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Sample records for bone tissue regeneration

  1. Nanocomposites for bone tissue regeneration.

    Science.gov (United States)

    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.

  2. 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

  3. 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.

  4. 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...

  5. 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.

  6. 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.

  7. 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.

  8. 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

  9. 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

  10. 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.

  11. 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.

  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. 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.

  15. 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.

  16. 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.

  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. 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.

  19. 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.

  20. 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

  1. 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.

  2. 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.

  3. 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.

  4. 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.

  5. 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

  6. 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

  7. 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

  8. 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.

  9. 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....

  10. 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

  11. 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.

  12. 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.

  13. 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

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

    Directory of Open Access Journals (Sweden)

    Guo H

    2012-07-01

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

  15. 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.

  16. 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.

  17. 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.

  18. 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.

  19. Secretomes from bone marrow-derived mesenchymal stromal cells enhance periodontal tissue regeneration.

    Science.gov (United States)

    Kawai, Takamasa; Katagiri, Wataru; Osugi, Masashi; Sugimura, Yukiko; Hibi, Hideharu; Ueda, Minoru

    2015-04-01

    Periodontal tissue regeneration with the use of mesenchymal stromal cells (MSCs) has been regarded as a future cell-based therapy. However, low survival rates and the potential tumorigenicity of implanted MSCs could undermine the efficacy of cell-based therapy. The use of conditioned media from MSCs (MSC-CM) may be a feasible approach to overcome these limitations. The aim of this study was to confirm the effect of MSC-CM on periodontal regeneration. MSC-CM were collected during their cultivation. The concentrations of the growth factors in MSC-CM were measured with the use of enzyme-linked immunoassay. Rat MSCs (rMSCs) and human umbilical vein endothelial cells cultured in MSC-CM were assessed on wound-healing and angiogenesis. The expressions of osteogenetic- and angiogenic-related genes of rMSCs cultured in MSC-CM were quantified by means of real-time reverse transcriptase-polymerase chain reaction analysis. In vivo, periodontal defects were prepared in the rat models and the collagen sponges with MSC-CM were implanted. MSC-CM includes insulin-like growth factor-1, vascular endothelial growth factor, transforming growth factor-β1 and hepatocyte growth factor. In vitro, wound-healing and angiogenesis increased significantly in MSC-CM. The levels of expression of osteogenetic- and angiogenic-related genes were significantly upregulated in rMSCs cultured with MSC-CM. In vivo, in the MSC-CM group, 2 weeks after implantation, immunohistochemical analysis showed several CD31-, CD105-or FLK-1-positive cells occurring frequently. At 4 weeks after implantation, regenerated periodontal tissue was observed in MSC-CM groups. The use of MSC-CM may be an alternative therapy for periodontal tissue regeneration because several cytokines included in MSC-CM will contribute to many processes of complicated periodontal tissue regeneration. Copyright © 2015 International Society for Cellular Therapy. Published by Elsevier Inc. All rights reserved.

  20. 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

  1. 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

  2. In vivo study of chitosan-natural nano hydroxyapatite scaffolds for bone tissue regeneration.

    Science.gov (United States)

    Lee, Jong Seo; Baek, Sang Dae; Venkatesan, Jayachandran; Bhatnagar, Ira; Chang, Hee Kyung; Kim, Hui Taek; Kim, Se-Kwon

    2014-06-01

    Significant development has been achieved with bioceramics and biopolymer scaffolds in the construction of artificial bone. In the present study, we have developed and compared chitosan-micro hydroxyapatite (chitosan-mHA) and chitosan-nano hydroxyapatite (chitosan-nHA) scaffolds as bone graft substitutes. The biocompatibility and cell proliferation of the prepared scaffolds were checked with preosteoblast (MC3T3-E1) cells. Total Volume (TV), bone volume (BV), bone surface (BS), trabecular thickness (Tb.Th), trabecular number (Tb.N) and trabecular separation (Tb.Sp) were found to be higher in chitosan-nHA than chitosan-mHA scaffold. Hence, we suggest that chitosan-nHA scaffold could be a promising biomaterial for bone tissue engineering. Copyright © 2014 Elsevier B.V. All rights reserved.

  3. Analysis of tissue neogenesis in extraction sockets treated with guided bone regeneration: clinical, histologic, and micro-CT results.

    Science.gov (United States)

    Neiva, Rodrigo; Pagni, Giorgio; Duarte, Frederico; Park, Chan Ho; Yi, Erica; Holman, Lindsay A; Giannobile, William V

    2011-01-01

    The aims of this article were to perform a detailed evaluation of the healing of extraction sockets covered with a resorbable collagen membrane 12 weeks following exodontia and to determine if this device had ossifying properties. Ten consecutive subjects in need of extraction of maxillary premolars were recruited. Each subject had a hopeless maxillary premolar extracted with minimal trauma. Sockets were then covered with a collagen barrier membrane alone. At 12 weeks, reentry surgery was performed, clinical measurements were repeated, and bone core biopsies were obtained prior to dental implant placement for histologic and microcomputed tomography (micro-CT) analysis. Study sites showed mean bone regeneration horizontally of 7.7 mm (buccopalatally) and 4.6 mm (mesiodistally). Vertical bone repair showed a mean gain of 10.9 mm. Subtraction radiography showed a mean apical shift of the crestal bone at the center of the socket of 2.1 mm (range, 0.7 to 4.3 mm). Micro-CT and histology revealed formation of well-mineralized tissue at 12 weeks, with a mean percentage of vital bone of 45.87% ± 12.35%. No signs of membrane ossification were observed. A detailed analysis of tissue neogenesis in extraction sites protected by this barrier membrane has demonstrated that adequate bone formation for implant placement occurs as early as 12 weeks following exodontia, with minimal changes in alveolar ridge dimensions. No evidence of membrane ossification was observed.

  4. 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

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

    Directory of Open Access Journals (Sweden)

    Wen-Ling Wang

    2014-01-01

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

  6. 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.

  7. Regenerating articular tissue by converging technologies

    NARCIS (Netherlands)

    Moroni, Lorenzo; Hamann, D.; Paoluzzi, Luca; Pieper, Jeroen; de Wijn, J.R.; van Blitterswijk, Clemens

    2008-01-01

    Scaffolds for osteochondral tissue engineering should provide mechanical stability, while offering specific signals for chondral and bone regeneration with a completely interconnected porous network for cell migration, attachment, and proliferation. Composites of polymers and ceramics are often

  8. 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

  9. Guided Bone Regeneration with Novel Bioabsorbable Membranes

    Science.gov (United States)

    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.

  10. Ribose mediated crosslinking of collagen-hydroxyapatite hybrid scaffolds for bone tissue regeneration using biomimetic strategies.

    Science.gov (United States)

    Krishnakumar, Gopal Shankar; Gostynska, Natalia; Campodoni, Elisabetta; Dapporto, Massimiliano; Montesi, Monica; Panseri, Silvia; Tampieri, Anna; Kon, Elizaveta; Marcacci, Maurilio; Sprio, Simone; Sandri, Monica

    2017-08-01

    This study explores for the first time the application of ribose as a highly biocompatible agent for the crosslinking of hybrid mineralized constructs, obtained by bio-inspired mineralization of self-assembling Type I collagen matrix with magnesium-doped-hydroxyapatite nanophase, towards a biomimetic mineralized 3D scaffolds (MgHA/Coll) with excellent compositional and structural mimicry of bone tissue. To this aim, two different crosslinking mechanisms in terms of pre-ribose glycation (before freeze drying) and post-ribose glycation (after freeze drying) were investigated. The obtained results explicate that with controlled freeze-drying, highly anisotropic porous structures with opportune macro-micro porosity are obtained. The physical-chemical features of the scaffolds characterized by XRD, FTIR, ICP and TGA demonstrated structural mimicry analogous to the native bone. The influence of ribose greatly assisted in decreasing solubility and increased enzymatic resistivity of the scaffolds. In addition, enhanced mechanical behaviour in response to compressive forces was achieved. Preliminary cell culture experiments reported good cytocompatibility with extensive cell adhesion, proliferation and colonization. Overall, scaffolds developed by pre-ribose glycation process are preferred, as the related crosslinking technique is more facile and robust to obtain functional scaffolds. As a proof of concept, we have demonstrated that ribose crosslinking is cost-effective, safe and functionally effective. This study also offers new insights and opportunities in developing promising scaffolds for bone tissue engineering. Copyright © 2017 Elsevier B.V. All rights reserved.

  11. Novel biomimetic hydroxyapatite/alginate nanocomposite fibrous scaffolds for bone tissue regeneration.

    Science.gov (United States)

    Chae, Taesik; Yang, Heejae; Leung, Victor; Ko, Frank; Troczynski, Tom

    2013-08-01

    Hydroxyapatite/alginate nanocomposite fibrous scaffolds were fabricated via electrospinning and a novel in situ synthesis of hydroxyapatite (HAp) that mimics mineralized collagen fibrils in bone tissue. Poorly crystalline HAp nanocrystals, as confirmed by X-ray diffractometer peak approximately at 2θ = 32° and Fourier transform infrared spectroscopy spectrum with double split bands of PO4(v 4) at 564 and 602 cm(-1), were induced to nucleate and grow at the [-COO(-)]-Ca(2+)-[-COO(-)] linkage sites on electrospun alginate nanofibers impregnated with PO4 (3-) ions. This novel process resulted in a uniform deposition of HAp nanocrystals on the nanofibers, overcoming the severe agglomeration of HAp nanoparticles processed by the conventional mechanical blending/electrospinning method. Preliminary in vitro cell study showed that rat calvarial osteoblasts attached more stably on the surface of the HAp/alginate scaffolds than on the pure alginate scaffold. In general, the osteoblasts were stretched and elongated into a spindle-shape on the HAp/alginate scaffolds, whereas the cells had a round-shaped morphology on the alginate scaffold. The unique nanofibrous topography combined with the hybridization of HAp and alginate can be advantageous in bone tissue regenerative medicine applications.

  12. Ornamenting 3D printed scaffolds with cell-laid extracellular matrix for bone tissue regeneration.

    Science.gov (United States)

    Pati, Falguni; Song, Tae-Ha; Rijal, Girdhari; Jang, Jinah; Kim, Sung Won; Cho, Dong-Woo

    2015-01-01

    3D printing technique is the most sophisticated technique to produce scaffolds with tailorable physical properties. But, these scaffolds often suffer from limited biological functionality as they are typically made from synthetic materials. Cell-laid mineralized ECM was shown to be potential for improving the cellular responses and drive osteogenesis of stem cells. Here, we intend to improve the biological functionality of 3D-printed synthetic scaffolds by ornamenting them with cell-laid mineralized extracellular matrix (ECM) that mimics a bony microenvironment. We developed bone graft substitutes by using 3D printed scaffolds made from a composite of polycaprolactone (PCL), poly(lactic-co-glycolic acid) (PLGA), and β-tricalcium phosphate (β-TCP) and mineralized ECM laid by human nasal inferior turbinate tissue-derived mesenchymal stromal cells (hTMSCs). A rotary flask bioreactor was used to culture hTMSCs on the scaffolds to foster formation of mineralized ECM. A freeze/thaw cycle in hypotonic buffer was used to efficiently decellularize (97% DNA reduction) the ECM-ornamented scaffolds while preserving its main organic and inorganic components. The ECM-ornamented 3D printed scaffolds supported osteoblastic differentiation of newly-seeded hTMSCs by upregulating four typical osteoblastic genes (4-fold higher RUNX2; 3-fold higher ALP; 4-fold higher osteocalcin; and 4-fold higher osteopontin) and increasing calcium deposition compared to bare 3D printed scaffolds. In vivo, in ectopic and orthotopic models in rats, ECM-ornamented scaffolds induced greater bone formation than that of bare scaffolds. These results suggest a valuable method to produce ECM-ornamented 3D printed scaffolds as off-the-shelf bone graft substitutes that combine tunable physical properties with physiological presentation of biological signals. Copyright © 2014 Elsevier Ltd. All rights reserved.

  13. Three-dimensional scaffolds of carbonized polyacrylonitrile for bone tissue regeneration.

    Science.gov (United States)

    Ryu, Seungmi; Lee, Choonghyeon; Park, Jooyeon; Lee, Jun Seop; Kang, Seokyung; Seo, Young Deok; Jang, Jyongsik; Kim, Byung-Soo

    2014-08-25

    Carbon-based materials have been extensively studied for stem cell culture. However, difficulties associated with engineering pure carbon materials into 3D scaffolds have hampered applications in tissue engineering and regenerative medicine. Carbonized polyacrylonitrile (cPAN) could be a promising alternative, as cPAN is a highly ordered carbon isomorph that resembles the graphitic structure and can be easily processed into 3D scaffolds. Despite the notable features of cPAN, application of cPAN in tissue engineering and regenerative medicine have not been explored. This study, for the first time, demonstrates the fabrication of microporous 3D scaffolds of cPAN and excellent osteoinductivity of cPAN, suggesting utility of 3D cPAN scaffolds as synthetic bone graft materials. The combination of excellent processability and unique bioactive properties of cPAN may lead to future applications in orthopedic regenerative medicine. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  14. Bone tissue engineering in osteoporosis.

    Science.gov (United States)

    Jakob, Franz; Ebert, Regina; Ignatius, Anita; Matsushita, Takashi; Watanabe, Yoshinobu; Groll, Juergen; Walles, Heike

    2013-06-01

    Osteoporosis is a polygenetic, environmentally modifiable disease, which precipitates into fragility fractures of vertebrae, hip and radius and also confers a high risk of fractures in accidents and trauma. Aging and the genetic molecular background of osteoporosis cause delayed healing and impair regeneration. The worldwide burden of disease is huge and steadily increasing while the average life expectancy is also on the rise. The clinical need for bone regeneration applications, systemic or in situ guided bone regeneration and bone tissue engineering, will increase and become a challenge for health care systems. Apart from in situ guided tissue regeneration classical ex vivo tissue engineering of bone has not yet reached the level of routine clinical application although a wealth of scaffolds and growth factors has been developed. Engineering of complex bone constructs in vitro requires scaffolds, growth and differentiation factors, precursor cells for angiogenesis and osteogenesis and suitable bioreactors in various combinations. The development of applications for ex vivo tissue engineering of bone faces technical challenges concerning rapid vascularization for the survival of constructs in vivo. Recent new ideas and developments in the fields of bone biology, materials science and bioreactor technology will enable us to develop standard operating procedures for ex vivo tissue engineering of bone in the near future. Once prototyped such applications will rapidly be tailored for compromised conditions like vitamin D and sex hormone deficiencies, cellular deficits and high production of regeneration inhibitors, as they are prevalent in osteoporosis and in higher age. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

  15. Bone regeneration potential of stem cells derived from periodontal ligament or gingival tissue sources encapsulated in RGD-modified alginate scaffold.

