared alveolar ridge bone defects. Prior to surgery, the membrane’s vitality analysis showed statistically significant higher cell proliferation in the test membrane over the commercial one. In six beagle dogs, commercial bone xenograft was packed in lateral ridge bone defects prepared in the left and right side and then covered with test porcine collagen membrane or commercial collagen membrane. Alveolar height changes were measured. Histomorphometric results, in vitro and in vivo properties indicated that the new porcine collagen membrane is biocompatible, enhances bone xenograft osteoconduction, and reduces the alveolar ridge height reabsorption rate.

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

    International Nuclear Information System (INIS)

    Giannitelli, S.M.; Basoli, F.; Mozetic, P.; Piva, P.; Bartuli, F.N.; Luciani, F.; Arcuri, C.; Trombetta, M.; Rainer, A.; Licoccia, S.

    2015-01-01

    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

  15. 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.

  16. 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.

  17. Characteristic features of bone tissue regeneration in the vertebral bodies in the experiment with osteograft

    Science.gov (United States)

    Zaydman, A. M.; Predein, Yu. A.; Korel, A. V.; Shchelkunova, E. I.; Strokova, E. I.; Lastevskiy, A. D.; Rerikh, V. V.; Fomichev, N. G.; Falameeva, O. V.; Shevchenko, A. I.; Shevtcov, V. I.

    2017-09-01

    In the practice of orthopedic and trauma surgeons, there is a need to close bone tissue defects after removal of tumors or traumatic and dystrophic lesions. Currently, as cellular technologies are being developed, stem embryonic and pluripotent cells are widely introduced into practical medicine. The unpredictability of the spectrum of cell differentiations, up to oncogenesis, raised the question of creating biological structures committed toward osteogenic direction, capable of regenerating organo-specific graft at the optimal time. Such osteograft was created at the Novosibirsk Institute of Traumatology and Orthopaedics (patent RU 2574942). Its osteogenic orientation was confirmed by the morphological and immunohistochemical methods, and by the expression of bone genes. The regeneration potential of the osteograft was studied in the vertebral bodies of the mini piglet model. The study revealed that the regeneration of the vertebral body defect and the integration of the osteograft with the bed of the recipient proceeds according to the type of primary angiogenic osteogenesis within 30 days.

  18. Periodontal regeneration using an injectable bone cement combined with BMP-2 or FGF-2

    NARCIS (Netherlands)

    Oortgiesen, D.A.W.; Walboomers, X.F.; Bronckers, A.L.J.J.; Meijer, G.J.; Jansen, J.A.

    2014-01-01

    Periodontitis is a frequently diagnosed oral disease characterized by bone resorption and soft tissue loss around teeth. Unfortunately, currently available therapies only slow or arrest progress of the disease. Ideally, treatment of periodontal defects should be focused on complete regeneration of

  19. Bone marrow adipocytes promote the regeneration of stem cells and haematopoiesis by secreting SCF.

    Science.gov (United States)

    Zhou, Bo O; Yu, Hua; Yue, Rui; Zhao, Zhiyu; Rios, Jonathan J; Naveiras, Olaia; Morrison, Sean J

    2017-08-01

    Endothelial cells and leptin receptor + (LepR + ) stromal cells are critical sources of haematopoietic stem cell (HSC) niche factors, including stem cell factor (SCF), in bone marrow. After irradiation or chemotherapy, these cells are depleted while adipocytes become abundant. We discovered that bone marrow adipocytes synthesize SCF. They arise from Adipoq-Cre/ER + progenitors, which represent ∼5% of LepR + cells, and proliferate after irradiation. Scf deletion using Adipoq-Cre/ER inhibited haematopoietic regeneration after irradiation or 5-fluorouracil treatment, depleting HSCs and reducing mouse survival. Scf from LepR + cells, but not endothelial, haematopoietic or osteoblastic cells, also promoted regeneration. In non-irradiated mice, Scf deletion using Adipoq-Cre/ER did not affect HSC frequency in long bones, which have few adipocytes, but depleted HSCs in tail vertebrae, which have abundant adipocytes. A-ZIP/F1 'fatless' mice exhibited delayed haematopoietic regeneration in long bones but not in tail vertebrae, where adipocytes inhibited vascularization. Adipocytes are a niche component that promotes haematopoietic regeneration.

  20. 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

  1. Guided bone regeneration in rat mandibular defects using resorbable poly(trimethylene carbonate) barrier membranes

    NARCIS (Netherlands)

    van Leeuwen, A.C.; Huddelston Slater, J.J.R.; Gielkens, P.F.M.; de Jong, J.R.; Grijpma, Dirk W.; Bos, R.R.M.

    2012-01-01

    The present study evaluates a new synthetic degradable barrier membrane based on poly(trimethylene carbonate) (PTMC) for use in guided bone regeneration. A collagen membrane and an expanded polytetrafluoroethylene (e-PTFE) membrane served as reference materials. In 192 male Sprague–Dawley rats, a

  2. Guided bone regeneration in rat mandibular defects using resorbable poly(trimethylene carbonate) barrier membranes

    NARCIS (Netherlands)

    van Leeuwen, A. C.; Huddleston Slater, J. J. R.; Gielkens, P. F. M.; de Jong, J. R.; Grijpma, D. W.; Bos, R. R. M.

    The present study evaluates a new synthetic degradable barrier membrane based on poly(trimethylene carbonate) (PTMC) for use in guided bone regeneration. A collagen membrane and an expanded polytetrafluoroethylene (e-PTFE) membrane served as reference materials. In 192 male Sprague-Dawley rats, a

  3. 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.

  4. Particulate bioglass in the regeneration of alveolar bone in dogs: clinical, surgical and radiographic evaluations

    Directory of Open Access Journals (Sweden)

    Alexandre Couto Tsiomis

    2011-04-01

    Full Text Available Bone loss, either by trauma or other diseases, generates an increasing need for substitutes of this tissue. This study evaluated Bioglass as a bone substitute in the regeneration of the alveolar bone in mandibles of dogs by clinical, surgical and radiological analysis. Twenty-eight adult dogs were randomly separated into two equal groups. In each animal, a bone defect was created on the vestibular surface of the alveolar bone between the roots of the fourth right premolar tooth. In the treated group, the defect was immediately filled with bioglass, while in the control, it remained unfilled. Clinical evaluations were performed daily for a week, as well as x-rays immediately after surgery and at 8, 14, 21, 42, 60, 90 and 120 days post-operative. Most animals in both groups showed no signs of inflammation and wound healing was similar. Radiographic examination revealed a gradual increase of radiopacity in the region of the defect in the control group. In the treated group, initial radiopacity was higher than that of adjacent bone, decreasing until 21 days after surgery. Then it gradually increased until 120 days after surgery, when the defect became undetectable. The results showed that Bioglass integrates into bone tissue, is biocompatible and reduced the period for complete bone regeneration.

  5. Contemporary guided bone regeneration therapy for unaesthetic anterior peri-implantitis case

    Directory of Open Access Journals (Sweden)

    Benso Sulijaya

    2016-12-01

    Full Text Available Background: Dental implant is one of an alternative solutions reconstruction therapy for missing teeth. Complication of dental implant could occurs and leading to implant failure. In order to restore the complication, surgical treatment with guided bone regeneration (GBR is indicated. The potential use of bone substitutes is widely known to be able to regenerate the bone surrounding the implant and maintain bone volume. Purpose: The study aimed to demonstrate the effectiveness of implant-bone fully coverage by using sandwich technique of biphasic calcium phosphate (BCP and demineralized freeze-dried bone allografts (DFDBA bone substitutes combined with collagen resorbable membrane. Case: A 24-year-old male came with diagnosis of peri-implantitis on implant #11. Clinical finding indicated that implant thread was exposed on the labial aspect. Case management: After initial therapy including oral hygiene improvement performed, an operator did a contemporary GBR to correct the defect. Bone graft materials used were 40% β-tri calcium phosphate (β-TCP-60% hydroxyapatite (HA on the outer layer and DFDBA on the inner layer of the defect. Resorbable collagen membrane was used to cover the graft. Conclusion: GBR with sandwich technique could serve as one of the treatment choices for correcting an exposed anterior implant that would enhance the successful aesthetic outcome.

  6. 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.

  7. [Novel software-based and validated evaluation method for objective quantification of bone regeneration in experimental bone defects].

    Science.gov (United States)

    Schönberger, T; Kasten, P; Fechner, K; Südkamp, N P; Pearce, S; Niemeyer, P

    2010-01-01

    The quantification of newly formed bone in experimental defect models is a problem in various experimental set-ups. Several methods have been described to evaluate and quantify the regeneration of newly formed bone in various animal models. Most methods only describe the amount of regenerated tissue on a semi-quantitative level, the results significantly depend on the subjective rating of the observer and such evaluation methods have not been validated in terms of objectivity and reliability. The aim of the present study was to introduce a novel evaluation method for the accurate quantification of bone regeneration on digital X-ray images using a freely available digital image software analysis programme (GIMP, GNU General Public Licence). The method introduced here contains 5 steps: standardisation of size and colour, determination of range of interest (ROI), defining different qualities of mineralisation, pixel analysis with histogram function, similar to the Hondsfield index, and quantification. In order to evaluate the objectivity and reliability, the quantification method was compared to semi-quantitative scores described by Mosheiff and Werntz for inter- and intraobserver variability. Six observers were asked to determine bone regeneration in 16 X-ray images of 2 different animal models. In order to describe intraobserver variability, the evaluation was repeated after a period of 4 weeks. Statistical analysis including determination of intra- and interobserver variability (Bland-Altman coefficient of reproduction) was performed using SAS software. For both experimental set-ups analysed in this project (rabbit and sheep bone defects), the objectivity was significantly higher in the GIMP-based evaluation compared to the evaluation according to Mosheiff and Werntz using the Bland-Altman coefficient (rabbit: GIMP: 0.095, Mosheiff: 0.272, Werntz: 0.283; sheep: GIMP: 0.098, Mosheiff: 0.658, Werntz: 0.668). Analogous results were obtained for reliability (rabbit

  8. 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.

  9. Hydroxyapatite nanorod and microsphere functionalized with bioactive lactoferrin as a new biomaterial for enhancement bone regeneration.

    Science.gov (United States)

    Shi, Pujie; Wang, Qun; Yu, Cuiping; Fan, Fengjiao; Liu, Meng; Tu, Maolin; Lu, Weihong; Du, Ming

    2017-07-01

    Lactoferrin (LF) has been recently recognized as a promising new novel bone growth factor for the beneficial effects on bone cells and promotion of bone growth. Currently, it has been attracted wide attention in bone regeneration as functional food additives or a potential bioactive protein in bone tissue engineering. The present study investigated the possibility that hydroxyapatite (HAP) particles, a widely used bone substitute material for high biocompatibility and osteoconductivity, functionalized with lactoferrin as a composite material are applied to bone tissue engineering. Two kinds of hydroxyapatite samples with different sizes, including nanorods and microspheres particles, were functionalized with lactoferrin molecules, respectively. A detailed characterization of as-prepared HAP-LF complex is presented, combining thermal gravimetric analysis (TGA) and Fourier Transform Infrared Spectroscopy (FT-IR). Zeta potential and the analysis of electrostatic surface potential of lactoferrin were carried to reveal the mechanism of adsorption. The effects of HAP-LF complex on MC3T3-E1 osteoblast proliferation and morphology were systematically evaluated at different culture time. Interestingly, results showed that cell viability of HAP-LF group was significantly higher than HAP group indicating that the HAP-LF can improve the biocompatibility of HAP, which mainly originated from a combination of HAP-LF interaction. These results indicated that hydroxyapatite particles can work as a controlled releasing carrier of lactoferrin successfully, and lactoferrin showed better potentiality on using in the field of bone regeneration by coupling with hydroxyapatite. This study would provide a new biomaterial and might offer a new insight for enhancement of bone regeneration. Copyright © 2017 Elsevier B.V. All rights reserved.

  10. Botulinum Toxin Induces Muscle Paralysis and Inhibits Bone Regeneration in Zebrafish

    Science.gov (United States)

    Recidoro, Anthony M.; Roof, Amanda C.; Schmitt, Michael; Worton, Leah E.; Petrie, Timothy; Strand, Nicholas; Ausk, Brandon J.; Srinivasan, Sundar; Moon, Randall T.; Gardiner, Edith M.; Kaminsky, Werner; Bain, Steven D.; Allan, Christopher H.; Gross, Ted S.; Kwon, Ronald Y.

    2016-01-01

    Intramuscular administration of Botulinum toxin (BTx) has been associated with impaired osteogenesis in diverse conditions of bone formation (e.g., development, growth, and healing), yet the mechanisms of neuromuscular-bone crosstalk underlying these deficits have yet to be identified. Motivated by the emerging utility of zebrafish (Danio rerio) as a rapid, genetically tractable, and optically transparent model for human pathologies (as well as the potential to interrogate neuromuscular-mediated bone disorders in a simple model that bridges in vitro and more complex in vivo model systems), in this study we developed a model of BTx-induced muscle paralysis in adult zebrafish, and examined its effects on intramembranous ossification during tail fin regeneration. BTx administration induced rapid muscle paralysis in adult zebrafish in a manner that was dose-dependent, transient, and focal, mirroring the paralytic phenotype observed in animal and human studies. During fin regeneration, BTx impaired continued bone ray outgrowth, morphology, and patterning, indicating defects in early osteogenesis. Further, BTx significantly decreased mineralizing activity and crystalline mineral accumulation, suggesting delayed late-stage osteoblast differentiation and/or altered secondary bone apposition. Bone ray transection proximal to the amputation site focally inhibited bone outgrowth in the affected ray, implicating intra- and/or inter-ray nerves in this process. Taken together, these studies demonstrate the potential to interrogate pathological features of BTx-induced osteoanabolic dysfunction in the regenerating zebrafish fin, define the technological toolbox for detecting bone growth and mineralization deficits in this process, and suggest that pathways mediating neuromuscular regulation of osteogenesis may be conserved beyond established mammalian models of bone anabolic disorders. PMID:24806738

  11. Effects of osteoinduction on bone regeneration in distraction: results of a pilot study.

    Science.gov (United States)

    Kroczek, A; Park, J; Birkholz, T; Neukam, F W; Wiltfang, J; Kessler, P

    2010-07-01

    Rate and frequency of distraction as well as stimulatory effects transmitted by growth factors and local gene therapy have a decisive influence on bone regeneration. In a pilot study we tested the effect of four different morphogenetic and mitotic proteins and a genetically transferred vector system on bone healing in continuous osteodistraction in a large animal experiment on 24 Goettingen mini-pigs. For this purpose bone morphogenetic protein (BMP-2), BMP-7, TGF-beta, IGF-1 and a liposome vector were instilled into the distraction gap. The animals were killed after 1-4 weeks of consolidation. Histological and radiological evaluations showed maximum bone formation after the application of BMP-2/7, whereas the application of TGF-beta, IGF-1 and the liposomal vector had only a limited effect on bone regeneration. The quantitative analysis demonstrated an average amount of bone in the distraction gap of 50% and 61% after instillation of BMP-2 and 7, respectively. The BMP-2 expression, however, was maximal after induction with the non-viral vector. Only after BMP-2/7 application could physical, radiographic and histological evidence of bone union be detected. In bone distraction with a short observation period the application of morphogenetic proteins seems to enhance bone regeneration significantly. Before application in humans further studies are necessary to measure the dose-effect relationship, the mode of application and the efficacy of different inductive proteins. The combination of osteodistraction with osteoinduction, however, could shorten treatment times dramatically. Copyright 2009 European Association for Cranio-Maxillo-Facial Surgery. Published by Elsevier Ltd. All rights reserved.

  12. Novel Therapy for Bone Regeneration in Large Segmental Defects

    Science.gov (United States)

    2016-10-01

    scaffolds. Biomaterials. 2008;29(32):4300–5. 90. Raschke M, Kolbeck S, Bail H, Schmidmaier G, Flyvbjerg A, Lindner T, et al. Homologous growth hormone ...contralateral tibia. • No adverse effects from TPO treatment have been identified from blood measurements, organ pathology, or veterinary inspection...morphologically appears to promote robust bone growth by direct bone healing, which takes longer to accomplish than BMP-2. Thus, if our fixation fails before

  13. Temporal requirement for bone morphogenetic proteins in regeneration of the tail and limb of Xenopus tadpoles.

    Science.gov (United States)

    Beck, Caroline W; Christen, Bea; Barker, Donna; Slack, Jonathan M W

    2006-09-01

    Bone morphogenetic protein (BMP) signalling is necessary for both the development of the tail bud and for tail regeneration in Xenopus laevis tadpoles. Using a stable transgenic line in which expression of the soluble BMP inhibitor noggin is under the control of the temperature inducible hsp70 promoter, we have investigated the timing of the requirement for BMP signalling during tail regeneration. If noggin expression is induced followed by partial amputation of the tail, then wound closure and the formation of the neural ampulla occur normally but outgrowth of the regeneration bud is inhibited. Furthermore, we show that BMP signalling is also necessary for limb bud regeneration, which occurs in Xenopus tadpoles prior to differentiation. When noggin expression is induced, limb bud regeneration fails at an early stage and a stump is formed. The situation appears similar to the tail, with formation of the limb bud blastema occurring but renewed outgrowth inhibited. The transcriptional repressor Msx1, a direct target of BMP signalling with known roles in vertebrate appendage regeneration, fails to be re-expressed in both tail and limb in the presence of noggin. DNA labelling studies show that proliferation in the notochord and spinal cord of the tail, and of the blastema in the limb bud, is significantly inhibited by noggin induction, suggesting that in the context of these regenerating appendages BMP is mainly required, directly or indirectly, as a mitogenic factor.

  14. Platelet-rich plasma for bone healing and regeneration.

    Science.gov (United States)

    Oryan, Ahmad; Alidadi, Soodeh; Moshiri, Ali

    2016-01-01

    Successful healing of large bone defects (LBDs) is a complicated phenomenon because the body's natural ability often fails to effectively repair the LBDs. New modalities should be utilized to increase the quality and accelerate bone healing. Platelet concentrates in different forms can be considered an attractive option for such purpose. Platelets as a natural source of growth factors, cytokines, and other micro and macromolecules are hypothesized to improve bone healing. This review has covered important concepts regarding platelet-rich plasma (PRP) including mechanisms of action, preparation protocols and their differences, and factors affecting the PRP efficacy during bone healing. In addition, the most recent studies in different levels which evaluated the role of PRP on bone repair has been reviewed and discussed to clarify the controversies and conflicts, and to illustrate a future prospective and directions for orthopedic surgeons to overcome current limitations and difficulties. As the efficacy of PRP is dependent on various factors, the outcome of PRP therapy is variable and unpredictable in orthopedic patients. Therefore, it is still too soon to suggest PRP as the first line treatment option in complicated bone injuries such as LBDs and nonunions. However, combination of PRP with natural and synthetic biomaterials can enhance the effectiveness of PRP.

  15. Evaluation of perforated demineralized dentin scaffold on bone regeneration in critical-size sheep iliac defects.

    Science.gov (United States)

    Kabir, Md Arafat; Murata, Masaru; Akazawa, Toshiyuki; Kusano, Kaoru; Yamada, Katsuhisa; Ito, Manabu

    2017-11-01

    Regenerating critical-size bone injury is a major problem that continues to inspire the design of new graft materials. Therefore, tissue engineering has become a novel approach for targeting bone regeneration applications. Human teeth are a rich source of stem cells, matrix, trace metal ions, and growth factors. A vital tooth-derived demineralized dentin matrix is acid-insoluble and composed of cross-linked collagen with growth factors. In this study, we recycled human non-functional tooth into a unique geometric dentin scaffold, entitled perforated root-demineralized dentin matrix (PR-DDM). The aim of this study was to evaluate the feasibility of PR-DDM as the scaffold for regenerating bone in critical-size iliac defects. Artificial macro-pores (1 mm in diameter) were added to human vital wisdom tooth after removing the enamel and pulp portions. The modified tooth was demineralized in 0.34 N HNO 3 for 30 min and is referred to as PR-DDM scaffold. Critical-size defect (10 mm × 15 mm × 9 mm Ø) was created in the iliac crest of six adult sheep. The in vivo bone regeneration by the scaffold was evaluated by micro-CT, 3D micro-CT, and histological examination at 2 and 4 months post-implantation. PR-DDM exhibited better bone ingrowth, especially in the artificial macro-pores. The results of micro-CT and 3D micro-CT revealed good union between scaffold and native bone. New bone formation was observed in almost all portions of PR-DDM. Higher bone volume inside the scaffold was detected at 4 months compared with 2 months. New bone ingrowth was ankylosed with PR-DDM, and both osteoinduction and osteoconduction capability of PR-DDM were confirmed histologically. The ratio of new bone formation was higher at 4 months compared with 2 months by histomorphometric analysis. Altogether, these results demonstrated that the human tooth-derived graft material with a unique geometric structure, PR-DDM, contributed to active bone ingrowth in critical-size bone

  16. 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. 

  17. Bone Regeneration after Treatment with Covering Materials Composed of Flax Fibers and Biodegradable Plastics: A Histological Study in Rats

    Science.gov (United States)

    Gedrange, Tomasz

    2016-01-01

    The aim of this study was to examine the osteogenic potential of new flax covering materials. Bone defects were created on the skull of forty rats. Materials of pure PLA and PCL and their composites with flax fibers, genetically modified producing PHB (PLA-transgen, PCL-transgen) and unmodified (PLA-wt, PCL-wt), were inserted. The skulls were harvested after four weeks and subjected to histological examination. The percentage of bone regeneration by using PLA was less pronounced than after usage of pure PCL in comparison with controls. After treatment with PCL-transgen, a large amount of new formed bone could be found. In contrast, PCL-wt decreased significantly the bone regeneration, compared to the other tested groups. The bone covers made of pure PLA had substantially less influence on bone regeneration and the bone healing proceeded with a lot of connective tissue, whereas PLA-transgen and PLA-wt showed nearly comparable amount of new formed bone. Regarding the histological data, the hypothesis could be proposed that PCL and its composites have contributed to a higher quantity of the regenerated bone, compared to PLA. The histological studies showed comparable bone regeneration processes after treatment with tested covering materials, as well as in the untreated bone lesions. PMID:27597965

  18. Bone Regeneration after Treatment with Covering Materials Composed of Flax Fibers and Biodegradable Plastics: A Histological Study in Rats

    Directory of Open Access Journals (Sweden)

    Tomasz Gredes

    2016-01-01

    Full Text Available The aim of this study was to examine the osteogenic potential of new flax covering materials. Bone defects were created on the skull of forty rats. Materials of pure PLA and PCL and their composites with flax fibers, genetically modified producing PHB (PLA-transgen, PCL-transgen and unmodified (PLA-wt, PCL-wt, were inserted. The skulls were harvested after four weeks and subjected to histological examination. The percentage of bone regeneration by using PLA was less pronounced than after usage of pure PCL in comparison with controls. After treatment with PCL-transgen, a large amount of new formed bone could be found. In contrast, PCL-wt decreased significantly the bone regeneration, compared to the other tested groups. The bone covers made of pure PLA had substantially less influence on bone regeneration and the bone healing proceeded with a lot of connective tissue, whereas PLA-transgen and PLA-wt showed nearly comparable amount of new formed bone. Regarding the histological data, the hypothesis could be proposed that PCL and its composites have contributed to a higher quantity of the regenerated bone, compared to PLA. The histological studies showed comparable bone regeneration processes after treatment with tested covering materials, as well as in the untreated bone lesions.

  19. Bone Regeneration after Treatment with Covering Materials Composed of Flax Fibers and Biodegradable Plastics: A Histological Study in Rats.

    Science.gov (United States)

    Gredes, Tomasz; Kunath, Franziska; Gedrange, Tomasz; Kunert-Keil, Christiane

    2016-01-01

    The aim of this study was to examine the osteogenic potential of new flax covering materials. Bone defects were created on the skull of forty rats. Materials of pure PLA and PCL and their composites with flax fibers, genetically modified producing PHB (PLA-transgen, PCL-transgen) and unmodified (PLA-wt, PCL-wt), were inserted. The skulls were harvested after four weeks and subjected to histological examination. The percentage of bone regeneration by using PLA was less pronounced than after usage of pure PCL in comparison with controls. After treatment with PCL-transgen, a large amount of new formed bone could be found. In contrast, PCL-wt decreased significantly the bone regeneration, compared to the other tested groups. The bone covers made of pure PLA had substantially less influence on bone regeneration and the bone healing proceeded with a lot of connective tissue, whereas PLA-transgen and PLA-wt showed nearly comparable amount of new formed bone. Regarding the histological data, the hypothesis could be proposed that PCL and its composites have contributed to a higher quantity of the regenerated bone, compared to PLA. The histological studies showed comparable bone regeneration processes after treatment with tested covering materials, as well as in the untreated bone lesions.

  20. Cell Sources for Bone Regeneration: The Good, the Bad, and the Ugly (But Promising)

    Science.gov (United States)

    2011-01-01

    Based on the extensive investigation of various ways to regenerate bone, bone marrow stromal cells, in conjunction with ceramic scaffolds, show great promise for application in human patients, and are already in use in a limited number of clinical trials. In preparing for clinical trials, scale-up current good manufacturing processes (cGMP) must incorporate the use of appropriate assays to ensure that the resulting cell product has maintained its biological activity. Future developments are needed to identify better scaffolds, and better ways to deliver cells with either injectable carriers, or by developing techniques to aide in their escape from the circulation and their incorporation into the pre-existing tissue. Lastly, development of methods that faithfully direct pluripotent stem cell differentiation into populations of osteogenic precursors (and ideally, containing skeletal stem cells) represents a new challenge in the field of bone regeneration, but also offer new opportunities to not only to study the biology of bone formation, but also to develop a robust cell source for bone regeneration. PMID:21797663

  1. Effects of 3D-Printed Polycaprolactone/β-Tricalcium Phosphate Membranes on Guided Bone Regeneration

    Science.gov (United States)

    Shim, Jin-Hyung; Won, Joo-Yun; Park, Jung-Hyung; Bae, Ji-Hyeon; Ahn, Geunseon; Kim, Chang-Hwan; Lim, Dong-Hyuk; Cho, Dong-Woo; Yun, Won-Soo; Bae, Eun-Bin; Jeong, Chang-Mo; Huh, Jung-Bo

    2017-01-01

    This study was conducted to compare 3D-printed polycaprolactone (PCL) and polycaprolactone/β-tricalcium phosphate (PCL/β-TCP) membranes with a conventional commercial collagen membrane in terms of their abilities to facilitate guided bone regeneration (GBR). Fabricated membranes were tested for dry and wet mechanical properties. Fibroblasts and preosteoblasts were seeded into the membranes and rates and patterns of proliferation were analyzed using a kit-8 assay and by scanning electron microscopy. Osteogenic differentiation was verified by alizarin red S and alkaline phosphatase (ALP) staining. An in vivo experiment was performed using an alveolar bone defect beagle model, in which defects in three dogs were covered with different membranes. CT and histological analyses at eight weeks after surgery revealed that 3D-printed PCL/β-TCP membranes were more effective than 3D-printed PCL, and substantially better than conventional collagen membranes in terms of biocompatibility and bone regeneration and, thus, at facilitating GBR. PMID:28441338

  2. Guided bone regeneration of a pronounced gingivo-alveolar cleft due to orthodontic space closure.

    Science.gov (United States)

    Pinheiro, Maria Letícia B; Moreira, Teresa Cristina; Feres-Filho, Eduardo J

    2006-06-01

    Gingival invagination is a relatively common occurrence following orthodontic closure of extraction sites. The present paper reports a combined periodontal and orthodontic treatment in a patient with a severe gingivo-alveolar cleft due to orthodontic closure of maxillary central incisor extraction space. A definite interdental gingival cleft, extending 8 mm into the alveolar bone, required the correction of the gingival deformity as a first step, followed by guided bone regeneration (GBR). The GBR approach included the emptying of the incisive foramen to approximately 5 mm in depth followed by the insertion of bioabsorbable hydroxyapatite and covering with a bioabsorbable barrier membrane. Six months afterward, the orthodontic therapy was resumed. Radiographs and clinical examination 4 years after the completion of therapy indicates functionally and aesthetically satisfactory and stable results. The present paper illustrates an additional application for the guided bone regeneration technique.

  3. Effects of 3D-Printed Polycaprolactone/β-Tricalcium Phosphate Membranes on Guided Bone Regeneration.

    Science.gov (United States)

    Shim, Jin-Hyung; Won, Joo-Yun; Park, Jung-Hyung; Bae, Ji-Hyeon; Ahn, Geunseon; Kim, Chang-Hwan; Lim, Dong-Hyuk; Cho, Dong-Woo; Yun, Won-Soo; Bae, Eun-Bin; Jeong, Chang-Mo; Huh, Jung-Bo

    2017-04-25

    This study was conducted to compare 3D-printed polycaprolactone (PCL) and polycaprolactone/β-tricalcium phosphate (PCL/β-TCP) membranes with a conventional commercial collagen membrane in terms of their abilities to facilitate guided bone regeneration (GBR). Fabricated membranes were tested for dry and wet mechanical properties. Fibroblasts and preosteoblasts were seeded into the membranes and rates and patterns of proliferation were analyzed using a kit-8 assay and by scanning electron microscopy. Osteogenic differentiation was verified by alizarin red S and alkaline phosphatase (ALP) staining. An in vivo experiment was performed using an alveolar bone defect beagle model, in which defects in three dogs were covered with different membranes. CT and histological analyses at eight weeks after surgery revealed that 3D-printed PCL/β-TCP membranes were more effective than 3D-printed PCL, and substantially better than conventional collagen membranes in terms of biocompatibility and bone regeneration and, thus, at facilitating GBR.

  4. Dried and free flowing granules of Spinacia oleracea accelerate bone regeneration and alleviate postmenopausal osteoporosis.

    Science.gov (United States)

    Adhikary, Sulekha; Choudhary, Dharmendra; Ahmad, Naseer; Kumar, Sudhir; Dev, Kapil; Mittapelly, Naresh; Pandey, Gitu; Mishra, Prabhat Ranjan; Maurya, Rakesh; Trivedi, Ritu

    2017-06-01

    The aim of this study was to demonstrate the efficacy of extract derived from Spinacia oleracea extract (SOE) in reversing bone loss induced by ovariectomy and bone healing properties in a drill-hole fracture model in rats. SOE was administered orally for 12 weeks in adult ovariectomized Sprague Dawley rats after inducing osteopenic condition. Bone micro-architecture, expressions of osteogenic and resorptive gene markers, biomechanical strength, new bone formation, and bone turnover markers were studied. Uterine histomorphometry was used to assess estrogenicity. Bone regeneration potential of SOE was assessed in a drill-hole fracture model. Fracture healing was assessed by calcein intensity and micro-CT analysis of callus at fracture region. SOE prevented ovariectomy-induced bone loss as evident from 122% increase in bone volume/tissue volume (BV/TV) and 29% decline in Tb.Sp in femoral trabecular micro-architecture. This was corroborated by the more than twofold stimulation in the expression of osteogenic genes runt-related transcription factor 2, osterix, osteocalcin, bone morphogenetic protein 2, collagen-1. Furthermore in the fracture healing model, we observed a 25% increase in BV/TV and enhancement in calcein intensity at the fractured site. The extract when converted into dried deliverable Spinaceae oleracea granule (SOG) form accelerated bone regeneration at fracture site, which was more efficient as evident by a 39% increase in BV/TV. Transforming SOE into dried granules facilitated prolonged systemic availability, thus providing enhanced activity for a period of 14 days. SOE treatment effectively prevents ovariectomy-induced bone loss and stimulated fracture healing in adult rats. The dried granular form of the extract of Spinaceae oleracea was effective in fracture healing at the same dose.

  5. Stem Cells for Bone Regeneration: From Cell-Based Therapies to Decellularised Engineered Extracellular Matrices

    Directory of Open Access Journals (Sweden)

    James N. Fisher

    2016-01-01

    Full Text Available Currently, autologous bone grafting represents the clinical gold standard in orthopaedic surgery. In certain cases, however, alternative techniques are required. The clinical utility of stem and stromal cells has been demonstrated for the repair and regeneration of craniomaxillofacial and long bone defects although clinical adoption of bone tissue engineering protocols has been very limited. Initial tissue engineering studies focused on the bone marrow as a source of cells for bone regeneration, and while a number of promising results continue to emerge, limitations to this technique have prompted the exploration of alternative cell sources, including adipose and muscle tissue. In this review paper we discuss the advantages and disadvantages of cell sources with a focus on adipose tissue and the bone marrow. Additionally, we highlight the relatively recent paradigm of developmental engineering, which promotes the recapitulation of naturally occurring developmental processes to allow the implant to optimally respond to endogenous cues. Finally we examine efforts to apply lessons from studies into different cell sources and developmental approaches to stimulate bone growth by use of decellularised hypertrophic cartilage templates.

  6. Multifunctional nano-hydroxyapatite and alginate/gelatin based sticky gel composites for potential bone regeneration

    Energy Technology Data Exchange (ETDEWEB)

    Cai, Yurong; Yu, Juhong [The Key Laboratory of Advanced Textile Materials and Manufacturing Technology of Ministry of Education, National Engineering Lab of Textile Fiber Materials & Processing Technology, College of Materials and Textile, Zhejiang Sci-Tech University, Hangzhou 310018 (China); Kundu, Subhas C. [Department of Biotechnology, Indian Institute of Technology (IIT) Kharagpur, West Bengal 721302 (India); Institute of Tissue Regeneration Engineering (ITREN), Dankook University, Cheonan 330-714 (Korea, Republic of); Yao, Juming, E-mail: yaoj@zstu.edu.cn [The Key Laboratory of Advanced Textile Materials and Manufacturing Technology of Ministry of Education, National Engineering Lab of Textile Fiber Materials & Processing Technology, College of Materials and Textile, Zhejiang Sci-Tech University, Hangzhou 310018 (China)

    2016-09-15

    To improve the fixations of the implant and implant-bone integration after joint arthroplasty from locally preventing inflammation and promoting the bone regeneration, we design a multifunctional biomaterial consisting of recombinant human bone morphogenetic protein 2 (rhBMP-2) and antibiotic loaded nano-hydroxyapatite with an alginate/gelatin sticky gel. We investigate its role for the prevention of the inflammation and possibility of inducing a new bone growth along with its adhesive ability. The stickiness exists in the composite, which may help to fix itself on the bone fracture surface. The composite sustains the antibacterial effect and promotes the proliferation and differentiation of MG63 cells in vitro. In vivo experimentation also shows that the composite gel has a role for the reduction of inflammation. It enhances the formation of new bone and blood vessels compared to both the sole rhBMP-2 and non-rhBMP-2/antibiotic loaded composite gels. The multifunctional composite provides a promising material for the prosthetic and bone tissue regeneration. - Highlights: • Multifunctional nanohydroxyapatite composite is fabricated. • The composite consists of nHAP, growth factor, antibiotic and alginate/gelatin gel. • The composite shows antibacterial effect and good cytocompatibility. • No adverse effect to the cells tested in vitro and in vivo.

  7. Experimental model for bone regeneration in oral and cranio-maxillo-facial surgery.

    Science.gov (United States)

    Mardas, Nikos; Dereka, Xanthippi; Donos, Nikolaos; Dard, Michel

    2014-02-01

    Bone and tooth loss, as a result of trauma, anatomical or congenital reasons, cancer, and periodontal disease, is a common therapeutic problem in the fields of cranio-maxillo-facial surgery and periodontics. The proposed techniques for the treatment of various bone defects encountered include bone grafts, bone substitutes, guided tissue regeneration, and distraction osteogenesis as well as their combinations. In addition, dental implants have been successfully utilized for the restoration of full or partial edentulism. The introduction and development of new therapeutic approaches and devices demand the use of appropriate animal models that present bone anatomy and healing comparable to human. Among other animal models, the pig is extensively documented in several biomedical areas and has been largely used in maxillo-facial surgery and implants dentistry-related research. Anatomical and physiological similarities with human in size, physiology, and bone biology contribute to a successful involvement of this animal to understand and treat various osseous lesions. However, improvements and standardization are requested with respect to consistency and discrimination abilities. The aim of this review is to provide a critical appraisal of the literature related to swine models for the evaluation of cranio-maxillo-facial osseous defect healing, regeneration, and bone-implant interface. This review should assist researchers in the field to select the most appropriate model for each dedicated purpose and also contribute to stimulate an innovative thinking on the use of porcine models.

  8. 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

  9. MicroRNA Regulation in Osteogenic and Adipogenic Differentiation of Bone Mesenchymal Stem Cells and its Application in Bone Regeneration.