    Science.gov (United States)

    Moshaverinia, Alireza; Chen, Chider; Xu, Xingtian; Akiyama, Kentaro; Ansari, Sahar; Zadeh, Homayoun H; Shi, Songtao

    2014-02-01

    Mesenchymal stem cells (MSCs) provide an advantageous alternative therapeutic option for bone regeneration in comparison to current treatment modalities. However, delivering MSCs to the defect site while maintaining a high MSC survival rate is still a critical challenge in MSC-mediated bone regeneration. Here, we tested the bone regeneration capacity of periodontal ligament stem cells (PDLSCs) and gingival mesenchymal stem cells (GMSCs) encapsulated in a novel RGD- (arginine-glycine-aspartic acid tripeptide) coupled alginate microencapsulation system in vitro and in vivo. Five-millimeter-diameter critical-size calvarial defects were created in immunocompromised mice and PDLSCs and GMSCs encapsulated in RGD-modified alginate microspheres were transplanted into the defect sites. New bone formation was assessed using microcomputed tomography and histological analyses 8 weeks after transplantation. Results confirmed that our microencapsulation system significantly enhanced MSC viability and osteogenic differentiation in vitro compared with non-RGD-containing alginate hydrogel microspheres with larger diameters. Results confirmed that PDLSCs were able to repair the calvarial defects by promoting the formation of mineralized tissue, while GMSCs showed significantly lower osteogenic differentiation capability. Further, results revealed that RGD-coupled alginate scaffold facilitated the differentiation of oral MSCs toward an osteoblast lineage in vitro and in vivo, as assessed by expression of osteogenic markers Runx2, ALP, and osteocalcin. In conclusion, these results for the first time demonstrated that MSCs derived from orofacial tissue encapsulated in RGD-modified alginate scaffold show promise for craniofacial bone regeneration. This treatment modality has many potential dental and orthopedic applications.

  16. Trophic Effects and Regenerative Potential of Mobilized Mesenchymal Stem Cells From Bone Marrow and Adipose Tissue as Alternative Cell Sources for Pulp/Dentin Regeneration.

    Science.gov (United States)

    Murakami, Masashi; Hayashi, Yuki; Iohara, Koichiro; Osako, Yohei; Hirose, Yujiro; Nakashima, Misako

    2015-01-01

    Dental pulp stem cell (DPSC) subsets mobilized by granulocyte-colony-stimulating factor (G-CSF) are safe and efficacious for complete pulp regeneration. The supply of autologous pulp tissue, however, is very limited in the aged. Therefore, alternative sources of mesenchymal stem/progenitor cells (MSCs) are needed for the cell therapy. In this study, DPSCs, bone marrow (BM), and adipose tissue (AD)-derived stem cells of the same individual dog were isolated using G-CSF-induced mobilization (MDPSCs, MBMSCs, and MADSCs). The positive rates of CXCR4 and G-CSFR in MDPSCs were similar to MADSCs and were significantly higher than those in MBMSCs. Trophic effects of MDPSCs on angiogenesis, neurite extension, migration, and antiapoptosis were higher than those of MBMSCs and MADSCs. Pulp-like loose connective tissues were regenerated in all three MSC transplantations. Significantly higher volume of regenerated pulp and higher density of vascularization and innervation were observed in response to MDPSCs compared to MBMSC and MADSC transplantation. Collagenous matrix containing dentin sialophosphoprotein (DSPP)-positive odontoblast-like cells was the highest in MBMSCs and significantly higher in MADSCs compared to MDPSCs. MBMSCs and MADSCs, therefore, have potential for pulp regeneration, although the volume of regenerated pulp tissue, angiogenesis, and reinnervation, were less. Thus, in conclusion, an alternative cell source for dental pulp/dentin regeneration are stem cells from BM and AD tissue.

  17. Effect of local administration of platelet-rich plasma and guided tissue regeneration on the level of bone resorption in early dental implant insertion

    Directory of Open Access Journals (Sweden)

    Duka Miloš

    2008-01-01

    Full Text Available Background/Aim. Osseointegration is a result of cellular migration, differentiation, bone formation, and bone remodeling on the surface of an implant. Each of these processes depends on platelets and blood coagulum. Platelet-rich plasma (PRP is used to improve osseointegration and stability of implants. The aim of the research was to test the influence that PRP and guided tissue regeneration in bone defects have on bone defect filling and the level of bone resorption in early implant insertion. Methods. This experimental study included 10 dogs. A total of 40 BCT implants were inserted, 4 in each dog (two on the left side and two on the right side, with guided tissue regeneration. Radiologic analyses were done immediately after the insertion and 10 weeks after the insertion. Bone defect filling was measured by a graduated probe 10 weeks after the implant insertion. The following protocols were tested: I - PRP in combination with bovine deproteinized bone (BDB and resorptive membrane of bovine origin (RBDM, II - BDB + RBDM, III - PRP + RBDM and IV - RBDM. Results. The applied protocols affected differently the bone defect filling and the level of bone resorption. Significantly better results (the lowest bone resorption were achieved with protocol I (PRP + BDB + RBDM in comparison with protocols III (PRP + RBDM and IV (RBDM, but not with protocol II (BDB + RBDM. On the other hand, no significant difference was found among protocols II (BDB + RBDM, III (PRP + RBDM and IV (RBDM in the level of bone tissue resorption. Conslusion. The bone defect filling was largest and the level of bone resorption was lowest in the protocol with PRP applied in combination with BDB and RBDM.

  18. Bone regeneration: current concepts and future directions

    Directory of Open Access Journals (Sweden)

    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.

  19. 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.

  20. 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

  1. Clinical comparison of guided tissue regeneration, with collagen membrane and bone graft, versus connective tissue graft in the treatment of gingival recessions

    Directory of Open Access Journals (Sweden)

    Haghighati F

    2006-06-01

    Full Text Available Background and Aim: Increasing patient demands for esthetic, put the root coverage procedures in particular attention. Periodontal regeneration with GTR based root coverage methods is the most common treatment used. The purpose of this study was to compare guided tissue regeneration (GTR with collagen membrane and a bone graft, with sub-epithelial connective tissue graft (SCTG, in treatment of gingival recession. Materials and Methods: In this randomized clinical trial study, eleven healthy patients with no systemic diseases who had miller’s class I or II recession defects (gingival recession  2mm were treated with SCTG or GTR using a collagen membrane and a bone graft. Clinical measurements were obtained at baseline and 6 months after surgery. These clinical measurements included recession depth (RD, recession width (RW, probing depth (PD, and clinical attachment level (CAL. Data were analyzed using independent t test with p<0.05 as the limit of significance. Results: Both treatment methods resulted in a statistically significant reduction of recession depth (SCTG=2.3mm, GTR=2.1mm; P<0.0001. CAL gain after 6 months was also improved in both groups (SCG= 2.5mm, GTR=2.1mm, compared to baseline (P<0.0001. No statistical differences were observed in RD, RW, CAL between test and control groups. Root coverage was similar in both methods (SCTG= 74.2%, GTR= 62.6%, P=0.87. Conclusion: Based on the results of this study, the two techniques are clinically comparable. Therefore the use of collagen membrane and a bovine derived xenograft may alleviate the need for connective tissue graft.

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

    Science.gov (United States)

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

    2016-10-01

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

  3. Synthetic Phage for Tissue Regeneration

    Directory of Open Access Journals (Sweden)

    So Young Yoo

    2014-01-01

    Full Text Available Controlling structural organization and signaling motif display is of great importance to design the functional tissue regenerating materials. Synthetic phage, genetically engineered M13 bacteriophage has been recently introduced as novel tissue regeneration materials to display a high density of cell-signaling peptides on their major coat proteins for tissue regeneration purposes. Structural advantages of their long-rod shape and monodispersity can be taken together to construct nanofibrous scaffolds which support cell proliferation and differentiation as well as direct orientation of their growth in two or three dimensions. This review demonstrated how functional synthetic phage is designed and subsequently utilized for tissue regeneration that offers potential cell therapy.

  4. 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.

  5. 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.

  6. Proliferation and mineralization of bone marrow cells cultured on macroporous hydroxyapatite scaffolds functionalized with collagen type I for bone tissue regeneration.

    Science.gov (United States)

    Teixeira, S; Fernandes, M H; Ferraz, M P; Monteiro, F J

    2010-10-01

    This study concerns the preparation and in vitro characterization of functionalized hydroxyapatite (HA) porous scaffolds, which are intended to be used as drug-delivery systems and bone-regeneration matrices. Hydroxyapatite scaffolds were prepared using the polymer replication method, and, after being submitted to a specific sintering cycle, collagen Type I was incorporated on the surface. After the coating procedure, collagen was crosslinked using the N-(3-dimethylaminopropyl)-N'-ethylcarbodiimide hydrochloride (EDC) and N-hydroxysuccinimide (NHS) conjugation method. In this study, hydroxyapatite scaffolds with uncrosslinked and crosslinked Type I collagen were evaluated. Cell morphology and deposition of extracellular matrix were assessed by scanning electron microscopy, whereas cell distribution was visualized by means of methylene blue staining. MTS and total DNA quantification assays were used to evaluate the viability and proliferation of human bone marrow cells cultured on all the materials for 28 days. Results showed that the cells were able to adhere, proliferate, and form a mineralized matrix on the surface of all the materials. Furthermore, the cells were able to spread from one pore to another and form cell clusters. The results show that these scaffolds are good candidates to serve as drug delivery vehicles and for tissue engineering purposes. Copyright 2010 Wiley Periodicals, Inc. J Biomed Mater Res Part A, 2010.

  7. Genipin-Crosslinked Chitosan Gels and Scaffolds for Tissue Engineering and Regeneration of Cartilage and Bone

    Science.gov (United States)

    Muzzarelli, Riccardo A. A.; El Mehtedi, Mohamad; Bottegoni, Carlo; Aquili, Alberto; Gigante, Antonio

    2015-01-01

    The present review article intends to direct attention to the technological advances made since 2009 in the area of genipin-crosslinked chitosan (GEN-chitosan) hydrogels. After a concise introduction on the well recognized characteristics of medical grade chitosan and food grade genipin, the properties of GEN-chitosan obtained with a safe, spontaneous and irreversible chemical reaction, and the quality assessment of the gels are reviewed. The antibacterial activity of GEN-chitosan has been well assessed in the treatment of gastric infections supported by Helicobacter pylori. Therapies based on chitosan alginate crosslinked with genipin include stem cell transplantation, and development of contraction free biomaterials suitable for cartilage engineering. Collagen, gelatin and other proteins have been associated to said hydrogels in view of the regeneration of the cartilage. Viability and proliferation of fibroblasts were impressively enhanced upon addition of poly-l-lysine. The modulation of the osteocytes has been achieved in various ways by applying advanced technologies such as 3D-plotting and electrospinning of biomimetic scaffolds, with optional addition of nano hydroxyapatite to the formulations. A wealth of biotechnological advances and know-how has permitted reaching outstanding results in crucial areas such as cranio-facial surgery, orthopedics and dentistry. It is mandatory to use scaffolds fully characterized in terms of porosity, pore size, swelling, wettability, compressive strength, and degree of acetylation, if the osteogenic differentiation of human mesenchymal stem cells is sought: in fact, the novel characteristics imparted by GEN-chitosan must be simultaneously of physico-chemical and cytological nature. Owing to their high standard, the scientific publications dated 2010–2015 have met the expectations of an interdisciplinary audience. PMID:26690453

  8. Assessment of Methods for Rapid Intraoperative Concentration and Selection of Marrow-Derived Connective Tissue Progenitors for Bone Regeneration Using the Canine Femoral Multidefect Model

    Science.gov (United States)

    Luangphakdy, Viviane; Boehm, Cynthia; Pan, Hui; Herrick, James; Zaveri, Phil

    2016-01-01

    Treatment of large bone defects remains an unsolved clinical challenge, despite a wide array of existing bone graft materials and strategies. Local deficiency in osteogenic connective tissue progenitors (CTP-Os) due to tissue loss is one of the central biological barriers to bone regeneration. Density separation (DS) and selective retention (SR) represent two promising methods that can be used intraoperatively to rapidly concentrate cells and potentially select CTP-Os. This project was designed to compare DS and SR using the canine femoral multidefect (CFMD) model. Mineralized cancellous allograft (MCA) was used as a standardized scaffold for cell transplantation. Two experiments were performed using a cohort of six animals in each comparison. In Cohort I, unprocessed bone marrow aspirate (BMA) clot was compared to DS processing. MCA combined with raw BMA or DS processed cells produced a robust and advanced stage of bone regeneration throughout the defect in 4 weeks with reconstitution of hematopoietic marrow. However, the retention of DS processed cells and CTP-Os in the MCA matrix was low compared to BMA clot. In Cohort II, MCA with DS-T cells (addition of calcium chloride thrombin to induce clotting and enhance cell and CTP-O retention) was compared to MCA with SR cells. A mean of 276 ± 86 million nucleated cells and 29,030 ± 10,510 CTP-Os were implanted per defect in the DS-T group. A mean of 76 ± 42 million nucleated cells and 30,266 ± 15,850 CTP-Os were implanted in the SR group. Bone formation was robust and not different between treatments. Histologically, both groups demonstrated regeneration of hematopoietic marrow tissue. However, SR sites contained more hematopoietic vascular tissues, less fibrosis, and less residual allograft, particularly in the intramedullary cavity, suggesting a more advanced stage of remodeling (p = 0.04). These data demonstrate excellent overall performance of DS and SR processing methods. Both methods

  9. Novel cerium doped glass-reinforced hydroxyapatite with antibacterial and osteoconductive properties for bone tissue regeneration

    International Nuclear Information System (INIS)

    Morais, D S; Fernandes, S; Santos, J D; Lopes, M A; Gomes, P S; Fernandes, M H; Sampaio, P; Ferraz, M P; Sooraj Hussain, N

    2015-01-01

    The aim of this work was to develop a bioactive bone substitute with an effective antibacterial ability based on a cerium (Ce) doped glass-reinforced hydroxyapatite (GR-HA) composite. Developed composites were physicochemically characterized, using x-ray diffraction (XRD) analysis, SEM, energy dispersive x-ray spectroscopy (EDS), and flexural bending strength (FBS) tests. X-ray photoelectron spectroscopy (XPS) analysis was performed to analyze the oxidation state of Ce in the prepared doped glass. The antimicrobial activity of the composites was evaluated against Staphylococcus aureus, Staphylococcus epidermidis and Pseudomonas aeruginosa; whether the cytocompatibility profile was assayed with human osteoblastic-like cells (Mg-63 cell line). The results revealed that the Ce inclusion in the GR-HA matrix induced the antimicrobial ability of the composite. In addition, Ce-doped materials reported an adequate biological behavior following seeding of osteoblastic populations, by inducing cell adhesion and proliferation. Developed materials were also found to enhance the expression of osteoblastic-related genes. Overall, the developed GR-HA-Ce composite is a prospective candidate to be used within the clinical scenario with a successful performance due to the effective antibacterial properties and capability of enhancing the osteoblastic cell response. (paper)

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

    Directory of Open Access Journals (Sweden)

    Jan Gessmann

    2012-03-01

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

  11. Longitudinal in vivo evaluation of bone regeneration by combined measurement of multi-pinhole SPECT and micro-CT for tissue engineering

    Science.gov (United States)

    Lienemann, Philipp S.; Metzger, Stéphanie; Kiveliö, Anna-Sofia; Blanc, Alain; Papageorgiou, Panagiota; Astolfo, Alberto; Pinzer, Bernd R.; Cinelli, Paolo; Weber, Franz E.; Schibli, Roger; Béhé, Martin; Ehrbar, Martin

    2015-05-01

    Over the last decades, great strides were made in the development of novel implants for the treatment of bone defects. The increasing versatility and complexity of these implant designs request for concurrent advances in means to assess in vivo the course of induced bone formation in preclinical models. Since its discovery, micro-computed tomography (micro-CT) has excelled as powerful high-resolution technique for non-invasive assessment of newly formed bone tissue. However, micro-CT fails to provide spatiotemporal information on biological processes ongoing during bone regeneration. Conversely, due to the versatile applicability and cost-effectiveness, single photon emission computed tomography (SPECT) would be an ideal technique for assessing such biological processes with high sensitivity and for nuclear imaging comparably high resolution (bone morphogenetic protein to guide the healing of critical sized calvarial bone defects. By combined in vivo longitudinal multi-pinhole SPECT and micro-CT evaluations we determine the spatiotemporal course of bone formation and remodeling within this synthetic hydrogel implant. End point evaluations by high resolution micro-CT and histological evaluation confirm the value of this approach to follow and optimize bone-inducing biomaterials.

  12. Piezoelectric materials for tissue regeneration: A review.

    Science.gov (United States)

    Rajabi, Amir Hossein; Jaffe, Michael; Arinzeh, Treena Livingston

    2015-09-01

    The discovery of piezoelectricity, endogenous electric fields and transmembrane potentials in biological tissues raised the question whether or not electric fields play an important role in cell function. It has kindled research and the development of technologies in emulating biological electricity for tissue regeneration. Promising effects of electrical stimulation on cell growth and differentiation and tissue growth has led to interest in using piezoelectric scaffolds for tissue repair. Piezoelectric materials can generate electrical activity when deformed. Hence, an external source to apply electrical stimulation or implantation of electrodes is not needed. Various piezoelectric materials have been employed for different tissue repair applications, particularly in bone repair, where charges induced by mechanical stress can enhance bone formation; and in neural tissue engineering, in which electric pulses can stimulate neurite directional outgrowth to fill gaps in nervous tissue injuries. In this review, a summary of piezoelectricity in different biological tissues, mechanisms through which electrical stimulation may affect cellular response, and recent advances in the fabrication and application of piezoelectric scaffolds will be discussed. The discovery of piezoelectricity, endogenous electric fields and transmembrane potentials in biological tissues has kindled research and the development of technologies using electrical stimulation for tissue regeneration. Piezoelectric materials generate electrical activity in response to deformations and allow for the delivery of an electrical stimulus without the need for an external power source. As a scaffold for tissue engineering, growing interest exists due to its potential of providing electrical stimulation to cells to promote tissue formation. In this review, we cover the discovery of piezoelectricity in biological tissues, its connection to streaming potentials, biological response to electrical stimulation and

  13. Regenerating articular tissue by converging technologies.

    Science.gov (United States)

    Moroni, Lorenzo; Hamann, Doreen; Paoluzzi, Luca; Pieper, Jeroen; de Wijn, Joost R; van Blitterswijk, Clemens A

    2008-08-21

    Scaffolds for osteochondral tissue engineering should provide mechanical stability, while offering specific signals for chondral and bone regeneration with a completely interconnected porous network for cell migration, attachment, and proliferation. Composites of polymers and ceramics are often considered to satisfy these requirements. As such methods largely rely on interfacial bonding between the ceramic and polymer phase, they may often compromise the use of the interface as an instrument to direct cell fate. Alternatively, here, we have designed hybrid 3D scaffolds using a novel concept based on biomaterial assembly, thereby omitting the drawbacks of interfacial bonding. Rapid prototyped ceramic particles were integrated into the pores of polymeric 3D fiber-deposited (3DF) matrices and infused with demineralized bone matrix (DBM) to obtain constructs that display the mechanical robustness of ceramics and the flexibility of polymers, mimicking bone tissue properties. Ostechondral scaffolds were then fabricated by directly depositing a 3DF structure optimized for cartilage regeneration adjacent to the bone scaffold. Stem cell seeded scaffolds regenerated both cartilage and bone in vivo.

  14. Regenerating articular tissue by converging technologies.

    Directory of Open Access Journals (Sweden)

    Lorenzo Moroni

    Full Text Available Scaffolds for osteochondral tissue engineering should provide mechanical stability, while offering specific signals for chondral and bone regeneration with a completely interconnected porous network for cell migration, attachment, and proliferation. Composites of polymers and ceramics are often considered to satisfy these requirements. As such methods largely rely on interfacial bonding between the ceramic and polymer phase, they may often compromise the use of the interface as an instrument to direct cell fate. Alternatively, here, we have designed hybrid 3D scaffolds using a novel concept based on biomaterial assembly, thereby omitting the drawbacks of interfacial bonding. Rapid prototyped ceramic particles were integrated into the pores of polymeric 3D fiber-deposited (3DF matrices and infused with demineralized bone matrix (DBM to obtain constructs that display the mechanical robustness of ceramics and the flexibility of polymers, mimicking bone tissue properties. Ostechondral scaffolds were then fabricated by directly depositing a 3DF structure optimized for cartilage regeneration adjacent to the bone scaffold. Stem cell seeded scaffolds regenerated both cartilage and bone in vivo.

  15. How Can Nanotechnology Help to Repair the Body? Advances in Cardiac, Skin, Bone, Cartilage and Nerve Tissue Regeneration

    Directory of Open Access Journals (Sweden)

    Juan Antonio Marchal

    2013-03-01

    Full Text Available Nanotechnologists have become involved in regenerative medicine via creation of biomaterials and nanostructures with potential clinical implications. Their aim is to develop systems that can mimic, reinforce or even create in vivo tissue repair strategies. In fact, in the last decade, important advances in the field of tissue engineering, cell therapy and cell delivery have already been achieved. In this review, we will delve into the latest research advances and discuss whether cell and/or tissue repair devices are a possibility. Focusing on the application of nanotechnology in tissue engineering research, this review highlights recent advances in the application of nano-engineered scaffolds designed to replace or restore the followed tissues: (i skin; (ii cartilage; (iii bone; (iv nerve; and (v cardiac.

  16. Mechanical device for tissue regeneration

    NARCIS (Netherlands)

    Herder, J.L.; Maij, E.

    2010-01-01

    The invention relates to a mechanical device for tissue- regeneration inside a patient, comprising means (2, 3) to place a scaffold for the tissue under mechanical stress. Said means comprise a first device-part (2) and a second device-part (3) which parts are arranged to be movable with respect to

  17. Aesthetic Surgical Approach for Bone Dehiscence Treatment by Means of Single Implant and Interdental Tissue Regeneration: A Case Report with Five Years of Follow-Up

    Directory of Open Access Journals (Sweden)

    Giorgio Lombardo

    2016-01-01

    Full Text Available The replacement of single anterior teeth by means of endosseous implants implies the achievement of success in restoring both aesthetic and function. However, the presence of wide endoperiodontal lesions can lead to horizontal hard and soft tissues defects after tooth extraction, making it impossible to correctly place an implant in the compromised alveolar socket. Vertical augmentation procedures have been proposed to solve these clinical situations, but the amount of new regenerated bone is still not predictable. Furthermore, bone augmentation can be complicated by the presence of adjacent teeth, especially if they bring with them periodontal defects. Therefore, it is used to restore periodontal health of adjacent teeth before making any augmentation procedures and to wait a certain healing period before placing an implant in vertically augmented sites, otherwise risking to obtain a nonsatisfactory aesthetic result. All of these procedures, however, lead to an expansion of treatment time which should affect patient compliance. For this reason, this case report suggests a surgical technique to perform vertical bone augmentation at a single gap left by a central upper incisor while placing an implant and simultaneously to regenerate the periodontal attachment of an adjacent lateral incisor, without compromising the aesthetic result.

  18. Aesthetic Surgical Approach for Bone Dehiscence Treatment by Means of Single Implant and Interdental Tissue Regeneration: A Case Report with Five Years of Follow-Up

    Science.gov (United States)

    Lombardo, Giorgio; Pighi, Jacopo; Corrocher, Giovanni; Mascellaro, Anna; Lehrberg, Jeffrey; Marincola, Mauro; Nocini, Pier Francesco

    2016-01-01

    The replacement of single anterior teeth by means of endosseous implants implies the achievement of success in restoring both aesthetic and function. However, the presence of wide endoperiodontal lesions can lead to horizontal hard and soft tissues defects after tooth extraction, making it impossible to correctly place an implant in the compromised alveolar socket. Vertical augmentation procedures have been proposed to solve these clinical situations, but the amount of new regenerated bone is still not predictable. Furthermore, bone augmentation can be complicated by the presence of adjacent teeth, especially if they bring with them periodontal defects. Therefore, it is used to restore periodontal health of adjacent teeth before making any augmentation procedures and to wait a certain healing period before placing an implant in vertically augmented sites, otherwise risking to obtain a nonsatisfactory aesthetic result. All of these procedures, however, lead to an expansion of treatment time which should affect patient compliance. For this reason, this case report suggests a surgical technique to perform vertical bone augmentation at a single gap left by a central upper incisor while placing an implant and simultaneously to regenerate the periodontal attachment of an adjacent lateral incisor, without compromising the aesthetic result. PMID:27119031

  19. Regeneration of human bones in hip osteonecrosis and human cartilage in knee osteoarthritis with autologous adipose-tissue-derived stem cells: a case series

    Directory of Open Access Journals (Sweden)

    Pak Jaewoo

    2011-07-01

    Full Text Available Abstract Introduction This is a series of clinical case reports demonstrating that a combination of percutaneously injected autologous adipose-tissue-derived stem cells, hyaluronic acid, platelet rich plasma and calcium chloride may be able to regenerate bones in human osteonecrosis, and with addition of a very low dose of dexamethasone, cartilage in human knee osteoarthritis. Case reports Stem cells were obtained from adipose tissue of abdominal origin by digesting lipoaspirate tissue with collagenase. These stem cells, along with hyaluronic acid, platelet rich plasma and calcium chloride, were injected into the right hip of a 29-year-old Korean woman and a 47-year-old Korean man. They both had a history of right hip osteonecrosis of the femoral head. For cartilage regeneration, a 70-year-old Korean woman and a 79-year-old Korean woman, both with a long history of knee pain due to osteoarthritis, were injected with stem cells along with hyaluronic acid, platelet rich plasma, calcium chloride and a nanogram dose of dexamethasone. Pre-treatment and post-treatment MRI scans, physical therapy, and pain score data were then analyzed. Conclusions The MRI data for all the patients in this series showed significant positive changes. Probable bone formation was clear in the patients with osteonecrosis, and cartilage regeneration in the patients with osteoarthritis. Along with MRI evidence, the measured physical therapy outcomes, subjective pain, and functional status all improved. Autologous mesenchymal stem cell injection, in conjunction with hyaluronic acid, platelet rich plasma and calcium chloride, is a promising minimally invasive therapy for osteonecrosis of femoral head and, with low-dose dexamethasone, for osteoarthritis of human knees.

  20. Mechanisms of Guided Bone Regeneration: A Review

    Science.gov (United States)

    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

  1. 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.

  2. Tissue Engineering Strategies in Ligament Regeneration

    Directory of Open Access Journals (Sweden)

    Caglar Yilgor

    2012-01-01

    Full Text Available Ligaments are dense fibrous connective tissues that connect bones to other bones and their injuries are frequently encountered in the clinic. The current clinical approaches in ligament repair and regeneration are limited to autografts, as the gold standard, and allografts. Both of these techniques have their own drawbacks that limit the success in clinical setting; therefore, new strategies are being developed in order to be able to solve the current problems of ligament grafting. Tissue engineering is a novel promising technique that aims to solve these problems, by producing viable artificial ligament substitutes in the laboratory conditions with the potential of transplantation to the patients with a high success rate. Direct cell and/or growth factor injection to the defect site is another current approach aiming to enhance the repair process of the native tissue. This review summarizes the current approaches in ligament tissue engineering strategies including the use of scaffolds, their modification techniques, as well as the use of bioreactors to achieve enhanced regeneration rates, while also discussing the advances in growth factor and cell therapy applications towards obtaining enhanced ligament regeneration.

  3. Fabrication and characterization of polycaprolactone cross- linked and highly-aligned 3-D artificial scaffolds for bone tissue regeneration via electrospinning technology

    Science.gov (United States)

    Gorodzha, S. N.; Surmeneva, M. A.; Surmenev, R. A.

    2015-11-01

    Novel technologies allowed the scientific community to develop scaffolds for regeneration of bone tissue. A successful scaffold should possess specific macroscopic geometry and internal architecture to perform biological and biophysical functions. In this study the process of polycaprolactone microfibrous development with either cross-linked or highly-aligned three-dimensional artificial mats via electrospinning technology for potential application in tissue engineering is described. The morphology and size of electrospun fibers were assessed systematically by varying the rotation speed of grounded collector. It was found that the diameter of the fibers decreased by increasing the rotation speed of collector. The morphology of the fibers changed from cross-linked to highly-aligned at appr. 1000-1100 rpm.

  4. 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.

  5. 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.

  6. Synthetic bone substitute material comparable with xenogeneic material for bone tissue regeneration in oral cancer patients: First and preliminary histological, histomorphometrical and clinical results.