    Science.gov (United States)

    Li, Binbin

    2018-01-01

    Bone mesenchymal stem cells (BMSCs) are multipotent stromal cells providing a useful cell source for treating bone diseases and metabolic disorders. BMSCs fate determination and lineage progression are controlled by multiple cytokines, transcriptional factors, signaling pathways, and microRNAs (miRNAs). MiRNAs are small non-coding RNAs that inhibit the posttranscriptional gene expression or degrade their targets. They are closely involved in controlling the key steps of osteogenesis and adipogenesis of BMSCs. We aim to summarize the roles of miRNAs and their pathways in regulating osteogenic and adipogenic differentiation of BMSCs, and sketch its preliminary applications in bone regeneration. We reviewed the published literature about the microRNA regulation in osteogenic and adipogenic differentiation of BMSCs. Most of miRNAs are expressed in BMSCs, perform as negative regulators of osteogenesis and have bidirectional effects on adipogenesis. Runx2 and PPARγ are two key transcriptional factors in osteogenesis and adipogenesis, respectively. Anti-miRNAs or miRNA mimics is potential therapeutic strategy to repress pathological miRNAs for cellular therapies to bone diseases. The preliminary applications of miRNAs in BMSCs strongly suggested their bright future in bone regeneration. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  10. 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.

  11. Leptin Overexpression in Bone Marrow Stromal Cells Promotes Periodontal Regeneration in a Rat Model of Osteoporosis.

    Science.gov (United States)

    Zheng, Baoyu; Jiang, Jun; Chen, Yuling; Lin, Minkui; Du, Zhibin; Xiao, Yin; Luo, Kai; Yan, Fuhua

    2017-08-01

    Osteoporosis is associated with widespread periodontitis and impaired periodontal healing. However, there is a lack of information about the outcomes of regenerative approaches under the influence of osteoporosis. This study investigates the effect of leptin (LEP) overexpression on the regenerative potential of bone marrow stromal cells (BMSCs) in an osteoporotic rat periodontal fenestration defect model. Rat BMSCs were transfected with adenoviruses harboring the human (h)LEP gene. Cell proliferation and osteogenic differentiation were evaluated. A β-tricalcium phosphate scaffold seeded with transfected cells was implanted into nude mice to investigate ectopic osteogenesis and into an osteoporotic rat defect to study periodontal regeneration. Regenerated periodontal and bone-like tissues were analyzed by histologic methods. hLEP overexpression induced osteogenic differentiation of BMSCs as evidenced by the upregulation of osteogenesis-related genes such as Runt-related transcription factor 2, alkaline phosphatase (ALP), and collagen Type I, as well as increased ALP activity and enhanced mineralization. Mice implanted with hLEP-BMSC-containing scaffolds showed more extensive formation of bone-like tissue than those in other groups. Periodontal defects were also filled to a greater degree when treated with hLEP-BMSCs and contained cementum and a well-organized periodontal ligament after 10 and 28 days. hLEP overexpression in BMSCs can stimulate periodontal regeneration in osteoporotic conditions and might be a promising strategy for periodontal regeneration in patients with osteoporosis.

  12. 3D-Printed Scaffolds and Biomaterials: Review of Alveolar Bone Augmentation and Periodontal Regeneration Applications

    Directory of Open Access Journals (Sweden)

    Farah Asa’ad

    2016-01-01

    Full Text Available 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.

  13. 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

  14. 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.

  15. Horizontal bone-augmentation procedures in implant dentistry: prosthetically guided regeneration.

    Science.gov (United States)

    Chiapasco, Matteo; Casentini, Paolo

    2018-02-25

    The rehabilitation of partially or totally edentulous patients with implant-supported prostheses has become routine, with excellent long-term outcome. A proper implant position is mandatory to achieve good functional and esthetic outcome and may require an adequate amount of alveolar bone and surrounding soft tissue. When this is lacking because of atrophy, sequelae of periodontal disease, traumas or congenital malformations, increased bone volume and/or keratinized mucosa can be obtained by guided bone regeneration, bone-grafting techniques and alveolar bone expansion. This article presents an evidence-based, prosthetically driven approach for the treatment of edentulous ridges with horizontal defects. The classification of bony defects, the main augmentation techniques, the selection criteria among different surgical procedures for different types of bony defects, and the advantages, disadvantages and limitations of each technique, are described in detail. © 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  16. 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

    OpenAIRE

    Washio, Ayako; Kitamura, Chiaki; Morotomi, Takahiko; Terashita, Masamichi; Nishihara, Tatsuji

    2012-01-01

    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 o...

  17. Effectiveness of Russian current in bone regeneration process in rats

    Directory of Open Access Journals (Sweden)

    Renata Aparecida de Oliveira Lima

    Full Text Available Abstract Introduction: Russian current is an electric current of average frequency that is able to restore the properties of skeletal muscle at a low treatment cost. It is essential to know the effects of Russian current in bone tissue, since electromagnetic energy could be an efficient and low cost method to treat bone disorders. Objective: The aim of the study was to evaluate the effectiveness of Russian current in the consolidation of tibia fracture in adult rats. Methods: 24 adult male Albinus Wistar rats wereused. The animals were divided randomly into two groups: control group (CG, composed of 12 animals, and Intervention Group (IG consisting of 12 animals, both groups were submitted to osteotomy (proximal medial surface of the tibia. The IG underwent an electrical stimulation protocol with Russian current, while the CG did not undergo any kind of intervention. Euthanasia was performed in three animals of each group on the following days: 5, 10, 20, and 30 days of treatment. Results: The results suggested higher primary ossification, intense osteogenic activity, and increased thickness of the periosteum, characterizing more advanced ossification and a greater presence of trabecular bone marrow in rats in the group subjected to the treatment. In this way, we can assign one more beneficial effect to interventions with Russian current, for the treatment of postfracture rehabilitation. Conclusion: In both groups the bone tissue repair process occurred, but in the electrically stimulated group the osteogenesis process was more advanced.

  18. Alveolar bone regeneration pattern following surgical and non ...

    African Journals Online (AJOL)

    2002-12-07

    Dec 7, 2002 ... hygiene and degree of mobility with loss of attachment were measured at baseline, 1,3 and 6 months after treatment. Standardized reproducible radiographs of the interproxi- mal sites were taken before and 6 months after treatment. Al- veolar bone levels pre and post treatment were measured with.

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

    DEFF Research Database (Denmark)

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

    1998-01-01

    group. Undecalcified sections were prepared for histologic evaluation after an observation period of 8 weeks. Complete bone healing of the defects was not observed in any of the specimens. The Polyglactin 910 material lacks physical strength, resulting in collapse of the membrane and brain tissue...

  20. Alveolar bone regeneration pattern following surgical and non ...

    African Journals Online (AJOL)

    One hundred and fifty six interproximal sites, with periodontal pockets deeper than 5mm and showing loss of bone on standard dental periapical radiographs, were treated by subgingival instrumentation and open periodontal flap debridement in 12 patients properly motivated and given thorough oral hygiene instructions.

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

    NARCIS (Netherlands)

    Ribeiro, N.; Sousa, S.R.; van Blitterswijk, Clemens; Moroni, Lorenzo; Monteiro, F.J.

    2014-01-01

    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

  2. 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.

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

    International Nuclear Information System (INIS)

    Nandi, Samit K.; Kundu, Biswanath; Mukherjee, Jayanta; Mahato, Arnab; Datta, Someswar; Balla, Vamsi Krishna

    2015-01-01

    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

  4. Fabrication of calcium phosphate-loaded carboxymethyl cellulose non-woven sheets for bone regeneration.

    Science.gov (United States)

    Qi, Pan; Ohba, Shinsuke; Hara, Yuichi; Fuke, Masaya; Ogawa, Takayuki; Ohta, Seiichi; Ito, Taichi

    2018-06-01

    Calcium phosphate-loaded carboxymethyl cellulose non-woven sheets (CMC/CaP sheet) were fabricated and their potential to induce in vitro osteoblast differentiation and in vivo bone regeneration were investigated. The CMC/CaP sheets were prepared by alternately soaking protonated-CMC non-woven sheets in CaCl 2 and Na 2 HPO 4 aqueous solutions. Because of its slow water uptake rate, the protonated-CMC was successfully loaded with a mixed phase of brushite and hydroxyapatite. In vitro, the CMC/CaP sheet induced osteoblast differentiation of human mesenchymal stromal cells (hMSCs), as shown by calcification and the upregulation of osteoblast marker genes. In absence of CaP, hMSCs on the CMC sheet had enhanced expression of alkaline phosphatase (ALP) only, indicative of early osteoblast differentiation. Finally, bone regeneration by the CMC/CaP sheet was demonstrated in a mouse calvarial defect model, based on micro-computed tomography (micro-CT), Masson's trichrome staining, and immunostaining for osteoblast markers. Cells expressing the transcription factor Sp7/Osterix, which is essential for osteoblast differentiation, were detected around the new bone. The combined effect of CMC and CaP enhanced osteoblast differentiation and the CMC/CaP non-woven sheet was found to be an easy-to-handle and flexible scaffold for bone regeneration. Copyright © 2018 Elsevier Ltd. All rights reserved.

  5. Evaluation of a starch-based double layer scaffold for bone regeneration in a rat model.

    Science.gov (United States)

    Requicha, Joao F; Moura, Tiago; Leonor, Isabel B; Martins, Teresa; Muñoz, Fernando; Reis, Rui L; Gomes, Manuela E; Viegas, Carlos A

    2014-07-01

    Damages in the maxillofacial bones are frequent in humans following trauma, metabolic diseases, neoplasia, or inflammatory processes. Many of the available treatments to regenerate bone are often ineffective. The goal of this work was to assess the in vivo behavior of an innovative double-layered scaffold based on a blend of starch and polycaprolactone (SPCL) that comprises a membrane obtained by solvent casting, which aims to act as a guided tissue regeneration membrane, and a wet-spun fiber mesh (in some cases functionalized with osteoconductive silanol groups) targeting bone regeneration. The behavior of the double layer scaffold, functionalized with silanol groups (SPCL-Si) or without (SPCL), was assessed in a mandibular rodent model and compared to a commercial collagen membrane (positive control) and to empty defects (negative control). After 8 weeks of implantation, the micro-computed tomography and the histomorphometric analysis revealed that the SPCL-Si scaffolds induced significantly higher new bone formation compared to the collagen membrane and to the empty defects, although they had a similar performance when compared to the SPCL scaffolds. © 2014 Orthopaedic Research Society. Published by Wiley Periodicals, Inc.

  6. 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.

  7. Stem cell technology for bone regeneration: current status and potential applications

    Directory of Open Access Journals (Sweden)

    Asatrian G

    2015-02-01

    Full Text Available Greg Asatrian,1 Dalton Pham,1,2 Winters R Hardy,3 Aaron W James,1–3 Bruno Peault3,4 1Dental and Craniofacial Research Institute and Section of Orthodontics, School of Dentistry, 2Department of Pathology and Laboratory Medicine, David Geffen School of Medicine, 3UCLA/Orthopaedic Hospital Department of Orthopaedic Surgery and the Orthopaedic Hospital Research Center, Los Angeles, CA, USA; 4Medical Research Council Centre for Regenerative Medicine, Edinburgh, Scotland, UK Abstract: Continued improvements in the understanding and application of mesenchymal stem cells (MSC have revolutionized tissue engineering. This is particularly true within the field of skeletal regenerative medicine. However, much remains unknown regarding the native origins of MSC, the relative advantages of different MSC populations for bone regeneration, and even the biologic safety of such unpurified, grossly characterized cells. This review will first summarize the initial discovery of MSC, as well as the current and future applications of MSC in bone tissue engineering. Next, the relative advantages and disadvantages of MSC isolated from distinct tissue origins are debated, including the MSC from adipose, bone marrow, and dental pulp, among others. The perivascular origin of MSC is next discussed. Finally, we briefly comment on pluripotent stem cell populations and their possible application in bone tissue engineering. While continually expanding, the field of MSC-based bone tissue engineering and regeneration shows potential to become a clinical reality in the not-so-distant future.Keywords: mesenchymal stem cell, pericyte, bone tissue engineering, MSC, ASC, DMSC

  8. Bone regeneration of osteoporotic vertevral body defects using PRP and gelatin β-TCP sponges.

    Science.gov (United States)

    Sakata, Munehiro; Tonomura, Hitoshi; Itsuji, Tomonori; Ishibashi, Hidenobu; Takatori, Ryota; Mikami, Yasuo; Nagae, Masateru; Matsuda, Ken-Ichi; Tabata, Yasuhiko; Tanaka, Masaki; Kubo, Toshikazu

    2017-12-22

    The objective of the present study was to investigate the effect of platelet-rich plasma (PRP) combined with gelatin β-tricalcium phosphate (β-TCP) sponge on bone generation in a lumbar vertebral body defect of ovariectomized rat. After creating critical size defects in the center of the anterior vertebral body, the defects were filled with the following materials: (1) no material (control group), (2) gelatin β-TCP sponge with PRP (PRP sponge group), and (3) gelatin β-TCP sponge with phosphate-buffered saline (PBS sponge group). Microcomputed tomography and histological evaluation were performed immediately after surgery and at 4, 8, and 12 weeks to assess bone regeneration. Biomechanical test was also performed at postoperative week 12. In the PRP sponge group, both imaging and histological examination showed that visible osteogenesis was first induced and additional growth of bone tissue was observed in the transplanted sponge, compared with the PBS sponge group. There was no negative effect of either PRP sponge or PBS sponge transplantation on bone tissue generation around the periphery of the defect. Biomechanical test showed increased stiffness of the affected vertebral bodies in the PRP sponge group. These results indicate that PRP-impregnated gelatin β-TCP sponge is effective for facilitating bone regeneration in lumbar vertebral bone defect under osteoporotic condition. PRP combined with gelatin β-TCP sponges could be potentially useful for developing a new approach to vertebroplasty for osteoporotic vertebral fracture.

  9. Clinical study of guided bone regeneration with resorbable polylactide-co-glycolide acid membrane.

    Science.gov (United States)

    Kawasaki, Takako; Ohba, Seigo; Nakatani, Yuya; Asahina, Izumi

    2018-02-10

    The guided bone regeneration (GBR) technique is often applied to provide sufficient bone for ideal implant placement. The objective of this study was to evaluate whether GC membrane ® , which has already been used for guided tissue regeneration (GTR), can also be available for GBR. Twenty-three implants in 18 patients were evaluated in the study. All patients underwent implant placement with GBR using GC membrane ® . Cone-beam computed tomography was performed at 13-30 weeks after surgery and the amount of augmented bone was assessed. The implant stability quotient (ISQ) was measured at the second operation to evaluate implant stability. Although wound dehiscence was observed at 4 of 23 regions (17.4%), all wounds closed quickly without any events by additional antibiotic administration. GBR-induced bone augmentation of 0.70-2.56 mm horizontally and 0-6.82 mm vertically. Only 0.18 mm of bone recession was observed at 16-24 months after implant placement. GBR with GC membrane ® induced sufficient bone augmentation, leading to successful implant treatment. The present results suggest that GC membrane ® is available not only for GTR, but also for GBR.

  10. The role of barrier membranes for guided bone regeneration and restoration of large bone defects: current experimental and clinical evidence

    Science.gov (United States)

    2012-01-01

    Treatment of large bone defects represents a great challenge in orthopedic and craniomaxillofacial surgery. Although there are several methods for bone reconstruction, they all have specific indications and limitations. The concept of using barrier membranes for restoration of bone defects has been developed in an effort to simplify their treatment by offering a sinlge-staged procedure. Research on this field of bone regeneration is ongoing, with evidence being mainly attained from preclinical studies. The purpose of this review is to summarize the current experimental and clinical evidence on the use of barrier membranes for restoration of bone defects in maxillofacial and orthopedic surgery. Although there are a few promising preliminary human studies, before clinical applications can be recommended, future research should aim to establish the 'ideal' barrier membrane and delineate the need for additional bone grafting materials aiming to 'mimic' or even accelerate the normal process of bone formation. Reproducible results and long-term observations with barrier membranes in animal studies, and particularly in large animal models, are required as well as well-designed clinical studies to evaluate their safety, efficacy and cost-effectiveness. PMID:22834465

  11. Acceleration of biomimetic mineralization to apply in bone regeneration

    International Nuclear Information System (INIS)

    Jayasuriya, A Champa; Shah, Chiragkumar; Ebraheim, Nabil A; Jayatissa, Ahalapitiya H

    2008-01-01

    The delivery of growth factors and therapeutic drugs into bone defects is a major clinical challenge. Biomimetically prepared bone-like mineral (BLM) containing a carbonated apatite layer can be used to deliver growth factors and drugs in a controlled manner. In the conventional biomimetic process, BLM can be deposited on the biodegradable polymer surfaces by soaking them in simulated body fluid (SBF) for 16 days or more. The aim of this study was to accelerate the biomimetic process of depositing BML in the polymer surfaces. We accelerated the deposition of mineral on 3D poly(lactic-co-glycolic acid) (PLGA) porous scaffolds to 36-48 h by modifying the biomimetic process parameters and applying surface treatments to PLGA scaffolds. The BLM was coated on scaffolds after surface treatments followed by incubation at 37 0 C in 15 ml of 5x SBF. We characterized the BLM created using the accelerated biomineralization process with wide angle x-ray diffraction (XRD), Fourier transform infrared (FTIR) microscopy, and scanning electron microscopy (SEM). The FTIR and XRD analyses of mineralized scaffolds show similarities between biomimetically prepared BLM, and bone bioapatite and carbonated apatite. We also found that the BLM layer on the surface of scaffolds was stable even after 21 days immersed in Tris buffered saline and cell culture media. This study suggests that BLM was stable for at least 3 weeks in both media, and therefore, BLM has a potential for use as a carrier for biological molecules for localized release applications as well as bone tissue engineering applications

  12. Novel Therapy for Bone Regeneration in Large Segmental Defects

    Science.gov (United States)

    2015-10-01

    blood samples and will begin blood chemistry analysis this reporting period. That said, the most significant findings during this period is that TPO is...able to heal the critical size defect in minipigs. Our xray data show significant improvement compared to saline treated controls. We however also...Task 2. Perform surgeries on minipigs and evaluate bone healing with xray . Task 2a. Fabricate Scaffolds –completed by Dr. Chu. Task 2b

  13. Strontium borate glass: potential biomaterial for bone regeneration

    OpenAIRE

    Pan, H. B.; Zhao, X. L.; Zhang, X.; Zhang, K. B.; Li, L. C.; Li, Z. Y.; Lam, W. M.; Lu, W. W.; Wang, D. P.; Huang, W. H.; Lin, K. L.; Chang, J.

    2009-01-01

    Boron plays important roles in many life processes including embryogenesis, bone growth and maintenance, immune function and psychomotor skills. Thus, the delivery of boron by the degradation of borate glass is of special interest in biomedical applications. However, the cytotoxicity of borate glass which arises with the rapid release of boron has to be carefully considered. In this study, it was found that the incorporation of strontium into borate glass can not only moderate the rapid relea...

  14. Optimizing Segmental Bone Regeneration Using Functionally Graded Scaffolds

    Science.gov (United States)

    2012-10-01

    demonstrated that the release of VEGF by HOBs can be enhanced with 1,25- dihydroxyvitamin D3 induction , but this enhancement was only observed in cocultures... Induction of bone formation using a recombinant adenoviral vector carrying the hu- man BMP-2 gene in a rabbit spinal fusion model. Calcif. Tissue...intranuclear targeting share a Runx2 motif required for osteogenic lineage induction and BMP2 responsive transcription. J Cell Physiol 2005;204:63e72. [21

  15. A Bone-Implant Interaction Mouse Model for Evaluating Molecular Mechanism of Biomaterials/Bone Interaction.

    Science.gov (United States)

    Liu, Wenlong; Dan, Xiuli; Wang, Ting; Lu, William W; Pan, Haobo

    2016-11-01

    The development of an optimal animal model that could provide fast assessments of the interaction between bone and orthopedic implants is essential for both preclinical and theoretical researches in the design of novel biomaterials. Compared with other animal models, mice have superiority in accessing the well-developed transgenic modification techniques (e.g., cell tracing, knockoff, knockin, and so on), which serve as powerful tools in studying molecular mechanisms. In this study, we introduced the establishment of a mouse model, which was specifically tailored for the assessment of bone-implant interaction in a load-bearing bone marrow microenvironment and could potentially allow the molecular mechanism study of biomaterials by using transgenic technologies. The detailed microsurgery procedures for developing a bone defect (Φ = 0.8 mm) at the metaphysis region of the mouse femur were recorded. According to our results, the osteoconductive and osseointegrative properties of a well-studied 45S5 bioactive glass were confirmed by utilizing our mouse model, verifying the reliability of this model. The feasibility and reliability of the present model were further checked by using other materials as objects of study. Furthermore, our results indicated that this animal model provided a more homogeneous tissue-implant interacting surface than the rat at the early stage of implantation and this is quite meaningful for conducting quantitative analysis. The availability of transgenic techniques to mechanism study of biomaterials was further testified by establishing our model on Nestin-GFP transgenic mice. Intriguingly, the distribution of Nestin + cells was demonstrated to be recruited to the surface of 45S5 glass as early as 3 days postsurgery, indicating that Nestin + lineage stem cells may participate in the subsequent regeneration process. In summary, the bone-implant interaction mouse model could serve as a potential candidate to evaluate the early stage tissue

  16. Pilot study on orthodontic space closure after guided bone regeneration.

    Science.gov (United States)

    Reichert, Christoph; Wenghöfer, Matthias; Götz, Werner; Jäger, Andreas

    2011-03-01

    In the present study, the benefit of moving teeth into extraction sockets preserved by a bone substitute was evaluated. This was performed to determine whether this was advantageous for orthodontic space closure. Socket preservation employing the bony alveolus in patients presenting the orthodontic indication for premolar extraction therapy was performed. Analogue premolars were extracted in a split-mouth design. One extraction alveolus was filled with a silica matrix-embedded, nanocrystalline hydroxyapatite bone substitute, with the other acting as a control. The orthodontic space was then closed using NiTi closed coil springs (200 g). Photographs and X-rays were acquired for documentation. Space closure succeeded without complications, e.g., root resorptions or inflammations. Gingival invaginations occurred in two of the control sites. A difference in the velocity of extraction space closure in one patient was also observed. Orthodontic tooth movement using this bone replacement material is possible according to these study results. This technique, thus, warrants further investigation in future clinical trials focusing on preventive means to reduce the development of gingival invaginations.

  17. Cellular and Molecular Mechanisms of Bone Remodeling*

    OpenAIRE

    Raggatt, Liza J.; Partridge, Nicola C.

    2010-01-01

    Physiological bone remodeling is a highly coordinated process responsible for bone resorption and formation and is necessary to repair damaged bone and to maintain mineral homeostasis. In addition to the traditional bone cells (osteoclasts, osteoblasts, and osteocytes) that are necessary for bone remodeling, several immune cells have also been implicated in bone disease. This minireview discusses physiological bone remodeling, outlining the traditional bone biology dogma in light of emerging ...

  18. Regeneration

    Science.gov (United States)

    George A. Schier; Wayne D. Shepperd; John R. Jones

    1985-01-01

    There are basically two approaches to regenerating aspen stands-sexual reproduction using seed, or vegetative regeneration by root suckering. In the West, root suckering is the most practical method. The advantage of having an existing, well established root system capable of producing numerous root suckers easily outweighs natural or artificial reforestation in the...

  19. 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

  20. Protein expression during early stages of bone regeneration under hydrophobic and hydrophilic titanium domes. A pilot study.

    Science.gov (United States)

    Calciolari, E; Mardas, N; Dereka, X; Anagnostopoulos, A K; Tsangaris, G T; Donos, N

    2018-04-01

    There is significant evidence that, during the early stages of osseointegration, moderately rough hydrophilic (SLActive) surfaces can accelerate osteogenesis and increase bone-to-implant contact in comparison to hydrophobic (SLA) surfaces. However, very little is known regarding the molecular mechanisms behind the influence that surface chemistry modifications to increase hydrophilicity determine on bone healing. The aim of this study was to describe for the first time the proteins and related signalling pathways expressed during early osseous healing stages under SLA and SLActive titanium domes for guided bone regeneration. One SLA and 1 SLActive dome with an internal diameter of 5.0 mm and a height of 3.0 mm were secured to the parietal bones of nine 6-month-old male New Zealand rabbits. Three animals were randomly euthanized at 4, 7 and 14 days and the newly formed tissues retrieved under the domes were analysed with liquid chromatography-mass spectrometry/mass spectrometry. STRING and KEGG databases were applied for Gene Ontology and pathway analyses. A different modulation of several pathways was detected between the 2 groups at all healing times. The main differences in the osseous healing response associated to the 2 surfaces were related to pathways involved in regulating the inflammatory response, differentiation of osteoblast precursors and skeletogenesis. At day 7, the highest number of proteins and the highest cellular activity were observed in both groups, although a more complex and articulated proteome in terms of cellular metabolism and signal transduction was observed in SLActive samples. This is the first study describing the proteome expressed during early healing stages of guided bone regeneration and osseointegration. A combination of enhanced early osteogenic response and reduced inflammatory response were suggested for the hydrophilic group. Future studies are needed to corroborate these findings and explore the molecular effects of

  1. Potential of magnetic nanofiber scaffolds with mechanical and biological properties applicable for bone regeneration.

    Science.gov (United States)

    Singh, Rajendra K; Patel, Kapil D; Lee, Jae Ho; Lee, Eun-Jung; Kim, Joong-Hyun; Kim, Tae-Hyun; Kim, Hae-Won

    2014-01-01

    Magnetic nanofibrous scaffolds of poly(caprolactone) (PCL) incorporating magnetic nanoparticles (MNP) were produced, and their effects on physico-chemical, mechanical and biological properties were extensively addressed to find efficacy for bone regeneration purpose. MNPs 12 nm in diameter were citrated and evenly distributed in PCL solutions up to 20% and then were electrospun into nonwoven nanofibrous webs. Incorporation of MNPs greatly improved the hydrophilicity of the nanofibers. Tensile mechanical properties of the nanofibers (tensile strength, yield strength, elastic modulus and elongation) were significantly enhanced with the addition of MNPs up to 15%. In particular, the tensile strength increase was as high as ∼25 MPa at 15% MNPs vs. ∼10 MPa in pure PCL. PCL-MNP nanofibers exhibited magnetic behaviors, with a high saturation point and hysteresis loop area, which increased gradually with MNP content. The incorporation of MNPs substantially increased the degradation of the nanofibers, with a weight loss of ∼20% in pure PCL, ∼45% in 10% MNPs and ∼60% in 20% MNPs. Apatite forming ability of the nanofibers tested in vitro in simulated body fluid confirmed the substantial improvement gained by the addition of MNPs. Osteoblastic cells favored the MNPs-incorporated nanofibers with significantly improved initial cell adhesion and subsequent penetration through the nanofibers, compared to pure PCL. Alkaline phosphatase activity and expression of genes associated with bone (collagen I, osteopontin and bone sialoprotein) were significantly up-regulated in cells cultured on PCL-MNP nanofibers than those on pure PCL. PCL-MNP nanofibers subcutaneously implanted in rats exhibited minimal adverse tissue reactions, while inducing substantial neoblood vessel formation, which however, greatly limited in pure PCL. In vivo study in radial segmental defects also signified the bone regeneration ability of the PCL-MNP nanofibrous scaffolds. The magnetic, bone

  2. The Bioresorption and Guided Bone Regeneration of Absorbable Hydroxyapatite-Coated Magnesium Mesh.

    Science.gov (United States)

    Byun, Soo-Hwan; Lim, Ho-Kyung; Kim, Soung-Min; Lee, Sung-Mi; Kim, Hyoun-Ee; Lee, Jong-Ho

    2017-03-01

    Nonabsorbable metallic membrane for guided bone regeneration is remained permanently even though after complete healing. There would be metallic exposure followed by the risk of infection; the membrane should be removed for the additional procedure such as implant installation. Since absorbable nonmetallic mesh is absorbed within 3 to 6 months, it is unnecessary to be removed. However, the absorbable membrane shows lower retention, lower mechanical strength, and difficulty of manipulation than the nonabsorbable ones.The purpose of this study is to evaluate the ability of absorbable metallic mesh (hydroxyapatite-coated magnesium mesh) with acceptable mechanical properties and satisfying biocompatibility. The bioresorption and fate of magnesium were evaluated in Sprague Dawley rat (SD rat) with critical defect of calvarium. The critical defect with a diameter of 8 mm was made on calvarium using trephine bur in 18 SD rats. The defected models were divided into 2 groups: the control group (9 SD rat) without mesh and the experimental group (9 SD rat) with the insertion of prototype HA-coated magnesium mesh. The 3 SD rats were sacrificed at 6, 12, and 18 weeks. The histopathological and radiographic examinations were performed afterward. In the control group, there was no specific symptom. The experimental group also showed no specific symptom including swelling and dehiscence related to hydrogen gas formation. From 6 to 18 weeks, the experimental group showed the progressive absorption and fracture of magnesium mesh. However, there was no specific effectiveness of guided bone regeneration in both groups. There was no significant difference in bone volume, bone surface, and bone volume fraction between the negative control group and the group with magnesium mesh (P >0.05). Hydroxyapatite-coated magnesium mesh showed reasonable process of bioresorption and bony reaction; however, the effectiveness of guided bone regeneration and management of the bioresorption rate

  3. [Factors affecting bone regeneration in Ilizarov callus distraction].

    Science.gov (United States)

    Fink, B; Krieger, M; Schneider, T; Menkhaus, S; Fischer, J; Rüther, W

    1995-12-01

    We evaluated the X-rays of 36 patients who underwent 50 callus distractions. With the aid of a computerized digitalisation system for analogue films, the relative X-ray density of the distraction area was calculated for each X-ray. These relative X-ray densities were figured graphically for the duration of treatment for each patient. In the consolidation phase, the graph of each patient had a logarithmic relationship. The gradients of the logarithmic density curves were considered an indicator of the quantity of new bone formation. These gradients were correlated to the following clinical parameters: age of the patient, beginning of distraction after corticotomy, average speed of distraction, average weight bearing during the distraction and consolidation phase, location of corticotomy (distal femur versus proximal tibia) and diclofenac medication. Except for the location of the corticotomy and diclofenac, all parameters had an influence on osteoneogenesis by callus distraction. The parameters affecting new bone formation the most were the age of the patient and weight bearing. Patients aged under 18 years (p = 0.005), beginning of distraction later than 8 days (p = 0.109), an average distraction speed below 1 mm/day (p = 0.079), and average weight bearing of more than 30 kg (p = 0.068 for the distraction phase and p = 0.089 for the consolidation phase) showed a quantitatively higher rate of new bone formation by callus distraction than the patients in the other groups. Patients with a shorter leg due to poliomyelitis and one patient with an amniotic leg tie showed a slower increase in X-ray density graphs than the other patients.

  4. Guided bone regeneration: dynamic procedures versus static shielding in an animal model.

    Science.gov (United States)

    Lethaus, Bernd; Tudor, Christian; Bumiller, Lars; Birkholz, Torsten; Wiltfang, Jörg; Kessler, Peter

    2010-10-01

    Due to its osteoinductive potential, the periosteum plays a crucial role in the process of neoosteogenesis. Therefore, periosteal elevation can lead to new bone formation in an artificially created space. In this study, we compared dynamic periosteal elevation with static shielding in an animal experiment. Different elevation/shielding heights of 5, 10, and 15 mm were tested with regard to various consolidation periods. Histological analysis, histomorphometry, and microradiography were used to measure the quantity and quality of the newly formed bone. No significant differences regarding bone quantity or quality were found between the two techniques. The cumulative results for the bone regeneration in the space created by distraction/elevation were about 66% in the dynamic and 67% in static procedure. The main advantages of both techniques are minimal invasion and low morbidity. In terms of clinical applications, periosteal elevation could be applied in cranio-maxillofacial surgery, in pre-implant augmentation and in reconstructive surgery.

  5. Molecular and Cellular Mechanisms of Axonal Regeneration After Spinal Cord Injury.

    Science.gov (United States)

    van Niekerk, Erna A; Tuszynski, Mark H; Lu, Paul; Dulin, Jennifer N

    2016-02-01

    Following axotomy, a complex temporal and spatial coordination of molecular events enables regeneration of the peripheral nerve. In contrast, multiple intrinsic and extrinsic factors contribute to the general failure of axonal regeneration in the central nervous system. In this review, we examine the current understanding of differences in protein expression and post-translational modifications, activation of signaling networks, and environmental cues that may underlie the divergent regenerative capacity of central and peripheral axons. We also highlight key experimental strategies to enhance axonal regeneration via modulation of intraneuronal signaling networks and the extracellular milieu. Finally, we explore potential applications of proteomics to fill gaps in the current understanding of molecular mechanisms underlying regeneration, and to provide insight into the development of more effective approaches to promote axonal regeneration following injury to the nervous system. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

  6. Biphasic Calcium Phosphate Ceramics for Bone Regeneration and Tissue Engineering Applications

    Directory of Open Access Journals (Sweden)

    Sonja Ellen Lobo

    2010-01-01

    Full Text Available Biphasic calcium phosphates (BCP have been sought after as biomaterials for the reconstruction of bone defects in maxillofacial, dental and orthopaedic applications. They have demonstrated proven biocompatibility, osteoconductivity, safety and predictability in in vitro, in vivo and clinical models. More recently, in vitro and in vivo studies have shown that BCP can be osteoinductive. In the field of tissue engineering, they represent promising scaffolds capable of carrying and modulating the behavior of stem cells. This review article will highlight the latest advancements in the use of BCP and the characteristics that create a unique microenvironment that favors bone regeneration.

  7. Electrospun silk fibroin/poly(lactide-co-ε-caprolactone) nanofibrous scaffolds for bone regeneration

    Science.gov (United States)

    Wang, Zi; Lin, Ming; Xie, Qing; Sun, Hao; Huang, Yazhuo; Zhang, DanDan; Yu, Zhang; Bi, Xiaoping; Chen, Junzhao; Wang, Jing; Shi, Wodong; Gu, Ping; Fan, Xianqun

    2016-01-01

    Background Tissue engineering has become a promising therapeutic approach for bone regeneration. Nanofibrous scaffolds have attracted great interest mainly due to their structural similarity to natural extracellular matrix (ECM). Poly(lactide-co-ε-caprolactone) (PLCL) has been successfully used in bone regeneration, but PLCL polymers are inert and lack natural cell recognition sites, and the surface of PLCL scaffold is hydrophobic. Silk fibroin (SF) is a kind of natural polymer with inherent bioactivity, and supports mesenchymal stem cell attachment, osteogenesis, and ECM deposition. Therefore, we fabricated hybrid nanofibrous scaffolds by adding different weight ratios of SF to PLCL in order to find a scaffold with improved properties for bone regeneration. Methods Hybrid nanofibrous scaffolds were fabricated by blending different weight ratios of SF with PLCL. Human adipose-derived stem cells (hADSCs) were seeded on SF/PLCL nanofibrous scaffolds of various ratios for a systematic evaluation of cell adhesion, proliferation, cytotoxicity, and osteogenic differentiation; the efficacy of the composite of hADSCs and scaffolds in repairing critical-sized calvarial defects in rats was investigated. Results The SF/PLCL (50/50) scaffold exhibited favorable tensile strength, surface roughness, and hydrophilicity, which facilitated cell adhesion and proliferation. Moreover, the SF/PLCL (50/50) scaffold promoted the osteogenic differentiation of hADSCs by elevating the expression levels of osteogenic marker genes such as BSP, Ocn, Col1A1, and OPN and enhanced ECM mineralization. In vivo assays showed that SF/PLCL (50/50) scaffold improved the repair of the critical-sized calvarial defect in rats, resulting in increased bone volume, higher trabecular number, enhanced bone mineral density, and increased new bone areas, compared with the pure PLCL scaffold. Conclusion The SF/PLCL (50/50) nanofibrous scaffold facilitated hADSC proliferation and osteogenic differentiation in

  8. Influence of bone marrow-derived mesenchymal stem cells pre-implantation differentiation approach on periodontal regeneration in vivo.