    Science.gov (United States)

    Ghanaati, Shahram; Barbeck, Mike; Lorenz, Jonas; Stuebinger, Stefan; Seitz, Oliver; Landes, Constantin; Kovács, Adorján F; Kirkpatrick, Charles J; Sader, Robert A

    2013-07-01

    The present study was first to evaluate the material-specific cellular tissue response of patients with head and neck cancer to a nanocrystalline hydroxyapatite bone substitute NanoBone (NB) in comparison with a deproteinized bovine bone matrix Bio-Oss (BO) after implantation into the sinus cavity. Eight patients with tumor resection for oral cancer and severely resorbed maxillary bone received materials according to a split mouth design for 6 months. Bone cores were harvested prior to implantation and analyzed histologically and histomorphometrically. Implant survival was followed-up to 2 years after placement. Histologically, NB underwent a higher vascularization and induced significantly more tartrate-resistant acid phosphatase-positive (TRAP-positive) multinucleated giant cells when compared with BO, which induced mainly mononuclear cells. No significant difference was observed in the extent of new bone formation between both groups. The clinical follow-up showed undisturbed healing of all implants in the BO-group, whereas the loss of one implant was observed in the NB-group. Within its limits, the present study showed for the first time that both material classes evaluated, despite their induction of different cellular tissue reactions, may be useful as augmentation materials for dental and maxillofacial surgical applications, particularly in patients who previously had oral cancer.

  7. Formulation and in vitro and in vivo evaluation of a new osteoprotegerin-chitosan gel for bone tissue regeneration.

    Science.gov (United States)

    Jayash, Soher Nagi; Hashim, Najihah Mohd; Misran, Misni; Baharuddin, N A

    2017-02-01

    The osteoprotegerin (OPG) system plays a critical role in bone remodelling by regulating osteoclast formation and activity. The study aimed to determine the physicochemical properties and biocompatibility of a newly formulated OPG-chitosan gel. The OPG-chitosan gel was formulated using human OPG protein and water-soluble chitosan. The physicochemical properties were determined using Fourier transform infrared (FTIR) spectroscopy, thermogravimetric analysis (TGA) and differential scanning calorimetry (DSC). Gel morphology was determined using scanning electron microscopy (SEM) and then it was subjected to a protein release assay and biodegradability test. An in vitro cytotoxicity test on normal human periodontal ligament (NHPL) fibroblasts and normal human (NH) osteoblasts was carried out using the AlamarBlue assay. In vivo evaluation in a rabbit model involved creating critical-sized defects in calvarial bone, filling with the OPG-chitosan gel and sacrificing at 12 weeks. In vitro results demonstrated that the 25 kDa OPG-chitosan gel had the highest rate of protein release and achieved 90% degradation in 28 days. At 12 weeks, the defects filled with 25 kDa OPG-chitosan gel showed significant (p < 0.05) new bone formation and the highest expression of osteocalcin and osteopontin compared to controls. Thus, the 25 kDa OPG-chitosan gel could be a promising new biomaterial for tissue engineering. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 105A: 398-407, 2017. © 2016 Wiley Periodicals, Inc.

  8. Fabrication and in vivo evaluation of an osteoblast-conditioned nano-hydroxyapatite/gelatin composite scaffold for bone tissue regeneration.

    Science.gov (United States)

    Samadikuchaksaraei, Ali; Gholipourmalekabadi, Mazaher; Erfani Ezadyar, Elham; Azami, Mahmoud; Mozafari, Masoud; Johari, Behrooz; Kargozar, Saeid; Jameie, Seyed Behnamedin; Korourian, Alireza; Seifalian, Alexander M

    2016-08-01

    In this study, the effects of osteoblast-conditioning on mechanical behavior, biocompatibility, biodegradation and osteoinductive properties of a nano-hydroxyapatite/gelatin (HA/GEL) nanocomposite scaffold was investigated. The scaffold was fabricated using the layer solvent casting combined with the freeze-drying and lamination techniques. The scaffolds were conditioned by culture of osteoblasts on their surface and their elimination by a repeated freeze-thawing process. The potential of the osteoblast-conditioned HA/GEL (HA/GEL/OC) scaffold to support cell adhesion and growth and its cytotoxicity was assessed in vitro using rat mesenchymal stem cells. For in vivo studies, the HA/GEL/OC nanocomposite was implanted in the critical size bone defect created on rat calvarium and studied after 7, 30 and 90 days. The results showed that mechanical and in vitro biological properties of the scaffold were not affected by the process of conditioning. However, in vivo studies demonstrated that osteoblast-conditioning enhanced biocompatibility and osteoinductivity and of the nanocomposite scaffold. The osteoblast conditioning also accelerated collagen content during the bone healing. In the experimental group that received the HA/GEL/OC and MSCs, the newly formed bone occupied almost the entire defect (93.4 ± 3.3%) within 3 months. In conclusion, this study indicates that osteoblast-conditioning is a viable strategy for the development of bone tissue engineering scaffolds. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 104A: 2001-2010, 2016. © 2016 Wiley Periodicals, Inc.

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

    Science.gov (United States)

    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.

  10. Bone regeneration in 3D printing bioactive ceramic scaffolds with improved tissue/material interface pore architecture in thin-wall bone defect.

    Science.gov (United States)

    Shao, Huifeng; Ke, Xiurong; Liu, An; Sun, Miao; He, Yong; Yang, Xianyan; Fu, Jianzhong; Liu, Yanming; Zhang, Lei; Yang, Guojing; Xu, Sanzhong; Gou, Zhongru

    2017-04-12

    Three-dimensional (3D) printing bioactive ceramics have demonstrated alternative approaches to bone tissue repair, but an optimized materials system for improving the recruitment of host osteogenic cells into the bone defect and enhancing targeted repair of the thin-wall craniomaxillofacial defects remains elusive. Herein we systematically evaluated the role of side-wall pore architecture in the direct-ink-writing bioceramic scaffolds on mechanical properties and osteogenic capacity in rabbit calvarial defects. The pure calcium silicate (CSi) and dilute Mg-doped CSi (CSi-Mg6) scaffolds with different layer thickness and macropore sizes were prepared by varying the layer deposition mode from single-layer printing (SLP) to double-layer printing (DLP) and then by undergoing one-, or two-step sintering. It was found that the dilute Mg doping and/or two-step sintering schedule was especially beneficial for improving the compressive strength (∼25-104 MPa) and flexural strength (∼6-18 MPa) of the Ca-silicate scaffolds. The histological analysis for the calvarial bone specimens in vivo revealed that the SLP scaffolds had a high osteoconduction at the early stage (4 weeks) but the DLP scaffolds displayed a higher osteogenic capacity for a long time stage (8-12 weeks). Although the DLP CSi scaffolds displayed somewhat higher osteogenic capacity at 8 and 12 weeks, the DLP CSi-Mg6 scaffolds with excellent fracture resistance also showed appreciable new bone tissue ingrowth. These findings demonstrate that the side-wall pore architecture in 3D printed bioceramic scaffolds is required to optimize for bone repair in calvarial bone defects, and especially the Mg doping wollastontie is promising for 3D printing thin-wall porous scaffolds for craniomaxillofacial bone defect treatment.

  11. Bone regeneration using the freshly isolated autologous stromal vascular fraction of adipose tissue in combination with calcium phosphate ceramics

    NARCIS (Netherlands)

    Prins, H.J.; Schulten, E.A.J.M.; ten Bruggenkate, C.M.; Klein-Nulend, J.; Helder, M.N.

    2016-01-01

    In patients undergoing maxillary sinus floor elevation (MSFE) for dental implant placement, bone substitutes are currently evaluated as alternatives for autologous bone. However, bone substitutes have only osteoconductive properties and lack osteoinductive potential. Therefore, this phase I study

  12. Tissue type plasminogen activator regulates myeloid-cell dependent neoangiogenesis during tissue regeneration

    DEFF Research Database (Denmark)

    Ohki, Makiko; Ohki, Yuichi; Ishihara, Makoto

    2010-01-01

    tissue regeneration is not well understood. Bone marrow (BM)-derived myeloid cells facilitate angiogenesis during tissue regeneration. Here, we report that a serpin-resistant form of tPA by activating the extracellular proteases matrix metalloproteinase-9 and plasmin expands the myeloid cell pool...

  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. Reduction and shaping of graphene-oxide by laser-printing for controlled bone tissue regeneration and bacterial killing

    Science.gov (United States)

    Palmieri, Valentina; Barba, Marta; Di Pietro, Lorena; Gentilini, Silvia; Chiara Braidotti, Maria; Ciancico, Carlotta; Bugli, Francesca; Ciasca, Gabriele; Larciprete, Rosanna; Lattanzi, Wanda; Sanguinetti, Maurizio; De Spirito, Marco; Conti, Claudio; Papi, Massimiliano

    2018-01-01

    Graphene and graphene oxide (GO) are capable of inducing stem cells differentiation into bone tissue with variable efficacy depending on reductive state of the material. Thus, modulation of osteogenic process and of bone mineral density distribution is theoretically possible by controlling the GO oxidative state. In this study, we laser-printed GO surfaces in order to obtain both a local photo-thermal GO reduction and the formation of nano-wrinkles along precise geometric pattern. Initially, after cells adhered on the surface, stem cells migrated and accumulated on the reduced and wrinkled surface. When the local density of the stem cells on the reduced stripes was high, cells started to proliferate and occupy the oxidized/flat area. The designed surfaces morphology guided stem cell orientation and the reduction accelerated differentiation. Furthermore the reduced sharp nano-wrinkles were able to enhance the GO antibacterial activity against methicillin-resistant Staphylococcus aureus (MRSA), a common cause of prosthetic joints infections. This strategy can offer a revolution in present and future trends of scaffolds design for regenerative medicine.

  15. Clinical and Radiographic Assessment of Peri-Implant Tissue in Posterior Areas with and Without the Need for Guided Bone Regeneration

    Directory of Open Access Journals (Sweden)

    Seyed Reza Arabi

    2016-07-01

    Full Text Available Background Dental implants are increasingly used in resorbed alveolar ridges, and the success of implants inserted concomitantly with guided bone regeneration (GBR needs to be evaluated. Objectives This study aimed to clinically and radiographically assess the peri-implant tissues in the posterior maxilla and mandible in cases in which dehiscence or fenestration occurred at the time of implant surgery and treated with GBR (simultaneously with implant placement in one session. A comparison was also made between the above-mentioned patients and controls in which implants were placed in intact bone (entire length of implant in bone. Patients and Methods This study was conducted on 12 patients as cases who received 17 standard implants (dehiscence or fenestration occurred after placement of 4 mm diameter standard implants and GBR was performed and 10 patients as the control group (those who received 17 standard implants, 4 mm in diameter and 10 mm in length, in adequate bone. Periapical (PA radiographs were obtained in the first 24 hours post-surgery. Radiographs were repeated at one month, at the time of loading (two months post-surgery, and at three and six months after loading to assess marginal bone loss. To assess the peri-implant soft tissue, thickness and width of the keratinized gingiva were evaluated. Data were analyzed using t-test and repeated measures analysis of variance. The level of significance was set to P = 0.05. Results The difference in distance from the bone crest to the implant shoulder between the two groups of cases and controls was significant at the following time points: baseline and 2 months post-surgery (P = 0.000, baseline and 6 months after loading (P = 0.01, 2 months post-surgery and 3 months after loading (P = 0.00, and 2 months post-surgery and 6 months after loading (P = 0.00. Changes in the width of the keratinized gingiva were not significant in the two groups of cases and controls at 2 months post-surgery (P = 0

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

    Science.gov (United States)

    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.

  17. 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.

  18. Human DPSCs fabricate vascularized woven bone tissue: A new tool in bone tissue engineering

    Czech Academy of Sciences Publication Activity Database

    Paino, F.; Noce, M.L.; Giuliani, A.; de Rosa, A.; Mazzoni, F.; Laino, L.; Amler, Evžen; Papaccio, G.; Desiderio, V.; Tirino, V.

    2017-01-01

    Roč. 131, č. 8 (2017), s. 699-713 ISSN 0143-5221 Institutional support: RVO:68378041 Keywords : bone differentiation * bone regeneration * bone tissue engineering Subject RIV: FP - Other Medical Disciplines OBOR OECD: Orthopaedics Impact factor: 4.936, year: 2016

  19. Multifunctional bioactive glass and glass-ceramic biomaterials with antibacterial properties for repair and regeneration of bone tissue.

    Science.gov (United States)

    Fernandes, João S; Gentile, Piergiorgio; Pires, Ricardo A; Reis, Rui L; Hatton, Paul V

    2017-09-01

    Bioactive glasses (BGs) and related glass-ceramic biomaterials have been used in bone tissue repair for over 30years. Previous work in this field was comprehensively reviewed including by their inventor Larry Hench, and the key features and properties of BGs are well understood. More recently, attention has focused on their modification to further enhance the osteogenic behaviour, or further compositional changes that may introduce additional properties, such as antimicrobial activity. Evidence is emerging that BGs and related glass-ceramics may be modified in such a way as to simultaneously introduce more than one desirable property. The aim of this review is therefore to consider the evidence that these more recent inorganic modifications to glass and glass-ceramic biomaterials are effective, and whether or not these new compositions represent sufficiently versatile systems to underpin the development of a new generation of truly multifunctional biomaterials to address pressing clinical needs in orthopaedic and dental surgery. Indeed, a number of classical glass compositions exhibited antimicrobial activity, however the structural design and the addition of specific ions, i.e. Ag + , Cu + , and Sr 2+ , are able to impart a multifunctional character to these systems, through the combination of, for example, bioactivity with bactericidal activity. In this review we demonstrate the multifunctional potential of bioactive glasses and related glass-ceramics as biomaterials for orthopaedic and craniofacial/dental applications. Therefore, it considers the evidence that the more recent inorganic modifications to glass and glass-ceramic biomaterials are able to impart antimicrobial properties alongside the more classical bone bonding and osteoconduction. These properties are attracting a special attention nowadays that bacterial infections are an increasing challenge in orthopaedics. We also focus the manuscript on the versatility of these systems as a basis to underpin

  20. Bone Tissue Engineering: Recent Advances and Challenges

    Science.gov (United States)

    Amini, Ami R.; Laurencin, Cato T.; Nukavarapu, Syam P.

    2013-01-01

    The worldwide incidence of bone disorders and conditions has trended steeply upward and is expected to double by 2020, especially in populations where aging is coupled with increased obesity and poor physical activity. Engineered bone tissue has been viewed as a potential alternative to the conventional use of bone grafts, due to their limitless supply and no disease transmission. However, bone tissue engineering practices have not proceeded to clinical practice due to several limitations or challenges. Bone tissue engineering aims to induce new functional bone regeneration via the synergistic combination of biomaterials, cells, and factor therapy. In this review, we discuss the fundamentals of bone tissue engineering, highlighting the current state of this field. Further, we review the recent advances of biomaterial and cell-based research, as well as approaches used to enhance bone regeneration. Specifically, we discuss widely investigated biomaterial scaffolds, micro- and nano-structural properties of these scaffolds, and the incorporation of biomimetic properties and/or growth factors. In addition, we examine various cellular approaches, including the use of mesenchymal stem cells (MSCs), embryonic stem cells (ESCs), adult stem cells, induced pluripotent stem cells (iPSCs), and platelet-rich plasma (PRP), and their clinical application strengths and limitations. We conclude by overviewing the challenges that face the bone tissue engineering field, such as the lack of sufficient vascularization at the defect site, and the research aimed at functional bone tissue engineering. These challenges will drive future research in the field. PMID:23339648

  1. The use of beta-tricalcium phosphate and bovine bone matrix in the guided tissue regeneration treatment of deep infra-bony defects

    Directory of Open Access Journals (Sweden)

    Luković Natalija

    2009-01-01

    Full Text Available Introduction. The primary goal of bone regeneration procedures with application of various regenerative biologic agents and biomaterials is to facilitate the formation of periodontal tissues lost as a result of periodontitis. Objective. The aim of the study was to compare clinical outcome of the guided tissue regeneration (GTR treatment with the use of β-tricalcium phosphate and with bovine bone matrix in human deep intra-osseous defects. Methods. Twenty-one systemically healthy subjects with moderate to advanced periodontitis, between 30 and 56 years of age, 11 females and 10 males, were selected. Patients having two similar inter-proximal defects with pocket probing depths following initial therapy greater than 5 mm were recruited for the study. Experimental sites were grafted with pure β-tricalcium phosphate biomaterial (Cerasorb® and a biomembrane, while control sites were treated with bovine-bone hydroxiapatite xenograft (Bio-oss® and a biomembrane. Immediately before surgery and 12 months after surgery, pocket probing depth (PPD, epithelial attachment level (EAL and gingival recession (GR were evaluated. Results. In the experimental group PPD amounted to 6.76±0.83 mm before surgery, and decreased significantly to 2.67±0.48 mm 12 months following surgery, while in the control group PPD significantly decreased from 7.14±0.65 mm presurgically to 2.85±0.57 mm postsurgically. After one year, EAL gain was 2.76±0.99 mm in the experimental group, and 3.24±0.16 mm in the control group. After twelve months postoperatively GR amounted to 1.33±0.79 mm in the experimental group and to 1.05±0.80 mm in the control group. No statistically significant differences for PPD reduction, EAL gain and GR increase were detected between the groups. Conclusion. Results from the present study indicate that GTR treatment of deep intra-osseous defects with Bio-oss® and Cerasorb® resulted in clinically and statistically significant improvement of EAL gain

  2. Nanotechnology in bone tissue engineering.

    Science.gov (United States)

    Walmsley, Graham G; McArdle, Adrian; Tevlin, Ruth; Momeni, Arash; Atashroo, David; Hu, Michael S; Feroze, Abdullah H; Wong, Victor W; Lorenz, Peter H; Longaker, Michael T; Wan, Derrick C

    2015-07-01

    Nanotechnology represents a major frontier with potential to significantly advance the field of bone tissue engineering. Current limitations in regenerative strategies include impaired cellular proliferation and differentiation, insufficient mechanical strength of scaffolds, and inadequate production of extrinsic factors necessary for efficient osteogenesis. Here we review several major areas of research in nanotechnology with potential implications in bone regeneration: 1) nanoparticle-based methods for delivery of bioactive molecules, growth factors, and genetic material, 2) nanoparticle-mediated cell labeling and targeting, and 3) nano-based scaffold construction and modification to enhance physicochemical interactions, biocompatibility, mechanical stability, and cellular attachment/survival. As these technologies continue to evolve, ultimate translation to the clinical environment may allow for improved therapeutic outcomes in patients with large bone deficits and osteodegenerative diseases. Traditionally, the reconstruction of bony defects has relied on the use of bone grafts. With advances in nanotechnology, there has been significant development of synthetic biomaterials. In this article, the authors provided a comprehensive review on current research in nanoparticle-based therapies for bone tissue engineering, which should be useful reading for clinicians as well as researchers in this field. Copyright © 2015 Elsevier Inc. All rights reserved.

  3. 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.

  4. Evaluation of osteoinduction and proliferation on nano-Sr-HAP: a novel orthopedic biomaterial for bone tissue regeneration.

    Science.gov (United States)

    Hao, Yongqiang; Yan, Huanqing; Wang, Xuepeng; Zhu, Bangshang; Ning, Congqin; Ge, Shengfang

    2012-01-01

    Hydroxyapatite (HAP), a CaP compound similar to the mineral phase present in bone, has excellent biocompatibility but little osseous inductivity. In this study, we evaluated the novel nano-Sr-HAP, in which the calcium of hydroxyapatite was substituted with strontium, which acts as a bone-forming agent. Its biocompatibility and osteoinduction were assayed using marrow mesenchymal stem cells (MSCs) and osteoblasts (OBs) in vitro. We were able to demonstrate that nano-Sr-HAP supported increased OB cell adhesion, proliferation and viability up to 4 days in culture when compared with nano-HAP. MSCs cultured with nano-Sr-HAP showed higher alkaline phosphatase (ALP) activity. More extracellular mineralized nodules were found with nano-Sr-HAP compared to nano-HAP, especially in images of ALP staining. We suggest that nano-Sr-HAP powders possess osteoconductive and osteoinductive properties and have the potential to be used in the repair of bone defects caused by osteoporotic fractures.

  5. Autogenous tooth bone graft: Ingenious bone regeneration material

    Directory of Open Access Journals (Sweden)

    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.

  6. 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

  7. A comparative clinico-radiographic study of guided tissue regeneration with bioresorbable membrane and a composite synthetic bone graft for the treatment of periodontal osseous defects

    Directory of Open Access Journals (Sweden)

    Sumedha Srivastava

    2015-01-01

    Full Text Available Aim: The aim was to evaluate the bonefill in periodontal osseous defects with the help of guided tissue regeneration, bioresorbable membrane (PerioCol + bone graft (Grabio Glascera in combination and with bonegraft (Grabio Glascera alone. Materials and Methods: The study involved total 30 sites in systemically healthy 19 patients. The parameters for evaluation includes plaque index sulcus bleeding index with one or more periodontal osseous defects having (i probing depth (PD of ≥ 5 mm (ii clinical attachment loss (CAL of ≥ 5 mm and (iii ≥3 mm of radiographic periodontal osseous defect (iv bonefill (v crestal bone loss (vi defect resolution. The study involved the three wall and two wall defects which should be either located interproximally or involving the furcation area. The statistical analysis was done using Statistical Package for Social Sciences, the Wilcoxon signed rank statistic W + for Mann-Whitney U-test. Results: The net gain in PD and CAL after 6 months for Group I ([PerioCol] + [Grabio Glascera] and Group II (Grabio Glascera was 3.94 ± 1.81 mm, 3.57 ± 2.21 mm and 3.94 ± 1.81, 3.57 ± 2.21 mm, respectively. The results of the study for Group I and Group II with regards to mean net bonefill, was 3.25 ± 2.32 (58% mm and 5.14 ± 3.84 (40.26 ± 19.14% mm, crestal bone loss − 0.25 ± 0.68 mm and − 0.79 ± 1.19 mm. Defect resolution 3.50 ± 2.34 mm and 5.93 ± 4.01 mm, respectively. Conclusion: On comparing both the groups together after 6 months of therapy, the results were equally effective for combination of graft and membrane versus bone graft alone since no statistical significant difference was seen between above parameters for both the groups. Thus, both the treatment modalities are comparable and equally effective.

  8. Sea Buckthorn Leaf Extract Protects Jejunum and Bone Marrow of 60Cobalt-Gamma-Irradiated Mice by Regulating Apoptosis and Tissue Regeneration

    Directory of Open Access Journals (Sweden)

    Madhu Bala

    2015-01-01

    Full Text Available A single dose (30 mg/kg body weight of standardized sea buckthorn leaf extract (SBL-1, administered 30 min before whole body 60Co-gamma-irradiation (lethal dose, 10 Gy, protected >90% of mice population. The purpose of this study was to investigate the mechanism of action of SBL-1 on jejunum and bone marrow, quantify key bioactive compounds, and analyze chemical composition of SBL-1. Study with 9-week-old inbred male Swiss albino Strain ‘A’ mice demonstrated that SBL-1 treatment before 60Co-gamma-irradiation (10 Gy significantly (p<0.05 countered radiation induced decreases in jejunum crypts (1.27-fold, villi number (1.41-fold, villus height (1.25-fold, villus cellularity (2.27-fold, cryptal Paneth cells (1.89-fold, and Bcl2 level (1.54-fold. It countered radiation induced increases in cryptal apoptotic cells (1.64-fold and Bax levels (1.88-fold. It also countered radiation (2 Gy and 3 Gy induced bone marrow apoptosis (1.59-fold and 1.85-fold and micronuclei frequency (1.72-fold and 2.6-fold. SBL-1 rendered radiation protection by promoting cryptal stem cells proliferation, by regulating apoptosis, and by countering radiation induced chromosomal damage. Quercetin, Ellagic acid, Gallic acid, high contents polyphenols, tannins, and thiols detected in SBL-1 may have contributed to radiation protection by neutralization of radiation induced oxidative species, supporting stem cell proliferation and tissue regeneration.

  9. PLANT REGENERATION THROUGH TISSUE CULTURE OF PEAR ...

    African Journals Online (AJOL)

    AISA

    culture media, calli embryogenic potential and fertile plants regeneration were conserved for more than 12 months. Characteristics of regenerated plants were similar to control. It appears that dissected shoot apex was a new appropriate tool in tissue culture. Key words: Tissue culture, culture medium, callus induction, shoot ...

  10. 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.

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

    Science.gov (United States)

    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.

  12. 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.

  13. Platelets, inflammation and tissue regeneration.

    Science.gov (United States)

    Nurden, Alan T

    2011-05-01

    Blood platelets have long been recognised to bring about primary haemostasis with deficiencies in platelet production and function manifesting in bleeding while upregulated function favourises arterial thrombosis. Yet increasing evidence indicates that platelets fulfil a much wider role in health and disease. First, they store and release a wide range of biologically active substances including the panoply of growth factors, chemokines and cytokines released from a-granules. Membrane budding gives rise to microparticles (MPs), another active participant within the blood stream. Platelets are essential for the innate immune response and combat infection (viruses, bacteria, micro-organisms). They help maintain and modulate inflammation and are a major source of pro-inflammatory molecules (e.g. P-selectin, tissue factor, CD40L, metalloproteinases). As well as promoting coagulation, they are active in fibrinolysis; wound healing, angiogenesis and bone formation as well as in maternal tissue and foetal vascular remodelling. Activated platelets and MPs intervene in the propagation of major diseases. They are major players in atherosclerosis and related diseases, pathologies of the central nervous system (Alzheimers disease, multiple sclerosis), cancer and tumour growth. They participate in other tissue-related acquired pathologies such as skin diseases and allergy, rheumatoid arthritis, liver disease; while, paradoxically, autologous platelet-rich plasma and platelet releasate are being used as an aid to promote tissue repair and cellular growth. The above mentioned roles of platelets are now discussed.

  14. Guided bone regeneration and abutment connection augment the buccal soft tissue contour: 3-year results of a prospective comparative clinical study.

    Science.gov (United States)

    Benic, Goran I; Ge, Yanjun; Gallucci, German O; Jung, Ronald E; Schneider, David; Hämmerle, Christoph H F

    2017-02-01

    To test whether implant placement with simultaneous guided bone regeneration (GBR) differs from implant placement without GBR regarding the change in marginal mucosal contour. In 28 patients, single implants were placed >4 months after tooth extraction. Eighteen implants were completely surrounded by native bone, and no bone augmentation was performed. At 10 implant sites, bone defects and thin bone plates were grafted with deproteinized bovine-derived bone mineral and covered with collagen membrane. Impressions were taken prior to implant placement (baseline), at 3 months before abutment connection, at 6 months immediately after crown insertion, at 1 year, and at 3 years. Models were optically scanned and 3D images were superimposed for the evaluation of mucosal contour changes at the mid-buccal aspect. The nonparametric Mann-Whitney U-test was applied to detect differences. From baseline to 6 months, horizontal contour change at the level 1 and 2 mm apical to the mucosal margin measured 0.65 ± 0.74 mm and 0.55 ± 0.56 mm at sites without GBR, and 1.92 ± 0.87 mm and 1.76 ± 0.70 mm at sites with GBR (P < 0.05). In the period from baseline to 1 year, the corresponding values amounted to 0.81 ± 0.67 mm and 0.60 ± 0.55 mm in the group without GBR, and to 1.81 ± 0.86 mm and 1.37 ± 0.62 mm in the group with GBR (P < 0.05). From baseline to 6 months, mucosal margin moved 0.16 ± 0.49 mm in the coronal direction in the group without GBR and 0.82 ± 0.65 mm in the group with GBR (P < 0.05). In the period from baseline to 1 year, vertical change of mucosal margin amounted to 0.64 ± 0.54 mm in the group without GBR and to 1.17 ± 0.53 mm in the GBR group (P < 0.05). From 1 to 3 years, the mucosal contours remained stable. Implant placement with simultaneous GBR resulted in more gain of buccal soft tissue contour in comparison with implant placement without GBR. Abutment connection increased the contour of the

  15. 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.

  16. Bone Tissue Engineering: Past-Present-Future.

    Science.gov (United States)

    Quarto, Rodolfo; Giannoni, Paolo

    2016-01-01

    Bone is one of the few tissues to display a true potential for regeneration. Fracture healing is an obvious example where regeneration occurs through tightly regulated sequences of molecular and cellular events which recapitulate tissue formation seen during embryogenesis. Still in some instances, bone regeneration does not occur properly (i.e. critical size lesions) and an appropriate therapeutic intervention is necessary. Successful replacement of bone by tissue engineering will likely depend on the recapitulation of this flow of events. In fact, bone regeneration requires cross-talk between microenvironmental factors and cells; for example, resident mesenchymal progenitors are recruited and properly guided by soluble and insoluble signaling molecules. Tissue engineering attempts to reproduce and to mimic this natural milieu by delivering cells capable of differentiating into osteoblasts, inducing growth factors and biomaterials to support cellular attachment, proliferation, migration, and matrix deposition. In the last two decades, a significant effort has been made by the scientific community in the development of methods and protocols to repair and regenerate tissues such as bone, cartilage, tendons, and ligaments. In this same period, great advancements have been achieved in the biology of stem cells and on the mechanisms governing "stemness". Unfortunately, after two decades, effective clinical translation does not exist, besides a few limited examples. Many years have passed since cell-based regenerative therapies were first described as "promising approaches", but this definition still engulfs the present literature. Failure to envisage translational cell therapy applications in routine medical practice evidences the existence of unresolved scientific and technical struggles, some of which still puzzle researchers in the field and are presented in this chapter.