    Science.gov (United States)

    Cai, Xinjie; Yang, Fang; Yan, Xiangzhen; Yang, Wanxun; Yu, Na; Oortgiesen, Daniel A W; Wang, Yining; Jansen, John A; Walboomers, X Frank

    2015-04-01

    The implantation of bone marrow-derived mesenchymal stem cells (MSCs) has previously been shown successful to achieve periodontal regeneration. However, the preferred pre-implantation differentiation strategy (e.g. maintenance of stemness, osteogenic or chondrogenic induction) to obtain optimal periodontal regeneration is still unknown. This in vivo study explored which differentiation approach is most suitable for periodontal regeneration. Mesenchymal stem cells were obtained from Fischer rats and seeded onto poly(lactic-co-glycolic acid)/poly(ɛ-caprolactone) electrospun scaffolds, and then pre-cultured under different in vitro conditions: (i) retention of multilineage differentiation potential; (ii) osteogenic differentiation approach; and (iii) chondrogenic differentiation approach. Subsequently, the cell-scaffold constructs were implanted into experimental periodontal defects of Fischer rats, with empty scaffolds as controls. After 6 weeks of implantation, histomorphometrical analyses were applied to evaluate the regenerated periodontal tissues. The chondrogenic differentiation approach showed regeneration of alveolar bone and ligament tissues. The retention of multilineage differentiation potential supported only ligament regeneration, while the osteogenic differentiation approach boosted alveolar bone regeneration. Chondrogenic differentiation of MSCs before implantation is a useful strategy for regeneration of alveolar bone and periodontal ligament, in the currently used rat model. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  9. The temporal course of mucoperiosteal flap revascularization at guided bone regeneration-treated implant sites: a pilot study

    NARCIS (Netherlands)

    Milstein, Dan M. J.; Mathura, Keshen R.; Lindeboom, Jerôme A. H.; Ramsoekh, Dewkoemar; Lindeboom, Robert; Ince, Can

    2009-01-01

    P>Aims To investigate post-operative capillary density regeneration in healing mucoperiosteal flaps at guided bone regeneration-treated implant sites. Material and Methods A non-invasive post-operative investigation was performed in 10 patients using orthogonal polarization spectral (OPS) imaging

  10. The temporal course of mucoperiosteal flap revascularization at guided bone regeneration treated implant sites: a pilot study

    NARCIS (Netherlands)

    Milstein, D.M.J.; Mathura, K.R.; Lindeboom, J.A.H.; Ramsoekh, D.; Lindeboom, R.; Ince, C.

    2009-01-01

    Aims: To investigate post-operative capillary density regeneration in healing mucoperiosteal flaps at guided bone regeneration-treated implant sites. Material and Methods: A non-invasive post-operative investigation was performed in 10 patients using orthogonal polarization spectral (OPS) imaging

  11. Enhanced bone regeneration using an insulin-loaded nano-hydroxyapatite/collagen/PLGA composite scaffold.

    Science.gov (United States)

    Wang, Xing; Zhang, Guilan; Qi, Feng; Cheng, Yongfeng; Lu, Xuguang; Wang, Lu; Zhao, Jing; Zhao, Bin

    2018-01-01

    Insulin is widely considered as a classical hormone and drug in maintaining energy and glucose homeostasis. Recently, insulin has been increasingly recognized as an indispensable factor for osteogenesis and bone turnover, but its applications in bone regeneration have been restricted because of the short periods of activity and uncontrolled release. In this study, we incorporated insulin-loaded poly lactic-co-glycolic-acid (PLGA) nanospheres into nano-hydroxyapatite/collagen (nHAC) scaffolds and investigated the bioactivity of the composite scaffolds in vitro and in vivo. Bioactive insulin was successfully released from the nanospheres within the scaffold, and the release kinetics of insulin could be efficiently controlled by uniform-sized nanospheres. The physical characterizations of the composite scaffolds demonstrated that incorporation of nanospheres in nHAC scaffolds using this method did not significantly change the porosity, pore diameters, and compressive strengths of nHAC. In vitro, the insulin-loaded nHAC/PLGA composite scaffolds possessed favorable biological function for bone marrow mesenchymal stem cells adhesion and proliferation, as well as the differentiation into osteoblasts. In vivo, the optimized bone regenerative capability of this composite scaffold was confirmed in rabbit mandible critical size defects. These results demonstrated successful development of a functional insulin-PLGA-nHAC composite scaffold that enhances the bone regeneration capability of nHAC.

  12. Bone regeneration of calvarial defect using marine calcareous-derived beta-tricalcium phosphate macrospheres

    Directory of Open Access Journals (Sweden)

    Joshua Chou

    2014-02-01

    Full Text Available The aim of this study was to examine the bone regeneration properties of beta-tricalcium phosphate hydrothermally converted from foraminifera carbonate exoskeleton in the repair of rat calvarial defect. These natural materials possess unique interconnected porous network with uniform pore size distribution, which can be potentially advantageous. In total, 20 adult male Wistar rats received full-thickness calvarial defect with a diameter of 5 mm. The rate of newly formed bone was measured radiologically by X-ray and micro-computed tomography and by histologic examination. After 2 weeks, the beta-tricalcium phosphate group exhibited full closure of the defect site, while control group remained unrestored at the end of the 6-week experimentation. It was observed that the newly regenerated bone thickened over the course of the experiment in the beta-tricalcium phosphate group. No soft tissue reaction was observed around the beta-tricalcium phosphate implant and the rats remained healthy. These results showed that repair of the calvarial defect can be achieved by biomimetic beta-tricalcium phosphate macrospheres, which hold potential for application as bone grafts for bone augmentation surgeries.

  13. Graded porous polyurethane foam: a potential scaffold for oro-maxillary bone regeneration.

    Science.gov (United States)

    Giannitelli, S M; Basoli, F; Mozetic, P; Piva, P; Bartuli, F N; Luciani, F; Arcuri, C; Trombetta, M; Rainer, A; Licoccia, S

    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. Copyright © 2015 Elsevier B.V. All rights reserved.

  14. Electrospun PCL/gelatin composite nanofiber structures for effective guided bone regeneration membranes.

    Science.gov (United States)

    Ren, Ke; Wang, Yi; Sun, Tao; Yue, Wen; Zhang, Hongyu

    2017-09-01

    Guided bone regeneration (GBR) membranes have been proved of great benefit for bone tissue engineering due to the improvement of cell attachment and proliferation. To develop GBR membranes with better biocompatibility and more proper degradation ability, here we fabricated polycaprolactone (PCL, polymer)/gelatin (protein) hybrid nanofibrous GBR membranes via electrospinning, followed by crosslinking with genipin. Acetic acid (HAc) was utilized to resolve the phase separation of PCL and gelatin, therefore homogeneous PCL/gelatin hybrid nanofibers with different ratios were successfully prepared. FTIR, XPS, TGA, DSC results proved that the proportion of PCL and gelatin in the as-spun nanofiber membranes could be simply adjusted by changing the weight ratio of PCL and gelatin in the spinning solution. SEM and AFM images demonstrated that all the nanofibers possessed uniform and smooth structures both in two dimension (2D) and three dimension (3D). The mechanical tests showed that these nanofibers exhibited appropriate tensile and strength properties, which were suitable for bone tissue engineering. CCK-8 and SEM images revealed that all the membranes were biocompatible to MC3T3-e1 cells. In addition, the in vitro osteogenesis characterizations, alizarin red in normal medium and osteogenesis medium, indicated that the nanofibers could promote bone formation. Therefore, all these results could suggest that our design of electrospun polymer/protein nanofiber membranes was effective for guided bone regeneration. Copyright © 2017. Published by Elsevier B.V.

  15. Biodegradable inorganic-organic hybrids of methacrylate star polymers for bone regeneration.

    Science.gov (United States)

    Chung, Justin J; Fujita, Yuki; Li, Siwei; Stevens, Molly M; Kasuga, Toshihiro; Georgiou, Theoni K; Jones, Julian R

    2017-05-01

    Hybrids that are molecular scale co-networks of organic and inorganic components are promising biomaterials, improving the brittleness of bioactive glass and the strength of polymers. Methacrylate polymers have high potential as the organic source for hybrids since they can be produced, through controlled polymerization, with sophisticated polymer architectures that can bond to silicate networks. Previous studies showed the mechanical properties of hybrids can be modified by polymer architecture and molar mass (MM). However, biodegradability is critical if hybrids are to be used as tissue engineering scaffolds, since the templates must be remodelled by host tissue. Degradation by-products have to either completely biodegrade or be excreted by the kidneys. Enzyme, or bio-degradation is preferred to hydrolysis by water uptake as it is expected to give a more controlled degradation rate. Here, branched and star shaped poly(methyl methacrylate-co-3-(trimethoxysilyl)propyl methacrylate) (poly(MMA-co-TMSPMA)) were synthesized with disulphide based dimethacrylate (DSDMA) as a biodegradable branching agent. Biodegradability was confirmed by exposing the copolymers to glutathione, a tripeptide which is known to cleave disulphide bonds. Cleaved parts of the star polymer from the hybrid system were detected after 2weeks of immersion in glutathione solution, and MM was under threshold of kidney filtration. The presence of the branching agent did not reduce the mechanical properties of the hybrids and bone progenitor cells attached on the hybrids in vitro. Incorporation of the DSDMA branching agent has opened more possibilities to design biodegradable methacrylate polymer based hybrids for regenerative medicine. Bioactive glasses can regenerate bone but are brittle. Hybrids can overcome this problem as intimate interactions between glass and polymer creates synergetic properties. Implants have previously been made with synthetic polymers that degrade by water, however, they

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

    International Nuclear Information System (INIS)

    Tavakol, Shima; Ragerdi Kashani, Iraj; Azami, Mahmood; Khoshzaban, Ahad; Tavakol, Behnaz; Kharrazi, Sharmin; Ebrahimi, Somayeh; Rezayat Sorkhabadi, Seyed Mahdi

    2012-01-01

    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.

  17. Effects of calcium ions on titanium surfaces for bone regeneration.

    Science.gov (United States)

    Anitua, Eduardo; Piñas, Laura; Murias, Alia; Prado, Roberto; Tejero, Ricardo

    2015-06-01

    The chemistry and topography of implant surfaces are of paramount importance for the successful tissue integration of load-bearing dental and orthopedic implants. Here we evaluate in vitro and in vivo titanium implant surfaces modified with calcium ions (Ca(2+) surfaces). Calcium ions produce a durable chemical and nano-topographical modification of the titanium oxide interface. Time of flight secondary ion mass spectrometry examination of the outermost surface composition, shows that calcium ions in Ca(2+) surfaces effectively prevent adventitious hydrocarbon passivation of the oxide layer. In aqueous solutions Ca(2+) surfaces release within the first minute, 2/3 of the total measured Ca(2+), the rest is released over the following 85 days. Additionally, Ca(2+) surfaces significantly increase human fetal osteoblasts-like cell adhesion, proliferation and differentiation, as measured by the autocrine synthesis of osteopontin. Relevant for clinical application, after 12 weeks of healing in sheep tibia, microcomputer tomography and histomorphometric analysis show that Ca(2+) surfaces develop significantly more bone contacts and higher bone density in the 1mm region around the implant. Consequently, titanium implants modified with calcium ions represent a valuable tool to improve endosseous integration in the clinical practice. Copyright © 2015 Elsevier B.V. All rights reserved.

  18. Effects of 3D-Printed Polycaprolactone/β-Tricalcium Phosphate Membranes on Guided Bone Regeneration

    OpenAIRE

    Jin-Hyung Shim; Joo-Yun Won; Jung-Hyung Park; Ji-Hyeon Bae; Geunseon Ahn; Chang-Hwan Kim; Dong-Hyuk Lim; Dong-Woo Cho; Won-Soo Yun; Eun-Bin Bae; Chang-Mo Jeong; Jung-Bo Huh

    2017-01-01

    This study was conducted to compare 3D-printed polycaprolactone (PCL) and polycaprolactone/?-tricalcium phosphate (PCL/?-TCP) membranes with a conventional commercial collagen membrane in terms of their abilities to facilitate guided bone regeneration (GBR). Fabricated membranes were tested for dry and wet mechanical properties. Fibroblasts and preosteoblasts were seeded into the membranes and rates and patterns of proliferation were analyzed using a kit-8 assay and by scanning electron micro...

  19. Effect of autologous platelet-rich plasma on bone regeneration in mandibular fractures.

    Science.gov (United States)

    Daif, Emad T

    2013-10-01

    The aim of this study was to assess the effect of autologous platelet-rich plasma (PRP) on bone regeneration in mandibular fractures via a cone beam computed tomography (CBCT). Twenty-four patients having parasymphyseal fractures participated in this study. They were randomly divided into two equal groups. Group A was treated by two titanium miniplates and screws plus local application of activated PRP along the fracture line, whereas group B was treated by the same bone plates and screws without application of PRP. The patients were recalled at 1 week, 3 and 6 months after surgery for clinical assessment and measuring the bone density via CBCT at a region of interest (ROI) including the fracture line. The mean values of the bone density measurements, in both groups, were higher at 3 and 6 months than 1 week after surgery. At 1 week after surgery, the values were 542 ± 93 HU and 515 ± 81 HU in group A and B, respectively. In group A, the mean value of bone density measurements was 728 ± 58 HU (range 620-796 HU) at 3 months after surgery and it was 1024 ± 188 HU (range 825-1490 HU) 6 months later. While in group B, the mean values of the bone density measurements at the ROI were 600 ± 78 HU (range 520-790 HU) and 756 ± 53 HU (range 710-890 HU) at 3 and 6 months after surgery, respectively. The increase in the bone density measurements at 3 and 6 months after surgery was statistically significant only in group A (P = 0.0002 and P = 0.0001, respectively). It can be concluded that direct application of the PRP along the fracture lines may enhance the bone regeneration in mandibular fractures. © 2012 John Wiley & Sons A/S.

  20. 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.

  1. 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.

  2. Interim endodontic therapy for alveolar socket bone regeneration of infected hopeless teeth prior to implant therapy.

    Science.gov (United States)

    Rass, Marwan Abou

    2010-01-01

    The immediate placement of implants in the fresh extraction sockets of infected teeth with periradicular and periapical lesions is contraindicated because of both the infection and the loss of architecture required for proper implant placement. There are 4 approaches for implant replacement of a hopeless tooth with lesions: (1) extraction and delayed implant placement; (2) extraction, debridement, guided bone regeneration (GBR), guided tissue regeneration (GTR), and delayed implant placement; (3) extraction, intrasocket debridement, and immediate implant placement; or (4) extraction, debridement, GBR, GTR, and simultaneous implant placement. The extraction of such hopeless teeth often results in large bone and soft tissue defects that are difficult to repair. This article introduces an alternative approach: interim endodontic implant site preparation, defined as a transitional, surgical, or nonsurgical endodontic treatment to regenerate the hopeless tooth bone defects and prepare the site for proper implant placement. This article describes 3 distinct interim endodontic protocols used to manage 5 patients, all of whom had severely infected hopeless teeth with large lesions and were treatment planned for implant replacement: the first, interim nonsurgical endodontic treatment to restore the normal anatomy of the infected hopeless tooth; the second, interim surgical endodontics on the hopeless tooth with preexisting endodontic treatment to regenerate apical bone for primary implant stability, thus avoiding the involvement of the maxillary sinus and other critical anatomic structures; and the third, interim surgical endodontics on the hopeless tooth with preexisting endodontic treatment to confine the size of the osseous defect and simplify the GBR and GTR procedures. The outcome of interim endodontic treatment on these 5 patients demonstrated that tooth extraction would have been a less predictable approach. The interim treatment changed the overall direction of the

  3. Dose reduction of bone morphogenetic protein-2 for bone regeneration using a delivery system based on lyophilization with trehalose

    Directory of Open Access Journals (Sweden)

    Zhang X

    2018-01-01

    Full Text Available Xiaochen Zhang,1,* Quan Yu,2,* Yan-an Wang,1 Jun Zhao2 1Department of Oral and Maxillofacial-Head and Neck Oncology, 2Department of Orthodontics, College of Stomatology, Ninth People’s Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China *These authors contributed equally to this work Introduction: To induce sufficient new bone formation, high doses of bone morphogenetic protein-2 (BMP-2 are applied in regenerative medicine that often induce serious side effects. Therefore, improved treatment strategies are required. Here, we investigate whether the delivery of BMP-2 lyophilized in the presence of trehalose reduced the dose of BMP-2 required for bone regeneration. Materials and methods: A new growth factor delivery system was fabricated using BMP-2-loaded TiO2 nanotubes by lyophilization with trehalose (TiO2-Lyo-Tre-BMP-2. We measured BMP-2 release characteristics, bioactivity, and stability, and determined the effects on the osteogenic differentiation of bone marrow stromal cells in vitro. Additionally, we evaluated the ability of this formulation to regenerate new bone around implants in rat femur defects by micro-computed tomography (micro-CT, sequential fluorescent labelling, and histological analysis. Results: Compared with absorbed BMP-2-loaded TiO2 nanotubes (TiO2-BMP-2, TiO2-Lyo-Tre-BMP-2 exhibited sustained release, consistent bioactivity, and higher stability of BMP-2, and resulted in greater osteogenic differentiation of BMSCs. Eight weeks post-operation, TiO2-Lyo-Tre-BMP-2 nanotubes, with various dosages of BMP-2, regenerated larger amounts of new bone than TiO2-BMP-2 nanotubes. Conclusion: Our findings indicate that delivery of BMP-2 lyophilized with trehalose may be a promising method to reduce the dose of BMP-2 and avoid the associated side effects. Keywords: bone morphogenetic protein-2, dose reduction, delivery system, trehalose, lyophilization, TiO2 nanotubes, BMP-2, regenerative medicine, surface

  4. Platelet-Rich Plasma in Bone Regeneration: Engineering the Delivery for Improved Clinical Efficacy

    Directory of Open Access Journals (Sweden)

    Isaac A. Rodriguez

    2014-01-01

    Full Text Available Human bone is a tissue with a fairly remarkable inherent capacity for regeneration; however, this regenerative capacity has its limitations, and defects larger than a critical size lack the ability to spontaneously heal. As such, the development and clinical translation of effective bone regeneration modalities are paramount. One regenerative medicine approach that is beginning to gain momentum in the clinical setting is the use of platelet-rich plasma (PRP. PRP therapy is essentially a method for concentrating platelets and their intrinsic growth factors to stimulate and accelerate a healing response. While PRP has shown some efficacy in both in vitro and in vivo scenarios, to date its use and delivery have not been optimized for bone regeneration. Issues remain with the effective delivery of the platelet-derived growth factors to a localized site of injury, the activation and temporal release of the growth factors, and the rate of growth factor clearance. This review will briefly describe the physiological principles behind PRP use and then discuss how engineering its method of delivery may ultimately impact its ability to successfully translate to widespread clinical use.

  5. 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.

  6. Virus immobilization on biomaterial scaffolds through biotin-avidin interaction for improving bone regeneration.

    Science.gov (United States)

    Hu, Wei-Wen; Wang, Zhuo; Krebsbach, Paul H

    2016-02-01

    To spatially control therapeutic gene delivery for potential tissue engineering applications, a biotin-avidin interaction strategy was applied to immobilize viral vectors on biomaterial scaffolds. Both adenoviral vectors and gelatin sponges were biotinylated and avidin was applied to link them in a virus-biotin-avidin-biotin-material (VBABM) arrangement. The tethered viral particles were stably maintained within scaffolds and SEM images illustrated that viral particles were evenly distributed in three-dimensional (3D) gelatin sponges. An in vivo study demonstrated that transgene expression was restricted to the implant sites only and transduction efficiency was improved using this conjugation method. For an orthotopic bone regeneration model, adenovirus encoding BMP-2 (AdBMP2) was immobilized to gelatin sponges before implanting into critical-sized bone defects in rat calvaria. Compared to gelatin sponges with AdBMP2 loaded in a freely suspended form, the VBABM method enhanced gene transfer and bone regeneration was significantly improved. These results suggest that biotin-avidin immobilization of viral vectors to biomaterial scaffolds may be an effective strategy to facilitate tissue regeneration. Copyright © 2013 John Wiley & Sons, Ltd.

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

    Science.gov (United States)

    O'Valle, Francisco; Lanis, Alejandro; Dohan Ehrenfest, David M.; Wang, Hom-Lay; Galindo-Moreno, Pablo

    2015-01-01

    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. PMID:26064899

  8. Global MicroRNA Profiling in Human Bone Marrow Skeletal—Stromal or Mesenchymal–Stem Cells Identified Candidates for Bone Regeneration

    DEFF Research Database (Denmark)

    Chang, Chi Chih; Venø, Morten T.; Chen, Li

    2018-01-01

    Bone remodeling and regeneration are highly regulated multistep processes involving posttranscriptional regulation by microRNAs (miRNAs). Here, we performed a global profiling of differentially expressed miRNAs in bone-marrow-derived skeletal cells (BMSCs; also known as stromal or mesenchymal stem......RNAs for enhancing bone tissue regeneration. Scaffolds functionalized with miRNA nano-carriers enhanced osteoblastogenesis in 3D culture and retained this ability at least 2 weeks after storage. Additionally, anti-miR-222 enhanced in vivo ectopic bone formation through targeting the cell-cycle inhibitor CDKN1B...... (cyclin-dependent kinase inhibitor 1B). A number of additional miRNAs exerted additive osteoinductive effects on BMSC differentiation, suggesting that pools of miRNAs delivered locally from an implanted scaffold can provide a promising approach for enhanced bone regeneration....

  9. Induction of Biological Apatite Orientation as a Bone Quality Parameter in Bone Regeneration Using Hydroxyapatite/Poly ɛ-Caprolactone Composite Scaffolds.

    Science.gov (United States)

    Lee, Jee-Wook; Yun, Hui-Suk; Nakano, Takayoshi

    2016-09-01

    Changes in the biological apatite (BAp) c-axis orientation were investigated as a bone quality parameter in bone regeneration using hydroxyapatite/poly ɛ-caprolactone (HA/PCL) composite scaffolds. Three-dimensional (3D) HA/PCL composite scaffolds were fabricated using a layer manufacturing process in three grid sizes (200-, 600-, and 1000 μm) and grafted into the forearm ulna of New Zealand white rabbits. The cross-sectional areas of the bones regenerated from the scaffolds with 600- and 1000-μm grid sizes were significantly larger than those from the scaffold with 200-μm grid sizes, whereas bone mineral density in the regenerated regions did not differ between the three grid sizes. Moreover, the BAp c-axis orientation in the bones regenerated from the scaffolds with grid sizes of 600- and 1000 μm was not significantly different; however, both scaffolds showed enhanced BAp orientation, although the degree of BAp orientation was lower than that in intact bones. In conclusion, HA/PCL composite 3D scaffolds with 600- and 1000-μm grid sizes induced BAp c-axis orientation and showed good bone regeneration behavior in vivo.

  10. Biomimetic Engineering of Nanofibrous Gelatin Scaffolds with Noncollagenous Proteins for Enhanced Bone Regeneration

    Science.gov (United States)

    Sun, Yao; Jiang, Yong; Liu, Qilin; Gao, Tian; Feng, Jian Q.; Dechow, Paul; D'Souza, Rena N.; Qin, Chunlin

    2013-01-01

    Biomimetic approaches are widely used in scaffolding designs to enhance tissue regeneration. In this study, we integrated noncollagenous proteins (NCPs) from bone extracellular matrix (ECM) with three-dimensional nanofibrous gelatin (NF-Gelatin) scaffolds to form an artificial matrix (NF-Gelatin-NCPs) mimicking both the nano-structured architecture and chemical composition of natural bone ECM. Through a chemical coupling process, the NCPs were evenly distributed over all the surfaces (inner and outer) of the NF-gelatin-NCPs. The in vitro study showed that the number of osteoblasts (MC3T3-E1) on the NF-Gelatin-NCPs was significantly higher than that on the NF-Gelatin after being cultured for 14 days. Both the alkaline phosphatase (ALP) activity and the expression of osteogenic genes (OPN, BSP, DMP1, CON, and Runx2) were significantly higher in the NF-Gelatin-NCPs than in the NF-Gelatin at 3 weeks. Von Kossa staining, backscattered scanning electron microscopy, and microcomputed tomography all revealed a higher amount of mineral deposition in the NF-Gelatin-NCPs than in the NF-Gelatin after in vitro culturing for 3 weeks. The in vivo calvarial defect study indicated that the NF-Gelatin-NCPs recruited more host cells to the defect and regenerated a higher amount of bone than the controls after implantation for 6 weeks. Immunohistochemical staining also showed high-level mineralization of the bone matrix in the NF-Gelatin-NCPs. Taken together, both the in vitro and in vivo results confirmed that the incorporation of NCPs onto the surfaces of the NF-Gelatin scaffold significantly enhanced osteogenesis and mineralization. Biomimetic engineering of the surfaces of the NF-Gelatin scaffold with NCPs, therefore, is a promising strategy to enhance bone regeneration. PMID:23469769

  11. Guided Bone Regeneration with Collagen Membranes and Particulate Graft Materials: A Systematic Review and Meta-Analysis.

    Science.gov (United States)

    Wessing, Bastian; Lettner, Stefan; Zechner, Werner

    The aim of this meta-analysis was to evaluate different methods for guided bone regeneration using collagen membranes and particulate grafting materials in implant dentistry. An electronic database search and hand search were performed for all relevant articles dealing with guided bone regeneration in implant dentistry published between 1980 and 2014. Only randomized clinical trials and prospective controlled studies were included. The primary outcomes of interest were survival rates, membrane exposure rates, bone gain/defect reduction, and vertical bone loss at follow-up. A meta-analysis was performed to determine the effects of presence of membrane cross-linking, timing of implant placement, membrane fixation, and decortication. Twenty studies met the inclusion criteria. Implant survival rates were similar between simultaneous and subsequent implant placement. The membrane exposure rate of cross-linked membranes was approximately 30% higher than that of non-cross-linked membranes. The use of anorganic bovine bone mineral led to sufficient newly regenerated bone and high implant survival rates. Membrane fixation was weakly associated with increased vertical bone gain, and decortication led to higher horizontal bone gain (defect depth). Guided bone regeneration with particulate graft materials and resorbable collagen membranes is an effective technique for lateral alveolar ridge augmentation. Because implant survival rates for simultaneous and subsequent implant placement were similar, simultaneous implant placement is recommended when possible. Additional techniques like membrane fixation and decortication may represent beneficial implications for the practice.

  12. Ionic Colloidal Molding as a Biomimetic Scaffolding Strategy for Uniform Bone Tissue Regeneration.

    Science.gov (United States)

    Zhang, Jian; Jia, Jinpeng; Kim, Jimin P; Shen, Hong; Yang, Fei; Zhang, Qiang; Xu, Meng; Bi, Wenzhi; Wang, Xing; Yang, Jian; Wu, Decheng

    2017-05-01

    Inspired by the highly ordered nanostructure of bone, nanodopant composite biomaterials are gaining special attention for their ability to guide bone tissue regeneration through structural and biological cues. However, bone malformation in orthopedic surgery is a lingering issue, partly due to the high surface energy of traditional nanoparticles contributing to aggregation and inhomogeneity. Recently, carboxyl-functionalized synthetic polymers have been shown to mimic the carboxyl-rich surface motifs of non-collagenous proteins in stabilizing hydroxyapatite and directing intrafibrillar mineralization in-vitro. Based on this biomimetic approach, it is herein demonstrated that carboxyl functionalization of poly(lactic-co-glycolic acid) can achieve great material homogeneity in nanocomposites. This ionic colloidal molding method stabilizes hydroxyapatite precursors to confer even nanodopant packing, improving therapeutic outcomes in bone repair by remarkably improving mechanical properties of nanocomposites and optimizing controlled drug release, resulting in better cell in-growth and osteogenic differentiation. Lastly, better controlled biomaterial degradation significantly improved osteointegration, translating to highly regular bone formation with minimal fibrous tissue and increased bone density in rabbit radial defect models. Ionic colloidal molding is a simple yet effective approach of achieving materials homogeneity and modulating crystal nucleation, serving as an excellent biomimetic scaffolding strategy to rebuild natural bone integrity. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  13. 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.

  14. Ovalbumin-BasedPorous Scaffolds for Bone Tissue Regeneration

    Directory of Open Access Journals (Sweden)

    Gabrielle Farrar

    2010-01-01

    Full Text Available Cell differentiation on glutaraldehyde cross-linked ovalbumin scaffolds was the main focus of this research. Salt leaching and freeze drying were used to create a three-dimensional porous structure. Average pore size was 147.84±40.36 μm and 111.79±30.71 μm for surface and cross sectional area, respectively. Wet compressive strength and elastic modulus were 6.8±3.6 kPa. Average glass transition temperature was 320.1±1.4°C. Scaffolds were sterilized with ethylene oxide prior to seeding MC3T3-E1 cells. Cells were stained with DAPI and Texas red to determine morphology and proliferation. Average cell numbers increased between 4-hour- and 96-hour-cultured scaffolds. Alkaline phosphatase and osteocalcin levels were measured at 3, 7, 14, and 21 days. Differentiation studies showed an increase in osteocalcin at 21 days and alkaline phosphatase levels at 14 days, both indicating differentiation occurred. This work demonstrated the use of ovalbumin scaffolds for a bone tissue engineering application.

  15. Ridge preservation after ridge expansion with simultaneous guided bone regeneration: a preclinical study.

    Science.gov (United States)

    Stricker, Andres; Fleiner, Jonathan; Stübinger, Stefan; Fleiner, Henrik; Buser, Daniel; Bosshardt, Dieter D

    2016-11-01

    To evaluate ridge preservation after ridge splitting with simultaneous implant placement and guided bone regeneration (GBR) in a miniature pig model. In miniature pigs, the mandibular premolars and first molars were extracted together with removal of the interdental and buccal bone. Three months later, ridge splitting and expansion of the buccal plate were performed with simultaneous placement of two titanium implants per quadrant. On the test side, access by a mucoperiosteal flap followed by GBR with a biphasic calcium phosphate and a collagen membrane was performed. On the contralateral control side, a mucosal flap (MF), leaving the periosteum attached to the buccal bone, was elevated. After healing periods of 6 and 12 weeks, eight and four animals, respectively, were sacrificed for histological and histometric evaluation. In the MF group, all 16 implants were osseointegrated, while in the GBR group, one bone fracture occurred, and six of 16 implants were lost. After 6 weeks, significantly higher bone crest levels were found for the GBR group than for the MF group both buccally and lingually (P bone thickness was greater in the GBR group than in the MF group (P bone was significantly higher in the GBR group compared to the MF group. Furthermore, buccal bone thickness in the GBR group was 0.93, 4.5, and 5.94 mm at, and 2 and 4 mm apical to the IS, respectively. The corresponding values in the MF group were greatly reduced (0, 0.21, and 2.56 mm). Bone loss on the buccal side compared to the lingual side was significantly greater only in the MF group. In this ridge expansion model in miniature pigs, the buccal bone volume was significantly better preserved with GBR when compared to a mucosal access flap, provided that soft tissue healing occurred complication free. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  16. Molecular and Cellular Mechanisms of Axonal Regeneration After Spinal Cord Injury*

    Science.gov (United States)

    van Niekerk, Erna A.; Tuszynski, Mark H.; Lu, Paul; Dulin, Jennifer N.

    2016-01-01

    Following axotomy, a complex temporal and spatial coordination of molecular events enables regeneration of the peripheral nerve. In contrast, multiple intrinsic and extrinsic factors contribute to the general failure of axonal regeneration in the central nervous system. In this review, we examine the current understanding of differences in protein expression and post-translational modifications, activation of signaling networks, and environmental cues that may underlie the divergent regenerative capacity of central and peripheral axons. We also highlight key experimental strategies to enhance axonal regeneration via modulation of intraneuronal signaling networks and the extracellular milieu. Finally, we explore potential applications of proteomics to fill gaps in the current understanding of molecular mechanisms underlying regeneration, and to provide insight into the development of more effective approaches to promote axonal regeneration following injury to the nervous system. PMID:26695766

  17. Augmented cartilage regeneration by implantation of cellular versus acellular implants after bone marrow stimulation: a systematic review and meta-analysis of animal studies

    NARCIS (Netherlands)

    Pot, M.W.; Kuppevelt, T.H. van; Gonzales, V.K.; Buma, P.; Hout, J. in't; Vries, R.B.M. de; Daamen, W.F.

    2017-01-01

    Bone marrow stimulation may be applied to regenerate focal cartilage defects, but generally results in transient clinical improvement and formation of fibrocartilage rather than hyaline cartilage. Tissue engineering and regenerative medicine strive to develop new solutions to regenerate hyaline

  18. Effects of laser photherapy on bone defects grafted with mineral trioxide aggregate, bone morphogenetic proteins, and guided bone regeneration: a Raman spectroscopic study.

    Science.gov (United States)

    Pinheiro, Antonio L B; Aciole, Gilberth T S; Cangussú, Maria Cristina T; Pacheco, Marcos T T; Silveira, Landulfo

    2010-12-15

    We have used Raman analysis to assess bone healing on different models. Benefits on the isolated or combined use of mineral trioxide aggregate, bone morphogenetic proteins, guided bone regeneration and laser on bone repair have been reported, but not their combination. We studied peaks of hydroxyapatite and CH groups on defects grafted with MTA, treated or not with laser, BMPs, and GBR. Ninety rats were divided in 10 groups each, subdivided into three subgroups. Laser (λ850 nm) was applied at every other day for 2 weeks. Raman readings were taken at the surface of the defect. Statistical analysis (CHA) showed significant differences between all groups (p = 0.001) and between Group II and all other (p bone is because of increased secretion of calcium hydroxyapatite (CHA) that is indicative of greater calcification and resistance of the bone. We conclude that the association of the MTA with laser phototherapy (LPT) and/or not with GBR resulted in a better bone repair. The use of the MTA associated to IR LPT resulted in a more advanced and quality bone repair. Copyright © 2010 Wiley Periodicals, Inc.

  19. Use of a collagen membrane loaded with recombinant human bone morphogenetic protein-2 with collagen-binding domain for vertical guided bone regeneration.

    Science.gov (United States)

    Lai, Chun-Hua; Zhou, Lei; Wang, Zhong-Lei; Lu, Hai-Bin; Gao, Yan

    2013-07-01

    Vertical bone regeneration of severe atrophic alveolar ridges remains a challenging procedure in implant dentistry. The aim of this study, accordingly, is to use a rabbit vertical guided bone regeneration model to evaluate whether using a collagen membrane (CM) loaded with small doses of recombinant human bone morphogenetic protein-2 with collagen-binding domain (rhBMP-2/CBD) would enhance two-way vertical bone regeneration. In each of eight rabbits, four titanium cylinders were screwed in perforated slits made into the external cortical bones of the calvaria. The following four treatment modalities were randomly allocated: 1) cylinders filled with mineralized bone matrix and covered with CM/rhBMP-2/CBD; 2) cylinders filled with mineralized bone matrix and covered with CM/rhBMP-2; 3) cylinders filled with mineralized bone matrix and covered with CM alone; or 4) cylinders filled with mineralized bone matrix without a membrane cover. After 6 weeks, the new bones were examined by histologic analysis. Slender new bone trabeculae were observed in the superficial layer of the titanium cylinders covered with CM/rhBMP-2/CBD, and higher degrees of bone were observed in this group compared with the other three groups. The average area fraction of newly formed bone was significantly more in the CM/rhBMP-2/CBD group compared with the CM/rhBMP-2, CM, or the no membrane control groups (all P bone formation not only from the surface of the native bone, but also from the superficial structures. The augmented new bone, therefore, is improved in both quantity and quality.

  20. Effect of bioactive borate glass microstructure on bone regeneration, angiogenesis, and hydroxyapatite conversion in a rat calvarial defect model.