  17. 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.

  18. Deproteinized bovine bone in association with guided tissue regeneration or enamel matrix derivatives procedures in aggressive periodontitis patients: a 1-year retrospective study.

    Science.gov (United States)

    Artzi, Zvi; Tal, Haim; Platner, Ori; Wasersprung, Nadav; Weinberg, Evgeny; Slutzkey, Shimshon; Gozali, Nir; Carmeli, Guy; Herzberg, Ran; Kozlovsky, Avital

    2015-06-01

    To retrospectively evaluate and compare two regenerative periodontal procedures in young individuals with aggressive periodontitis (AgP). Thirty-two patients aged 14-25 years (mean ± SD 19.3 ± 5.7) were diagnosed as having AgP with multiple intra-bony defects (IBDs) and treated by one of two regenerative modalities of periodontal therapy: guided tissue regeneration (GTR) using deproteinized bone xenograft (DBX) particles and a resorbable membrane (the GTR group), or an application of enamel matrix derivatives (EMD) combined with DBX (the EMD/DBX group). Periodic monitoring of treated sites included recording of probing depth (PD), clinical attachment level (CAL) and gingival recession. Pre-treatment and 1-year post-operative findings were statistically analysed within and between groups. The PD and CAL values decreased significantly with time, but not those between study groups. The mean pre-treatment and 1-year post-treatment PDs of the IBDs of the GTR group (n = 16; sites = 67) were 8.93 ± 1.14 mm and 3.58 ± 0.50 mm, respectively, and the mean CALs were 9.03 ± 1.03 mm and 4.16 ± 0.53 mm respectively. The mean PDs of the EMD/DBX group (n = 16; sites = 73) were 8.77 ± 1.04 mm and 3.61 ± 0.36 mm, respectively, and the mean CALS were 8.79 ± 1.04 mm and 3.77 ± 0.22 mm respectively (p < 0.001 for all). Surgical treatment of AgP patients by either GTR or by application of EMD/DBX yielded similarly successful clinical results at 1-year post-treatment. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  19. Regeneration of rat corpora cavernosa tissue by transplantation of CD133+ cells derived from human bone marrow and placement of biodegradable gel sponge sheet

    Directory of Open Access Journals (Sweden)

    Shogo Inoue

    2017-01-01

    Full Text Available The objective is to develop an easier technique for regenerating corpora cavernosa tissue through transplantation of human bone marrow-derived CD133 + cells into a rat corpora cavernosa defect model. We excised 2 mm × 2 mm squares of the right corpora cavernosa of twenty-three 8-week-old male nude rats. Alginate gel sponge sheets supplemented with 1 × 10 4 CD133 + cells were then placed over the excised area of nine rats. Functional and histological evaluations were carried out 8 weeks later. The mean intracavernous pressure/mean arterial pressure ratio for the nine rats (0.34258 ± 0.0831 was significantly higher than that for eight rats with only the excision (0.0580 ± 0.0831, P = 0.0238 and similar to that for five rats for which the penis was exposed, and there was no excision (0.37228 ± 0.1051, P = 0.8266. Immunohistochemical analysis revealed that the nine fully treated rats had venous sinus-like structures and quantitative reverse transcription polymerase chain reaction analysis of extracts from their alginate gel sponge sheets revealed that the amounts of mRNA encoding the nerve growth factor (NGF, and vascular endothelial growth factor (VEGF were significantly higher than those for rats treated with alginate gel sheets without cell supplementation (NGF: P = 0.0309; VEGF: P < 0.0001. These findings show that transplantation of CD133 + cells accelerates functional and histological recovery in the corpora cavernosa defect model.

  20. Printing bone : the application of 3D fiber deposition for bone tissue engineering

    NARCIS (Netherlands)

    Fedorovich, N.E.

    2011-01-01

    Bone chips are used by orthopaedic surgeons for treating spinal trauma and to augment large bone defects. A potential alternative to autologous bone is regeneration of bone tissue in the lab by developing hybrid implants consisting of osteogenic (stem) cells seeded on supportive matrices.

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

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    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.

  2. Stem cells in bone tissue engineering

    Energy Technology Data Exchange (ETDEWEB)

    Seong, Jeong Min [Department of Preventive and Social Dentistry and Institute of Oral Biology, College of Dentistry, Kyung Hee University, Seoul 130-701 (Korea, Republic of); Kim, Byung-Chul; Park, Jae-Hong; Kwon, Il Keun; Hwang, Yu-Shik [Department of Maxillofacial Biomedical Engineering and Institute of Oral Biology, College of Dentistry, Kyung Hee University, Seoul 130-701 (Korea, Republic of); Mantalaris, Anathathios, E-mail: yshwang@khu.ac.k [Department of Chemical Engineering, Imperial College London, South Kensington Campus, London SW7 2AZ (United Kingdom)

    2010-12-15

    Bone tissue engineering has been one of the most promising areas of research, providing a potential clinical application to cure bone defects. Recently, various stem cells including embryonic stem cells (ESCs), bone marrow-derived mesenchymal stem cells (BM-MSCs), umbilical cord blood-derived mesenchymal stem cells (UCB-MSCs), adipose tissue-derived stem cells (ADSCs), muscle-derived stem cells (MDSCs) and dental pulp stem cells (DPSCs) have received extensive attention in the field of bone tissue engineering due to their distinct biological capability to differentiate into osteogenic lineages. The application of these stem cells to bone tissue engineering requires inducing in vitro differentiation of these cells into bone forming cells, osteoblasts. For this purpose, efficient in vitro differentiation towards osteogenic lineage requires the development of well-defined and proficient protocols. This would reduce the likelihood of spontaneous differentiation into divergent lineages and increase the available cell source for application to bone tissue engineering therapies. This review provides a critical examination of the various experimental strategies that could be used to direct the differentiation of ESC, BM-MSC, UCB-MSC, ADSC, MDSC and DPSC towards osteogenic lineages and their potential applications in tissue engineering, particularly in the regeneration of bone. (topical review)

  3. Stem cells in bone tissue engineering

    International Nuclear Information System (INIS)

    Seong, Jeong Min; Kim, Byung-Chul; Park, Jae-Hong; Kwon, Il Keun; Hwang, Yu-Shik; Mantalaris, Anathathios

    2010-01-01

    Bone tissue engineering has been one of the most promising areas of research, providing a potential clinical application to cure bone defects. Recently, various stem cells including embryonic stem cells (ESCs), bone marrow-derived mesenchymal stem cells (BM-MSCs), umbilical cord blood-derived mesenchymal stem cells (UCB-MSCs), adipose tissue-derived stem cells (ADSCs), muscle-derived stem cells (MDSCs) and dental pulp stem cells (DPSCs) have received extensive attention in the field of bone tissue engineering due to their distinct biological capability to differentiate into osteogenic lineages. The application of these stem cells to bone tissue engineering requires inducing in vitro differentiation of these cells into bone forming cells, osteoblasts. For this purpose, efficient in vitro differentiation towards osteogenic lineage requires the development of well-defined and proficient protocols. This would reduce the likelihood of spontaneous differentiation into divergent lineages and increase the available cell source for application to bone tissue engineering therapies. This review provides a critical examination of the various experimental strategies that could be used to direct the differentiation of ESC, BM-MSC, UCB-MSC, ADSC, MDSC and DPSC towards osteogenic lineages and their potential applications in tissue engineering, particularly in the regeneration of bone. (topical review)

  4. Proteomic Analysis of Gingival Tissue and Alveolar Bone during Alveolar Bone Healing*

    OpenAIRE

    Yang, Hee-Young; Kwon, Joseph; Kook, Min-Suk; Kang, Seong Soo; Kim, Se Eun; Sohn, Sungoh; Jung, Seunggon; Kwon, Sang-Oh; Kim, Hyung-Seok; Lee, Jae Hyuk; Lee, Tae-Hoon

    2013-01-01

    Bone tissue regeneration is orchestrated by the surrounding supporting tissues and involves the build-up of osteogenic cells, which orchestrate remodeling/healing through the expression of numerous mediators and signaling molecules. Periodontal regeneration models have proven useful for studying the interaction and communication between alveolar bone and supporting soft tissue. We applied a quantitative proteomic approach to analyze and compare proteins with altered expression in gingival sof...

  5. Regulation of tissue repair and regeneration by electric fields.

    Science.gov (United States)

    Wang, En-tong; Zhao, Min

    2010-02-01

    Endogenous electric fields (EFs) have been detected at wounds and damaged tissues. The potential roles of EFs in tissue repair and regeneration have been an intriguing topic for centuries. Recent researches have provided significant insights into how naturally occurring EFs may participate in the control of tissue repair and regeneration. Applied EFs equivalent to the size of fields measured in vivo direct cell migration, cell proliferation and nerve sprouting at wounds. More remarkably, physiological EFs are a guidance cue that directs cell migration which overrides other well accepted directional signals including initial injury stimulation, wound void, contact inhibition release, population pressure and chemotaxis. EFs activate many intracellular signaling pathways in a directional manner. Modulation of endogenous wound EFs affects epithelial cell migration, cell proliferation, and nerve growth at cornea wounds in vivo. Electric stimulation is being tested clinically for the treatments of bone fracture, wound healing and spinal cord injury. EFs thus may represent a novel type of signaling paradigm in tissue repair and regeneration. Combination of the electric stimulation and other well understood biochemical regulatory mechanisms may offer powerful and effective therapies for tissue repair and regeneration. This review introduces experimental evidence for the existence of endogenous EFs and discusses their roles in tissue repair and regeneration.

  6. 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.

  7. 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.

  8. Alveolar bone tissue engineering using composite scaffolds for drug delivery

    Directory of Open Access Journals (Sweden)

    Tomonori Matsuno

    2010-08-01

    Full Text Available For many years, bone graft substitutes have been used to reconstruct bone defects in orthopedic and dental fields. However, synthetic bone substitutes such as hydroxyapatite or β-tricalcium phosphate have no osteoinductive or osteogenic abilities. Bone tissue engineering has also been promoted as an alternative approach to regenerating bone tissue. To succeed in bone tissue engineering, osteoconductive scaffolding biomaterials should provide a suitable environment for osteogenic cells and provide local controlled release of osteogenic growth factors. In addition, the scaffold for the bone graft substitute should biodegrade to replace the newly formed bone. Recent advances in bone tissue engineering have allowed the creation of composite scaffolds with tailored functional properties. This review focuses on composite scaffolds that consist of synthetic ceramics and natural polymers as drug delivery carriers for alveolar bone tissue engineering.

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

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    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

  10. Protein based devices for oral tissue repair and regeneration

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    Iriczalli Cruz-Maya

    2018-03-01

    Full Text Available In the last decades, a goal of tissue engineering has been devoted to the design of devices with multiple micro- or nano-structures and loaded with bioactive molecules, to mimic the extracellular matrix (ECM so generating a conducive microenvironment for new tissue replacement/regeneration. The ECM, naturally, is composed of fibrous proteins which provide structural support for tissues, mainly regulating cells behavior in terms of proliferation, growth, survival, shape, migration and differentiation by cell-matrix interactions. Several studies have been just investigated the fabrication of different platforms for the regeneration of teeth, oral mucosa, salivary glands, bone, and periodontium. In this context, many proteins—from a natural or biological source—have been used as instructive substances to in vitro guide tissue organization and functions. In particular, new advances in the definition of protein-based formulations currently represent a great challenge to promote a more effective regeneration of dental tissues to be transplanted into patients to replace damaged, diseased or missing tissues. Hence, the purpose of this review is to discuss the use of protein-based systems for the regeneration of oral tissues.

  11. 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

  12. 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.

  13. 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.

  14. Mechanisms of lymphatic regeneration after tissue transfer.

    Directory of Open Access Journals (Sweden)

    Alan Yan

    2011-02-01

    Full Text Available Lymphedema is the chronic swelling of an extremity that occurs commonly after lymph node resection for cancer treatment. Recent studies have demonstrated that transfer of healthy tissues can be used as a means of bypassing damaged lymphatics and ameliorating lymphedema. The purpose of these studies was to investigate the mechanisms that regulate lymphatic regeneration after tissue transfer.Nude mice (recipients underwent 2-mm tail skin excisions that were either left open or repaired with full-thickness skin grafts harvested from donor transgenic mice that expressed green fluorescent protein in all tissues or from LYVE-1 knockout mice. Lymphatic regeneration, expression of VEGF-C, macrophage infiltration, and potential for skin grafting to bypass damaged lymphatics were assessed.Skin grafts healed rapidly and restored lymphatic flow. Lymphatic regeneration occurred beginning at the peripheral edges of the graft, primarily from ingrowth of new lymphatic vessels originating from the recipient mouse. In addition, donor lymphatic vessels appeared to spontaneously re-anastomose with recipient vessels. Patterns of VEGF-C expression and macrophage infiltration were temporally and spatially associated with lymphatic regeneration. When compared to mice treated with excision only, there was a 4-fold decrease in tail volumes, 2.5-fold increase in lymphatic transport by lymphoscintigraphy, 40% decrease in dermal thickness, and 54% decrease in scar index in skin-grafted animals, indicating that tissue transfer could bypass damaged lymphatics and promote rapid lymphatic regeneration.Our studies suggest that lymphatic regeneration after tissue transfer occurs by ingrowth of lymphatic vessels and spontaneous re-connection of existing lymphatics. This process is temporally and spatially associated with VEGF-C expression and macrophage infiltration. Finally, tissue transfer can be used to bypass damaged lymphatics and promote rapid lymphatic regeneration.

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

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    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.

  16. Bacterial Cellulose-Hydroxyapatite Nanocomposites for Bone Regeneration

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    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.

  17. 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

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

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    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

  19. 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.

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

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    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.

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

    Science.gov (United States)

    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.

  2. 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.

  3. Reparative inflammation takes charge of tissue regeneration

    NARCIS (Netherlands)

    Karin, Michael; Clevers, Hans

    2016-01-01

    Inflammation underlies many chronic and degenerative diseases, but it also mitigates infections, clears damaged cells and initiates tissue repair. Many of the mechanisms that link inflammation to damage repair and regeneration in mammals are conserved in lower organisms, indicating that it is an

  4. 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.).

  5. 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.

  6. Tissue regeneration the material enablers

    OpenAIRE

    Marsh, George

    2001-01-01

    The potential rewards are well worth the effort. Estimates in the US put the number of patients on transplant waiting lists at over 75,000. Recent figures from the United Network for Organ Sharing indicate that around 5% of these die while waiting for a transplant organ to become available. Interest and investment levels are high—the US National Institute of Standards and Technology's Advanced Technology Program has poured millions of dollars into tissue engineering product development and th...

  7. 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.

  8. Alginate based scaffolds for bone tissue engineering

    Energy Technology Data Exchange (ETDEWEB)

    Valente, J.F.A.; Valente, T.A.M. [CICS-UBI - Centro de Investigacao em Ciencias da Saude, Faculdade de Ciencias da Saude, Universidade da Beira Interior, Covilha (Portugal); Alves, P.; Ferreira, P. [CIEPQPF, Departamento de Engenharia Quimica, Universidade de Coimbra, Polo II, Pinhal de Marrocos, 3030-290 Coimbra (Portugal); Silva, A. [Centro de Ciencia e Tecnologia Aeroespaciais, Universidade da Beira Interior, Covilha (Portugal); Correia, I.J., E-mail: icorreia@ubi.pt [CICS-UBI - Centro de Investigacao em Ciencias da Saude, Faculdade de Ciencias da Saude, Universidade da Beira Interior, Covilha (Portugal)

    2012-12-01

    The design and production of scaffolds for bone tissue regeneration is yet unable to completely reproduce the native bone properties. In the present study new alginate microparticle and microfiber aggregated scaffolds were produced to be applied in this area of regenerative medicine. The scaffolds' mechanical properties were characterized by thermo mechanical assays. Their morphological characteristics were evaluated by isothermal nitrogen adsorption and scanning electron microscopy. The density of both types of scaffolds was determined by helium pycnometry and mercury intrusion porosimetry. Furthermore, scaffolds' cytotoxic profiles were evaluated in vitro by seeding human osteoblast cells in their presence. The results obtained showed that scaffolds have good mechanical and morphological properties compatible with their application as bone substitutes. Moreover, scaffold's biocompatibility was confirmed by the observation of cell adhesion and proliferation after 5 days of being seeded in their presence and by non-radioactive assays. - Highlights: Black-Right-Pointing-Pointer Design and production of scaffolds for bone tissue regeneration. Black-Right-Pointing-Pointer Microparticle and microfiber alginate scaffolds were produced through a particle aggregation technique; Black-Right-Pointing-Pointer Scaffolds' mechanically and biologically properties were characterized through in vitro studies;.

  9. Biomimetic electrospun nanofibers for tissue regeneration

    International Nuclear Information System (INIS)

    Liao, Susan; Li Bojun; Ma Zuwei; Wei He; Chan Casey; Ramakrishna, Seeram

    2006-01-01

    Nanofibers exist widely in human tissue with different patterns. Electrospinning nanotechnology has recently gained a new impetus due to the introduction of the concept of biomimetic nanofibers for tissue regeneration. The advanced electrospinning technique is a promising method to fabricate a controllable continuous nanofiber scaffold similar to the natural extracellular matrix. Thus, the biomedical field has become a significant possible application field of electrospun fibers. Although electrospinning has developed rapidly over the past few years, electrospun nanofibers are still at a premature research stage. Further comprehensive and deep studies on electrospun nanofibers are essential for promoting their biomedical applications. Current electrospun fiber materials include natural polymers, synthetic polymers and inorganic substances. This review briefly describes several typically electrospun nanofiber materials or composites that have great potential for tissue regeneration, and describes their fabrication, advantages, drawbacks and future prospects. (topical review)

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

    Science.gov (United States)

    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.

  11. 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

  12. 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

  13. 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.

  14. In vitro simulation of pathological bone conditions to predict clinical outcome of bone tissue engineered materials

    Science.gov (United States)

    Nguyen, Duong Thuy Thi

    According to the Centers for Disease Control, the geriatric population of ≥65 years of age will increase to 51.5 million in 2020; 40% of white women and 13% of white men will be at risk for fragility fractures or fractures sustained under normal stress and loading conditions due to bone disease, leading to hospitalization and surgical treatment. Fracture management strategies can be divided into pharmaceutical therapy, surgical intervention, and tissue regeneration for fracture prevention, fracture stabilization, and fracture site regeneration, respectively. However, these strategies fail to accommodate the pathological nature of fragility fractures, leading to unwanted side effects, implant failures, and non-unions. Compromised innate bone healing reactions of patients with bone diseases are exacerbated with protective bone therapy. Once these patients sustain a fracture, bone healing is a challenge, especially when fracture stabilization is unsuccessful. Traditional stabilizing screw and plate systems were designed with emphasis on bone mechanics rather than biology. Bone grafts are often used with fixation devices to provide skeletal continuity at the fracture gap. Current bone grafts include autologous bone tissue and donor bone tissue; however, the quality and quantity demanded by fragility fractures sustained by high-risk geriatric patients and patients with bone diseases are not met. Consequently, bone tissue engineering strategies are advancing towards functionalized bone substitutes to provide fracture reconstruction while effectively mediating bone healing in normal and diseased fracture environments. In order to target fragility fractures, fracture management strategies should be tailored to allow bone regeneration and fracture stabilization with bioactive bone substitutes designed for the pathological environment. The clinical outcome of these materials must be predictable within various disease environments. Initial development of a targeted

  15. 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

  16. Tissue regenerating functions of coagulation factor XIII

    DEFF Research Database (Denmark)

    Soendergaard, C; Kvist, P H; Seidelin, J B

    2013-01-01

    The protransglutaminase factor XIII (FXIII) has recently gained interest within the field of tissue regeneration, as it has been found that FXIII significantly influences wound healing by exerting a multitude of functions. It supports haemostasis by enhancing platelet adhesion to damaged endothel......The protransglutaminase factor XIII (FXIII) has recently gained interest within the field of tissue regeneration, as it has been found that FXIII significantly influences wound healing by exerting a multitude of functions. It supports haemostasis by enhancing platelet adhesion to damaged...... endothelium, and by its cross-linking activity it stabilizes the formed fibrin clot. Furthermore, FXIII limits bacterial dissemination from the wound and incorporates macromolecules of importance for cellular infiltration supporting cell migration and survival. FXIII-mediated complex formation of the VEGF...

  17. 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.

  18. Endurance Exercise Mobilizes Developmentally Early Stem Cells into Peripheral Blood and Increases Their Number in Bone Marrow: Implications for Tissue Regeneration

    Directory of Open Access Journals (Sweden)

    Krzysztof Marycz

    2016-01-01

    Full Text Available Endurance exercise has been reported to increase the number of circulating hematopoietic stem/progenitor cells (HSPCs in peripheral blood (PB as well as in bone marrow (BM. We therefore became interested in whether endurance exercise has the same effect on very small embryonic-like stem cells (VSELs, which have been described as a population of developmentally early stem cells residing in BM. Mice were run daily for 1 hour on a treadmill for periods of 5 days or 5 weeks. Human volunteers had trained in long-distance running for one year, six times per week. FACS-based analyses and RT-PCR of murine and human VSELs and HSPCs from collected bone marrow and peripheral blood were performed. We observed that endurance exercise increased the number of VSELs circulating in PB and residing in BM. In parallel, we observed an increase in the number of HSPCs. These observations were subsequently confirmed in young athletes, who showed an increase in circulating VSELs and HSPCs after intensive running exercise. We provide for the first time evidence that endurance exercise may have beneficial effects on the expansion of developmentally early stem cells. We hypothesize that these circulating stem cells are involved in repairing minor exercise-related tissue and organ injuries.

  19. Endurance Exercise Mobilizes Developmentally Early Stem Cells into Peripheral Blood and Increases Their Number in Bone Marrow: Implications for Tissue Regeneration.

    Science.gov (United States)

    Marycz, Krzysztof; Mierzejewska, Katarzyna; Śmieszek, Agnieszka; Suszynska, Ewa; Malicka, Iwona; Kucia, Magda; Ratajczak, Mariusz Z

    2016-01-01

    Endurance exercise has been reported to increase the number of circulating hematopoietic stem/progenitor cells (HSPCs) in peripheral blood (PB) as well as in bone marrow (BM). We therefore became interested in whether endurance exercise has the same effect on very small embryonic-like stem cells (VSELs), which have been described as a population of developmentally early stem cells residing in BM. Mice were run daily for 1 hour on a treadmill for periods of 5 days or 5 weeks. Human volunteers had trained in long-distance running for one year, six times per week. FACS-based analyses and RT-PCR of murine and human VSELs and HSPCs from collected bone marrow and peripheral blood were performed. We observed that endurance exercise increased the number of VSELs circulating in PB and residing in BM. In parallel, we observed an increase in the number of HSPCs. These observations were subsequently confirmed in young athletes, who showed an increase in circulating VSELs and HSPCs after intensive running exercise. We provide for the first time evidence that endurance exercise may have beneficial effects on the expansion of developmentally early stem cells. We hypothesize that these circulating stem cells are involved in repairing minor exercise-related tissue and organ injuries.

  20. 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.

  1. Electromechanical Properties of Bone Tissue.

    Science.gov (United States)

    Regimbal, Raymond L.

    Discrepancies between calculated and empirical properties of bone are thought to be due to a general lack of consideration for the extent and manner(s) with which bone components interact at the molecular level. For a bone component in physiological fluid or whenever two phases are in contact, there is a region between the bulk phases called the electrical double layer which is marked by a separation of electric charges. For the purpose of studying electrical double layer interactions, the method of particle microelectrophoresis was used to characterize bone and its major constituents on the basis of the net charge they bear when suspended in ionic media of physiological relevance. With the data presented as pH versus zeta (zeta ) potential, the figures reveal an isoelectric point (IEP) for bone mineral near pH 8.6, whereas intact and EDTA demineralized bone tissue both exhibit IEPs near pH 5.1. While these data demonstrate the potential for a significant degree of coulombic interaction between the bone mineral and organic constituent double layers, it was also observed that use of inorganic phosphate buffers, as a specific marker for bone mineral, resulted in (1) an immediate reversal, from positive to negative, of the bone mineral zeta potential (2) rendered the zeta potential of intact bone more negative in a manner linearly dependent on both time and temperature and (3) had no affect on demineralized bone (P load for a 3 day period. While it is thus demonstrated that the major inorganic and organic phases of bone are electromechanically coupled, a thermodynamic consideration of the data suggests that the nature of the bond is to preserve mineral and organic phase electroneutralities by participating in electrical double layer interactions. The results are discussed in terms of bone mechanical modeling, electrokinetic properties, aging, tissue-implant compatibility and the etiologies of bone pathologic conditions.

  2. 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.

  3. MSC/ECM Cellular Complexes Induce Periodontal Tissue Regeneration.

    Science.gov (United States)

    Takewaki, M; Kajiya, M; Takeda, K; Sasaki, S; Motoike, S; Komatsu, N; Matsuda, S; Ouhara, K; Mizuno, N; Fujita, T; Kurihara, H

    2017-08-01

    Transplantation of mesenchymal stem cells (MSCs), which possess self-renewing properties and multipotency, into a periodontal defect is thought to be a useful option for periodontal tissue regeneration. However, developing more reliable and predictable implantation techniques is still needed. Recently, we generated clumps of an MSC/extracellular matrix (ECM) complex (C-MSC), which consisted of cells and self-produced ECM. C-MSCs can regulate their cellular functions in vitro and can be grafted into a defect site, without any artificial scaffold, to induce bone regeneration. Accordingly, this study aimed to evaluate the effect of C-MSC transplantation on periodontal tissue regeneration in beagle dogs. Seven beagle dogs were employed to generate a premolar class III furcation defect model. MSCs isolated from dog ilium were seeded at a density of 7.0 × 10 4 cells/well into 24-well plates and cultured in growth medium supplemented with 50 µg/mL ascorbic acid for 4 d. To obtain C-MSCs, confluent cells were scratched using a micropipette tip and were then torn off as a cellular sheet. The sheet was rolled up to make round clumps of cells. C-MSCs were maintained in growth medium or osteoinductive medium (OIM) for 5 or 10 d. The biological properties of C-MSCs were evaluated in vitro, and their periodontal tissue regenerative activity was tested by using a dog class III furcation defect model. Immunofluorescence analysis revealed that type I collagen fabricated the form of C-MSCs. OIM markedly elevated calcium deposition in C-MSCs at day 10, suggesting its osteogenic differentiation capacity. Both C-MSCs and C-MSCs cultured with OIM transplantation without an artificial scaffold into the dog furcation defect induced periodontal tissue regeneration successfully compared with no graft, whereas osteogenic-differentiated C-MSCs led to rapid alveolar bone regeneration. These findings suggested that the use of C-MSCs refined by self-produced ECM may represent a novel

  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. Injectable silk foams for soft tissue regeneration.

    Science.gov (United States)

    Bellas, Evangelia; Lo, Tim J; Fournier, Eric P; Brown, Joseph E; Abbott, Rosalyn D; Gil, Eun S; Marra, Kacey G; Rubin, J Peter; Leisk, Gary G; Kaplan, David L

    2015-02-18

    Soft tissue fillers are needed for restoration of a defect or augmentation of existing tissues. Autografts and lipotransfer have been under study for soft tissue reconstruction but yield inconsistent results, often with considerable resorption of the grafted tissue. A minimally invasive procedure would reduce scarring and recovery time as well as allow the implant and/or grafted tissue to be placed closer to existing vasculature. Here, the feasibility of an injectable silk foam for soft tissue regeneration is demonstrated. Adipose-derived stem cells survive and migrate through the foam over a 10-d period in vitro. The silk foams are also successfully injected into the subcutaneous space in a rat and over a 3-month period integrating with the surrounding native tissue. The injected foams are palpable and soft to the touch through the skin and returning to their original dimensions after pressure is applied and then released. The foams readily absorb lipoaspirate making the foams useful as a scaffold or template for existing soft tissue filler technologies, useful either as a biomaterial alone or in combination with the lipoaspirate. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

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

    Directory of Open Access Journals (Sweden)

    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.

  7. 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.

  8. 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.

  9. Tissue-specific composite cell aggregates drive periodontium tissue regeneration by reconstructing a regenerative microenvironment.