    Science.gov (United States)

    Bi, Lianxiang; Rahaman, Mohamed N; Day, Delbert E; Brown, Zackary; Samujh, Christopher; Liu, Xin; Mohammadkhah, Ali; Dusevich, Vladimir; Eick, J David; Bonewald, Lynda F

    2013-08-01

    Borate bioactive glasses are biocompatible and enhance new bone formation, but the effect of their microstructure on bone regeneration has received little attention. In this study scaffolds of borate bioactive glass (1393B3) with three different microstructures (trabecular, fibrous, and oriented) were compared for their capacity to regenerate bone in a rat calvarial defect model. 12weeks post-implantation the amount of new bone, mineralization, and blood vessel area in the scaffolds were evaluated using histomorphometric analysis and scanning electron microscopy. The amount of new bone formed was 33%, 23%, and 15%, respectively, of the total defect area for the trabecular, oriented, and fibrous microstructures. In comparison, the percent new bone formed in implants composed of silicate 45S5 bioactive glass particles (250-300μm) was 19%. Doping the borate glass with copper (0.4 wt.% CuO) had little effect on bone regeneration in the trabecular and oriented scaffolds, but significantly enhanced bone regeneration in the fibrous scaffolds (from 15 to 33%). The scaffolds were completely converted to hydroxyapatite within the 12week implantation. The amount of hydroxyapatite formed, 22%, 35%, and 48%, respectively, for the trabecular, oriented, and fibrous scaffolds, increased with increasing volume fraction of glass in the as-fabricated scaffold. Blood vessels infiltrated into all the scaffolds, but the trabecular scaffolds had a higher average blood vessel area compared with the oriented and fibrous scaffolds. While all three scaffold microstructures were effective in supporting bone regeneration, the trabecular scaffolds supported more bone formation and may be more promising in bone repair. Copyright © 2013 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

  1. In vitro and in vivo bioactivity assessment of a polylactic acid/hydroxyapatite composite for bone regeneration

    NARCIS (Netherlands)

    Danoux, Charlene; Barbieri, D.; Yuan, Huipin; de Bruijn, Joost Dick; van Blitterswijk, Clemens; Habibovic, Pamela

    2014-01-01

    Synthetic bone graft substitutes based on composites consisting of a polymer and a calcium-phosphate (CaP) ceramic are developed with the aim to satisfy both mechanical and bioactivity requirements for successful bone regeneration. In the present study, we have employed extrusion to produce a

  2. Histological evaluation of degradable guided bone regeneration membranes prepared from poly(trimethylene carbonate) and biphasic calcium phosphate composites

    NARCIS (Netherlands)

    Zeng, Ni; van Leeuwen, Anne; Bos, Ruud R.M.; Grijpma, Dirk W.; Kuijer, Roel

    2013-01-01

    In oral and maxillofacial surgery, guided bone regeneration using barrier membranes is an important strategy to treat bone defects. The currently used barrier membranes have important disadvantages. Barrier membranes prepared from resorbable poly(trimethylene carbonate) (PTMC) performed as well as

  3. Histological Evaluation of Degradable Guided Bone Regeneration Membranes Prepared from Poly(trimethylene carbonate) and Biphasic Calcium Phosphate Composites

    NARCIS (Netherlands)

    Zeng, Ni; van Leeuwen, Anne; Bos, Ruud R.M.; Grijpma, Dirk W.; Kuijer, Roel

    2013-01-01

    In oral and maxillofacial surgery, guided bone regeneration using barrier membranes is an important strategy to treat bone defects. The currently used barrier membranes have important disadvantages. Barrier membranes prepared from resorbable poly(trimethylene carbonate) (PTMC) performed as well as

  4. 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

  5. Incorporation of stromal cell-derived factor-1 alpha in PCL/gelatin electrospun membranes for guided bone regeneration

    NARCIS (Netherlands)

    Ji, W.; Yang, F.; Ma, J.L.; Bouma, M.J.; Boerman, O.C.; Chen, Z.; Beucken, J.J.J.P van den; Jansen, J.A.

    2013-01-01

    The goal of this work was to evaluate the effect of membrane functionalization with a chemotactic factor on cell recruitment and bone formation in order to develop a bioactive membrane for guided bone regeneration (GBR) applications. To this end. GBR membranes were prepared by electrospinning using

  6. Effect of Wnt3a delivery on early healing events during guided bone regeneration.

    Science.gov (United States)

    Moschouris, P; Retzepi, M; Petrie, A; Donos, N

    2017-03-01

    To evaluate the effect of recombinant Wnt3a delivery on the bone regeneration potential following application of the guided bone regeneration (GBR) principle. A critical-size calvarial defect was created on each parietal bone of 14 Wistar strain rats. One defect was used as the test side and was treated with a collagen sponge carrying 2.0 μg of recombinant Wnt3a protein, whereas the contralateral side served as sham-operated control. Both defects were covered at both the extracranial and intracranial aspects with ePTFE non-resorbable membranes, according to the GBR principle. Following healing periods of 4 and 7 days, qualitative histological and histomorphometric evaluation of undecalcified sections was performed in subgroups of seven animals. The primary outcome parameter was the mean percentage of defect closure in the test and control defects. At 4 days of healing, a network of coagulum and fibrin was observed and initial signs of granulation tissue formation were evident with no apparent differences between the test and control groups. At 7 days of healing, the test group presented newly formed woven bone, originating from the borders of the defect, as opposed to the control group, whereby woven bone formation was not observed in any of the specimens. The delivery of mouse recombinant Wnt-3a protein in combination with GBR may promote woven bone formation in critical-size calvarial defects at 7 days of healing. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  7. Molecular mechanism and potential targets for bone metastasis

    International Nuclear Information System (INIS)

    Iguchi, Haruo

    2007-01-01

    The incidence of bone metastasis has been increasing in all cancers in recent years. Bone metastasis is associated with substantial morbidity, including bone pain, pathological fracture, neurological deficit and/or hypercalcemia. Thus, the management of bone metastasis in patients is a clinically significant issue. In the process of bone metastasis, the primary mechanism responsible for bone destruction is cancer cell-mediated stimulation of osteoclastic bone resorption, which results in osteolysis and release of various growth factors from the bone matrix. These growth factors are prerequisites for successful colonization and subsequent invasive growth of cancer cells in bone, which is called a 'vicious cycle.' Thus, it is important to elucidate what molecules are involved in this step of bone destruction, and the understanding of these molecular mechanisms could lead to develop molecular-target therapies for bone metastasis. Bisphosphonates introduced in the treatment for bone metastasis have been shown to reduce skeletal morbidity. In Japan, the most potent bisphosphonate, zoledronate (ZOMETA), was introduced in this past April, and a phase III clinical trial of humanized anti-receptor activator of NF-κB ligand (RANKL) monoclonal antibody (Denosumab) against bone metastasis is under way as a global study. These new agents, which are targeted to osteoclasts, are considered to be standard management in the care of bone metastasis patients in combination with chemotherapy and/or hormone therapy. (author)

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

    International Nuclear Information System (INIS)

    Beolchi, Rafael da Silva

    2009-01-01

    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)

  9. Biomimetic spiral-cylindrical scaffold based on hybrid chitosan/cellulose/nano-hydroxyapatite membrane for bone regeneration.

    Science.gov (United States)

    Jiang, Hong; Zuo, Yi; Zou, Qin; Wang, Huanan; Du, Jingjing; Li, Yubao; Yang, Xiaochao

    2013-11-27

    Natural bone is a complex material with well-designed architecture. To achieve successful bone integration and regeneration, the constituent and structure of bone-repairing scaffolds need to be functionalized synergistically based on biomimetics. In this study, a hybrid membrane composed of chitosan (CS), sodium carboxymethyl cellulose (CMC), and nano-hydroxyapatite (n-HA) was curled in a concentric manner to generate an anisotropic spiral-cylindrical scaffold, with compositional and structural properties mimicking natural bone. After optimization in terms of morphology, hydrophilicity, swelling and degradation pattern, the osteoblast cells seeded on the membrane of 60 wt% n-HA exhibited the highest cell viability and osteocalcin expression. In vivo osteogenesis assessment revealed that the spiral-cylindrical architecture played a dominant role in bone regeneration and osseointegration. Newly formed bone tissue grew through the longitudinal direction of the cylinder-shaped scaffold bridging both ends of the defect, bone marrow penetrated the entire scaffold and formed a medullary cavity in the center of the spiral cylinder. This study for the first time demonstrates that the spiral-cylindrical scaffold can promote complete infiltration of bone tissues in vivo, leading to successful osteointegration and functional reconstruction of bone defects. It suggests that the biomimetic spiral-cylindrical scaffold could be a promising candidate for bone regeneration applications.

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

    NARCIS (Netherlands)

    J. van der Stok (Johan); O.P. van der Jagt (Olav); S. Amin Yavari (Saber); M.F.P. de Haas (Mirthe); J.H. Waarsing (Jan); H. Jahr (Holger); E.M.M. van Lieshout (Esther); P. Patka (Peter); J.A.N. Verhaar (Jan); A.A. Zadpoor (Amir Abbas); H.H. Weinans (Harrie)

    2013-01-01

    textabstractPorous 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

  11. Bone augmentation at peri-implant dehiscence defects comparing a synthetic polyethylene glycol hydrogel matrix vs. standard guided bone regeneration techniques.

    Science.gov (United States)

    Thoma, Daniel S; Jung, Ui-Won; Park, Jin-Young; Bienz, Stefan P; Hüsler, Jürg; Jung, Ronald E

    2017-07-01

    The aim of the study was to test whether or not the use of a polyethylene glycol (PEG) hydrogel with or without the addition of an arginylglycylaspartic acid (RGD) sequence applied as a matrix in combination with hydroxyapatite/tricalciumphosphate (HA/TCP) results in similar peri-implant bone regeneration as traditional guided bone regeneration procedures. In 12 beagle dogs, implant placement and peri-implant bone regeneration were performed 2 months after tooth extraction in the maxilla. Two standardized box-shaped defects were bilaterally created, and dental implants were placed in the center of the defects with a dehiscence of 4 mm. Four treatment modalities were randomly applied: i)HA/TCP mixed with a synthetic PEG hydrogel, ii)HA/TCP mixed with a synthetic PEG hydrogel supplemented with an RGD sequence, iii)HA/TCP covered with a native collagen membrane (CM), iv)and no bone augmentation (empty). After a healing period of 8 or 16 weeks, micro-CT and histological analyses were performed. Histomorphometric analysis revealed a greater relative augmented area for groups with bone augmentation (43.3%-53.9% at 8 weeks, 31.2%-42.8% at 16 weeks) compared to empty controls (22.9% at 8 weeks, 1.1% at 16 weeks). The median amount of newly formed bone was greatest in group CM at both time-points. Regarding the first bone-to-implant contact, CM was statistically significantly superior to all other groups at 8 weeks. Bone can partially be regenerated at peri-implant buccal dehiscence defects using traditional guided bone regeneration techniques. The use of a PEG hydrogel applied as a matrix mixed with a synthetic bone substitute material might lack a sufficient stability over time for this kind of defect. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  12. Bone marrow concentrate promotes bone regeneration with a suboptimal-dose of rhBMP-2.

    Directory of Open Access Journals (Sweden)

    Kazuhiro Egashira

    Full Text Available Bone marrow concentrate (BMC, which is enriched in mononuclear cells (MNCs and platelets, has recently attracted the attention of clinicians as a new optional means for bone engineering. We previously reported that the osteoinductive effect of bone morphogenetic protein-2 (BMP-2 could be enhanced synergistically by co-transplantation of peripheral blood (PB-derived platelet-rich plasma (PRP. This study aims to investigate whether BMC can effectively promote bone formation induced by low-dose BMP-2, thereby reducing the undesirable side-effects of BMP-2, compared to PRP. Human BMC was obtained from bone marrow aspirates using an automated blood separator. The BMC was then seeded onto β-TCP granules pre-adsorbed with a suboptimal-dose (minimum concentration to induce bone formation at 2 weeks in mice of recombinant human (rh BMP-2. These specimens were transplanted subcutaneously to the dorsal skin of immunodeficient-mice and the induction of ectopic bone formation was assessed 2 and 4 weeks post-transplantation. Transplantations of five other groups [PB, PRP, platelet-poor plasma (PPP, bone marrow aspirate (BM, and BM-PPP] were employed as experimental controls. Then, to clarify the effects on vertical bone augmentation, specimens from the six groups were transplanted for on-lay placement on the craniums of mice. The results indicated that BMC, which contained an approximately 2.5-fold increase in the number of MNCs compared to PRP, could accelerate ectopic bone formation until 2 weeks post-transplantation. On the cranium, the BMC group promoted bone augmentation with a suboptimal-dose of rhBMP-2 compared to other groups. Particularly in the BMC specimens harvested at 4 weeks, we observed newly formed bone surrounding the TCP granules at sites far from the calvarial bone. In conclusion, the addition of BMC could reduce the amount of rhBMP-2 by one-half via its synergistic effect on early-phase osteoinduction. We propose here that BMC

  13. Effect of concentrated growth factor combined with guided bone regeneration on cell proliferation and bone resorption in patients with severe periodontitis

    Directory of Open Access Journals (Sweden)

    Qiang Gao

    2017-10-01

    Full Text Available Objective: To study the effect of concentrated growth factor (CGF combined with guided bone regeneration on cell proliferation and bone resorption in patients with severe periodontitis. Methods: Patients with severe periodontitis who were treated in Stomatology Department of Shenmu Hospital between May 2014 and February 2017 were selected as the research subjects and randomly divided into two groups, surgery + CGF group received concentrated growth factor combined with guided bone regeneration, and pure surgery group received guided bone regeneration. The contents of inflammatory response, cell proliferation and bone resorption markers in gingival crevicular fluid were determined 1 week after treatment. Results: 1 week after treatment, HMGB1, ICAM1, E-selectin, Smac, FasL, Caspase-8, Caspase-9, Caspase-3, RANKL and NTX contents in gingival crevicular fluid of surgery + CGF group were significantly lower than those of pure surgery group while PD-L1, hBD-3, Wnt3a, BGP and OPG contents were significantly higher than those of pure surgery group. Conclusion: Concentrated growth factor combined with guided bone regeneration for severe periodontitis can inhibit inflammatory response, apoptosis and bone resorption, which is beneficial to the reconstruction of periodontal tissue.

  14. Recombinant bone morphogenetic protein-2 and platelet-derived growth factor-BB for localized bone regeneration. Histologic and radiographic outcomes of a rabbit study.

    Science.gov (United States)

    Thoma, Daniel S; Lim, Hyun-Chang; Sapata, Vitor M; Yoon, Sora R; Jung, Ronald E; Jung, Ui-Won

    2017-11-01

    Improvement in localized bone regeneration is needed to avoid the use of autogenous tissue. For that purpose, the use biologic mediators was proposed. The aim was to test whether or not one of two biologic mediators, recombinant human bone morphogenetic protein-2 (rhBMP-2) or recombinant platelet-derived growth factor (rhPDGF-BB), is superior to the other and to control groups for localized bone regeneration. Four cylinders (height: 5 mm; diameter: 7 mm) were screwed on the parietal and frontal bones at the cranium in 12 rabbits. The cylinders either received (i) deproteinized bovine bone mineral (DBBM) mixed rhBMP-2 (DBBM/BMP-2), (ii) DBBM mixed with rhPDGF-BB (DBBM/PDGF), (iii) DBBM (DBBM), and (iv) empty control (control). Rabbits were euthanized at 2 and 8 weeks (n = 6, respectively). Conventional histomorphometric and micro-CT analyses were performed. Parametric linear mixed models were applied for the analyses with Bonferroni correction for the multiple group comparisons. The area of bone regeneration (histology; AA H isto ) at 2 weeks peaked for DBBM (41.91%) with statistically significantly greater values compared to DBBM/PDGF and the control group (P  0.05). The use of rhBMP-2 significantly enhanced bone regeneration compared to all other groups including the group with rhPDGF-BB. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  15. Treatment of Severely Resorbed Maxilla Due to Peri-Implantitis by Guided Bone Regeneration Using a Customized Allogenic Bone Block: A Case Report

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    Oliver Blume

    2017-10-01

    Full Text Available The objective of this case report is to introduce a customized CAD/CAM freeze-dried bone allograft (FDBA block for its use in Guided Bone Regeneration (GBR procedures for severely deficient maxillary bones. Additionally, a special newly developed remote incision technique is presented to avoid wound dehiscence. The results show optimal integration behavior of the FDBA block after six months and the formation of new vital bone. Thus, the results of the present case report confirm the use of the customized CAD/CAM bone block for augmentation of complex defects in the maxillary aesthetic zone as a successful treatment concept.

  16. Comparison of Bone Resorption Rates after Intraoral Block Bone and Guided Bone Regeneration Augmentation for the Reconstruction of Horizontally Deficient Maxillary Alveolar Ridges

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    B. Alper Gultekin

    2016-01-01

    Full Text Available Purpose. Bone atrophy after tooth loss may leave insufficient bone for implant placement. We compared volumetric changes after autogenous ramus block bone grafting (RBG or guided bone regeneration (GBR in horizontally deficient maxilla before implant placement. Materials and Methods. In this retrospective study, volumetric changes at RBG or GBR graft sites were evaluated using cone-beam computed tomography. The primary outcome variable was the volumetric resorption rate. Secondary outcomes were bone gain, graft success, and implant insertion torque. Results. Twenty-four patients (28 grafted sites were included (GBR, 15; RBG, 13. One patient (RBG suffered mucosal dehiscence at the recipient site 6 weeks after surgery, which healed spontaneously. Mean volume reduction in the GBR and RBG groups was 12.48 ± 2.67% and 7.20 ± 1.40%, respectively. GBR resulted in significantly more bone resorption than RBG (P0.05. Conclusions. Both RBG and GBR hard-tissue augmentation techniques provide adequate bone graft volume and stability for implant insertion. However, GBR causes greater resorption at maxillary augmented sites than RBG, which clinicians should consider during treatment planning.

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

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    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.

  18. Scaffold of chitosan-sodium alginate and hydroxyapatite with application potential for bone regeneration

    International Nuclear Information System (INIS)

    Rebelo, Marcia de A.; Alves, Thais F.R.; Lopes, Francielly C.C.N; Oliveira Junior, Jose Martins de; Pontes, Katiusca S.; Fogaca, Bruna A.C.; Chaud, Marco V.

    2015-01-01

    Scaffold for organic tissue regeneration are architectural, three-dimensional, porous, biocompatible and biodegradable devices. The first challenges to be met in the development of these devices to mimic the biomechanical properties of the target tissue. The aim of this study was to develop and to characterize scaffolds composed of chitosan (Ch), sodium alginate (SA), hydroxyapatite (HA). The scaffolds were obtained by lyophilization. HA has been incorporated into the polymer dispersion in Ch-AS concentration of 20 and 60%. The mechanical properties of the scaffold were determined by tensile and compression tests. Swelling capacity was assessed in the presence of simulated saliva, purified water, HCl 0.01M, NaOH 0.01M. The calcium content was quantified using fluorescence X-rays. Analysis of the results indicates that the Qt-AS-HA-60% scaffold obtained by lyophilization meets promising properties for bone tissue regeneration. (author)

  19. Msh homeobox 1 (Msx1)- and Msx2-overexpressing bone marrow-derived mesenchymal stem cells resemble blastema cells and enhance regeneration in mice.

    Science.gov (United States)

    Taghiyar, Leila; Hesaraki, Mahdi; Sayahpour, Forough Azam; Satarian, Leila; Hosseini, Samaneh; Aghdami, Naser; Baghaban Eslaminejad, Mohamadreza

    2017-06-23

    Amputation of the proximal region in mammals is not followed by regeneration because blastema cells (BCs) and expression of regenerative genes, such as Msh homeobox ( Msx ) genes, are absent in this animal group. The lack of BCs and positional information in other cells is therefore the main obstacle to therapeutic approaches for limb regeneration. Hence, this study aimed to create blastema-like cells (BlCs) by overexpressing Msx1 and Msx2 genes in mouse bone marrow-derived mesenchymal stem cells (mBMSCs) to regenerate a proximally amputated digit tip. We transduced mBMSCs with Msx1 and Msx2 genes and compared osteogenic activity and expression levels of several Msx -regulated genes ( Bmp4 , Fgf8 , and keratin 14 ( K14 )) in BlC groups, including MSX1, MSX2, and MSX1/2 (in a 1:1 ratio) with those in mBMSCs and BCs in vitro and in vivo following injection into the amputation site. We found that Msx gene overexpression increased expression of specific blastemal markers and enhanced the proliferation rate and osteogenesis of BlCs compared with mBMSCs and BCs via activation of Fgf8 and Bmp4 Histological analyses indicated full regrowth of digit tips in the Msx -overexpressing groups, particularly in MSX1/2, through endochondral ossification 6 weeks post-injection. In contrast, mBMSCs and BCs formed abnormal bone and nail. Full digit tip was regenerated only in the MSX1/2 group and was related to boosted Bmp4, Fgf8 , and K14 gene expression and to limb-patterning properties resulting from Msx1 and Msx2 overexpression. We propose that Msx -transduced cells that can regenerate epithelial and mesenchymal tissues may potentially be utilized in limb regeneration. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

  20. Effects of 3D-Printed Polycaprolactone/β-Tricalcium Phosphate Membranes on Guided Bone Regeneration

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    Jin-Hyung Shim

    2017-04-01

    Full Text Available This study was conducted to compare 3D-printed polycaprolactone (PCL and polycaprolactone/β-tricalcium phosphate (PCL/β-TCP membranes with a conventional commercial collagen membrane in terms of their abilities to facilitate guided bone regeneration (GBR. Fabricated membranes were tested for dry and wet mechanical properties. Fibroblasts and preosteoblasts were seeded into the membranes and rates and patterns of proliferation were analyzed using a kit-8 assay and by scanning electron microscopy. Osteogenic differentiation was verified by alizarin red S and alkaline phosphatase (ALP staining. An in vivo experiment was performed using an alveolar bone defect beagle model, in which defects in three dogs were covered with different membranes. CT and histological analyses at eight weeks after surgery revealed that 3D-printed PCL/β-TCP membranes were more effective than 3D-printed PCL, and substantially better than conventional collagen membranes in terms of biocompatibility and bone regeneration and, thus, at facilitating GBR.

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

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

    2015-12-09

    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. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

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

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    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.

  3. Bio-functionalized MWCNT/hyperbranched polyurethane bionanocomposite for bone regeneration.

    Science.gov (United States)

    Das, Beauty; Chattopadhyay, Pronobesh; Maji, Somnath; Upadhyay, Aadesh; Das Purkayastha, Manashi; Mohanta, Charu Lata; Maity, Tapas Kumar; Karak, Niranjan

    2015-04-17

    The proper fabrication of biomaterials, particularly for purposes like bone regeneration, is of the utmost importance for the clinical success of materials that fulfill the design criteria at bio-interfacial milieu. Building on this aspect, a polyurethane nanocomposite (PNC) was fabricated by the combination of rapeseed protein functionalized multi-walled carbon nanotubes (MWCNTs) and vegetable-oil-based hyperbranched polyurethane. Biofunctionalized MWCNTs showed incredible biocompatibility compared to pristine MWCNTs as ascertained via in vitro and in vivo studies. PNC showed enhanced MG63 cell differentiation ability compared to the control and carboxyl functionalized MWCNT-based nanocomposite, as postulated by alkaline phosphatase activity together with better cellular adhesion, spreading and proliferation. Consequently, a critical-sized fracture gap (6 mm) bridged by the sticky PNC scaffold illustrated rapid bone neoformation within 30-45 d, with 90-93% of the defect area filling up. Histopathological studies demonstrated the reorganization of the normal tibial architecture and biodegradation of the implant. The subsequent toxicological study through cytokine expression, biochemical analysis and hematological studies suggested non-immunogenic and non-toxic effects of PNCs and their degraded/leached products. Their excellent bio-physiological features with high load-bearing ability (49-55.5 Mpa), ductility (675-790%) and biodegradability promote them as the best alternative biomaterials for bone regeneration in a comprehensive manner.

  4. A case of mandible hypoplasia treated with autologous bone graft from mandibular symphysis: Expression of VEGF and receptors in bone regeneration.

    Science.gov (United States)

    Marini, Mirca; Bertolai, Roberto; Manetti, Mirko; Sgambati, Eleonora

    2016-07-01

    The vascular endothelial growth factor (VEGF)/VEGF receptor (VEGFR) system plays an important role in angiogenesis and osteogenesis during both skeletal development and postnatal bone growth and repair. Indeed, protein expression changes of this system could contribute to craniofacial defects commonly associated with a variety of congenital syndromes. Similarly to other craniofacial bones, mandible arises from neural crest cells of the neuroectodermal germ layer, and undergoes membranous ossification. Here, we report a case of left mandibular hypoplasia in a 42-year-old man treated with autologous bone graft from mandibular symphysis. After 3 months from surgical reconstruction, the protein expression of VEGF and receptors (VEGFR-1, -2 and -3) in regenerated bone tissue was evaluated by immunohistochemistry. At variance with the mandibular symphysis bone harvested for graft surgery, we observed de novo expression of VEGF and VEGFRs in osteoblasts and osteocytes from post-graft regenerating mandible bone tissue. In particular, while VEGFR-1 and VEGFR-3 immunopositivity was widespread in osteoblasts, that of VEGFR-2 was scattered. Among the three receptors, VEGFR-3 was the more intensively expressed both in osteoblasts and osteocytes. These findings suggest that VEGFR-2 might be produced during the early period of regeneration, while VEGFR-1 might participate in bone cell maintenance during the middle or late consolidation period. VEGFR-3 might, instead, represent a specific signal for ectomesenchymal lineage differentiation during bone regeneration. Modulation of VEGF/VEGFR signaling could contribute to graft integration and new bone formation during mandibular regeneration. Copyright © 2016 Elsevier GmbH. All rights reserved.

  5. The combined use of rhBMP-2/ACS, autogenous bone graft, a bovine bone mineral biomaterial, platelet-rich plasma, and guided bone regeneration at nonsubmerged implant placement for supracrestal bone augmentation. A case report.

    Science.gov (United States)

    Sclar, Anthony G; Best, Steven P

    2013-01-01

    This case report presents the clinical application and outcomes of the use of a combined approach to treat a patient with a severe alveolar defect. Recombinant human bone morphogenetic protein-2 in an absorbable collagen sponge carrier, along with autogenous bone graft, bovine bone mineral, platelet-rich plasma, and guided bone regeneration, were used simultaneous with nonsubmerged implant placement. At 1 year postsurgery, healthy peri-implant soft tissues and radiographically stable peri-implant crestal bone levels were observed along with locally increased radiographic bone density. In addition, a cone beam computed tomography (CBCT) scan demonstrated apparent supracrestal peri-implant bone augmentation with the appearance of normal alveolar ridge contours, including the facial bone wall.

  6. One-stage horizontal guided bone regeneration with autologous bone, anorganic bovine bone and collagen membranes: Follow-up of a prospective study 30 months after loading.

    Science.gov (United States)

    Meloni, Silvio Mario; Jovanovic, Sascha Alexander; Pisano, Milena; De Riu, Giacomo; Baldoni, Edoardo; Tallarico, Marco

    2018-01-01

    To present the medium-term results of one-stage guided bone regeneration (GBR) using autologous bone and anorganic bovine bone, placed in layers, in association with resorbable collagen membranes, for the reconstruction of horizontal bony defects. This study was designed as an uncontrolled prospective study. Partially edentulous patients, having less than 6.0 mm and more than 4.0 mm of residual horizontal bone width were selected and consecutively treated with simultaneously implant installation and bone regeneration by using 2.0 mm of autologous bone and 2.0 mm of anorganic bovine bone that was placed in layers and then covered with a resorbable collagen membrane. Outcome measures were: implant and prosthesis failures, any complications, peri-implant marginal bone level changes, probing pocket depth (PPD) and bleeding on probing (BOP). In total, 45 consecutive patients (20 male, 25 female) with a mean age of 52.1 years each received at least one GBR procedure, with contemporary placement of 63 implants. At the 3-year follow-up examination, no patient had dropped out and no deviation from the original protocol had occurred. No implant or prosthesis failed. In six patients (13.3%) the collagen membrane was slightly exposed 1 to 2 weeks after bone reconstruction. Four of these patients were moderate smokers. Post-hoc analysis using Fisher's exact test found significant association (P = 0.0139) between a smoking habit and early membrane exposure. Mean marginal bone loss experienced between initial loading and 30 months afterwards was 0.60 ± 0.20 mm (95% CI 0.54 - 0.66). The mean BOP values measured at the definitive restoration delivery were 1.23 ± 0.93, while 2 years later they were 1.17 ± 0.78. The difference was not statistically significant (-0.06 ± 0.76; P = 0.569). The mean PPD values measured at the definitive restoration delivery were 2.62 ± 0.59 mm, while 2 years later they were 2.60 ± 0.54 mm. The difference was not statistically significant (-0.03

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

    International Nuclear Information System (INIS)

    Tavakol, S.; Nikpour, M. R.; Amani, A.; Soltani, M.; Rabiee, S. M.; Rezayat, S. M.; Chen, P.; Jahanshahi, M.

    2013-01-01

    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.

  8. 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. Copyright © 2012 Orthopaedic Research Society.

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

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    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.

  10. The effects of newly formed synthetic peptide on bone regeneration in rat calvarial defects.

    Science.gov (United States)

    Choi, Jung-Yoo; Jung, Ui-Won; Kim, Chang-Sung; Eom, Tae-Kwan; Kang, Eun-Jung; Cho, Kyoo-Sung; Kim, Chong-Kwan; Choi, Seong-Ho

    2010-02-01

    Significant interest has emerged in the design of cell scaffolds that incorporate peptide sequences that correspond to known signaling domains in extracellular matrix and bone morphogenetic protein. The purpose of this study was to evaluate the bone regenerative effects of the synthetic peptide in a critical-size rat calvarial defect model. Eight millimeter diameter standardized, circular, transosseus defects created on the cranium of forty rats were implanted with synthetic peptide, collagen, or both synthetic peptide and collagen. No material was was implanted the control group. The healing of each group was evaluated histologically and histomorphometrically after 2- and 8-week healing intervals. Surgical implantation of the synthetic peptide and collagen resulted in enhanced local bone formation at both 2 and 8 weeks compared to the control group. When the experimental groups were compared to each other, they showed a similar pattern of bone formation. The defect closure and new bone area were significantly different in synthetic peptide and collagen group at 8 weeks. Concerning the advantages of biomaterials, synthetic peptide can be an effective biomaterial for damaged periodontal regeneration.

  11. Sandwich-type PLLA-nanosheets loaded with BMP-2 induce bone regeneration in critical-sized mouse calvarial defects.

    Science.gov (United States)

    Huang, Kuo-Chin; Yano, Fumiko; Murahashi, Yasutaka; Takano, Shuta; Kitaura, Yoshiaki; Chang, Song Ho; Soma, Kazuhito; Ueng, Steve W N; Tanaka, Sakae; Ishihara, Kazuhiko; Okamura, Yosuke; Moro, Toru; Saito, Taku

    2017-09-01

    To overcome serious clinical problems caused by large bone defects, various approaches to bone regeneration have been researched, including tissue engineering, biomaterials, stem cells and drug screening. Previously, we developed a free-standing biodegradable polymer nanosheet composed of poly(L-lactic acid) (PLLA) using a simple fabrication process consisting of spin-coating and peeling techniques. Here, we loaded recombinant human bone morphogenetic protein-2 (rhBMP-2) between two 60-nm-thick PLLA nanosheets, and investigated these sandwich-type nanosheets in bone regeneration applications. The PLLA nanosheets displayed constant and sustained release of the loaded rhBMP-2 for over 2months in vitro. Moreover, we implanted the sandwich-type nanosheets with or without rhBMP-2 into critical-sized defects in mouse calvariae. Bone regeneration was evident 4weeks after implantation, and the size and robustness of the regenerated bone had increased by 8weeks after implantation in mice implanted with the rhBMP-2-loaded nanosheets, whereas no significant bone formation occurred over a period of 20weeks in mice implanted with blank nanosheets. The PLLA nanosheets loaded with rhBMP-2 may be useful in bone regenerative medicine; furthermore, the sandwich-type PLLA nanosheet structure may potentially be applied as a potent prolonged sustained-release carrier of other molecules or drugs. Here we describe sandwich-type poly(L-lactic acid) (PLLA) nanosheets loaded with recombinant human bone morphogenetic protein-2 (rhBMP-2) as a novel method for bone regeneration. Biodegradable 60-nm-thick PLLA nanosheets display strong adhesion without any adhesive agent. The sandwich-type PLLA nanosheets displayed constant and sustained release of the loaded rhBMP-2 for over 2months in vitro. The nanosheets with rhBMP-2 markedly enhanced bone regeneration when they were implanted into critical-sized defects in mouse calvariae. In addition to their application for bone regeneration, PLLA

  12. Effects of LED phototherapy on bone defects grafted with MTA, bone morphogenetic proteins and guided bone regeneration: a Raman spectroscopic study.

    Science.gov (United States)

    Pinheiro, Antonio L B; Soares, Luiz G P; Cangussú, Maria Cristina T; Santos, Nicole R S; Barbosa, Artur Felipe S; Silveira Júnior, Landulfo

    2012-09-01

    We studied peaks of calcium hydroxyapatite (CHA) and protein and lipid CH groups in defects grafted with mineral trioxide aggregate (MTA) treated or not with LED irradiation, bone morphogenetic proteins and guided bone regeneration. A total of 90 rats were divided into ten groups each of which was subdivided into three subgroups (evaluated at 15, 21 and 30 days after surgery). Defects were irradiated with LED light (wavelength 850 ± 10 nm) at 48-h intervals for 15 days. Raman readings were taken at the surface of the defects. There were no statistically significant differences in the CHA peaks among the nonirradiated defects at any of the experimental time-points. On the other hand, there were significant differences between the defects filled with blood clot and the irradiated defects at all time-points (p LED light irradiation improves the deposition of CHA in healing bone grafted or not with MTA.

  13. Setd7 and its contribution to boron-induced bone regeneration in B-MBG scaffolds.

    Science.gov (United States)

    Yin, Chengcheng; Jia, Xiaoshi; Miron, Richard J; Long, Qiaoyun; Xu, Hudi; Wei, Yan; Wu, Min; Zhang, Yufeng; Li, Zubing

    2018-04-20

    Boron (B), a trace element found in the human body, plays an important role for health of bone by promoting the proliferation and differentiation of osteoblasts. Our research group previously fabricated B-mesoporous bioactive glass (MBG) scaffolds, which successfully promoted osteogenic differentiation of osteoblasts when compared to pure MBG scaffolds without boron. However, the mechanisms of the positive effect of B-MBG scaffolds on osteogenesis remains unknown. Therefore, we performed in-vivo experiments in an OVX rat models with pure MBG scaffolds and compared them to B-MBG scaffold. As a result, we found that B-MBG scaffold induced more new bone regeneration compared to pure MBG scaffold and examined genes related to bone regeneration induced by B-MBG scaffold through RNA-seq to obtain target genes and epigenetic mechanisms. The results demonstrated an increased expression and affiliation of Setd7 in the B-MBG group when compared to the MBG group. Immunofluorescent staining from our in vivo samples further demonstrated a higher localization of Setd7 and H3K4me3 in Runx2-positive cells in defects treated with B-MBG scaffolds. KEGG results suggested that specifically Wnt/β-catenin signaling pathway was highly activated in new bone area associated with B-MBG scaffolds. Thereafter, in vitro studies with human bone marrow stem cells (hBMSCs) stimulated by extracted liquid of B-MBG was associated with significantly elevated levels of Setd7, as well as H3K4me3 when compared to MBG alone. To verify the role of Setd7 in new bone formation in the presence of Boron, Setd7 was knocked down in hBMSCs with stimulation of the extracted liquids of B-MBG or MBG scaffolds. The result showed that osteoblast differentiation of hBMSCs was inhibited when Setd7 was knocked down, which could not be rescued by the extract liquids of B-MBG scaffolds confirming its role in osteoblast differentiation and bone regeneration. As a histone methylase, Setd7 may be expected to be a potential

  14. Periodontal materials and cell biology for guided tissue and bone regeneration.

    Science.gov (United States)

    Andrei, Mihai; Dinischiotu, Anca; Didilescu, Andreea Cristiana; Ionita, Daniela; Demetrescu, Ioana

    2018-03-01

    The present review is intended to find links between periodontal materials of the dentomaxillary apparatus and cell biology at the beginning of a century fraught with various forms of periodontal diseases and needing new treatment strategies. The manuscript has two different parts. The first describes the anatomy of tooth supporting structures, as well as related pathologies. The second part is related to cell and molecular biology in the context of periodontal regeneration. Copyright © 2017. Published by Elsevier GmbH.

  15. Sandcastle Worm-Inspired Blood-Resistant Bone Graft Binder Using a Sticky Mussel Protein for Augmented In Vivo Bone Regeneration.

    Science.gov (United States)

    Kim, Hyo Jeong; Choi, Bong-Hyuk; Jun, Sang Ho; Cha, Hyung Joon

    2016-12-01

    Xenogenic bone substitutes are commonly used during orthopedic reconstructive procedures to assist bone regeneration. However, huge amounts of blood accompanied with massive bone loss usually increase the difficulty of placing the xenograft into the bony defect. Additionally, the lack of an organic matrix leads to a decrease in the mechanical strength of the bone-grafted site. For effective bone grafting, this study aims at developing a mussel adhesion-employed bone graft binder with great blood-resistance and enhanced mechanical properties. The distinguishing water (or blood) resistance of the binder originates from sandcastle worm-inspired complex coacervation using negatively charged hyaluronic acid (HA) and a positively charged recombinant mussel adhesive protein (rMAP) containing tyrosine residues. The rMAP/HA coacervate stabilizes the agglomerated bone graft in the presence of blood. Moreover, the rMAP/HA composite binder enhances the mechanical and hemostatic properties of the bone graft agglomerate. These outstanding features improve the osteoconductivity of the agglomerate and subsequently promote in vivo bone regeneration. Thus, the blood-resistant coacervated mussel protein glue is a promising binding material for effective bone grafting and can be successfully expanded to general bone tissue engineering. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  16. Cells responding to surface structure of calcium phosphate ceramics for bone regeneration.

    Science.gov (United States)

    Zhang, Jingwei; Sun, Lanying; Luo, Xiaoman; Barbieri, Davide; de Bruijn, Joost D; van Blitterswijk, Clemens A; Moroni, Lorenzo; Yuan, Huipin

    2017-11-01

    Surface structure largely affects the inductive bone-forming potential of calcium phosphate (CaP) ceramics in ectopic sites and bone regeneration in critical-sized bone defects. Surface-dependent osteogenic differentiation of bone marrow stromal cells (BMSCs) partially explained the improved bone-forming ability of submicron surface structured CaP ceramics. In this study, we investigated the possible influence of surface structure on different bone-related cells, which may potentially participate in the process of improved bone formation in CaP ceramics. Besides BMSCs, the response of human brain vascular pericytes (HBVP), C2C12 (osteogenic inducible cells), MC3T3-E1 (osteogenic precursors), SV-HFO (pre-osteoblasts), MG63 (osteoblasts) and SAOS-2 (mature osteoblasts) to the surface structure was evaluated in terms of cell proliferation, osteogenic differentiation and gene expression. The cells were cultured on tricalcium phosphate (TCP) ceramics with either micron-scaled surface structure (TCP-B) or submicron-scaled surface structure (TCP-S) for up to 14 days, followed by DNA, alkaline phosphatase (ALP) and quantitative polymerase chain reaction gene assays. HBVP were not sensitive to surface structure with respect to cell proliferation and osteogenic differentiation, but had downregulated angiogenesis-related gene expression (i.e. vascular endothelial growth factor) on TCP-S. Without additional osteogenic inducing factors, submicron-scaled surface structure enhanced ALP activity and osteocalcin gene expression of human (h)BMSCs and C2C12 cells, favoured the proliferation of MC3T3-E1, MG63 and SAOS-2, and increased ALP activity of MC3T3-E1 and SV-HFO. The results herein indicate that cells with osteogenic potency (either osteogenic inducible cells or osteogenic cells) could be sensitive to surface structure and responded to osteoinductive submicron-structured CaP ceramics in cell proliferation, ALP production or osteogenic gene expression, which favour bone

  17. The Effect of Bisphasic Calcium Phosphate Block Bone Graft Materials with Polysaccharides on Bone Regeneration.

    Science.gov (United States)

    Yoo, Hyun-Sang; Bae, Ji-Hyeon; Kim, Se-Eun; Bae, Eun-Bin; Kim, So-Yeun; Choi, Kyung-Hee; Moon, Keum-Ok; Jeong, Chang-Mo; Huh, Jung-Bo

    2017-01-01

    In this study, bisphasic calcium phosphate (BCP) and two types of polysaccharide, carboxymethyl cellulose (CMC) and hyaluronic acid (HyA), were used to fabricate composite block bone grafts, and their physical and biological features and performances were compared and evaluated in vitro and in vivo. Specimens of the following were prepared as 6 mm diameter, 2 mm thick discs; BPC mixed with CMC (the BCP/CMC group), BCP mixed with crosslinked CMC (the BCP/c-CMC group) and BCP mixed with HyA (the BCP/HyA group) and a control group (specimens were prepared using particle type BCP). A scanning electron microscope study, a compressive strength analysis, and a cytotoxicity assessment were conducted. Graft materials were implanted in each of four circular defects of 6 mm diameter in calvarial bone in seven rabbits. Animals were sacrificed after four weeks for micro-CT and histomorphometric analyses, and the findings obtained were used to calculate new bone volumes (mm³) and area percentages (%). It was found that these two values were significantly higher in the BCP/c-CMC group than in the other three groups ( p block bone graft material incorporating crosslinked CMC has potential utility when bone augmentation is needed.

  18. The Effect of Bisphasic Calcium Phosphate Block Bone Graft Materials with Polysaccharides on Bone Regeneration

    Directory of Open Access Journals (Sweden)

    Hyun-Sang Yoo

    2017-01-01

    Full Text Available In this study, bisphasic calcium phosphate (BCP and two types of polysaccharide, carboxymethyl cellulose (CMC and hyaluronic acid (HyA, were used to fabricate composite block bone grafts, and their physical and biological features and performances were compared and evaluated in vitro and in vivo. Specimens of the following were prepared as 6 mm diameter, 2 mm thick discs; BPC mixed with CMC (the BCP/CMC group, BCP mixed with crosslinked CMC (the BCP/c-CMC group and BCP mixed with HyA (the BCP/HyA group and a control group (specimens were prepared using particle type BCP. A scanning electron microscope study, a compressive strength analysis, and a cytotoxicity assessment were conducted. Graft materials were implanted in each of four circular defects of 6 mm diameter in calvarial bone in seven rabbits. Animals were sacrificed after four weeks for micro-CT and histomorphometric analyses, and the findings obtained were used to calculate new bone volumes (mm3 and area percentages (%. It was found that these two values were significantly higher in the BCP/c-CMC group than in the other three groups (p < 0.05. Within the limitations of this study, BCP composite block bone graft material incorporating crosslinked CMC has potential utility when bone augmentation is needed.

  19. A molecular wound response program associated with regeneration initiation in planarians.

    Science.gov (United States)

    Wenemoser, Danielle; Lapan, Sylvain W; Wilkinson, Alex W; Bell, George W; Reddien, Peter W

    2012-05-01

    Planarians are capable of regenerating any missing body part and present an attractive system for molecular investigation of regeneration initiation. The gene activation program that occurs at planarian wounds to coordinate regenerative responses remains unknown. We identified a large set of wound-induced genes during regeneration initiation in planarians. Two waves of wound-induced gene expression occurred in differentiated tissues. The first wave includes conserved immediate early genes. Many second-wave genes encode conserved patterning factors required for proper regeneration. Genes of both classes were generally induced by wounding, indicating that a common initial gene expression program is triggered regardless of missing tissue identity. Planarian regeneration uses a population of regenerative cells (neoblasts), including pluripotent stem cells. A class of wound-induced genes was activated directly within neoblasts, including the Runx transcription factor-encoding runt-1 gene. runt-1 was required for specifying different cell types during regeneration, promoting heterogeneity in neoblasts near wounds. Wound-induced gene expression in neoblasts, including that of runt-1, required SRF (serum response factor) and sos-1. Taken together, these data connect wound sensation to the activation of specific cell type regeneration programs in neoblasts. Most planarian wound-induced genes are conserved across metazoans, and identified genes and mechanisms should be important broadly for understanding wound signaling and regeneration initiation.

  20. Regeneration and molecular analysis of date palm ( Phoenix ...

    African Journals Online (AJOL)

    Clonal plants of date palm (Poenix dactylifera L.) were regenerated from juvenile leaves on regimes consisting of the use of 2,4-D. Success depended on the concentrations of 2,4-D tested. The cultures produced adventitious shoot buds directly at the basal part of leaves as well as excessive calli. Somaclonal variation in ...

  1. Effects of the bilayer nano-hydroxyapatite/mineralized collagen-guided bone regeneration membrane on site preservation in dogs.

    Science.gov (United States)

    Sun, Yi; Wang, Chengyue; Chen, Qixin; Liu, Hai; Deng, Chao; Ling, Peixue; Cui, Fu-Zhai

    2017-08-01

    This study was aimed at assessing the effects of the porous mineralized collagen plug with or without the bilayer mineralized collagen-guided bone regeneration membrane on alveolar ridge preservation in dogs. The third premolars in the bilateral maxilla of mongrel dogs ( N = 12) were extracted. Twenty-four alveolar sockets were thus randomly divided into three groups: membrane + collagen plug (MP, n = 8), nonmembrane + collagen plug (NP, n = 8) and blank group without any implantation (BG, n = 8). Radiographic assessment was carried out immediately and in the 2nd, 6th, and 12th week after surgery. The bone-repairing effects of the two grafts were respectively evaluated by clinical observation, X-ray micro-computed tomography examination, and histological analysis in the 8th and 12th week after surgery. Three groups presented excellent osseointegration without any inflammation or dehiscence. X-ray micro-computed tomography and histological assessment indicated that the ratios of new bone formation of MP group were significantly higher than those of NP group and BG group in the 8th and 12th week after surgery ( P guided bone regeneration membrane could reduce the absorption of alveolar ridge compared to BG group, and the combined use of porous mineralized collagen plug and bilayer mineralized collagen-guided bone regeneration could further improve the activity of bone regeneration.

  2. Guided osteoporotic bone regeneration with composite scaffolds of mineralized ECM/heparin membrane loaded with BMP2-related peptide

    Science.gov (United States)

    Yao, Sheng; Ji, Yanhui; Shi, Lei; Tang, Kai; Xiong, Zekang; Yang, Fan; Chen, Kaifang

    2018-01-01

    Introduction At present, the treatment of osteoporotic defects poses a great challenge to clinicians, owing to the lower regeneration capacity of the osteoporotic bone as compared with the normal bone. The guided bone regeneration (GBR) technology provides a promising strategy to cure osteoporotic defects using bioactive membranes. The decellularized matrix from the small intestinal submucosa (SIS) has gained popularity for its natural microenvironment, which induces cell response. Materials and methods In this study, we developed heparinized mineralized SIS loaded with bone morphogenetic protein 2 (BMP2)-related peptide P28 (mSIS/P28) as a novel GBR membrane for guided osteoporotic bone regeneration. These mSIS/P28 membranes were obtained through the mineralization of SIS (mSIS), followed by P28 loading onto heparinized mSIS. The heparinized mSIS membrane was designed to improve the immobilization efficacy and facilitate controlled release of P28. P28 release from mSIS-heparin-P28 and its effects on the proliferation, viability, and osteogenic differentiation of bone marrow stromal stem cells from ovariectomized rats (rBMSCs-OVX) were investigated in vitro. Furthermore, a critical-sized OVX calvarial defect model was used to assess the bone regeneration capability of mSIS-heparin-P28 in vivo. Results In vitro results showed that P28 release from mSIS-heparin-P28 occurred in a controlled manner, with a long-term release time of 40 days. Moreover, mSIS-heparin-P28 promoted cell proliferation and viability, alkaline phosphatase activity, and mRNA expression of osteogenesis-related genes in rBMSCs-OVX without the addition of extra osteogenic components. In vivo experiments revealed that mSIS-heparin-P28 dramatically stimulated osteoporotic bone regeneration. Conclusion The heparinized mSIS loaded with P28 may serve as a potential GBR membrane for repairing osteoporotic defects. PMID:29440901

  3. Guided osteoporotic bone regeneration with composite scaffolds of mineralized ECM/heparin membrane loaded with BMP2-related peptide.

    Science.gov (United States)

    Sun, Tingfang; Liu, Man; Yao, Sheng; Ji, Yanhui; Shi, Lei; Tang, Kai; Xiong, Zekang; Yang, Fan; Chen, Kaifang; Guo, Xiaodong

    2018-01-01

    At present, the treatment of osteoporotic defects poses a great challenge to clinicians, owing to the lower regeneration capacity of the osteoporotic bone as compared with the normal bone. The guided bone regeneration (GBR) technology provides a promising strategy to cure osteoporotic defects using bioactive membranes. The decellularized matrix from the small intestinal submucosa (SIS) has gained popularity for its natural microenvironment, which induces cell response. In this study, we developed heparinized mineralized SIS loaded with bone morphogenetic protein 2 (BMP2)-related peptide P28 (mSIS/P28) as a novel GBR membrane for guided osteoporotic bone regeneration. These mSIS/P28 membranes were obtained through the mineralization of SIS (mSIS), followed by P28 loading onto heparinized mSIS. The heparinized mSIS membrane was designed to improve the immobilization efficacy and facilitate controlled release of P28. P28 release from mSIS-heparin-P28 and its effects on the proliferation, viability, and osteogenic differentiation of bone marrow stromal stem cells from ovariectomized rats (rBMSCs-OVX) were investigated in vitro. Furthermore, a critical-sized OVX calvarial defect model was used to assess the bone regeneration capability of mSIS-heparin-P28 in vivo. In vitro results showed that P28 release from mSIS-heparin-P28 occurred in a controlled manner, with a long-term release time of 40 days. Moreover, mSIS-heparin-P28 promoted cell proliferation and viability, alkaline phosphatase activity, and mRNA expression of osteogenesis-related genes in rBMSCs-OVX without the addition of extra osteogenic components. In vivo experiments revealed that mSIS-heparin-P28 dramatically stimulated osteoporotic bone regeneration. The heparinized mSIS loaded with P28 may serve as a potential GBR membrane for repairing osteoporotic defects.

  4. 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

  5. Stable subcutaneous cartilage regeneration of bone marrow stromal cells directed by chondrocyte sheet.

    Science.gov (United States)

    Li, Dan; Zhu, Lian; Liu, Yu; Yin, Zongqi; Liu, Yi; Liu, Fangjun; He, Aijuan; Feng, Shaoqing; Zhang, Yixin; Zhang, Zhiyong; Zhang, Wenjie; Liu, Wei; Cao, Yilin; Zhou, Guangdong

    2017-05-01

    In vivo niche plays an important role in regulating differentiation fate of stem cells. Due to lack of proper chondrogenic niche, stable cartilage regeneration of bone marrow stromal cells (BMSCs) in subcutaneous environments is always a great challenge. This study explored the feasibility that chondrocyte sheet created chondrogenic niche retained chondrogenic phenotype of BMSC engineered cartilage (BEC) in subcutaneous environments. Porcine BMSCs were seeded into biodegradable scaffolds followed by 4weeks of chondrogenic induction in vitro to form BEC, which were wrapped with chondrocyte sheets (Sheet group), acellular small intestinal submucosa (SIS, SIS group), or nothing (Blank group) respectively and then implanted subcutaneously into nude mice to trace the maintenance of chondrogenic phenotype. The results showed that all the constructs in Sheet group displayed typical cartilaginous features with abundant lacunae and cartilage specific matrices deposition. These samples became more mature with prolonged in vivo implantation, and few signs of ossification were observed at all time points except for one sample that had not been wrapped completely. Cell labeling results in Sheet group further revealed that the implanted BEC directly participated in cartilage formation. Samples in both SIS and Blank groups mainly showed ossified tissue at all time points with partial fibrogenesis in a few samples. These results suggested that chondrocyte sheet could create a chondrogenic niche for retaining chondrogenic phenotype of BEC in subcutaneous environment and thus provide a novel research model for stable ectopic cartilage regeneration based on stem cells. In vivo niche plays an important role in directing differentiation fate of stem cells. Due to lack of proper chondrogenic niche, stable cartilage regeneration of bone marrow stromal cells (BMSCs) in subcutaneous environments is always a great challenge. The current study demonstrated that chondrocyte sheet generated by

  6. 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

    2016-04-12

    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.

  7. Bone Marrow–Derived Cells Home to and Regenerate Retinal Pigment Epithelium after Injury

    Science.gov (United States)

    Harris, Jeffrey R.; Brown, Gary A. J.; Jorgensen, Marda; Kaushal, Shalesh; Ellis, E. Ann; Grant, Maria B.; Scott, Edward W.

    2013-01-01

    Purpose To determine whether hematopoietic stem and progenitor cells (HSCs/HPCs) can home to and regenerate the retinal pigment epithelium (RPE) after induced injury. Methods Enriched HSCs/HPCs from green fluorescent protein (gfp) transgenic mice were transplanted into irradiated recipient mice to track bone marrow–derived cells. Physical damage was induced by breaching Bruch’s membrane and inducing vascular endothelial growth factor A (VEGFa) expression to promote neovascularization. RPE damage was also induced by sodium iodate injection (40 mg/kg) into wild-type or albino C57Bl/6 mice. Cell morphology, gfp expression, the presence of the Y chromosome, and the presence of melanosomes were used to determine whether the injured RPE was being repaired by the donor bone marrow. Results Injury to the RPE recruits HSC/HPC–derived cells to incorporate into the RPE layer and differentiate into an RPE phenotype. A portion of the HSCs/HPCs adopt RPE morphology, express melanosomes, and integrate into the RPE without cell fusion. Conclusions HSCs/HPCs can migrate to the RPE layer after physical or chemical injury and regenerate a portion of the damaged cell layer. PMID:16639022

  8. Accelerated craniofacial bone regeneration through dense collagen gel scaffolds seeded with dental pulp stem cells

    Science.gov (United States)

    Chamieh, Frédéric; Collignon, Anne-Margaux; Coyac, Benjamin R.; Lesieur, Julie; Ribes, Sandy; Sadoine, Jérémy; Llorens, Annie; Nicoletti, Antonino; Letourneur, Didier; Colombier, Marie-Laure; Nazhat, Showan N.; Bouchard, Philippe; Chaussain, Catherine; Rochefort, Gael Y.

    2016-12-01

    Therapies using mesenchymal stem cell (MSC) seeded scaffolds may be applicable to various fields of regenerative medicine, including craniomaxillofacial surgery. Plastic compression of collagen scaffolds seeded with MSC has been shown to enhance the osteogenic differentiation of MSC as it increases the collagen fibrillary density. The aim of the present study was to evaluate the osteogenic effects of dense collagen gel scaffolds seeded with mesenchymal dental pulp stem cells (DPSC) on bone regeneration in a rat critical-size calvarial defect model. Two symmetrical full-thickness defects were created (5 mm diameter) and filled with either a rat DPSC-containing dense collagen gel scaffold (n = 15), or an acellular scaffold (n = 15). Animals were imaged in vivo by microcomputer tomography (Micro-CT) once a week during 5 weeks, whereas some animals were sacrificed each week for histology and histomorphometry analysis. Bone mineral density and bone micro-architectural parameters were significantly increased when DPSC-seeded scaffolds were used. Histological and histomorphometrical data also revealed significant increases in fibrous connective and mineralized tissue volume when DPSC-seeded scaffolds were used, associated with expression of type I collagen, osteoblast-associated alkaline phosphatase and osteoclastic-related tartrate-resistant acid phosphatase. Results demonstrate the potential of DPSC-loaded-dense collagen gel scaffolds to benefit of bone healing process.

  9. Three-Dimensional Printing of Hollow-Struts-Packed Bioceramic Scaffolds for Bone Regeneration.

    Science.gov (United States)

    Luo, Yongxiang; Zhai, Dong; Huan, Zhiguang; Zhu, Haibo; Xia, Lunguo; Chang, Jiang; Wu, Chengtie

    2015-11-04

    Three-dimensional printing technologies have shown distinct advantages to create porous scaffolds with designed macropores for application in bone tissue engineering. However, until now, 3D-printed bioceramic scaffolds only possessing a single type of macropore have been reported. Generally, those scaffolds with a single type of macropore have relatively low porosity and pore surfaces, limited delivery of oxygen and nutrition to surviving cells, and new bone tissue formation in the center of the scaffolds. Therefore, in this work, we present a useful and facile method for preparing hollow-struts-packed (HSP) bioceramic scaffolds with designed macropores and multioriented hollow channels via a modified coaxial 3D printing strategy. The prepared HSP scaffolds combined high porosity and surface area with impressive mechanical strength. The unique hollow-struts structures of bioceramic scaffolds significantly improved cell attachment and proliferation and further promoted formation of new bone tissue in the center of the scaffolds, indicating that HSP ceramic scaffolds can be used for regeneration of large bone defects. In addition, the strategy can be used to prepare other HSP ceramic scaffolds, indicating a universal application for tissue engineering, mechanical engineering, catalysis, and environmental materials.

  10. Regenerating Mandibular Bone Using rhBMP-2: Part 1-Immediate Reconstruction of Segmental Mandibulectomies.

    Science.gov (United States)

    Arzi, Boaz; Verstraete, Frank J M; Huey, Daniel J; Cissell, Derek D; Athanasiou, Kyriacos A

    2015-05-01

    To describe a surgical technique using a regenerative approach and internal fixation for immediate reconstruction of critical size bone defects after segmental mandibulectomy in dogs. Prospective case series. Dogs (n = 4) that had reconstruction after segmental mandibulectomy for treatment of malignant or benign tumors. Using a combination of extraoral and intraoral approaches, a locking titanium plate was contoured to match the native mandible. After segmental mandibulectomy, the plate was secured and a compression resistant matrix (CRM) infused with rhBMP-2, implanted in the defect. The implant was then covered with a soft tissue envelope followed by intraoral and extraoral closure. All dogs that had mandibular reconstruction healed with intact gingival covering over the mandibular defect and had immediate return to normal function and occlusion. Mineralized tissue formation was observed clinically within 2 weeks and solid cortical bone formation within 3 months. CT findings at 3 months showed that the newly regenerated mandibular bone had ∼50% of the bone density and porosity compared to the contralateral side. No significant complications occurred. Mandibular reconstruction using internal fixation and CRM infused with rhBMP-2 is an excellent solution for immediate reconstruction of segmental mandibulectomy defects in dogs. © Copyright 2014 by The American College of Veterinary Surgeons.

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

    Science.gov (United States)

    Guan, Junjie; Zhang, Jieyuan; Li, Haiyan; Zhu, Zhenzhong; Guo, Shangchun; Niu, Xin; Wang, Yang; Zhang, Changqing

    2015-01-01

    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. 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.

  13. Delayed minimally invasive injection of allogenic bone marrow stromal cell sheets regenerates large bone defects in an ovine preclinical animal model.

    Science.gov (United States)

    Berner, Arne; Henkel, Jan; Woodruff, Maria A; Steck, Roland; Nerlich, Michael; Schuetz, Michael A; Hutmacher, Dietmar W

    2015-05-01

    Cell-based tissue engineering approaches are promising strategies in the field of regenerative medicine. However, the mode of cell delivery is still a concern and needs to be significantly improved. Scaffolds and/or matrices loaded with cells are often transplanted into a bone defect immediately after the defect has been created. At this point, the nutrient and oxygen supply is low and the inflammatory cascade is incited, thus creating a highly unfavorable microenvironment for transplanted cells to survive and participate in the regeneration process. We therefore developed a unique treatment concept using the delayed injection of allogenic bone marrow stromal cell (BMSC) sheets to regenerate a critical-sized tibial defect in sheep to study the effect of the cells' regeneration potential when introduced at a postinflammatory stage. Minimally invasive percutaneous injection of allogenic BMSCs into biodegradable composite scaffolds 4 weeks after the defect surgery led to significantly improved bone regeneration compared with preseeded scaffold/cell constructs and scaffold-only groups. Biomechanical testing and microcomputed tomography showed comparable results to the clinical reference standard (i.e., an autologous bone graft). To our knowledge, we are the first to show in a validated preclinical large animal model that delayed allogenic cell transplantation can provide applicable clinical treatment alternatives for challenging bone defects in the future. ©AlphaMed Press.

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

    International Nuclear Information System (INIS)

    Jung, Ui-Won; Song, Kun-Young; Kim, Chang-Sung; Lee, Yong-Keun; Cho, Kyoo-Sung; Kim, Chong-Kwan; Choi, Seong-Ho

    2007-01-01

    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

  15. 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.

  16. Systemic Delivery of Bone Marrow Mesenchymal Stem Cells for In Situ Intervertebral Disc Regeneration

    Science.gov (United States)

    Almeida, Catarina R.; Almeida, Maria Inês; Silva, Andreia M.; Molinos, Maria; Lamas, Sofia; Pereira, Catarina L.; Teixeira, Graciosa Q.; Monteiro, António T.; Santos, Susana G.; Gonçalves, Raquel M.; Barbosa, Mário A.

    2016-01-01

    Abstract Cell therapies for intervertebral disc (IVD) regeneration presently rely on transplantation of IVD cells or stem cells directly to the lesion site. Still, the harsh IVD environment, with low irrigation and high mechanical stress, challenges cell administration and survival. In this study, we addressed systemic transplantation of allogeneic bone marrow mesenchymal stem cells (MSCs) intravenously into a rat IVD lesion model, exploring tissue regeneration via cell signaling to the lesion site. MSC transplantation was performed 24 hours after injury, in parallel with dermal fibroblasts as a control; 2 weeks after transplantation, animals were killed. Disc height index and histological grading score indicated less degeneration for the MSC‐transplanted group, with no significant changes in extracellular matrix composition. Remarkably, MSC transplantation resulted in local downregulation of the hypoxia responsive GLUT‐1 and in significantly less herniation, with higher amounts of Pax5+ B lymphocytes and no alterations in CD68+ macrophages within the hernia. The systemic immune response was analyzed in the blood, draining lymph nodes, and spleen by flow cytometry and in the plasma by cytokine array. Results suggest an immunoregulatory effect in the MSC‐transplanted animals compared with control groups, with an increase in MHC class II+ and CD4+ cells, and also upregulation of the cytokines IL‐2, IL‐4, IL‐6, and IL‐10, and downregulation of the cytokines IL‐13 and TNF‐α. Overall, our results indicate a beneficial effect of systemically transplanted MSCs on in situ IVD regeneration and highlight the complex interplay between stromal cells and cells of the immune system in achieving successful tissue regeneration. Stem Cells Translational Medicine 2017;6:1029–1039 PMID:28297581

  17. Tyrosine-derived polycarbonate scaffolds for bone regeneration in a rabbit radius critical-size defect model

    International Nuclear Information System (INIS)

    Kim, Jinku; McBride, Sean; Donovan, Amy; Hollinger, Jeffrey O; Darr, Aniq; Magno, Maria Hanshella R

    2015-01-01

    The aim of the study was to determine bone regeneration in a rabbit radius critical-size defect (CSD) model using a specific polymer composition (E1001(1k)) from a library of tyrosine-derived polycarbonate scaffolds coated with a calcium phosphate (CP) formulation (E1001(1k) + CP) supplemented with recombinant human bone morphogenetic protein-2 (rhBMP-2). Specific doses of rhBMP-2 (0, 17, and 35 μg/scaffold) were used. E1001(1k) + CP scaffolds were implanted in unilateral segmental defects (15 mm length) in the radial diaphyses of New Zealand White rabbits. At 4 and 8 weeks post-implantation, bone regeneration was determined using micro-computed tomography (µCT), histology, and histomorphometry. The quantitative outcome data suggest that E1001(1k) + CP scaffolds with rhBMP-2 were biocompatible and promoted bone regeneration in segmental bone defects. Histological examination of the implant sites showed that scaffolds made of E1001(1k) + CP did not elicit adverse cellular or tissue responses throughout test periods up to 8 weeks. Noteworthy is that the incorporation of a very small amount of rhBMP-2 into the scaffolds (as low as 17 μg/defect site) promoted significant bone regeneration compared to scaffolds consisting of E1001(1k) + CP alone. This finding indicates that E1001(1k) + CP may be an effective platform for bone regeneration in a critical size rabbit radius segmental defect model, requiring only a minimal dose of rhBMP-2. (paper)

  18. Enzymatic, urease-mediated mineralization of gellan gum hydrogel with calcium carbonate, magnesium-enriched calcium carbonate and magnesium carbonate for bone regeneration applications

    DEFF Research Database (Denmark)

    Douglas, Timothy E L; Łapa, Agata; Samal, Sangram Keshari

    2017-01-01

    Mineralization of hydrogel biomaterials is considered desirable to improve their suitability as materials for bone regeneration. Calcium carbonate (CaCO3 ) has been successfully applied as a bone regeneration material, but hydrogel-CaCO3 composites have received less attention. Magnesium (Mg) has...

  19. Porous Alpha-Tricalcium Phosphate with Immobilized Basic Fibroblast Growth Factor Enhances Bone Regeneration in a Canine Mandibular Bone Defect Model

    Directory of Open Access Journals (Sweden)

    Nobuhiro Kobayashi

    2016-10-01

    Full Text Available The effect of porous alpha-tricalcium phosphate (α-TCP with immobilized basic fibroblast growth factor (bFGF on bone regeneration was evaluated in a canine mandibular bone defect model. Identical bone defects were made in the canine mandible; six defects in each animal were filled with porous α-TCP with bFGF bound via heparin (bFGF group, whereas the other was filled with unmodified porous α-TCP (control group. Micro-computed tomography and histological evaluation were performed two, four and eight weeks after implantation. The bone mineral density of the bFGF group was higher than that of the control group at each time point (p < 0.05, and the bone mineral content of the bFGF group was higher than that of the control group at four and eight weeks (p < 0.05. Histological evaluation two weeks after implantation revealed that the porous α-TCP had degraded and bone had formed on the surface of α-TCP particles in the bFGF group. At eight weeks, continuous cortical bone with a Haversian structure covered the top of bone defects in the bFGF group. These findings demonstrate that porous α-TCP with immobilized bFGF can promote bone regeneration.

  20. PDLLA scaffolds with Cu- and Zn-doped bioactive glasses having multifunctional properties for bone regeneration.

    Science.gov (United States)

    Bejarano, Julian; Detsch, Rainer; Boccaccini, Aldo R; Palza, Humberto

    2017-03-01

    Novel multifunctional scaffolds for bone regeneration can be developed by incorporation of bioactive glasses (BG) doped with therapeutic and antibacterial metal ions, such as copper (Cu) and zinc (Zn), into a biodegradable polymer. In this context, porous composite materials of biodegradable poly(d, l-lactide) (PDLLA) mixed with sol-gel BG of chemical composition 60SiO 2 ; 25CaO; 11Na 2 O; and 4P 2 O 5 (mol %) doped with either 1 mol % of CuO or ZnO, and with both metals, were prepared. The cytocompatibility of the scaffolds on bone marrow stromal cells (ST-2) depended on both, the amount of glass filler and the concentration of metal ion, as evaluated by lactate dehydrogenase (LDH) activity, cell viability (water-soluble tetrazolium salt [WST-8]), and by cell morphology (scanning electron microscopy [SEM]) tests. In particular, scaffolds having a filler content of 10 wt % showed the highest cytocompatibility. In addition, compared to the neat polymer, the scaffolds containing Cu promoted the angiogenesis marker (Vascular endothelial growth factor concentration) to a larger extent while scaffolds containing Zn increased the osteogenesis marker (specific alkaline phosphatase-activity). Noteworthy, the scaffolds with both metal ions showed a combined effect on both properties. Cu- and Zn-doped glasses also provided higher antibacterial capacity to PDLLA-based scaffolds against methicillin-resistant S. aureus bacteria than undoped glass. In combination, our results showed that by a proper addition of Cu- and Zn-doped BG to a PDLLA matrix, multifunctional composite scaffolds with enhanced biological activity can be designed for bone tissue regeneration. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 105A: 746-756, 2017. © 2016 Wiley Periodicals, Inc.

  1. Bone morphogenetic protein signaling promotes morphogenesis of blood vessels, wound epidermis, and actinotrichia during fin regeneration in zebrafish.

    Science.gov (United States)

    Thorimbert, Valentine; König, Désirée; Marro, Jan; Ruggiero, Florence; Jaźwińska, Anna

    2015-10-01

    Zebrafish fin regeneration involves initial formation of the wound epidermis and the blastema, followed by tissue morphogenesis. The mechanisms coordinating differentiation of distinct tissues of the regenerate are poorly understood. Here, we applied pharmacologic and transgenic approaches to address the role of bone morphogenetic protein (BMP) signaling during fin restoration. To map the BMP transcriptional activity, we analyzed the expression of the evolutionarily conserved direct phospho-Smad1 target gene, id1, and its homologs id2a and id3. This analysis revealed the BMP activity in the distal blastema, wound epidermis, osteoblasts, and blood vessels of the regenerate. Blocking the BMP function with a selective chemical inhibitor of BMP type I receptors, DMH1, suppressed id1 and id3 expression and arrested regeneration after blastema formation. We identified several previously uncharacterized functions of BMP during fin regeneration. Specifically, BMP signaling is required for remodeling of plexus into structured blood vessels in the rapidly growing regenerate. It organizes the wound epithelium by triggering wnt5b expression and promoting Collagen XIV-A deposition into the basement membrane. BMP represents the first known signaling that induces actinotrichia formation in the regenerate. Our data reveal a multifaceted role of BMP for coordinated morphogenesis of distinct tissues during regeneration of a complex vertebrate appendage. © FASEB.

  2. 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

    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 that knowledge...

  3. Utilization of d-PTFE Barriers for Post-Extraction Bone Regeneration in Preparation for Dental Implants.

    Science.gov (United States)

    Greenstein, Gary; Carpentieri, Joseph R

    2015-01-01

    Guided bone regeneration (GBR) can be used to restore a defective alveolar ridge after extractions before or in combination with implant placement. It may also be employed after extractions to reduce crestal bone resorption and maximize bone fill of sockets. Resorbable or nonresorbable barriers (eg, expanded polytetrafluoroethylene [e-PTFE]) can be used when performing GBR procedures, but they need to be completely submerged to attain optimal results. Dense polytetrafluoroethylene (d-PTFE) is a type of nonresorbable barrier that circumvents the necessity to attain primary closure after placement of bone grafts, thereby reducing patient morbidity. This article addresses topics pertaining to d-PTFE utilization, including characteristics and advantages of d-PTFE barriers, time needed for osteoid tissue to become impervious to penetration by flap connective tissue, relevant clinical studies, and limitations of available data. Clinical photographs and radiographs of successfully treated cases are presented to illustrate the efficacy of d-PTFE barriers in regenerating defective bony plates after extractions.

  4. Tritium recovery from helium purge stream of solid breeder blanket by cryogenic molecular sieve bed. 2. Regeneration operation of cryogenic molecular sieve bed

    Energy Technology Data Exchange (ETDEWEB)

    Kawamura, Yoshinori; Enoeda, Mikio; Nishi, Masataka [Japan Atomic Energy Research Inst., Tokai, Ibaraki (Japan). Tokai Research Establishment

    1998-03-01

    Regeneration operation is a very important operation, because it is the most influential factor for deciding the net operation cycle time and the minimum dimension of Cryogenic Molecular Sieve Bed (CMSB). However, the experimental data of CMSB regeneration operation was not so sufficient that even the optimum regeneration procedure could not be decided yet. This work was focused on getting the primary information about various regeneration procedures. (author)

  5. [The application of guided bone regeneration technique in the restoration of maxillary lateral incisor with bone defect].

    Science.gov (United States)

    Li, Zhuo-rui; Liu, Zhong-hao; Xu, Sheng; Xiao, Hui-juan; Zhou, Wen-juan

    2012-04-01

    To evaluate the clinical effectiveness and the satisfaction on aesthetic effectiveness of application of guided bone regeneration (GBR) technique in maxillary lateral incisor implant site. Ninety patients were selected who only lost maxillary lateral incisor and placed with 101 implants(the implant systems were 3i, Osstem, ITI, Ankylos, BLB). The final restorations were porcelain-fused-to-metal crowns. Clinical and X-ray examinations were conducted and esthetic results were observed at 3, 6,12 months after dental implant prosthetics. The follow-up time was 12 months, all patients achieved successful implantation and good osseointegration around the implant. The esthetic results were perfect .Among the 90 cases, 90.7%, 92.8% and 95.5% of the patients were satisfied with the final outcomes 3,6,12 months after prosthetics. Good clinical effectiveness and satisfaction on aesthetic effectiveness can be obtained with GBR technique applied in maxillary lateral incisor implant site. Appropriate use of GBR technique is the solution of bone defect of maxillary lateral incisor implant site.

  6. Platelet-Rich Fibrin with Bone Grafts for Regeneration of Bony Defect following Extraction of Supernumerary Teeth: A Case Report.

    Science.gov (United States)

    Chandrasekaran, Balamanikandasrinivasan; Suresh, Nanditha; Muthusamy, Senthilkumar

    Supernumerary teeth are hyperdontic variants due to abnormalities during tooth development. Here, we report a case on regeneration of bony defect, which ensued following extraction of two supernumerary teeth in the mandibular premolar region, using a combination of bone grafts and platelet-rich fibrin. To the best of our knowledge, it is the first time synergistic use of biomaterials with bone grafts have been used for this type of management.

  7. Evaluation of the effect of a gamma irradiated DBM-pluronic F127 composite on bone regeneration in Wistar rat.

    Directory of Open Access Journals (Sweden)

    Tamer Al Kayal

    Full Text Available Demineralized bone matrix (DBM is widely used for bone regeneration. Since DBM is prepared in powder form its handling properties are not optimal and limit the clinical use of this material. Various synthetic and biological carriers have been used to enhance the DBM handling. In this study we evaluated the effect of gamma irradiation on the physical-chemical properties of Pluronic and on bone morphogenetic proteins (BMPs amount in DBM samples. In vivo studies were carried out to investigate the effect on bone regeneration of a gamma irradiated DBM-Pluronic F127 (DBM-PF127 composite implanted in the femur of rats. Gamma irradiation effects (25 kGy on physical-chemical properties of Pluronic F127 were investigated by rheological and infrared analysis. The BMP-2/BMP-7 amount after DBM irradiation was evaluated by ELISA. Bone regeneration capacity of DBM-PF127 containing 40% (w/w of DBM was investigated in transcortical holes created in the femoral diaphysis of Wistar rat. Bone porosity, repaired bone volume and tissue organization were evaluated at 15, 30 and 90 days by Micro-CT and histological analysis. The results showed that gamma irradiation did not induce significant modification on physical-chemical properties of Pluronic, while a decrease in BMP-2/BMP-7 amount was evidenced in sterilized DBM. Micro-CT and histological evaluation at day 15 post-implantation revealed an interconnected trabeculae network in medullar cavity and cellular infiltration and vascularization of DBM-PF127 residue. In contrast a large rate of not connected trabeculae was observed in Pluronic filled and unfilled defects. At 30 and 90 days the DBM-PF127 samples shown comparable results in term of density and thickness of the new formed tissue respect to unfilled defect. In conclusion a gamma irradiated DBM-PF127 composite, although it may have undergone a significant decrease in the concentration of BMPs, was able to maintains bone regeneration capability.

  8. Guided bone regeneration in osteoporotic conditions following treatment with zoledronic acid.

    Science.gov (United States)

    Mardas, Nikos; Busetti, Juliano; de Figueiredo, José Antonio Poli; Mezzomo, Luis André; Scarparo, Roberta Kochenborger; Donos, Nikolaos

    2017-03-01

    To evaluate new bone formation in calvarial critical size defects (CSD) under dense polytetrafluoroethylene (d-PTFE), microporous membranes for guided bone regeneration (GBR) in healthy, osteoporotic and osteoporotic treated with zoledronic acid (ZA) rats. Forty-eight, female, 6-month old Wistar rats were included in the study. Osteoporosis was induced by ovariectomy (OVX) and calcium-deficient diet in 32 rats. Sixteen OVX rats were treated with a single dose of Zolendronic Acid (ZA) (OZ), while 16 OVX rats received no treatment (O). The remaining 16 rats were sham-operated and used as healthy controls (C). At 6 weeks following osteoporosis induction, two 5 mm CSD were created in the parietal bones and one of them was treated with a double d-PTFE membrane. The healing periods were 30 and 60 days. New bone formation (NB) was assessed by qualitative and quantitative histological analysis. After 30 days of healing, NB (mean% (95% CI)) was 78.9% (21), 93.1% (9.3) and 84.2% (26.9) in the membrane treated defects and 18.8% (24.1), 27.1% (7.9) and 31% (38.8) in the untreated defects of group O, OZ and C, respectively. After 60 days of healing, NB was 78.3% (14.4), 95.8% (9) and 90.1% (26.1) in the membrane treated defects and 10.8% (17.4), 51.6% (39.4) and 15.7% (12.1) in the untreated defects of group O, OZ and C, respectively. Hierarchical analysis of variance showed that treatment with ZA (P = 0.001) and the use of membrane (P = 0.000) significantly increased new bone formation while presence of osteoporosis may have reduced new bone formation (P = 0.028). d-PTFE membranes for GBR promote bone healing in osteoporotic and healthy rats. Treatment with ZA may improve new bone formation in osteoporotic rats. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  9. Combining classical and molecular approaches elaborates on the complexity of mechanisms underpinning anterior regeneration.

    Science.gov (United States)

    Evans, Deborah J; Owlarn, Suthira; Tejada Romero, Belen; Chen, Chen; Aboobaker, A Aziz

    2011-01-01

    The current model of planarian anterior regeneration evokes the establishment of low levels of Wnt signalling at anterior wounds, promoting anterior polarity and subsequent elaboration of anterior fate through the action of the TALE class homeodomain PREP. The classical observation that decapitations positioned anteriorly will regenerate heads more rapidly than posteriorly positioned decapitations was among the first to lead to the proposal of gradients along an anteroposterior (AP) axis in a developmental context. An explicit understanding of this phenomenon is not included in the current model of anterior regeneration. This raises the question what the underlying molecular and cellular basis of this temporal gradient is, whether it can be explained by current models and whether understanding the gradient will shed light on regenerative events. Differences in anterior regeneration rate are established very early after amputation and this gradient is dependent on the activity of Hedgehog (Hh) signalling. Animals induced to produce two tails by either Smed-APC-1(RNAi) or Smed-ptc(RNAi) lose anterior fate but form previously described ectopic anterior brain structures. Later these animals form peri-pharyngeal brain structures, which in Smed-ptc(RNAi) grow out of the body establishing a new A/P axis. Combining double amputation and hydroxyurea treatment with RNAi experiments indicates that early ectopic brain structures are formed by uncommitted stem cells that have progressed through S-phase of the cell cycle at the time of amputation. Our results elaborate on the current simplistic model of both AP axis and brain regeneration. We find evidence of a gradient of hedgehog signalling that promotes posterior fate and temporarily inhibits anterior regeneration. Our data supports a model for anterior brain regeneration with distinct early and later phases of regeneration. Together these insights start to delineate the interplay between discrete existing, new, and then

  10. Combining classical and molecular approaches elaborates on the complexity of mechanisms underpinning anterior regeneration.

    Directory of Open Access Journals (Sweden)

    Deborah J Evans

    Full Text Available The current model of planarian anterior regeneration evokes the establishment of low levels of Wnt signalling at anterior wounds, promoting anterior polarity and subsequent elaboration of anterior fate through the action of the TALE class homeodomain PREP. The classical observation that decapitations positioned anteriorly will regenerate heads more rapidly than posteriorly positioned decapitations was among the first to lead to the proposal of gradients along an anteroposterior (AP axis in a developmental context. An explicit understanding of this phenomenon is not included in the current model of anterior regeneration. This raises the question what the underlying molecular and cellular basis of this temporal gradient is, whether it can be explained by current models and whether understanding the gradient will shed light on regenerative events. Differences in anterior regeneration rate are established very early after amputation and this gradient is dependent on the activity of Hedgehog (Hh signalling. Animals induced to produce two tails by either Smed-APC-1(RNAi or Smed-ptc(RNAi lose anterior fate but form previously described ectopic anterior brain structures. Later these animals form peri-pharyngeal brain structures, which in Smed-ptc(RNAi grow out of the body establishing a new A/P axis. Combining double amputation and hydroxyurea treatment with RNAi experiments indicates that early ectopic brain structures are formed by uncommitted stem cells that have progressed through S-phase of the cell cycle at the time of amputation. Our results elaborate on the current simplistic model of both AP axis and brain regeneration. We find evidence of a gradient of hedgehog signalling that promotes posterior fate and temporarily inhibits anterior regeneration. Our data supports a model for anterior brain regeneration with distinct early and later phases of regeneration. Together these insights start to delineate the interplay between discrete existing, new

  11. [Molecular mechanism of brain regeneration and reconstruction of dopaminergic neural network in planarians].

    Science.gov (United States)

    Nishimura, Kaneyasu; Kitamura, Yoshihisa; Agata, Kiyokazu

    2008-04-01

    Recently, planarians have received much attention because of their contributions to research on the basic science of stem cell systems, neural regeneration, and regenerative medicine. Planarians can regenerate complete organs, including a well-organized central nervous system (CNS), within about 7 days. This high regenerative capacity is supported by pluripotent stem cells present in the mesenchymal space throughout the body. Interestingly, planarians can regenerate their brain via a molecular mechanism similar to that of mammalian brain development. The regeneration process of the planarian brain can be divided into five steps: (1) anterior blastema formation, (2) brain rudiment formation, (3) brain pattern formation, (4) neural network formation, and (5) functional recovery, with several kinds of genes and molecular cascades acting at each step. Recently, we have identified a planarian tyrosine hydroxylase (TH) gene, a rate-limiting enzyme for dopamine (DA) biosynthesis, and produced TH-knockdown planarians by the RNA interference technique. Studies of TH-knockdown planarians showed that DA has an important role of the modification in behavioral movement in planarians. Using monoclonal anti-planarian TH antibody, we also found that dopaminergic neurons are mainly localized in the planarian brain. When the planarian body was amputated, newly generated TH-immunopositive neurons were detected in the anterior region at day 3 of regeneration (i.e., the period of neural network formation), and the TH-immunopositive axonal and dendritic neural network in the CNS was reconstructed during day 5-7 of regeneration. In this article, recent advances in elucidating the molecular mechanism of planarian brain regeneration and dopaminergic neurons are reviewed, and its future prospects for contribution of this system to basic science and medical science research are described.

  12. Effect of a low-level laser on bone regeneration after rapid maxillary expansion.

    Science.gov (United States)

    Cepera, Fernanda; Torres, Fernando C; Scanavini, Marco A; Paranhos, Luiz R; Capelozza Filho, Leopoldino; Cardoso, Mauricio A; Siqueira, Danieli C R; Siqueira, Danilo F

    2012-04-01

    In this study, we evaluated the effects of a low-level laser on bone regeneration in rapid maxillary expansion procedures. Twenty-seven children, aged 8 to 12 years, took part in the experiment, with a mean age of 10.2 years, divided into 2 groups: the laser group (n = 14), in which rapid maxillary expansion was performed in conjunction with laser use, and the no-laser group (n = 13), with rapid maxillary expansion only. The activation protocol of the expansion screw was 1 full turn on the first day and a half turn daily until achieving overcorrection. The laser type used was a laser diode (TWIN Laser; MMOptics, São Carlos, Brazil), according to the following protocol: 780 nm wavelength, 40 mW power, and 10 J/cm(2) density at 10 points located around the midpalatal suture. The application stages were 1 (days 1-5 of activation), 2 (at screw locking, on 3 consecutive days), 3, 4, and 5 (7, 14, and 21 days after stage 2). Occlusal radiographs of the maxilla were taken with the aid of an aluminum scale ruler as a densitometry reference at different times: T1 (initial), T2 (day of locking), T3 (3-5 days after T2), T4 (30 days after T3), and T5 (60 days after T4). The radiographs were digitized and submitted to imaging software (Image Tool; UTHSCSA, San Antonio, Tex) to measure the optic density of the previously selected areas. To perform the statistical test, analysis of covariance was used, with the time for the evaluated stage as the covariable. In all tests, a significance level of 5% (P laser improved the opening of the midpalatal suture and accelerated the bone regeneration process. The low-level laser, associated with rapid maxillary expansion, provided efficient opening of the midpalatal suture and influenced the bone regeneration process of the suture, accelerating healing. Copyright © 2012 American Association of Orthodontists. Published by Mosby, Inc. All rights reserved.

  13. Evaluation of Guided Bone Regeneration around Oral Implants over Different Healing Times Using Two Different Bovine Bone Materials: A Randomized, Controlled Clinical and Histological Investigation.

    Science.gov (United States)

    Kohal, Ralf Joachim; Straub, Lisa Marie; Wolkewitz, Martin; Bächle, Maria; Patzelt, Sebastian Berthold Maximilian

    2015-10-01

    To evaluate the potential of two bone substitute materials and the influence of different healing periods in guided bone regeneration therapy of osseous defects around implants. Twenty-four edentulous patients received implants in the region of the lost lower incisors. Around two standardized osseous defects were created, treated either with a 50:50 mixture of PepGen P-15® and OsteoGraf®/N-700 (test group) or with BioOss® (control group), and covered with titanium membranes. After healing periods of 2, 4, 6, or 9 months, the implants were removed together with the surrounding bone and subsequently prepared for histological evaluations. Defect depths in both groups showed a clinical reduction after intervention. The histologically measured distance from the implant shoulder to the first point of bone-implant contact (BIC) after treatment did not differ between the two groups. The healing time influenced the level of the first point of BIC, with a longer healing period producing a more coronal first point of BIC. A greater percentage BIC and a higher fraction of mineralized bone were found in the pristine bone area compared with the augmented defect area. It can be concluded that in the treatment of osseous defects around oral implants, both materials were equally effective bone substitute materials when used in combination with guided bone regeneration. © 2014 Wiley Periodicals, Inc.

  14. 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. Copyright © 2016. Published by Elsevier Ltd.

  15. Light microscopic description of the effects of laser phototherapy on bone defects grafted with mineral trioxide aggregate, bone morphogenetic proteins, and guided bone regeneration in a rodent model.

    Science.gov (United States)

    Pinheiro, Antonio L B; Soares, Luiz G P; Aciole, Gilberth T S; Correia, Neandder A; Barbosa, Artur F S; Ramalho, Luciana M P; Dos Santos, Jean N

    2011-08-01

    We carried out a histological analysis on bone defects grafted with mineral trioxide aggregate (MTA) treated or not with laser, bone morphogenetic protein (BMP), and guided bone regeneration (GBR). Benefits of the use of MTA, laser, BMPs, and GBR on bone repair are well known, but there is no report on their association with laser light. Ninety rats were divided into 10 groups each subdivided into 3. Defects on G II and I were filled with the blood clot. G II was further irradiated with LED. G III and IV were filled with MTA; G IV was further irradiated with laser. G V and VI, the defects filled with MTA and covered with a membrane (GBR). G VI was further irradiated with laser. G VII and VIII, BMPs were added to the MTA and group VIII further irradiated with laser. G IX and X, the MTA + BMP graft was covered with a membrane (GBR). G X was further irradiated with laser. Laser light (λ = 850 nm, 150 mW, 4 J/cm(2) ) was applied over the defect at 48-h intervals and repeated for 15 days. Specimens were processed, cut and stained with H&E and Sirius red and underwent histological analysis. Subjects on group X were irradiated. The results showed different tissue response on all groups during the experimental time. Major changes were seen on irradiated subjects and included marked deposition of new bone in advanced maturation. It is concluded that near infrared laser phototherapy improved the results of the use of the MTA on bone defects. Copyright © 2011 Wiley Periodicals, Inc.

  16. Influence of bone marrow-derived mesenchymal stem cells pre-implantation differentiation approach on periodontal regeneration in vivo.

    NARCIS (Netherlands)

    Cai, X; Yang, F.; Yan, X.; Yang, W; Yu, N.; Oortgiesen, D.A.; Wang, Y.; Jansen, J.A.; Walboomers, X.F.

    2015-01-01

    AIM: The implantation of bone marrow-derived mesenchymal stem cells (MSCs) has previously been shown successful to achieve periodontal regeneration. However, the preferred pre-implantation differentiation strategy (e.g. maintenance of stemness, osteogenic or chondrogenic induction) to obtain optimal

  17. 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.

  18. Vertical Bone Augmentation with an Autogenous Block or Particles in Combination with Guided Bone Regeneration: A Clinical and Histological Preliminary Study in Humans.

    Science.gov (United States)

    Rocchietta, Isabella; Simion, Massimo; Hoffmann, Maria; Trisciuoglio, Davide; Benigni, Marco; Dahlin, Christer

    2016-02-01

    Vertical ridge augmentation with the use of solid bone blocks or particulate bone autograft, exposed or covered by a nonresorbable expanded polytetrafluoroethylene (ePTFE) membrane, are well known in the literature and have been shown to be effective in treating bone atrophy. The aim of our study was to assess the two techniques in respect to biological properties of transplanted bone in graft revascularization and bone remodeling in conjunction with dental implants. Ten patients were treated within the study, with a total of 12 sites with posterior mandibular edentulous ridges with insufficient bone to allow implant placement. Bone regeneration was performed using autogenous intraoral block graft or autogenous particulate graft with an ePTFE barrier membrane. At 6-10 months, reentry surgery was performed; bone biopsies, including microscrews, were harvested; and implants were placed. Eleven sites out of 12 healed uneventfully. A mean height gain of 5.03 mm was achieved. Mean bone-to-implant contact and bone fill were assessed by means of histomorphometric analysis. The block specimens revealed a bone-to-implant contact of 42.34%, and the particulate grafts had a bone-to-implant contact of 26.62% (p Bone fill values reported were 68.32% and 48.28% (p bone remodeling, of the two techniques differed significantly. The block grafts outperformed the particulate grafts in terms of bone-to-implant contact and bone fill values; however, the morbidity associated with the donor site of the block must be considered. © 2015 Wiley Periodicals, Inc.

  19. Guided Bone Regeneration With or Without a Collagen Membrane in Rats with Induced Diabetes Mellitus: Histomorphometric and Immunolocalization Analysis of Angiogenesis and Bone Turnover Markers.

    Science.gov (United States)

    Jardini, Maria Aparecida; Tera, Tábata Mello; Meyer, Augusto Andrade; Moretto, Camilla Magnoni; Prado, Renata Falchete; Santamaria, Mauro Pedrine

    2016-01-01

    Diabetes mellitus (DM) affects the processes of repair, wound healing, and bone remodeling. This study was conducted to evaluate autologous bone graft integration, either with or without guided bone regeneration, through analyzing the expression of bone reabsorption markers and neovascularization in rats suffering from DM. Thirty adult Wistar rats were divided into two groups: The DM group received an injection of alloxan monohydrate (150 mg/kg), and the control group received an injection of sterile saline. Fifteen days afterward, an autologous bone grafting was performed in each of their arches, with the insertion of a membrane into the left arch. Euthanasia occurred in 7, 21, or 60 days after the surgery. Bone samples were processed for histomorphometric and immunohistochemical analyses. After a statistical analysis of the data, the presence of DM did not interfere negatively in the bone autograft repair. The collagen membrane favored the graft integration into the recipient bed and the bone neoformation around the graft. Greater vascularization was observed between 21 and 60 days after the surgery, which increased bone formation and resulted in the graft integration. Only the RANK marker showed a significant difference in the glycemic groups. Transglutaminase 2 was significant for the membrane presence and experimental time. It is hence concluded that diabetes mellitus does not interfere with bone reabsorption via the RANK/RANKL/OPG. The graft integration was similar between the groups; however, the results of hyperglycemia with the collagen membrane indicate greater bone growth after graft placement.

  20. Bone regeneration in experimental animals using calcium phosphate cement combined with platelet growth factors and human growth hormone.

    Science.gov (United States)

    Emilov-Velev, K; Clemente-de-Arriba, C; Alobera-García, M Á; Moreno-Sansalvador, E M; Campo-Loarte, J

    2015-01-01

    Many substances (growth factors and hormones) have osteoinduction properties and when added to some osteoconduction biomaterial they accelerate bone neoformation properties. The materials included 15 New Zealand rabbits, calcium phosphate cement (Calcibon(®)), human growth hormone (GH), and plasma rich in platelets (PRP). Each animal was operated on in both proximal tibias and a critical size bone defect of 6mm of diameter was made. The animals were separated into the following study groups: Control (regeneration only by Calcibon®), PRP (regeneration by Calcibon® and PRP), GH (regeneration by Calcibon® and GH). All the animals were sacrificed at 28 days. An evaluation was made of the appearance of the proximal extreme of rabbit tibiae in all the animals, and to check the filling of the critical size defect. A histological assessment was made of the tissue response, the presence of new bone formation, and the appearance of the biomaterial. Morphometry was performed using the MIP 45 image analyser. ANOVA statistical analysis was performed using the Statgraphics software application. The macroscopic appearance of the critical defect was better in the PRP and the GH group than in the control group. Histologically greater new bone formation was found in the PRP and GH groups. No statistically significant differences were detected in the morphometric study between bone formation observed in the PRP group and the control group. Significant differences in increased bone formation were found in the GH group (p=0.03) compared to the other two groups. GH facilitates bone regeneration in critical defects filled with calcium phosphate cement in the time period studied in New Zealand rabbits. Copyright © 2014 SECOT. Published by Elsevier Espana. All rights reserved.

  1. Long-term stable vertical bone regeneration after sinus floor elevation and simultaneous implant placement with and without grafting.

    Science.gov (United States)

    Verdugo, Fernando; Uribarri, Agurne; Laksmana, Theresia; D'addona, Antonio

    2017-12-01

    Less invasive surgical approaches to regenerate bone intra-sinus and allow long-term functional implant stability are needed. To evaluate long-term vertical bone regeneration after sinus floor elevation and simultaneous implant placement with and without bone grafting. Vertical bone gains (VBG) post-sinus elevation, with and without grafting, were evaluated in thirty individuals presenting an average residual bone height (RBH) of 4.2 mm using a standardized digital technique. Measurements were taken preoperatively, and at an average of 64.6 months follow-up. Clinically, peri-implant tissues were assessed for pocket formation and presence of inflammation to evaluate established success criteria. Overall, RBH averaged 4.2 ± 1.1 mm (range: 1.8-5.8) and VBG 7.7 ± 1.6 mm (range: 6.0-12.9). Mean difference of 7.6 mm between vertical bone heights (VBH) at augmented implants sites and initial RBH, 11.8 versus 4.2 mm, (P implant site. Long-term follow-ups average 64.6 months (range: 36-144) and all implants met the success criteria. VBG ≥ 7 mm were 7.3 times more likely to develop on grafted sites (OR = 7.3, P = 0.02, CI95%: 1.2-46.2). None to negligible amounts of grafting material are required to regenerate substantial amounts of autogenous bone into atrophic sinus cavities after simultaneous implant placement. The regenerated VBH seems stable for functional implant stability long-term. Implant success rates were 100% at an average of 64.6 months. © 2017 Wiley Periodicals, Inc.

  2. Wound Models for Periodontal and Bone Regeneration: the role of biological research

    Science.gov (United States)

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

    2015-01-01

    The ultimate goal of periodontal therapy remains 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 to reestablish and sustain a heath promoting biofilm from one characterised by dysbiosis. This volume discusses the multiple facets of a transition during the late 1960’s to the present day, towards regenerative therapies founded upon a clearer understanding of the biophysiology of normal structure and function, rather than empiricism. This introductory manuscript provides an overview on the requirements of appropriate in-vitro laboratory models (e.g. cell culture), of pre-clinical (i.e. animal) models and 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 uni-dimensional and simplistic approach that does not account for the complexities of the in vivo situation, where 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 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 recession during the healing phase

  3. Trophic Actions of Bone Marrow-Derived Mesenchymal Stromal Cells for Muscle Repair/Regeneration

    Directory of Open Access Journals (Sweden)

    Lucia Formigli

    2012-10-01

    Full Text Available Bone marrow-derived mesenchymal stromal cells (BM-MSCs represent the leading candidate cell in tissue engineering and regenerative medicine. These cells can be easily isolated, expanded in vitro and are capable of providing significant functional benefits after implantation in the damaged muscle tissues. Despite their plasticity, the participation of BM-MSCs to new muscle fiber formation is controversial; in fact, emerging evidence indicates that their therapeutic effects occur without signs of long-term tissue engraftment and involve the paracrine secretion of cytokines and growth factors with multiple effects on the injured tissue, including modulation of inflammation and immune reaction, positive extracellular matrix (ECM remodeling, angiogenesis and protection from apoptosis. Recently, a new role for BM-MSCs in the stimulation of muscle progenitor cells proliferation has been demonstrated, suggesting the potential ability of these cells to influence the fate of local stem cells and augment the endogenous mechanisms of repair/regeneration in the damaged tissues.

  4. 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.

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

    Science.gov (United States)

    Tampieri, A.; Landi, E.; Valentini, F.; Sandri, M.; D'Alessandro, T.; Dediu, V.; Marcacci, M.

    2011-01-01

    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.

  6. Fabrication and characterization of two-layered nanofibrous membrane for guided bone and tissue regeneration application.

    Science.gov (United States)

    Masoudi Rad, Maryam; Nouri Khorasani, Saied; Ghasemi-Mobarakeh, Laleh; Prabhakaran, Molamma P; Foroughi, Mohammad Reza; Kharaziha, Mahshid; Saadatkish, Niloufar; Ramakrishna, Seeram

    2017-11-01

    Membranes used in dentistry act as a barrier to prevent invasion of intruder cells to defected area and obtains spaces that are to be subsequently filled with new bone and provide required bone volume for implant therapy when there is insufficient volume of healthy bone at implant site. In this study a two-layered bioactive membrane were fabricated by electrospinning whereas one layer provides guided bone regeneration (GBR) and fabricated using poly glycerol sebacate (PGS)/polycaprolactone (PCL) and Beta tri-calcium phosphate (β-TCP) (5, 10 and 15%) and another one containing PCL/PGS and chitosan acts as guided tissue regeneration (GTR). The morphology, chemical, physical and mechanical characterizations of the membranes were studied using scanning electron microscopy (SEM), Fourier transform infrared spectroscopy (FTIR), X-ray diffraction (XRD), tensile testing, then biodegradability and bioactivity properties were evaluated. In vitro cell culture study was also carried out to investigate proliferation and mineralization of cells on different membranes. Transmission electron microscope (TEM) and SEM results indicated agglomeration of β-TCP nanoparticles in the structure of nanofibers containing 15% β-TCP. Moreover by addition of β-TCP from 5% to 15%, contact angle decreased due to hydrophilicity of nanoparticles and bioactivity was found to increase. Mechanical properties of the membrane increased by incorporation of 5% and 10% of β-TCP in the structure of nanofibers, while addition of 15% of β-TCP was found to deteriorate mechanical properties of nanofibers. Although the presence of 5% and 10% of nanoparticles in the nanofibers increased proliferation of cells on GBR layer, cell proliferation was observed to decrease by addition of 15% β-TCP in the structure of nanofibers which is likely due to agglomeration of nanoparticles in the nanofiber structure. Our overall results revealed PCL/PGS containing 10% β-TCP could be selected as the optimum GBR membrane

  7. 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.

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

    Energy Technology Data Exchange (ETDEWEB)

    Paun, Irina Alexandra, E-mail: irina.paun@physics.pub.ro [Faculty of Applied Sciences, University Politehnica of Bucharest, RO-060042 (Romania); National Institute for Laser, Plasma and Radiation Physics, Magurele, Bucharest RO-077125 (Romania); Acasandrei, Adriana Maria [Horia Hulubei National Institute for Physics and Nuclear Engineering IFIN-HH, Magurele, Bucharest RO-077125 (Romania); Luculescu, Catalin Romeo, E-mail: catalin.luculescu@inflpr.ro [National Institute for Laser, Plasma and Radiation Physics, Magurele, Bucharest RO-077125 (Romania); Mustaciosu, Cosmin Catalin [Horia Hulubei National Institute for Physics and Nuclear Engineering IFIN-HH, Magurele, Bucharest RO-077125 (Romania); Ion, Valentin [National Institute for Laser, Plasma and Radiation Physics, Magurele, Bucharest RO-077125 (Romania); Mihailescu, Mona; Vasile, Eugenia [Faculty of Applied Sciences, University Politehnica of Bucharest, RO-060042 (Romania); Dinescu, Maria, E-mail: dinescum@nipne.ro [National Institute for Laser, Plasma and Radiation Physics, Magurele, Bucharest RO-077125 (Romania)

    2015-12-01

    Highlights: • PPy-based composite layers for bone regeneration were produced by MAPLE. • Conductive PPy nanograins were embedded in insulating PLGA and PU matrices. • PLGA was chosen for providing biodegradability and PU for toughness and elasticity. • The layers conductivities reached 10{sup −2} S/cm for PPy loadings of 1:10 weight ratios. • The layers promoted osteoblast viability, proliferation and mineralization. - Abstract: 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{sup −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

  9. Bone regeneration in osteoporosis by delivery BMP-2 and PRGF from tetronic-alginate composite thermogel.

    Science.gov (United States)

    Segredo-Morales, Elisabet; García-García, Patricia; Reyes, Ricardo; Pérez-Herrero, Edgar; Delgado, Araceli; Évora, Carmen

    2018-03-19

    As the life expectancy of the world population increases, osteoporotic (OP) fracture risk increase. Therefore in the present study a novel injectable thermo-responsive hydrogel loaded with microspheres of 17β-estradiol, microspheres of bone morphogenetic protein-2 (BMP-2) and plasma rich in growth factors (PRGF) was applied locally to regenerate a calvaria critical bone defect in OP female rats. Three systems were characterized: Tetronic® 1307 (T-1307) reinforced with alginate (T-A), T-A with PRGF and T-A-PRGF with microspheres. The addition of the microspheres increased the viscosity but the temperature for the maximum viscosity did not change (22-24 °C). The drugs were released during 6 weeks in one fast phase (three days) followed by a long slow phase. In vivo evaluation was made in non-OP and OP rats treated with T-A, T-A with microspheres of 17β-estradiol (T-A-βE), T-A-βE prepared with PRGF (T-A-PRGF-βE), T-A-βE with microspheres of BMP-2 (T-A-βE-BMP-2) and the combination of the three (T-A-PRGF-βE-BMP). After 12 weeks, histological and histomorphometric analyzes showed a synergic effect due to the addition of BMP-2 to the T-A-βE formulation. The PRGF did not increased the bone repair. The new bone filling the OP defect was less mineralized than in the non-OP groups. Copyright © 2018 Elsevier B.V. All rights reserved.

  10. Antibody-Mediated Osseous Regeneration for Bone Tissue Engineering in Canine Segmental Defects

    Directory of Open Access Journals (Sweden)

    A. Khojasteh

    2018-01-01

    Full Text Available Among many applications of therapeutic monoclonal antibodies (mAbs, a unique approach for regenerative medicine has entailed antibody-mediated osseous regeneration (AMOR. In an effort to identify a clinically relevant model of craniofacial defect, the present study investigated the efficacy of mAb specific for bone morphogenetic protein- (BMP- 2 to repair canine segmental mandibular continuity defect model. Accordingly, a 15 mm unilateral segmental defect was created in mandible and fixated with a titanium plate. Anorganic bovine bone mineral with 10% collagen (ABBM-C was functionalized with 25 μg/mL of either chimeric anti-BMP-2 mAb or isotype-matched mAb (negative control. Recombinant human (rh BMP-2 served as positive control. Morphometric analyses were performed on computed tomography (CT and histologic images. Bone densities within healed defect sites at 12 weeks after surgery were 1360.81 ± 10.52 Hounsfield Unit (HU, 1044.27 ± 141.16 HU, and 839.45 ± 179.41 HU, in sites with implanted anti-BMP-2 mAb, rhBMP-2, and isotype mAb groups, respectively. Osteoid bone formation in anti-BMP-2 mAb (42.99% ± 8.67 and rhBMP-2 (48.97% ± 2.96 groups was not significantly different but was higher (p<0.05 than in sites with isotype control mAb (26.8% ± 5.35. In view of the long-term objective of translational application of AMOR in humans, the results of the present study demonstrated the feasibility of AMOR in a large clinically relevant animal model.

  11. A Copolymer Scaffold Functionalized with Nanodiamond Particles Enhances Osteogenic Metabolic Activity and Bone Regeneration.

    Science.gov (United States)

    Yassin, Mohammed A; Mustafa, Kamal; Xing, Zhe; Sun, Yang; Fasmer, Kristine Eldevik; Waag, Thilo; Krueger, Anke; Steinmüller-Nethl, Doris; Finne-Wistrand, Anna; Leknes, Knut N

    2017-06-01

    Functionalizing polymer scaffolds with nanodiamond particles (nDPs) has pronounced effect on the surface properties, such as improved wettability, an increased active area and binding sites for cellular attachment and adhesion, and increased ability to immobilize biomolecules by physical adsorption. This study aims to evaluate the effect of poly(l-lactide-co-ε-caprolactone) (poly(LLA-co-CL)) scaffolds, functionalized with nDPs, on bone regeneration in a rat calvarial critical size defect. Poly(LLA-co-CL) scaffolds functionalized with nDPs are also compared with pristine scaffolds with reference to albumin adsorption and seeding efficiency of bone marrow stromal cells (BMSCs). Compared with pristine scaffolds, the experimental scaffolds exhibit a reduction in albumin adsorption and a significant increase in the seeding efficiency of BMSCs (p = 0.027). In the calvarial defects implanted with BMSC-seeded poly(LLA-co-CL)/nDPs scaffolds, live imaging at 12 weeks discloses a significant increase in osteogenic metabolic activity (p = 0.016). Microcomputed tomography, confirmed by histological data, reveals a substantial increase in bone volume (p = 0.021). The results show that compared with conventional poly(LLA-co-CL) scaffolds those functionalized with nDPs promote osteogenic metabolic activity and mineralization capacity. It is concluded that poly(LLA-co-CL) composite matrices functionalized with nDPs enhance osteoconductivity and therefore warrant further study as potential scaffolding material for bone tissue engineering. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  12. [Ultrasound scanning of the distraction regenerate in case of multilocus elongation of the fragments in patients with defects of long bones].

    Science.gov (United States)

    Menshikova, T I; Borzunov, D Iu; Dolganova, T I

    2014-01-01

    It was done ultrasound examination of distraction regenerates in patients with defect of bone tissue. The first group included 4 patients who had the size of congenital bone tissue defect 15.8±8.1 cm; the second group (3 patients) included posttraumatic defects with defect size 11.75±3.6 cm; the third group (4 patients) included posttraumatic defects with defect size 11±5.3 cm. It was discovered the particularities of distraction regenerate structural condition in case of low level of reparative osteogenesis. In the first group "ischemic" regenerate was characterized by slow formation of bone trabecules. In the second group "ischemic" regenerate had one or two hypo-echogenic cystic-like formations in the intermediate regenerate area. All patients of the third group had organotypic remodeling of the regenerate according to terms of distraction and fixation.

  13. Peri-Implant Bone Regeneration Using rhPDGF-BB, BMSCs, and β-TCP in a Canine Model.

    Science.gov (United States)

    Xu, Ling; Zhang, Wenjie; Lv, Kaige; Yu, Weiqiang; Jiang, Xinquan; Zhang, Fuqiang

    2016-04-01

    The presence of insufficient bone volume remains a major clinical problem for dental implant placement to restore oral function. Tissue engineering provides a promising approach for inducing bone regeneration and enhancing osseointegration in dental implants. The tissue-engineered bone consisting of recombinant human platelet-derived growth factor (rhPDGF-BB), bone marrow stem cells (BMSCs), and beta-tricalcium phosphate (β-TCP) particles was validated for the first time in a preclinical large animal canine model in terms of its ability to promote new bone formation around the implants, as well as osseointegration between the tissue-engineered bone and dental implants. Proliferation and osteogenic differentiation of canine BMSCs treated with rhPDGF-BB were evaluated with an MTT, alkaline phosphatase (ALP) activity, Alizarin Red staining, and real-time quantitative PCR (RT-qPCR) analysis of osteogenic genes. The therapeutic potential of tissue-engineered bone consisting of rhPDGF-BB/BMSCs/β-TCP in bone repair was evaluated in mesial-implant defects of immediate postextraction implants in the canine mandible. rhPDGF-BB treatment significantly increased proliferation and osteogenic differentiation of canine BMSCs. Furthermore, the tissue-engineered bone consisting of rhPDGF-BB/BMSCs/β-TCP significantly enhanced bone formation and osseointegration. This study provides important evidence that supports the potential application of rhPDGF-BB/BMSCs/β-TCP tissue-engineered bone in immediate implantation for oral function restoration. © 2015 Wiley Periodicals, Inc.

  14. The synergistic effects of Sr and Si bioactive ions on osteogenesis, osteoclastogenesis and angiogenesis for osteoporotic bone regeneration.

    Science.gov (United States)

    Mao, Lixia; Xia, Lunguo; Chang, Jiang; Liu, Jiaqiang; Jiang, Lingyong; Wu, Chengtie; Fang, Bing

    2017-10-01

    Bioactive ions released from bioceramics play important roles in bone regeneration; however, it is unclear how each ionic composition in complex bioceramics exerts its specific effect on bone regeneration. The aim of this study is to elucidate the functional effects of Sr and Si ions in bioceramics on the regeneration of osteoporotic bone. A model bioceramic with Sr- and Si-containing components (SMS) was successfully fabricated and the effects of ionic products from SMS bioceramics on the osteogenic, osteoclastic and angiogenic differentiation of rBMSCs-OVX and RANKL-induced osteoclasts were investigated. The results showed that SMS bioceramics could enhance ALP activity and expression of Col 1, OCN, Runx2, and angiogenic factors including VEGF and Ang-1. SMS bioceramics not only rebalanced the OPG/RANKL ratio of rBMSCs-OVX at early stage, but also repressed RANKL-induced osteoclast formation and expression of TRAP, DC-STAMP, V-ATPase a3, and NFATc1. The synergistic effects of Sr and Si ions were further investigated as compared with those of similar concentrations of Sr and Si ions alone. Sr and Si ions possessed synergistic effects on osteogenesis, osteoclastogenesis, and angiogenesis, attributed to the dominant effects of Sr ions on enhancing angiogenesis and repressing osteoclastogenesis, and the dominant effects of Si ions on stimulating osteogenesis. The in vivo study using critical-size mandibular defects of OVX rat models showed that SMS bioceramics could significantly enhance bone formation and mineralization compared with β-TCP bioceramics. Our results are the first to elucidate the specific effect of each ion from bioceramics on osteogenesis, osteoclastogenesis and angiogenesis for osteoporotic bone regeneration, paving the way for the design of functional biomaterials with complex compositions for tissue engineering and regenerative medicine. Bioactive ions released from bioceramics play important roles for bone regeneration; however, it is unclear

  15. Guided Bone Regeneration Using Collagen Scaffolds, Growth Factors, and Periodontal Ligament Stem Cells for Treatment of Peri-Implant Bone Defects In Vivo

    Directory of Open Access Journals (Sweden)

    Peer W. Kämmerer

    2017-01-01

    Full Text Available Introduction. The aim of the study was an evaluation of different approaches for guided bone regeneration (GBR of peri-implant defects in an in vivo animal model. Materials and Methods. In minipigs (n=15, peri-implant defects around calcium phosphate- (CaP-; n=46 coated implants were created and randomly filled with (1 blank, (2 collagen/hydroxylapatite/β-tricalcium phosphate scaffold (CHT, (3 CHT + growth factor cocktail (GFC, (4 jellyfish collagen matrix, (5 jellyfish collagen matrix + GFC, (6 collagen powder, and (7 collagen powder + periodontal ligament stem cells (PDLSC. Additional collagen membranes were used for coverage of the defects. After 120 days of healing, bone growth was evaluated histologically (bone to implant contact (BIC;%, vertical bone apposition (VBA; mm, and new bone height (NBH; %. Results. In all groups, new bone formation was seen. Though, when compared to the blank group, no significant differences were detected for all parameters. BIC and NBH in the group with collagen matrix as well as the group with the collagen matrix + GFC were significantly less when compared to the collagen powder group (all: p<0.003. Conclusion. GBR procedures, in combination with CaP-coated implants, will lead to an enhancement of peri-implant bone growth. There was no additional significant enhancement of osseous regeneration when using GFC or PDLSC.

  16. Regeneration of skull bones in adult rabbits after implantation of commercial osteoinductive materials and transplantation of a tissue-engineering construct.

    Science.gov (United States)

    Volkov, A V; Alekseeva, I S; Kulakov, A A; Gol'dshtein, D V; Shustrov, S A; Shuraev, A I; Arutyunyan, I V; Bukharova, T B; Rzhaninova, A A; Bol'shakova, G B; Grigor'yan, A S

    2010-10-01

    We performed a comparative study of reparative osteogenesis in rabbits with experimental critical defects of the parietal bones after implantation of commercial osteoinductive materials "Biomatrix", "Osteomatrix", "BioOss" in combination with platelet-rich plasma and transplantation of a tissue-engineering construct on the basis of autogenic multipotent stromal cells from the adipose tissue predifferentiated in osteogenic direction. It was found that experimental reparative osteogenesis is insufficiently stimulated by implantation materials and full-thickness trepanation holes were not completely closed. After transplantation of the studied tissue-engineering construct, the defect was filled with full-length bone regenerate (in the center of the regenerate and from the maternal bone) in contrast to control and reference groups, where the bone tissue was formed only on the side of the maternal bone. On day 120 after transplantation of the tissue-engineering construct, the percent of newly-formed bone tissue in the regenerate was 24% (the total percent of bone tissue in the regenerate was 39%), which attested to active incomplete regenerative process in contrast to control and reference groups. Thus, the study demonstrated effective regeneration of the critical defects of the parietal bones in rabbits 120 days after transplantation of the tissue-engineering construct in contrast to commercial osteoplastic materials for directed bone regeneration.

  17. Regeneration of Vascularized Corticocancellous Bone and Diploic Space Using Muscle-Derived Stem Cells: A Translational Biologic Alternative for Healing Critical Bone Defects.

    Science.gov (United States)

    Lough, Denver; Swanson, Edward; Sopko, Nikolai A; Madsen, Christopher; Miller, Devin; Wang, Howard; Guo, Qiongyu; Sursala, Srinivas M; Kumar, Anand R

    2017-04-01

    Regeneration of functional bone substrate remains a priority in reconstructive surgery especially for patients suffering from complex skeletal defects. Efforts to develop implantable osteoinductive constructs and novel osteoconductive materials remain at the forefront of industry forces and product line development. Despite advancement in clinical practice and bone biology, cancellous autograft remains the gold standard for procedures requiring osteogenic mechanisms of healing. This study investigates the utility of muscle-derived stem cells as a cellular therapy for definitive bone regeneration through a form of neo-osteogenesis. Adipose-derived stem cell, bone marrow-derived mesenchymal stem cell, and muscle-derived stem cell populations were isolated separately from C57BL/6 murine tissues and supplemented with collagen scaffolding with or without bone morphogenetic protein-2 to compare relative osteogenic potency and ultrastructure organization in both two- and three-dimensional systems. Parallel populations were bound to a deployable collagen implant within a syngeneic murine cranial defect model. Although all populations provided and maintained mesenchymal stem cell multilineage capacity, adipose-derived stem cell- and bone marrow-derived mesenchymal stem cell-enriched constructs were capable of forming small bone aggregates. Defects receiving muscle-derived stem cells self-assembled a form of organized corticocancellous structures within two- and three-dimensional in vitro systems and within the in vivo model. Muscle-derived stem cells also augmented healing, implant angiogenesis, and diploic space formation. Muscle-derived stem cell-enriched implants appear to provide an autologous response to current industry-derived products and an attractive alternative to mesenchymal stem cells for the regeneration of corticocancellous bone and a vascularized diploic space.

  18. In-situ tissue regeneration through SDF-1α driven cell recruitment and stiffness-mediated bone regeneration in a critical-sized segmental femoral defect.

    Science.gov (United States)

    Cipitria, Amaia; Boettcher, Kathrin; Schoenhals, Sophia; Garske, Daniela S; Schmidt-Bleek, Katharina; Ellinghaus, Agnes; Dienelt, Anke; Peters, Anja; Mehta, Manav; Madl, Christopher M; Huebsch, Nathaniel; Mooney, David J; Duda, Georg N

    2017-09-15

    In-situ tissue regeneration aims to utilize the body's endogenous healing capacity through the recruitment of host stem or progenitor cells to an injury site. Stromal cell-derived factor-1α (SDF-1α) is widely discussed as a potent chemoattractant. Here we use a cell-free biomaterial-based approach to (i) deliver SDF-1α for the recruitment of endogenous bone marrow-derived stromal cells (BMSC) into a critical-sized segmental femoral defect in rats and to (ii) induce hydrogel stiffness-mediated osteogenic differentiation in-vivo. Ionically crosslinked alginate hydrogels with a stiffness optimized for osteogenic differentiation were used. Fast-degrading porogens were incorporated to impart a macroporous architecture that facilitates host cell invasion. Endogenous cell recruitment to the defect site was successfully triggered through the controlled release of SDF-1α. A trend for increased bone volume fraction (BV/TV) and a significantly higher bone mineral density (BMD) were observed for gels loaded with SDF-1α, compared to empty gels at two weeks. A trend was also observed, albeit not statistically significant, towards matrix stiffness influencing BV/TV and BMD at two weeks. However, over a six week time-frame, these effects were insufficient for bone bridging of a segmental femoral defect. While mechanical cues combined with ex-vivo cell encapsulation have been shown to have an effect in the regeneration of less demanding in-vivo models, such as cranial defects of nude rats, they are not sufficient for a SDF-1α mediated in-situ regeneration approach in segmental femoral defects of immunocompetent rats, suggesting that additional osteogenic cues may also be required. Stromal cell-derived factor-1α (SDF-1α) is a chemoattractant used to recruit host cells for tissue regeneration. The concept that matrix stiffness can direct mesenchymal stromal cell (MSC) differentiation into various lineages was described a decade ago using in-vitro experiments. Recently

  19. An Experimental Study on Guided Bone Regeneration Using a Polylactide-co-glycolide Membrane-Immobilized Conditioned Medium.

    Science.gov (United States)

    Tsuchiya, Shuhei; Ohmori, Masahiro; Hara, Kenji; Fujio, Masahito; Ikeno, Masayuki; Hibi, Hideharu; Ueda, Minoru

    2015-01-01

    To investigate whether bone regeneration can be accelerated by using a conditioned medium (CM) and guided bone regeneration (GBR) technique. CM was harvested from rat bone marrow stromal cells (BMSCs). The components of CM were immobilized using a polylactide-co-glycolide (PLGA) membrane treated with and without 0.5 mol/L sodium hydroxide (NaOH) to elevate the hydrophilicity. Four experimental groups were prepared: PLGA membrane treated with (1) phosphate-buffered saline (PBS; PBS-M), (2) PBS and 0.5 mol/L NaOH (hydrophilic treatment; PBS-HM), (3) CM (CM-M), and (4) CM and 0.5 mol/L NaOH (CM-HM). These experimental membranes were observed using scanning electron microscopy. Proteins derived from BMSCs immobilized on the PLGA membrane were detected with liquid chromatography-tandem mass spectrometry (LC/MS/MS). Cell proliferation and alkaline phosphatase (ALP) activity were measured to analyze the effect of CM on the BMSCs. Experimental membranes were transplanted into a rat calvarial bone defect model. Microcomputed tomography and histologic analyses were performed 4 and 8 weeks after transplantation. The CM derived from BMSCs can be immobilized on the PLGA membrane. Hydrophilic treatment of the PLGA membrane enhanced the amount of CM immobilization. LC/MS/MS analysis showed that the immobilized proteins on the surface of PLGA membrane were extracellular matrix, such as collagen, decorin, and fibronectin. The proteins in the CM, which were released from the PLGA membrane, enhanced cell proliferation and ALP activity in rat BMSCs. Newly formed bone area at the bone defects that had been treated with CM-HM was significantly high compared with those at bone defects treated with the other membranes. The PLGA membrane treated with 0.5 mol/L NaOH and CM promoted bone regeneration in this rat calvarial defect model.

  20. Role of RHEB in Regulating Differentiation Fate of Mesenchymal Stem Cells for Cartilage and Bone Regeneration

    Directory of Open Access Journals (Sweden)

    Sajjad Ashraf

    2017-04-01

    Full Text Available Advances in mesenchymal stem cells (MSCs and cell replacement therapies are promising approaches to treat cartilage and bone defects since substantial differentiation capacities of MSCs match the demands of tissue regeneration. Our understanding of the dynamic process requiring indispensable differentiation of MSCs remains limited. Herein, we describe the role of RHEB (Ras homolog enriched in brain regulating gene signature for differentiation of human adipose derived mesenchymal stem cells (ASCs into chondrogenic, osteogenic, and adipogenic lineages. RHEB-overexpression increases the proliferation of the ASCs. RHEB enhances the chondrogenic differentiation of ASCs in 3D culture via upregulation of SOX9 with concomitant increase in glycosaminoglycans (GAGs, and type II collagen (COL2. RHEB increases the osteogenesis via upregulation of runt related transcription factor 2 (RUNX2 with an increase in the calcium and phosphate contents. RHEB also increases the expression of osteogenic markers, osteonectin and osteopontin. RHEB knockdown ASCs were incapable of expressing sufficient SRY (Sex determining region Y-box 9 (SOX9 and RUNX2, and therefore had decreased chondrogenic and osteogenic differentiation. RHEB-overexpression impaired ASCs differentiation into adipogenic lineage, through downregulation of CCAAT/enhancer binding protein beta (C/EBPβ. Conversely, RHEB knockdown abolished the negative regulation of adipogenesis. We demonstrate that RHEB is a novel regulator, with a critical role in ASCs lineage determination, and RHEB-modulated ASCs may be useful as a cell therapy for cartilage and bone defect treatments.

  1. 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.

  2. Rhombicuboctahedron unit cell based scaffolds for bone regeneration: geometry optimization with a mechanobiology - driven algorithm.

    Science.gov (United States)

    Boccaccio, Antonio; Fiorentino, Michele; Uva, Antonio E; Laghetti, Luca N; Monno, Giuseppe

    2018-02-01

    In a context more and more oriented towards customized medical solutions, we propose a mechanobiology-driven algorithm to determine the optimal geometry of scaffolds for bone regeneration that is the most suited to specific boundary and loading conditions. In spite of the huge number of articles investigating different unit cells for porous biomaterials, no studies are reported in the literature that optimize the geometric parameters of such unit cells based on mechanobiological criteria. Parametric finite element models of scaffolds with rhombicuboctahedron unit cell were developed and incorporated into an optimization algorithm that combines them with a computational mechanobiological model. The algorithm perturbs iteratively the geometry of the unit cell until the best scaffold geometry is identified, i.e. the geometry that allows to maximize the formation of bone. Performances of scaffolds with rhombicuboctahedron unit cell were compared with those of other scaffolds with hexahedron unit cells. We found that scaffolds with rhombicuboctahedron unit cell are particularly suited for supporting medium-low loads, while, for higher loads, scaffolds with hexahedron unit cells are preferable. The proposed algorithm can guide the orthopaedic/surgeon in the choice of the best scaffold to be implanted in a patient-specific anatomic region. Copyright © 2017 Elsevier B.V. All rights reserved.

  3. Foamed surfactant solution as a template for self-setting injectable hydroxyapatite scaffolds for bone regeneration.

    Science.gov (United States)

    Montufar, E B; Traykova, T; Gil, C; Harr, I; Almirall, A; Aguirre, A; Engel, E; Planell, J A; Ginebra, M P

    2010-03-01

    The application of minimally invasive surgical techniques in the field of orthopaedic surgery has created a growing need for new injectable synthetic materials that can be used for bone grafting. In this work a novel fully synthetic injectable calcium phosphate foam was developed by mixing alpha-tricalcium phosphate (alpha-TCP) powder with a foamed polysorbate 80 solution. Polysorbate 80 is a non-ionic surfactant approved for parenteral applications. The foam was able to retain the porous structure after injection provided that the foamed paste was injected shortly after mixing (typically 2.5 min), and set through the hydrolysis of alpha-TCP to a calcium-deficient hydroxyapatite, thus producing a hydroxyapatite solid foam in situ. The effect of different processing parameters on the porosity, microstructure, injectability and mechanical properties of the hydroxyapatite foams was analysed, and the ability of the pre-set foam to support osteoblastic-like cell proliferation and differentiation was assessed. Interestingly, the concentration of surfactant needed to obtain the foams was lower than that considered safe in drug formulations for parenteral administration. The possibility of combining bioactivity, injectability, macroporosity and self-setting ability in a single fully synthetic material represents a step forward in the design of new materials for bone regeneration compatible with minimally invasive surgical techniques. Copyright 2009 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

  4. Controlling Adult Stem Cell Behavior Using Nanodiamond-Reinforced Hydrogel: Implication in Bone Regeneration Therapy.

    Science.gov (United States)

    Pacelli, Settimio; Maloney, Ryan; Chakravarti, Aparna R; Whitlow, Jonathan; Basu, Sayantani; Modaresi, Saman; Gehrke, Stevin; Paul, Arghya

    2017-07-26

    Nanodiamonds (NDs) have attracted considerable attention as drug delivery nanocarriers due to their low cytotoxicity and facile surface functionalization. Given these features, NDs have been recently investigated for the fabrication of nanocomposite hydrogels for tissue engineering. Here we report the synthesis of a hydrogel using photocrosslinkable gelatin methacrylamide (GelMA) and NDs as a three-dimensional scaffold for drug delivery and stem cell-guided bone regeneration. We investigated the effect of different concentration of NDs on the physical and mechanical properties of the GelMA hydrogel network. The inclusion of NDs increased the network stiffness, which in turn augmented the traction forces generated by human adipose stem cells (hASCs). We also tested the ability of NDs to adsorb and modulate the release of a model drug dexamethasone (Dex) to promote the osteogenic differentiation of hASCs. The ND-Dex complexes modulated gene expression, cell area, and focal adhesion number in hASCs. Moreover, the integration of the ND-Dex complex within GelMA hydrogels allowed a higher retention of Dex over time, resulting in significantly increased alkaline phosphatase activity and calcium deposition of encapsulated hASCs. These results suggest that conventional GelMA hydrogels can be coupled with conjugated NDs to develop a novel platform for bone tissue engineering.

  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)

    Borissov, I.; Uzunov, N.; Paskalev, M.

    2004-01-01

    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. 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.

  7. 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

  8. Molecular cloning and characterization of Mustang, a novel nuclear protein expressed during skeletal development and regeneration.

    Science.gov (United States)

    Lombardo, Frank; Komatsu, David; Hadjiargyrou, Michael

    2004-01-01

    Bone regeneration occurs as a series of events that requires temporal and spatial orchestration of numerous cell types guided by the transcriptional activity of thousands of genes, as recently demonstrated by our laboratory. Using the rat femoral fracture model, bioinformatics, cloning, expression assays, fusion proteins, and transfection, we report on the identification and characterization of one such differentially expressed gene, termed Mustang (musculoskeletal temporally activated novel gene). Mustang encodes for an 82 amino acid nuclear protein with no homology to any known protein family. However, other species homologues (mouse, human, cow) were identified within EST (expressed sequence tag) databases. Nuclear localization was confirmed using a GFP-Mustang fusion protein. Using in situ hybridization, Mustang expression was localized to differentiating periosteal osteogenic cells, proliferating chondrocytes, and osteoblasts of the fracture callus. Unlike adult tissues, developing embryos abundantly express Mustang, especially in mesenchymal condensations of limbs, vertebral perichondrium, and mesenchymal cells of the intervertebral discs. Although the precise function of Mustang is unknown, its unique pattern of expression during bone development and regeneration, absence in adult tissues (except skeletal muscle and tendon), and nuclear localization suggest that Mustang is involved in the development and regeneration of the mammalian musculoskeletal system.

  9. Bone marrow mesenchymal stem cells (BMSCs) improved functional recovery of spinal cord injury partly by promoting axonal regeneration.

    Science.gov (United States)

    Lin, Liya; Lin, Hefeng; Bai, Shi; Zheng, Lianshun; Zhang, Xiaoming

    2018-05-01

    Spinal cord injury (SCI) disrupts the spinal cord and results in the loss of sensory and motor function below the lesion site. The treatment of SCI became a challenge because the injured neurons fail to axon regenerate and repair after injury. Promoting axonal regeneration plays a key role in the treatment strategies for SCI. It would meet the goal of reconstruction the injured spinal cord and improving the functional recovery. Bone marrow mesenchymal stem cells (BMSCs) are attractive therapeutic potential cell sources for SCI, and it could rebuild the injured spinal cord through neuroprotection, neural regeneration and remyelinating. Evidence has demonstrated that BMSCs play important roles in mediating axon regeneration, and glial scar formation after SCI in animal experiments and some clinical trials. We reviewed the role of BMSCs in regulating axon regeneration and glial scar formation after SCI. BMSCs based therapies may provide a therapeutic potential for the injured spinal cord by promoting axonal regeneration and repair. Copyright © 2018 Elsevier Ltd. All rights reserved.

  10. Progenitor cells in liver regeneration: molecular responses controlling their activation and expansion

    DEFF Research Database (Denmark)

    Santoni-Rugiu, Eric; Jelnes, Peter; Thorgeirsson, Snorri S

    2005-01-01

    created in the liver by a certain insult. This review will focus on molecular responses controlling activation and expansion of the hepatic progenitor cell niche, emphasizing similarities and differences in the microenvironments orchestrating regeneration by recruitment of progenitor cell populations...... cells, and recruited inflammatory cells as well as the variety of growth-modulating molecules produced and/or harboured by these elements. The cellular and molecular responses to different regenerative stimuli seem to depend on the injury inflicted and consequently on the molecular microenvironment...

  11. Comparative maxillary bone-defect healing by calcium-sulphate or deproteinized bovine bone particles and extra cellular matrix membranes in a guided bone regeneration setting: an experimental study in rabbits.

    Science.gov (United States)

    Turri, Alberto; Dahlin, Christer

    2015-05-01

    The aim of this study was to histologically compare the dynamics of bone healing response between calcium sulphate (CaS) and deproteinized bovine bone mineral (DBBM) particles in guided bone regeneration utilizing an extracellular matrix membrane (ECM) as barrier. Eighteen rabbits were used in thisstudy. 5 × 5 mm defects were created in the edentulous space between the incisors and molars in the maxilla. The CaS and DBBM particles were placed in the defects, with or without the placement of a membrane by means of random selection. Healing was evaluated at 2, 4 and 8 weeks by histology. A total resorption of the CaS material was seen already at 2 weeks. Only minor resorption could be seen of the DBBM particles. The CaS group showed significantly more bone regeneration at all three healing periods compared to the DBBM group. The addition of an ECM membrane demonstrated significant additional effect on bone regeneration. The CaS group showed significant increased amounts of blood vessels compared to the DBBM group. Thisstudy showed that CaS in combination with an ECM membrane provided synergistic effects on bone regeneration, seemingly due to stimulating angiogenesis in the early healing process. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  12. Preparation and Characterization of Resorbable Bacterial Cellulose Membranes Treated by Electron Beam Irradiation for Guided Bone Regeneration

    Directory of Open Access Journals (Sweden)

    Sung-Jun An

    2017-10-01

    Full Text Available Bacterial cellulose (BC is an excellent biomaterial with many medical applications. In this study, resorbable BC membranes were prepared for guided bone regeneration (GBR using an irradiation technique for applications in the dental field. Electron beam irradiation (EI increases biodegradation by severing the glucose bonds of BC. BC membranes irradiated at 100 kGy or 300 kGy were used to determine optimal electron beam doses. Electron beam irradiated BC membranes (EI-BCMs were evaluated by scanning electron microscopy (SEM, attenuated total reflectance-Fourier transform infrared (ATR-FTIR spectroscopy, thermal gravimetric analysis (TGA, and using wet tensile strength measurements. In addition, in vitro cell studies were conducted in order to confirm the cytocompatibility of EI-BCMs. Cell viabilities of NIH3T3 cells on 100k and 300k EI-BCMs (100 kGy and 300 kGy irradiated BC membranes were significantly greater than on NI-BCMs after 3 and 7 days (p < 0.05. Bone regeneration by EI-BCMs and their biodegradabilities were also evaluated using in vivo rat calvarial defect models for 4 and 8 weeks. Histometric results showed 100k EI-BCMs exhibited significantly larger new bone area (NBA; % than 300k EI-BCMs at 8 weeks after implantation (p < 0.05. Mechanical, chemical, and biological analyses showed EI-BCMs effectively interacted with cells and promoted bone regeneration.

  13. 3D-Printed Bioactive Ca3SiO5Bone Cement Scaffolds with Nano Surface Structure for Bone Regeneration.

    Science.gov (United States)

    Yang, Chen; Wang, Xiaoya; Ma, Bing; Zhu, Haibo; Huan, Zhiguang; Ma, Nan; Wu, Chengtie; Chang, Jiang

    2017-02-22

    Silicate bioactive materials have been widely studied for bone regeneration because of their eminent physicochemical properties and outstanding osteogenic bioactivity, and different methods have been developed to prepare porous silicate bioactive ceramics scaffolds for bone-tissue engineering applications. Among all of these methods, the 3D-printing technique is obviously the most efficient way to control the porous structure. However, 3D-printed bioceramic porous scaffolds need high-temperature sintering, which will cause volume shrinkage and reduce the controllability of the pore structure accuracy. Unlike silicate bioceramic, bioactive silicate cements such as tricalcium silicate (Ca 3 SiO 5 and C 3 S) can be self-set in water to obtain high mechanical strength under mild conditions. Another advantage of using C 3 S to prepare 3D scaffolds is the possibility of simultaneous drug loading. Herein, we, for the first time, demonstrated successful preparation of uniform 3D-printed C 3 S bone cement scaffolds with controllable 3D structure at room temperature. The scaffolds were loaded with two model drugs and showed a loading location controllable drug-release profile. In addition, we developed a surface modification process to create controllable nanotopography on the surface of pore wall of the scaffolds, which showed activity to enhance rat bone-marrow stem cells (rBMSCs) attachment, spreading, and ALP activities. The in vivo experiments revealed that the 3D-printed C 3 S bone cement scaffolds with nanoneedle-structured surfaces significantly improved bone regeneration, as compared to pure C 3 S bone cement scaffolds, suggesting that 3D-printed C 3 S bone cement scaffolds with controllable nanotopography surface are bioactive implantable biomaterials for bone repair.

  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. Regeneration of Cystic Bone Cavities and Bone Defects With Bioactive Glass S53P4 in the Upper and Lower Jaws.

    Science.gov (United States)

    Stoor, Patricia; Apajalahti, Satu; Kontio, Risto

    2017-07-01

    Cysts and tumors are common lesions in the jaws. To be able to retain a good volume of the alveolar ridge during healing as well as strengthening the angle and body of the mandible and provide an instant improved support for adjacent teeth, reliable long-term bone regeneration is needed. The purpose of this prospective study was to promote bone regeneration by filling bony defects in the upper or lower jaw with granules of the bioactive glass S53P4 (BAG), which have osteostimulative and antimicrobial properties.The authors treated 20 patients (21 defects) surgically; benign tumors, cysts, or infection related to impacted teeth in the maxilla or mandible. The tumor or cyst was removed or enucleated and thorough cleaning of the infected area was performed. The bone cavity was filled with granules of the BAG S53P4 despite signs of chronic infection in the area at the time of surgery. The patients were followed up for an average of 34 months clinically and with cone beam computerized tomography for 28 months. In 20 defects the final outcome was successful. Despite infection at the time of surgery in 65% of the patients, no material associated infection was seen during the follow-up. The BAG S53P4 granules were radiologically remodeled into bone after 2 years follow-up. The use of granules of the BAG S53P4 in the treatment of large bone defects provides infection-free reliable bone regeneration despite chronic infection at the time of surgery, which improves the prognosis of adjacent teeth.

  16. Current Molecular Targeted Therapies for Bone and Soft Tissue Sarcomas

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    Kenji Nakano

    2018-03-01

    Full Text Available Systemic treatment options for bone and soft tissue sarcomas remained unchanged until the 2000s. These cancers presented challenges in new drug development partly because of their rarity and heterogeneity. Many new molecular targeting drugs have been tried in the 2010s, and some were approved for bone and soft tissue sarcoma. As one of the first molecular targeted drugs approved for solid malignant tumors, imatinib’s approval as a treatment for gastrointestinal stromal tumors (GISTs has been a great achievement. Following imatinib, other tyrosine kinase inhibitors (TKIs have been approved for GISTs such as sunitinib and regorafenib, and pazopanib was approved for non-GIST soft tissue sarcomas. Olaratumab, the monoclonal antibody that targets platelet-derived growth factor receptor (PDGFR-α, was shown to extend the overall survival of soft tissue sarcoma patients and was approved in 2016 in the U.S. as a breakthrough therapy. For bone tumors, new drugs are limited to denosumab, a receptor activator of nuclear factor κB ligand (RANKL inhibitor, for treating giant cell tumors of bone. In this review, we explain and summarize the current molecular targeting therapies approved and in development for bone and soft tissue sarcomas.

  17. Vitamin C plus hydrogel facilitates bone marrow stromal cell-mediated endometrium regeneration in rats

    Directory of Open Access Journals (Sweden)

    Huan Yang

    2017-11-01

    Full Text Available Abstract Background Intrauterine adhesion (IUA is a common uterine cavity disease which can be caused by mechanical damage that may eventually lead to infertility and pregnancy abnormalities. Since the effect of therapeutic drugs appears disappointing, cell therapy has emerged as an alternative choice for endometrium regeneration. The aim of this study is to investigate whether the combination of hydrogel Pluronic F-127 (PF-127, Vitamin C (Vc, and a bone marrow stromal cell (BMSC mixture could be a feasible strategy to improve the endometrial regeneration in a mechanical damage model of IUA in rats. Methods Firstly, PF-127 cytotoxicity and the effect of Vc was tested in vitro using the Annexin V/propidium iodide (PI apoptosis test, cell count kit (CCK growth test, and enzyme-linked immunosorbent assay (ELISA. For the establishment of the rat IUA model, a 2-mm transverse incision in the uterus was prepared at the upper end, and 1.5- to 2.0-cm endometrial damage was scraped. Rats were randomly assigned to five groups to investigate the combined strategy on IUA uterine regeneration: a sham group, an IUA control group, an IUA BMSC encapsulated in PF-127 plus Vc group, an IUA BMSC plus Vc group, and an IUA PF-127 plus Vc group. A cell mixture was injected into the uterine horn while making the IUA model. Eight weeks after cell transplantation, the rats were sacrificed and the uterine was dissected for analysis. Endometrial thickness, gland number, fibrosis area, and the expression of marker proteins for endometrial membrane were examined by hematoxylin and eosin staining, Masson’s staining, and immunohistochemistry. Results Vc promoted the survival and health of PF-127-encapsulated BMSCs in vitro. When this combination was transplanted in vivo, the endometrium showed better restoration as the endometrium membrane became thicker and had more glands and less fibrosis areas. The expression of cytokeratin, von Willebrand Factor (vWF, was also restored

  18. Examining the feasibility of clinical grade CD271+ enrichment of mesenchymal stromal cells for bone regeneration.

    Directory of Open Access Journals (Sweden)

    Richard J Cuthbert

    Full Text Available Current clinical trials utilize mesenchymal stromal cells (MSCs expanded in culture, however these interventions carry considerable costs and concerns pertaining to culture-induced losses of potency. This study assessed the feasibility of new clinical-grade technology to obtain uncultured MSC isolates from three human intra-osseous tissue sources based on immunomagnetic selection for CD271-positive cells.MSCs were isolated from bone marrow (BM aspirates or surgical waste materials; enzymatically digested femoral heads (FHs and reamer irrigator aspirator (RIA waste fluids. Flow cytometry for the CD45-/lowCD73+CD271+ phenotype was used to evaluate uncultured MSCs before and after selection, and to measure MSC enrichment in parallel to colony forming-unit fibroblast assay. Trilineage differentiation assays and quantitative polymerase chain-reaction for key transcripts involved in bone regeneration was used to assess the functional utility of isolated cells for bone repair.Uncultured CD45-/lowCD271+ MSCs uniformly expressed CD73, CD90 and CD105 but showed variable expression of MSCA-1 and SUSD2 (BM>RIA>FH. MSCs were enriched over 150-fold from BM aspirates and RIA fluids, whereas the highest MSC purities were obtained from FH digests. Enriched fractions expressed increased levels of BMP-2, COL1A2, VEGFC, SPARC and CXCL12 transcripts (BM>RIA>FH, with the highest up-regulation detected for CXCL12 in BM (>1300-fold. Following culture expansion, CD271-selected MSCS were tri-potential and phenotypically identical to plastic adherence-selected MSCs.A CD271-based GMP-compliant immunomagnetic selection resulted in a substantial increase in MSC purity and elevated expression of transcripts involved in bone formation, vascularisation and chemo-attraction. Although this technology, particularly from RIA fluids, can be immediately applied by orthopaedic surgeons as autologous therapy, further improvements in MSC purities and pre-clinical testing of product

  19. The benefit of bone marrow concentrate in addition to a glass-reinforced hydroxyapatite for bone regeneration: An in vivo ovine study.

    Science.gov (United States)

    Torres, Joao; Gutierres, Manuel; Atayde, Luis; Cortez, Paulo; Lopes, M Ascenção; Santos, J Domingos; Cabral, Abel T; van Eck, Carola F

    2017-06-01

    This study evaluates the ability of a Glass Reinforced Hydroxyapatite Composite (GRHC), in a new microporous pellet formulation with autologous bone marrow concentrate (BMC), to enhance bone regeneration and new bone formation. Ninety non-critical sized bone defects were created in the femurs of nine Merino breed sheep and randomly left unfilled (group A), filled with GRHC pellets alone (group B) or filled with GRHC pellets combined with BMC (group C). The sheep were sacrificed at 3 weeks (three sheep), 6 weeks (three sheep) and 12 weeks (three sheep) and histological analysis (Light Microscopy-LM), scanning electron microscopy (SEM) and histomorphometric analysis (HM) were performed. At 3, 6, and 12 weeks, HM revealed an average percentage of new bone of 48, 72, 83%; 25, 73, 80%, and 16, 38, 78% for Groups C, B and A respectively (significantly different only at 3 weeks p < 0.05). LM and SEM evaluation revealed earlier formation of well-organized mature lamellar bone in Group C. This study demonstrates that the addition of a bone marrow concentrate to a glass reinforced hydroxyapatite composite in a pellet formulation promotes early bone healing. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 35:1176-1182, 2017. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc.

  20. Poly (glycerol sebacate) elastomer supports bone regeneration by its mechanical properties being closer to osteoid tissue rather than to mature bone.

    Science.gov (United States)

    Zaky, S H; Lee, K W; Gao, J; Jensen, A; Verdelis, K; Wang, Y; Almarza, A J; Sfeir, C

    2017-05-01

    Mechanical load influences bone structure and mass. Arguing the importance of load-transduction, we investigated the mechanisms inducing bone formation using an elastomeric substrate. We characterized Poly (glycerol sebacate) (PGS) in vitro for its mechanical properties, compatibility with osteoprogenitor cells regarding adhesion, proliferation, differentiation under compression versus static cultures and in vivo for the regeneration of a rabbit ulna critical size defect. The load-transducing properties of PGS were compared in vitro to a stiffer poly lactic-co-glycolic-acid (PLA/PGA) scaffold of similar porosity and interconnectivity. Under cyclic compression for 7days, we report focal adhesion kinase overexpression on the less stiff PGS and upregulation of the transcription factor Runx2 and late osteogenic markers osteocalcin and bone sialoprotein (1.7, 4.0 and 10.0 folds increase respectively). Upon implanting PGS in the rabbit ulna defect, histology and micro-computed tomography analysis showed complete gap bridging with new bone by the PGS elastomer by 8weeks while minimal bone formation was seen in empty controls. Immunohistochemical analysis demonstrated the new bone to be primarily regenerated by recruited osteoprogenitors cells expressing periostin protein during early phase of maturation similar to physiological endochondral bone development. This study confirms PGS to be osteoconductive contributing to bone regeneration by recruiting host progenitor/stem cell populations and as a load-transducing substrate, transmits mechanical signals to the populated cells promoting differentiation and matrix maturation toward proper bone remodeling. We hence conclude that the material properties of PGS being closer to osteoid tissue rather than to mineralized bone, allows bone maturation on a substrate mechanically closer to where osteoprogenitor/stem cells differentiate to develop mature load-bearing bone. The development of effective therapies for bone and

  1. Comparison of bone regeneration using three demineralized freeze-dried bone allografts: A histological and histomorphometric study in rabbit calvaria

    Directory of Open Access Journals (Sweden)

    Parichehr Behfarnia

    2012-01-01

    Conclusion: Both test and control groups resulted in successful new bone formation. No difference was noted in bone formation and remained particles between three commercial bone allografts. Further studies in this issue may be needed.

  2. Bone regeneration in rat calvarial defects implanted with fibrous scaffolds composed of a mixture of silicate and borate bioactive glasses.

    Science.gov (United States)

    Gu, Yifei; Huang, Wenhai; Rahaman, Mohamed N; Day, Delbert E

    2013-11-01

    Previous studies have evaluated the capacity of porous scaffolds composed of a single bioactive glass to regenerate bone. In the present study, scaffolds composed of a mixture of two different bioactive glasses (silicate 13-93 and borate 13-93B3) were created and evaluated for their response to osteogenic MLO-A5 cells in vitro and their capacity to regenerate bone in rat calvarial defects in vivo. The scaffolds, which have similar microstructures (porosity=58-67%) and contain 0, 25, 50 and 100 wt.% 13-93B3 glass, were fabricated by thermally bonding randomly oriented short fibers. The silicate 13-93 scaffolds showed a better capacity to support cell proliferation and alkaline phosphatase activity than the scaffolds containing borate 13-93B3 fibers. The amount of new bone formed in the defects implanted with the 13-93 scaffolds at 12 weeks was 31%, compared to values of 25, 17 and 20%, respectively, for the scaffolds containing 25, 50 and 100% 13-93B3 glass. The amount of new bone formed in the 13-93 scaffolds was significantly higher than in the scaffolds containing 50 and 100% 13-93B3 glass. While the 13-93 fibers were only partially converted to hydroxyapatite at 12 weeks, the 13-93B3 fibers were fully converted and formed a tubular morphology. Scaffolds composed of an optimized mixture of silicate and borate bioactive glasses could provide the requisite architecture to guide bone regeneration combined with a controllable degradation rate that could be beneficial for bone and tissue healing. Copyright © 2013 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

  3. The potential of chitosan combined with chicken shank collagen as scaffold on bone defect regeneration process in Rattus norvegicus

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    Fitria Rahmitasari

    2016-12-01

    Full Text Available Background: In the field of dentistry, alveolar bone damage can be caused by periodontal disease, traumatic injury due to tooth extraction, cyst enucleation, and tumor surgery. One of the ways to regenerate the bone defect is using graft scaffold. Thus, combination of chitosan and collagen can stimulate osteogenesis. Purpose: The aim of this study was to examine the potential of chitosan combined with chicken shank collagen on bone defect regeneration process. Method: Twelve Rattus norvegicus were prepared as animal models in this research. A bone defect was intentionally created at both of the right and left femoral bones of the models. Next, 24 samples were divided into four groups, namely Group 1 using chitosan – collagen scaffold (50:50, Group 2 using chitosan collagen-scaffold (80:20, Group 3 using chitosan scaffold only, and Control Group using 3% CMC-Na. On 14th day, those animals were sacrificed, and histopathological anatomy examination was conducted to observe osteoclast cells. In addition, immunohistochemistry examination was also performed to observe RANKL expressions. Result: There was a significant difference in RANKL expressions among the groups, except between Group 3 using chitosan scaffold only and control group (p value > 0.05. The highest expression of RANKL was found in Group 1 with chitosan – collagen scaffold (50:50, followed by Group 2 with chitosan-collagen scaffold (80:20. Moreover, there was also a significant difference in osteoclast generation, except between Group 1 using chitosan – collagen scaffold (50:50 and Group 2 using chitosan-collagen scaffold (80:20, p value 0.05. Less osteoclast was found in the groups using chitosan – collagen scaffold (Group 1 and Group 2. Conclusion: Combination of chitosan and chicken shank collagen scaffold can improve regeneration process of bone defect in Rattus novergicus animals through increasing of RANKL expressions, and decreasing of osteoclast.

  4. 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

  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

  6. External fixation of femoral defects in athymic rats: Applications for human stem cell implantation and bone regeneration

    Directory of Open Access Journals (Sweden)

    Terasa Foo

    2013-01-01

    Full Text Available An appropriate animal model is critical for the research of stem/progenitor cell therapy and tissue engineering for bone regeneration in vivo. This study reports the design of an external fixator and its application to critical-sized femoral defects in athymic rats. The external fixator consists of clamps and screws that are readily available from hardware stores as well as Kirschner wires. A total of 35 rats underwent application of the external fixator with creation of a 6-mm bone defect in one femur of each animal. This model had been used in several separate studies, including implantation of collagen gel, umbilical cord blood mesenchymal stem cells, endothelial progenitor cells, or bone morphogenetic protein-2. One rat developed fracture at the proximal pin site and two rats developed deep tissue infection. Pin loosening was found in nine rats, but it only led to the failure of external fixation in two animals. In 8 to 10 weeks, various degrees of bone growth in the femoral defects were observed in different study groups, from full repair of the bone defect with bone morphogenetic protein-2 implantation to fibrous nonunion with collagen gel implantation. The external fixator used in these studies provided sufficient mechanical stability to the bone defects and had a comparable complication rate in athymic rats as in immunocompetent rats. The external fixator does not interfere with the natural environment of a bone defect. This model is particularly valuable for investigation of osteogenesis of human stem/progenitor cells in vivo.

  7. Efficacy of platelet rich plasma and hydroxyapatite crystals in bone regeneration after surgical removal of mandibular third molars.

    Science.gov (United States)

    Kaur, Preeti; Maria, Anisha

    2013-03-01

    This study evaluates the efficacy of platelet rich plasma (PRP) & porous hydroxyapatite crystals in bone regeneration after surgical removal of mandibular third molar with the help of radiographs and its comparison with control side. A total of 40 patients; both male and female aged between 18 and 35 years, who had impacted mandibular third molars were randomly selected for this study. Twenty patients were taken for control group and 20 patients for study group. The extraction socket of the study group was packed with PRP and hydroxyapatite granules and that of control group was sutured without PRP and hydroxyapatite. The bone density of both extraction sockets were evaluated radiographically using gray level histogram and compared periodically on immediate postoperative day, 1st and 3rd month postoperatively and postoperative sequelae of both the control group and study group in terms of oedema & pain or any other adverse reactions were also assessed. Data suggested evidence of early bone formation and maturation radiographically in study group as compared to control group. The percentage of facial swelling was numerically greater on the control side as compared to the study side, Pain was also assessed with VAS and it was found that the severity of pain was equal in both study and control groups and the results were not significant. This study clearly indicated a definitive improvement in the wound healing, increase in bone density, which signifies and highlights the use of PRP and hydroxyapatite granules, certainly as a valid method in inducing and accelerating bone regeneration.

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

    Science.gov (United States)

    Im, Owen; Li, Jian; Wang, Mian; Zhang, Lijie Grace; Keidar, Michael

    2012-01-01

    Background 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 promising for further exploration for bone regeneration. PMID:22619545

  9. Novel naturally crosslinked electrospun nanofibrous chitosan mats for guided bone regeneration membranes: material characterization and cytocompatibility.

    Science.gov (United States)

    Norowski, Peter A; Fujiwara, Tomoko; Clem, William C; Adatrow, Pradeep C; Eckstein, Eugene C; Haggard, Warren O; Bumgardner, Joel D

    2015-05-01

    Guided bone regeneration (GBR) barrier membranes are used to prevent soft tissue infiltration into the graft space during dental procedures that involve bone grafting. Chitosan materials have shown promise as GBR barrier membranes, due to their biocompatibility and predictable biodegradability, but degradation rates may still be too high for clinical applications. In this study, chitosan GBR membranes were electrospun using chitosan (70% deacetylated, 312 kDa, 5.5 w/v%), with or without the addition of 5 or 10 mm genipin, a natural crosslinking agent, in order to extend the degradation to meet the clinical target time frame of 4-6 months. Membranes were evaluated for fibre diameter, tensile strength, biodegradation rate, bond structure and cytocompatibility. Genipin addition, at 5 or 10 mm, resulted in median fibre diameters 184, 144 and 154 nm for uncrosslinked, 5 mm and 10 mm crosslinked, respectively. Crosslinking, examined by Fourier transform infrared spectroscopy, showed a decrease in N-H stretch as genipin levels were increased. Genipin-crosslinked mats exhibited only 22% degradation based on mass loss, as compared to 34% for uncrosslinked mats at 16 weeks in vitro. The ultimate tensile strength of the mats was increased by 165% to 32 MPa with 10 mm crosslinking as compared to the uncrosslinked mats. Finally, genipin-crosslinked mats supported the proliferation of SAOS-2 cells in a 5 day growth study, similar to uncrosslinked mats. These results suggest that electrospun chitosan mats may benefit from genipin crosslinking and have the potential to meet clinical degradation time frames for GBR applications. Copyright © 2012 John Wiley & Sons, Ltd.

  10. Preparation and Characterization of Resorbable Bacterial Cellulose Membranes Treated by Electron Beam Irradiation for Guided Bone Regeneration

    OpenAIRE

    An, Sung-Jun; Lee, So-Hyoun; Huh, Jung-Bo; Jeong, Sung In; Park, Jong-Seok; Gwon, Hui-Jeong; Kang, Eun-Sook; Jeong, Chang-Mo; Lim, Youn-Mook

    2017-01-01

    Bacterial cellulose (BC) is an excellent biomaterial with many medical applications. In this study, resorbable BC membranes were prepared for guided bone regeneration (GBR) using an irradiation technique for applications in the dental field. Electron beam irradiation (EI) increases biodegradation by severing the glucose bonds of BC. BC membranes irradiated at 100 kGy or 300 kGy were used to determine optimal electron beam doses. Electron beam irradiated BC membranes (EI-BCMs) were evaluated b...

  11. [Development of a novel absorbable nanofiber chitosan-collagen membrane by electrospinning and the preliminary study on guided bone regeneration].

    Science.gov (United States)

    Gao, B; Li, X J; Lin, M; Li, Y Y; Dong, Y

    2018-02-09

    Objective: To evaluate the application effect of nanofiber chitosan-collagen membrane (NCM) on guided bone regeneration (GBR). Methods: The mixture of collagen, chitosan, polyethylene oxide was used to make up the NCM by electrospinning, then the NCM was crosslinked by glutaraldehyde vapor. The physical property of the NCM was measured by scanning electron microscopy (SEM) and Fourier transform infrared spectroscopy (FTIR). MC3T3-E1 osteoblasts were cultured on NCM to characterize the biocompatibility. The effectiveness of four groups [contrast group, Bio-gide membrane (BGM), compressed chitosan-collagen menbrane (CCM), NCM/CCM] on bone regeneration were evaluated in critical-sized defects (diameter = 5 mm) in SD rats. Results: When the mixed solution consists of 4.0% collagen, 1.0% chitosan and 3.5% polyethylene oxide, the NCM could be validly fabricated by electrospinning. After cross-linking by glutaraldehyde vapor, the tensile strength and the stability of NCM in damp was enhanced. No cytotoxicity of the NCM was detected on MC3T3-E1 osteoblasts. In vivo study showed that the new bone regeneration ratio of NCM/CCM group was [(43.10±1.49)%], and this was similar to that of the group of BGM [(41.36±2.60)%] ( P> 0.05), but higher than that of the CCM group [(33.10±1.41)%] and the contrast group [(7.22±2.46)%] ( P< 0.05). Conclusions: The NCM can promote new bone regeneration effectively in GBR procedure.

  12. A hybrid composite system of biphasic calcium phosphate granules loaded with hyaluronic acid-gelatin hydrogel for bone regeneration.

    Science.gov (United States)

    Faruq, Omar; Kim, Boram; Padalhin, Andrew R; Lee, Gun Hee; Lee, Byong-Taek

    2017-10-01

    An ideal bone substitute should be made of biocompatible materials that mimic the structure, characteristics, and functions of natural bone. Many researchers have worked on the fabrication of different bone scaffold systems including ceramic-polymer hybrid system. In the present study, we incorporated hyaluronic acid-gelatin hydrogel to micro-channeled biphasic calcium phosphate granules as a carrier to improve cell attachment and proliferation through highly interconnected porous structure. This hybrid system is composed of ceramic biphasic calcium phosphate granules measuring 1 mm in diameter with seven holes and hyaluronic acid-gelatin hydrogel. This combination of biphasic calcium phosphate and hyaluronic acid-gelatin retained suitable characteristics for bone regeneration. The resulting scaffold had a porosity of 56% with a suitable pore sizes. The mechanical strength of biphasic calcium phosphate granule increased after loading hyaluronic acid-gelatin from 4.26 ± 0.43 to 6.57 ± 0.25 MPa, which is highly recommended for cancellous bone substitution. Swelling and degradation rates decreased in the hybrid scaffold compared to hydrogel due to the presence of granules in hybrid scaffold. In vitro cytocompatibility studies were observed by preosteoblasts (MC3T3-E1) cell line and the result revealed that biphasic calcium phosphate/hyaluronic acid-gelatin significantly increased cell growth and proliferation compared to biphasic calcium phosphate granules. Analysis of micro-computed tomography data and stained tissue sections from the implanted samples showed that the hybrid scaffold had good osseointegration and better bone formation in the scaffold one and two months postimplantation. Histological section confirmed the formation of dense collagenous tissue and new bone in biphasic calcium phosphate/hyaluronic acid-gelatin scaffolds at two months. Our study demonstrated that such hybrid biphasic calcium phosphate/hyaluronic acid-gelatin scaffold is a

  13. Comparison of Guided Bone Regeneration Between Surface-Modified and Pristine Titanium Membranes in a Rat Calvarial Model.

    Science.gov (United States)

    Nguyen, Thuy-Duong; Moon, So-Hee; Oh, Tae-Ju; Seok, Jung-Jin; Lee, Min-Ho; Bae, Tae-Sung

    2016-01-01

    The objectives of this study were to evaluate bioactivity of a titanium membrane with anodization, cyclic precalcification, and heat (APH) treatment (APHTM), and to compare APHTM and nontreated titanium membrane (NTTM) in guided bone regeneration using histologic analysis and microcomputed tomography (micro-CT). APHTM samples were prepared and immersed in simulated body fluid for 2 days, then observed using field-emission scanning electron microscopy, followed by an analysis of calcium and phosphate precipitation using an energy dispersive x-ray spectroscopy. For the in vivo experiment, critical-size defects were created in rat calvaria (diameter, 8 mm) and treated with either APHTM or NTTM (n = 14 each). Biopsies were performed at 2 and 4 weeks for histologic analysis (n = 3 per group each time). Fluorochrome bone markers were injected in three rats in each group at 3 (alizarin red) and 5 weeks (calcein green), followed by histologic examination at 7 weeks. Micro-CT was performed at 8 weeks (n = 5 per group). APHTM exhibited high bioactivity, characterized by dense nano-sized flakelike crystals throughout the membrane and an increase in the calcium-phosphate concentrations after 2-day immersion in simulated body fluid. At 2 and 4 weeks, APHTM samples showed an intimate bone formation onto the membrane, whereas NTTM samples demonstrated interposition of connective tissue between the membrane and newly formed bone. The same pattern was found in the fluorescent study. The micro-CT analysis revealed significantly lower bone volume but higher bone mineral density in the APHTM samples than in the NTTM samples (P bone formation toward the membrane, thus increasing structural durability for bone regeneration. Further research is warranted to confirm the results found in these in vitro and in vivo experiments.

  14. Bone regeneration using a bone morphogenetic protein-2 saturated slow-release gelatin hydrogel sheet: evaluation in a canine orbital floor fracture model.

    Science.gov (United States)

    Asamura, Shinichi; Mochizuki, Yuichi; Yamamoto, Masaya; Tabata, Yasuhiko; Isogai, Noritaka

    2010-04-01

    Bone regeneration methods using bone inductive cytokines show promise, however, due to early diffusion and absorption of single applications of these cytokines, the bone inductive effects are limited. In this study, such a system was applied, using gelatin hydrogel as a carrier to slowly release (bone morphogenetic proteins) BMP-2 over a relatively long period in vivo. By coupling this slow-release system with a biodegradable copolymer, this composite was evaluated by grafting into bone defect sites of a canine orbital floor fracture model. Radio-iodinated BMP-2 incorporated into the gelatin hydrogel carrier and subcutaneously implanted into nude mice showed a similar slow release (approximately, 60% at 3 days and 80% at 14 days) as the radiolabeled hydrogel carrier alone. In contrast, greater than 90% of fluid-injected BMP-2 was lost in the injection site within the first 8 hours. Using a dog model of orbital floor fracture, a complex of BMP-2-saturated gelatin hydrogel and a polylactide-based biodegradable copolymer was implanted into the orbital bone defect. Bone structural analysis, using radiography, histologic examination, and microfocus CT, showed greatly enhanced new bone formation and defect healing at 5 weeks in comparison to implanted biodegradable copolymer directly saturated with the same amount of BMP-2 (no slow-release hydrogel carrier). A trabecular structure resembling that normal bone tissue was restored in the new bone tissue generated by the slow-release constructs. Thus study demonstrates the potential of slow-release BMP-2 for bone healing of difficult defects.

  15. [Biocompatibility of poly-L-lactic acid/Bioglass-guided bone regeneration membranes processed with oxygen plasma].

    Science.gov (United States)

    Fang, Wei; Zeng, Shu-Guang; Gao, Wen-Feng

    2015-04-01

    To prepare and characterize a nano-scale fibrous hydrophilic poly-L-lactic acid/ Bioglass (PLLA/BG) composite membrane and evaluate its biocompatibility as a composite membrane for guiding bone regeneration (GBR). PLLA/BG-guided bone regeneration membrane was treated by oxygen plasma to improved its hydrophilicity. The growth of MG-63 osteoblasts on the membrane was observed using Hoechst fluorescence staining, and the biocompatibility of the membrane was evaluated by calculating the cells adhesion rate and proliferation rate. Osteogenesis of MG-63 cells was assessed by detecting alkaline phosphatase (ALP), and the formation of calcified nodules and cell morphology changes were observed using scanning electron microscope (SEM). The cell adhesion rates of PLLA/BG-guided bone regeneration membrane treated with oxygen plasma were (30.570±0.96)%, (47.27±0.78)%, and (66.78±0.69)% at 1, 3, and 6 h, respectively, significantly higher than those on PLLA membrane and untreated PLLA/BG membrane (Pmembranes increased with time, but highest on oxygen plasma-treated PLLA/BG membrane (Pplasma treatment of the PLLA/BG membrane promoted cell adhesion. The membranes with Bioglass promoted the matrix secretion of the osteoblasts. Under SEM, the formation of calcified nodules and spindle-shaped cell morphology were observed on oxygen plasma-treated PLLA/BG membrane. Oxygen plasma-treated PLLA/BG composite membrane has good biocompatibility and can promote adhesion, proliferation and osteogenesis of the osteoblasts.

  16. 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

    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). 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. 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. 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.

  17. Exogenous stromal derived factor-1 releasing silk scaffold combined with intra-articular injection of progenitor cells promotes Bone-Ligament-Bone regeneration.

    Science.gov (United States)

    Hu, Yejun; Ran, Jisheng; Zheng, Zefeng; Jin, Zhangchu; Chen, Xiao; Yin, Zi; Tang, Chenqi; Chen, Yangwu; Huang, Jiayun; Le, Huihui; Yan, Ruijian; Zhu, Ting; Wang, Junjuan; Lin, Junxin; Xu, Kan; Zhou, Yiting; Zhang, Wei; Cai, Youzhi; Dominique, Pioletti; Chin Heng, Boon; Chen, Weishan; Shen, Weiliang; Ouyang, Hong-Wei

    2018-03-07

    Anterior cruciate ligament (ACL) is one of the most difficult tissues to heal once injured. Ligament regeneration and tendon-bone junction healing are two major goals of ACL reconstruction. This study aimed to investigate the synergistic therapeutic effects of Stromal cell-derived factor 1(SDF-1)-releasing collagen-silk (CSF) scaffold combined with intra-articular injection of ligament-derived stem/progenitor cells (LSPCs) for ACL regeneration and the amelioration in the long-term complication of osteoarthritis (OA). The stem cell recruitment ability of CSF scaffold and the multipotency, particularly the tendon forming ability of LSPCs from rabbits were characterized in vitro, while the synergistic effect of the CSF scaffold and LSPCs for ACL regeneration and OA amelioration were investigated in vivo at 1, 3, and 6 months with a rabbit ACL reconstruction model. The CSF scaffold was used as a substitute for the ACL, and LSPCs were injected into the joint cavity after 7 days of the ACL reconstruction. CSF scaffold displayed a controlled release pattern for the encapsulated protein for up to 7 days with an increased stiffness in the mechanical property. LSPCs, which exhibited highly I Collagen and CXCR4 expression, were attracted by SDF-1 and successfully relocated into the CSF scaffold at 1 month in vivo. At 3 and 6 months post-treatment, the CSF scaffold combined with LSPCs (CSFL group) enhanced the regeneration of ACL tissue, and promoted bone tunnel healing. Furthermore, the OA progression was impeded efficiently. Our findings here provided a new strategy that using stem cell recruiting CSF scaffold with tissue-specific stem cells, could be a promising solution for ACL regeneration. In this study, we developed a silk scaffold with increased stiffness and SDF-1 controlled release capacity for ligament repair. This advanced scaffold transplantation combined with intra-articular injection of LSPCs (which was isolated from rabbit ligament for the first time in this

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

    Science.gov (United States)

    Basile, Maria Assunta; d'Ayala, Giovanna Gomez; Malinconico, Mario; Laurienzo, Paola; Coudane, Jean; Nottelet, Benjamin; Ragione, Fulvio Della; Oliva, Adriana

    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. Copyright © 2014 Elsevier B.V. All rights reserved.

  19. 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.

  20. Immediate implant placement and provisionalization with simultaneous guided bone regeneration in the esthetic zone

    Directory of Open Access Journals (Sweden)

    Chih-Long Chen

    2011-03-01

    Full Text Available The procedure for immediate implant placement and provisionalization is time-saving, possibly with only one surgical intervention required, although allowing maximal preservation of peri-implant tissues. In this case, we extracted a fractured maxillary right central incisor of a 46-year-old woman with high esthetic expectations, and a transmucosal implant was immediately installed. Simultaneous guided bone regeneration was performed to correct the defects at the facial side of the socket and augment the alveolar ridge horizontally. Primary stability of the implant body and wound closure without tension were confirmed. Connection of a 15° angled abutment and fabrication of a provisional acrylic resin crown without occlusal contact were also completed in the same appointment. After intensive follow-up and soft-tissue molding for 6 months, the customized zirconia abutment and all-ceramic crown were definitively fabricated. During the 18-month follow-up period, the patient was satisfied with the esthetic and functional results.

  1. Polyurethane and PTFE membranes for guided bone regeneration: histopathological and ultrastructural evaluation.

    Science.gov (United States)

    Monteiro, Adriana-Socorro-Ferreira; Macedo, Luís-Guilherme-Scavone; Macedo, Nelson-Luiz; Balducci, Ivan

    2010-03-01

    The purpose of this study was to research a membrane material for use in guided bone regeneration. In this study, 25 male Wistar rats were used to analyze the biocompatibility and degradation process of biomembranes. The morphological changes in subcutaneous implantations were assessed after 7, 14, 21, 28 and 70 days. The materials were made of polyurethane polymer (AUG) obtained from vegetal oil (Ricinus communis) and polytetrafluoroethylene membrane (PTFE). The surface characteristics of the physical barriers in scanning electronic microscopic (SEM) were also evaluated. In both groups, the initial histological analysis showed moderate inflammatory infiltrate, which was predominantly polymorphonuclear. There was also a presence of edema, which was gradually replaced by granulation tissue, culminating in a fibrous capsule. In the AUG group, some multinucleated giant cells were present in the contact interface, with the space previously occupied by the material. However, membrane degradation was not observed during the period studied. According to the present SEM findings, porosity was not detected in the AUG or PTFE membranes. The researched material is biocompatible and the degradation process is extremely slow or may not even occur at all.

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

    Science.gov (United States)

    Meng, Yao; Liu, Man; Wang, Shao-An; Mo, An-Chun; Huang, Cui; Zuo, Yi; Li, Ji-Dong

    2008-11-01

    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 membrane.

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

    Energy Technology Data Exchange (ETDEWEB)

    Cheng Xianmiao [Research Center for Nano-Biomaterials, Analytical and Testing Center, Sichuan University, 610064 Chengdu (China); Department of Chemistry, Sichuan University, 610064 Chengdu (China); Li Yubao [Research Center for Nano-Biomaterials, Analytical and Testing Center, Sichuan University, 610064 Chengdu (China)], E-mail: nic7504@scu.edu.cn; Zuo Yi; Zhang Li [Research Center for Nano-Biomaterials, Analytical and Testing Center, Sichuan University, 610064 Chengdu (China); Li Jidong [Research Center for Nano-Biomaterials, Analytical and Testing Center, Sichuan University, 610064 Chengdu (China); Department of Chemistry, Sichuan University, 610064 Chengdu (China); Wang Huanan [Research Center for Nano-Biomaterials, Analytical and Testing Center, Sichuan University, 610064 Chengdu (China)

    2009-01-01

    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 -NH{sub 2} 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.

  4. 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.

  5. 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

  6. Comparative study of NMP-preloaded and dip-loaded membranes for guided bone regeneration of rabbit cranial defects.

    Science.gov (United States)

    Karfeld-Sulzer, Lindsay S; Ghayor, Chafik; Siegenthaler, Barbara; Gjoksi, Bebeka; Pohjonen, Timo H; Weber, Franz E

    2017-02-01

    Guided bone regeneration (GBR) has been utilized for several decades for the healing of cranio-maxillofacial bone defects and, particularly in the dental field, by creating space with a barrier membrane to exclude soft tissue and encourage bone growth in the membrane-protected volume. Although the first membranes were non-resorbable, a new generation of GBR membranes aims to biodegrade and provide bioactivity for better overall results. The Inion GTR™ poly(lactide-co-glycolide) (PLGA) membrane is not only resorbable but also bioactive, since it includes N-methylpyrrolidone (NMP), which has been shown to promote bone regeneration. In this study, the effects of loading different amounts of NMP onto the membrane through chemical vapour deposition or dipping have been explored. In vitro release demonstrated that lower levels of NMP led to lower NMP concentrations and slower release, based on total NMP loaded in the membrane. The dipped membrane released almost all of the NMP within 15 min, leading to a high NMP concentration. For the in vivo studies in rabbits, 6 mm calvarial defects were created and left untreated or covered with an ePTFE membrane or PLGA membranes dipped in, or preloaded with, NMP. Evaluation of the bony regeneration revealed that the barrier membranes improved bony healing and that a decrease in NMP content improved the performance. Overall, we have demonstrated the potential of these PLGA membranes with a more favourable NMP release profile and the significance of exploring the effect of NMP on these PLGA membranes with regard to bone ingrowth. Copyright © 2014 John Wiley & Sons, Ltd. Copyright © 2014 John Wiley & Sons, Ltd.

  7. 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.

  8. Histologic and histomorphometric evaluation of bone regeneration using nanocrystalline hydroxyapatite and human freeze-dried bone graft : An experimental study in rabbit.

    Science.gov (United States)

    Sadeghi, Rokhsareh; Najafi, Mohammad; Semyari, Hassan; Mashhadiabbas, Fatemeh

    2017-03-01

    Bone regeneration is an important concern in periodontal treatment and implant dentistry. Different biomaterials and surgical techniques have been used for this purpose. The aim of the present study was to compare the effect of nanocrystalline hydroxyapatite and human freeze-dried bone graft (FDBG) in regeneration of rabbit calvarium bony defects by histologic and histomorphometric evaluation. In this experimental study, three similar defects, measuring 8 mm in diameter, were created in the calvaria of 16 white New Zealand rabbits. Two defects were filled with FDBG and nanocrystalline hydroxyapatite silica gel, while the other one remained unfilled to be considered as control. All the defects were covered with collagen membranes. During the healing period, two animals perished; so 14 rabbits were divided into two groups: half of them were euthanized after 6 weeks of healing and the other half after 12 weeks. The specimens were subjected to histologic and histomorphometric examinations for assessment of the following variables: percentage of bone formation and residual graft material, inflammation scores, patterns of bone formation and type of newly formed bone. The percentages of new bone formation after 6 weeks were 14.22 ± 7.85, 21.57 ± 6.91, and 20.54 ± 10.07% in FDBG, NanoBone, and control defects. These values were 27.54 ± 20.19, 23.86 ± 6.27, and 26.48 ± 14.18% in 12-week specimens, respectively. No significant differences were found in the amount of bone formation between the groups. With regard to inflammation, the control and NanoBone groups showed significantly less inflammation compared to FDBG at the 6-week healing phase (P = 0.04); this difference was not significant in the 12-week specimens. Based on the results of this experimental study, both NanoBone and FDBG exhibited a similar effect on bone formation.

  9. Epigenetics and Shared Molecular Processes in the Regeneration of Complex Structures

    Directory of Open Access Journals (Sweden)

    Labib Rouhana

    2016-01-01

    Full Text Available The ability to regenerate complex structures is broadly represented in both plant and animal kingdoms. Although regenerative abilities vary significantly amongst metazoans, cumulative studies have identified cellular events that are broadly observed during regenerative events. For example, structural damage is recognized and wound healing initiated upon injury, which is followed by programmed cell death in the vicinity of damaged tissue and a burst in proliferation of progenitor cells. Sustained proliferation and localization of progenitor cells to site of injury give rise to an assembly of differentiating cells known as the regeneration blastema, which fosters the development of new tissue. Finally, preexisting tissue rearranges and integrates with newly differentiated cells to restore proportionality and function. While heterogeneity exists in the basic processes displayed during regenerative events in different species—most notably the cellular source contributing to formation of new tissue—activation of conserved molecular pathways is imperative for proper regulation of cells during regeneration. Perhaps the most fundamental of such molecular processes entails chromatin rearrangements, which prime large changes in gene expression required for differentiation and/or dedifferentiation of progenitor cells. This review provides an overview of known contributions to regenerative processes by noncoding RNAs and chromatin-modifying enzymes involved in epigenetic regulation.

  10. 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.

  11. 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.

  12. Comparative study of porous hydroxyapatite/chitosan and whitlockite/chitosan scaffolds for bone regeneration in calvarial defects

    Science.gov (United States)

    Zhou, Ding; Qi, Chao; Chen, Yi-Xuan; Zhu, Ying-Jie; Sun, Tuan-Wei; Chen, Feng; Zhang, Chang-Qing

    2017-01-01

    Hydroxyapatite (HAP; Ca10(PO4)6(OH)2) and whitlockite (WH; Ca18Mg2(HPO4)2(PO4)12) are widely utilized in bone repair because they are the main components of hard tissues such as bones and teeth. In this paper, we synthesized HAP and WH hollow microspheres by using creatine phosphate disodium salt as an organic phosphorus source in aqueous solution through microwave-assisted hydrothermal method. Then, we prepared HAP/chitosan and WH/chitosan composite membranes to evaluate their biocompatibility in vitro and prepared porous HAP/chitosan and WH/chitosan scaffolds by freeze drying to compare their effects on bone regeneration in calvarial defects in a rat model. The experimental results indicated that the WH/chitosan composite membrane had a better biocompatibility, enhancing proliferation and osteogenic differentiation ability of human mesenchymal stem cells than HAP/chitosan. Moreover, the porous WH/chitosan scaffold can significantly promote bone regeneration in calvarial defects, and thus it is more promising for applications in tissue engineering such as calvarial repair compared to porous HAP/chitosan scaffold. PMID:28435251

  13. Hydrophilized polycaprolactone nanofiber mesh-embedded poly(glycolic-co-lactic acid) membrane for effective guided bone regeneration.

    Science.gov (United States)

    Cho, Wan Jin; Kim, Jun Ho; Oh, Se Heang; Nam, Hyun Hee; Kim, Jin Man; Lee, Jin Ho

    2009-11-01

    A novel guided bone regeneration (GBR) membrane was fabricated by an immersion precipitation of poly (glycolic-co-lactic acid) (PLGA)/Pluronic F127 solution impregnated in an electrospun polycaprolactone (PCL)/Tween 80 nanofiber mesh. The prepared PCL/Tween 80 nanofiber mesh-embedded PLGA/Pluronic F127 membrane (hydrophilized PCL/PLGA hybrid membrane) had nano-size pores on the top side (which can prevent from fibrous connective tissue infiltration but allow permeation of oxygen and nutrients) and micro-size pores on the bottom side (which can improve adhesiveness with bone). From the comparisons of mechanical properties (tensile and suture pullout strengths), model nutrient (FITC-labeled bovine serum albumin) permeability, and bone regeneration behavior using a rat model (skull bone defect) of the hybrid membrane with those of PLGA/Pluronic F127 membrane (asymmetrically porous, hydrophilized PLGA membrane), PCL/Tween 80 nanofiber mesh (electrospun, hydrophilized PCL nanofiber mesh), and a commercialized GBR membrane, Bio-Gide (collagen type I/III membrane), it was observed that the PCL/PLGA hybrid membrane seems to be highly desirable as a GBR membrane for the selective permeability caused by its unique morphology and osteoconductivity provided by several tens micro-size pores of the bottom side as well as the excellent mechanical strengths by the hybridization of porous PLGA membrane and PCL nanofiber mesh. (c) 2008 Wiley Periodicals, Inc.

  14. Contribution of different bone marrow-derived cell types in endometrial regeneration using an irradiated murine model.

    Science.gov (United States)

    Gil-Sanchis, Claudia; Cervelló, Irene; Khurana, Satish; Faus, Amparo; Verfaillie, Catherine; Simón, Carlos

    2015-06-01

    To study the involvement of seven types of bone marrow-derived cells (BMDCs) in the endometrial regeneration in mice after total body irradiation. Prospective experimental animal study. University research laboratories. β-Actin-green fluorescent protein (GFP) transgenic C57BL/6-Tg (CAG-EGFP) and C57BL/6J female mice. The BMDCs were isolated from CAG-EGFP mice: unfractionated bone marrow cells, hematopoietic progenitor cells, endothelial progenitor cells (EPCs), and mesenchymal stem cells (MSCs). In addition three murine GFP(+) cell lines were used: mouse Oct4 negative BMDC multipotent adult progenitor cells (mOct4(-)BM-MAPCs), BMDC hypoblast-like stem cells (mOct4(+) BM-HypoSCs), and MSCs. All cell types were injected through the tail vein of 9 Gy-irradiated C57BL/6J female mice. Flow cytometry, cell culture, bone marrow transplantation assays, histologic evaluation, immunohistochemistry, proliferation, apoptosis, and statistical analysis. After 12 weeks, histologic analysis revealed that uteri of mice with mOct4(-)BM-MAPCs and MSC line were significantly smaller than uteri of mice with uncultured BMDCs or mOct4(+) BM-HypoSCs. The percentage of engrafted GFP(+) cells ranged from 0.13%-4.78%. Expression of Ki-67 was lower in all uteri from BMDCs treated mice than in the control, whereas TUNEL(+) cells were increased in the EPCs and mOct4(+)BM-HypoSCs groups. Low number of some BMDCs can be found in regenerating endometrium, including stromal, endotelial, and epithelial compartments. Freshly isolated MSCs and EPCs together with mOct4(+) BM-HypoSCs induced the greatest degree of regeneration, whereas culture isolated MSCs and mOct4(-)BM-MAPCs transplantation may have an inhibitory effect on endometrial regeneration. Copyright © 2015 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

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

    DEFF Research Database (Denmark)

    Aaboe, Merete; Schou, S.; Hjørting-Hansen, E.

    2000-01-01

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

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

    Science.gov (United States)

    Chen, Xiaohui; Zhao, Yanbing; Geng, Shinan; Miron, Richard J; Zhang, Qiao; Wu, Chengtie; Zhang, Yufeng

    2015-01-01

    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. 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 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 nanogels/B-MBG composite scaffolds when compared to PIB nanogels alone. Tartrate-resistant acid phosphatase-positive staining demonstrated that both scaffolds were degraded over time and bone remodeling occurred in the surrounding bone defect as early as 4 weeks post-implantation. The results from the present study indicate that PIB nanogels are a potential bone tissue engineering biomaterial able to treat defects of irregular shapes and deformities as an injectable, thermoresponsive, biocompatible hydrogel which undergoes rapid thermal gelation once body temperature is reached. Furthermore, its combination with B-MBG scaffolds improves the mechanical properties and ability to promote new bone formation when compared to PIB nanogels alone.

  17. Synthesis of calcium-phosphate and chitosan bioceramics for bone regeneration

    Directory of Open Access Journals (Sweden)

    MELLATIE R. FINISIE

    2001-12-01

    Full Text Available Bioceramic composites were obtained from chitosan and hydroxyapatite pastes synthesized at physiological temperature according to two different syntheses approaches. Usual analytical techniques (X-ray diffraction analysis, Fourier transformed infrared spectroscopy, Thermo gravimetric analysis, Scanning electron microscopy, X-ray dispersive energy analysis and Porosimetry were employed to characterize the resulting material. The aim of this investigation was to study the bioceramic properties of the pastes with non-decaying behavior from chitosan-hydroxyapatite composites. Chitosan, which also forms a water-insoluble gel in the presence of calcium ions, and has been reported to have pharmacologically beneficial effects on osteoconductivity, was added to the solid phase of the hydroxyapatite powder. The properties exhibited by the chitosan-hydroxyapatite composites were characteristic of bioceramics applied as bone substitutes. Hydroxyapatite contents ranging from 85 to 98% (w/w resulted in suitable bioceramic composites for bone regeneration, since they showed a non-decaying behavior, good mechanical properties and suitable pore sizes.Compósitos biocerâmicos foram obtidos a partir de pastas de quitosana e hidroxiapatita, preparadas a temperatura fisiológica seguindo dois métodos diferentes de síntese. As técnicas analíticas usuais (Análise de difração de raios-X, Espectroscopia de absorção no infravermelho com transformada de Fourier, Análise termogravimétrica, Microscopia eletrônica de varredura, Análise por energia dispersiva de raios-X, e Porosimetria foram empregadas para caracterizar o material resultante. O objetivo deste trabalho foi estudar as propriedades biocerâmicas das pastas relativas ao comportamento de não-desintegração dos compósitos de quitosana-hidroxiapatita. A quitosana, que também forma um gel insolúvel em água na presença de íons cálcio, e tem mostrado possuir efeitos farmacologicamente ben

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

    Energy Technology Data Exchange (ETDEWEB)

    Cholas, Rahmatullah, E-mail: rahmat.cholas@gmail.com; Kunjalukkal Padmanabhan, Sanosh, E-mail: sanosh2001@gmail.com; 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 6 μm, a specific surface area of 40 m{sup 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 16 nm. 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 200 μm, 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 15 days 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. - Highlights: • Mesoporous hydroxyapatite microsphere(mHA) synthesized by spray drying method • Porous collagen/mHA composite scaffold made by freeze

  19. 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

  20. 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.