    Science.gov (United States)

    Zhu, Bin; Liu, Wenjia; Zhang, Hao; Zhao, Xicong; Duan, Yan; Li, Dehua; Jin, Yan

    2017-06-01

    Periodontitis is the most common cause of periodontium destruction. Regeneration of damaged tissue is the expected treatment goal. However, the regeneration of a functional periodontal ligament (PDL) insertion remains a difficulty, due to complicated factors. Recently, periodontal ligament stem cells (PDLSCs) and bone marrow-derived mesenchymal stem cells (BMMSCs) have been shown to participate in PDL regeneration, both pathologically and physiologically. Besides, interactions affect the biofunctions of different derived cells during the regenerative process. Therefore, the purpose of this study was to discuss the different derived composite cell aggregate (CA) systems of PDLSCs and BMMSCs (iliac-derived or jaw-derived) for periodontium regeneration under regenerative microenvironment reconstruction. Our results showed although all three mono-MSC CAs were compacted and the cells arranged regularly in them, jaw-derived BMMSC (JBMMSC) CAs secreted more extracellular matrix than the others. Furthermore, PDLSC/JBMMSC compound CAs highly expressed ALP, Col-I, fibronectin, integrin-β1 and periostin, suggesting that their biofunction is more appropriate for periodontal structure regeneration. Inspiringly, PDLSC/JBMMSC compound CAs regenerated more functional PDL-like tissue insertions in both nude mice ectopic and minipig orthotopic transplantation. The results indicated that the different derived CAs of PDLSCs/JBMMSCs provided an appropriate regenerative microenvironment facilitating a more stable and regular regeneration of functional periodontium tissue. This method may provide a possible strategy to solve periodontium defects in periodontitis and powerful experimental evidence for clinical applications in the future. Copyright © 2015 John Wiley & Sons, Ltd. Copyright © 2015 John Wiley & Sons, Ltd.

  10. Periodontal tissue regeneration with PRP incorporated gelatin hydrogel sponges

    International Nuclear Information System (INIS)

    Nakajima, Dai; Tabata, Yasuhiko; Sato, Soh

    2015-01-01

    Gelatin hydrogels have been designed and prepared for the controlled release of the transforming growth factor (TGF-b1) and the platelet-derived growth factor (PDGF-BB). PRP (Platelet rich plasma) contains many growth factors including the PDGF and TGF-b1. The objective of this study was to evaluate the regeneration of periodontal tissue following the controlled release of growth factors in PRP. For the periodontal ligament cells and osteoblast, PRP of different concentrations was added. The assessment of DNA, mitochondrial activity and ALP activity were measured. To evaluate the TGF-β1 release from PRP incorporated gelatin sponge, amounts of TGF-β1 in each supernatant sample were determined by the ELISA. Transplantation experiments to prepare a bone defect in a rat alveolar bone were an implanted gelatin sponge incorporated with different concentration PRP. In DNA assay and MTT assay, after the addition of PRP to the periodontal ligament cells and osteoblast, the cell count and mitochondrial activity had increased the most in the group with the addition of 5  ×  PRP. In the ALP assay, after the addition of PRP to the periodontal ligament cells, the cell activity had increased the most in the group with the addition of 3  ×  PRP. In the transplantation, the size of the bone regenerated in the defect with 3  ×  PRP incorporated gelatin sponge was larger than that of the other group. (paper)

  11. 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

  12. Histone deacetylases and their roles in mineralized tissue regeneration

    Directory of Open Access Journals (Sweden)

    Nam Cong-Nhat Huynh

    2017-12-01

    Full Text Available Histone acetylation is an important epigenetic mechanism that controls expression of certain genes. It includes non-sequence-based changes of chromosomal regional structure that can alter the expression of genes. Acetylation of histones is controlled by the activity of two groups of enzymes: the histone acetyltransferases (HATs and histone deacetylases (HDACs. HDACs remove acetyl groups from the histone tail, which alters its charge and thus promotes compaction of DNA in the nucleosome. HDACs render the chromatin structure into a more compact form of heterochromatin, which makes the genes inaccessible for transcription. By altering the transcriptional activity of bone-associated genes, HDACs control both osteogenesis and osteoclastogenesis. This review presents an overview of the function of HDACs in the modulation of bone formation. Special attention is paid to the use of HDAC inhibitors in mineralized tissue regeneration from cells of dental origin.

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

    Directory of Open Access Journals (Sweden)

    Intini Francesco E

    2007-03-01

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

  14. Pulp and periodontal tissue repair - regeneration or tissue metaplasia after dental trauma. A review

    DEFF Research Database (Denmark)

    Andreasen, Jens O

    2012-01-01

    Healing subsequent to dental trauma is known to be very complex, a result explained by the variability of the types of dental trauma (six luxations, nine fracture types, and their combinations). On top of that, at least 16 different cellular systems get involved in more severe trauma types each...... of them with a different potential for healing with repair, i.e. (re-establishment of tissue continuity without functional restitution) and regeneration (where the injured or lost tissue is replaced with new tissue with identical tissue anatomy and function) and finally metaplasia (where a new type...... of tissue replaces the injured). In this study, a review is given of the impact of trauma to various dental tissues such as alveolar bone, periodontal ligament, cementum, Hertvigs epithelial root sheath, and the pulp....

  15. 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.

  16. 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.

  17. 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

  18. Rapid prototyping technology and its application in bone tissue engineering.

    Science.gov (United States)

    Yuan, Bo; Zhou, Sheng-Yuan; Chen, Xiong-Sheng

    Bone defects arising from a variety of reasons cannot be treated effectively without bone tissue reconstruction. Autografts and allografts have been used in clinical application for some time, but they have disadvantages. With the inherent drawback in the precision and reproducibility of conventional scaffold fabrication techniques, the results of bone surgery may not be ideal. This is despite the introduction of bone tissue engineering which provides a powerful approach for bone repair. Rapid prototyping technologies have emerged as an alternative and have been widely used in bone tissue engineering, enhancing bone tissue regeneration in terms of mechanical strength, pore geometry, and bioactive factors, and overcoming some of the disadvantages of conventional technologies. This review focuses on the basic principles and characteristics of various fabrication technologies, such as stereolithography, selective laser sintering, and fused deposition modeling, and reviews the application of rapid prototyping techniques to scaffolds for bone tissue engineering. In the near future, the use of scaffolds for bone tissue engineering prepared by rapid prototyping technology might be an effective therapeutic strategy for bone defects.

  19. 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.

  20. Osseointegration of subperiosteal implant via guided tissue regeneration. A pilot study

    DEFF Research Database (Denmark)

    Hjørting-Hansen, E; Helbo, M; Aaboe, M

    1995-01-01

    The principle of guided tissue regeneration was applied in an attempt to generate bone to cover a subperiosteal implant. Titanium frame works, casted on individual impressions of the anterior surface of the tibia of 4 Copenhagen White rabbits, were stabilized to the tibia by microscrews, and half...... of them were covered by an expanded polytetrafluoroethylene augmentation membrane. The observation period was 12 weeks. Guided bone regeneration partly covering the implants was seen at all experimental sides; on the control sides the implants were mainly embedded in fibrous tissue. Studies...

  1. 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 ...

  2. 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

  3. Functional attachment of soft tissues to bone: development, healing, and tissue engineering.

    Science.gov (United States)

    Lu, Helen H; Thomopoulos, Stavros

    2013-01-01

    Connective tissues such as tendons or ligaments attach to bone across a multitissue interface with spatial gradients in composition, structure, and mechanical properties. These gradients minimize stress concentrations and mediate load transfer between the soft and hard tissues. Given the high incidence of tendon and ligament injuries and the lack of integrative solutions for their repair, interface regeneration remains a significant clinical challenge. This review begins with a description of the developmental processes and the resultant structure-function relationships that translate into the functional grading necessary for stress transfer between soft tissue and bone. It then discusses the interface healing response, with a focus on the influence of mechanical loading and the role of cell-cell interactions. The review continues with a description of current efforts in interface tissue engineering, highlighting key strategies for the regeneration of the soft tissue-to-bone interface, and concludes with a summary of challenges and future directions.

  4. 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.

  5. STEM CELL ORIGIN DIFFERENTLY AFFECTS BONE TISSUE ENGINEERING STRATEGIES.

    Directory of Open Access Journals (Sweden)

    Monica eMattioli-Belmonte

    2015-09-01

    Full Text Available Bone tissue engineering is a promising research area for the improvement of traditional bone grafting procedure drawbacks. Thanks to the capability of self-renewal and multi-lineage differentiation, stem cells are one of the major actors in tissue engineering approaches, and adult mesenchymal stem cells (MSCs are considered to be appropriate for regenerative medicine strategies. Bone marrow MSCs (BM-MSCs are the earliest- discovered and well-known stem cell population used in bone tissue engineering. However, several factors hamper BM-MSC clinical application and subsequently, new stem cell sources have been investigated for these purposes. The successful identification and combination of tissue engineering, scaffold, progenitor cells, and physiologic signalling molecules enabled the surgeon to design, recreate the missing tissue in its near natural form. On the basis of these considerations, we analysed the capability of two different scaffolds, planned for osteochondral tissue regeneration, to modulate differentiation of adult stem cells of dissimilar local sources (i.e. periodontal ligament, maxillary periosteum as well as adipose-derived stem cells, in view of possible craniofacial tissue engineering strategies. We demonstrated that cells are differently committed toward the osteoblastic phenotype and therefore, considering their peculiar features, they may alternatively represent interesting cell sources in different stem cell-based bone/periodontal tissue regeneration approaches.

  6. 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.

  7. 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.

  8. 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.

  9. 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...

  10. 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.

  11. 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

  12. 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

  13. 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...

  14. 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.

  15. 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

  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. 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

  18. 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.

  19. Importance of dual delivery systems for bone tissue engineering.

    Science.gov (United States)

    Farokhi, Mehdi; Mottaghitalab, Fatemeh; Shokrgozar, Mohammad Ali; Ou, Keng-Liang; Mao, Chuanbin; Hosseinkhani, Hossein

    2016-03-10

    Bone formation is a complex process that requires concerted function of multiple growth factors. For this, it is essential to design a delivery system with the ability to load multiple growth factors in order to mimic the natural microenvironment for bone tissue formation. However, the short half-lives of growth factors, their relatively large size, slow tissue penetration, and high toxicity suggest that conventional routes of administration are unlikely to be effective. Therefore, it seems that using multiple bioactive factors in different delivery systems can develop new strategies for improving bone tissue regeneration. Combination of these factors along with biomaterials that permit tunable release profiles would help to achieve truly spatiotemporal regulation during delivery. This review summarizes the various dual-control release systems that are used for bone tissue engineering. Copyright © 2015 Elsevier B.V. All rights reserved.

  20. 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

  1. 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.

  2. A comparison of polymer and polymer-hydroxyapatite composite tissue engineered scaffolds for use in bone regeneration. An in vitro and in vivo study.

    Science.gov (United States)

    Tayton, E; Purcell, M; Aarvold, A; Smith, J O; Briscoe, A; Kanczler, J M; Shakesheff, K M; Howdle, S M; Dunlop, D G; Oreffo, R O C

    2014-08-01

    Previous in vitro work demonstrated porous PLA and PLGA both had the mechanical strength and sustained the excellent skeletal stem cell (SSC) growth required of an osteogenic bonegraft substitute, for use in impaction bone grafting. The purpose of this investigation was to assess the effects of the addition of hydroxyapatite (HA) to the scaffolds before clinical translation. PLA, PLA+10% HA, PLGA, and PLGA+10% HA were milled and impacted into discs before undergoing a standardized shear test. Cellular compatibility analysis followed 14 days incubation with human skeletal stems cells (SSC). The best two performing polymers were taken forward for in vivo analysis. SSC seeded polymer discs were implanted subcutaneously in mice. All polymers had superior mechanical shear strength compared with allograft (p bone formation on the PLA HA (p bone formation. PLA HA showed both enhanced osteoinductive and osteogenic capacity. This polymer composite has been selected for scaled-up experimentation before clinical translation. © 2013 Wiley Periodicals, Inc.

  3. Guided tissue regeneration with heterologous materials in primary subtalar arthrodesis: a case report.

    Science.gov (United States)

    Frangez, Igor; Kasnik, Tea; Cimerman, Matej; Smrke, Dragica Maja

    2016-05-03

    Calcaneal fractures are relatively rare and difficult to treat. Treatment options vary based on the type of fracture and the surgeon's experiences. In recent years, surgical procedures have increasingly been used due to the better long-term results. We present a case where guided tissue regeneration was performed in a calcaneal fracture that needed primary subtalar arthrodesis. We used the principles of guided tissue regeneration from oral surgery to perform primary subtalar arthrodesis and minimize the risk of non-union. We used a heterologous collagen membrane, which acts as a mechanical barrier and protects the bone graft from the invasion of unwanted cells that could lead to non-union. The collagenous membrane also has osteoconductive properties and is therefore able to increase the osteoblast proliferation rate. A 62-year-old Caucasian woman sustained multiple fractures of her lower limbs and spine after a fall from a ladder. Her left calcaneus had a comminuted multifragmental fracture (Sanders type IV) with severe destruction of the cartilage of her subtalar joint and depression of the Böhler's angle. Therefore, we performed primary arthrodesis of her subtalar joint with elevation of the Böhler's angle using a 7.3 mm titanium screw, a heterologous cortico-cancellous collagenated pre-hydrated bone mix, a heterologous cancellous collagenated bone wedge, and a heterologous collagen membrane (Tecnoss®, Italy). The graft was fully incorporated 12 weeks after the procedure and a year and a half later our patient walks without limping. We present a new use of guided tissue regeneration with heterologous materials that can be used to treat extensive bone defects after bone injuries. We believe that guided tissue regeneration using heterologous materials, including a heterologous collagen membrane that presents a mechanical barrier between soft tissues and bone as well as a stimulative component that enhances bone formation, could be more often used in bone surgery.

  4. 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.

  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. Epimorphic regeneration approach to tissue replacement in adult mammals

    Science.gov (United States)

    Urodeles and fetal mammals are capable of impressive epimorphic regeneration in a variety of tissues, whereas the typical default response to injury in adult mammals consists of inflammation and scar tissue formation. One component of epimorphic regeneration is the recruitment of resident progenitor...

  7. 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

  8. 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.

  9. 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.

  10. Mesenchymal Stem Cell Therapy for Nerve Regeneration and Immunomodulation after Composite Tissue Allotransplantation

    Science.gov (United States)

    2012-02-01

    10-1-0927 TITLE: Mesenchymal Stem Cell Therapy for Nerve Regeneration and Immunomodulation after Composite Tissue Allotransplantation...immunosuppression. Bone Marrow Derived Mesenchymal stem cells (BM-MSCs) are pluripotent cells, capable of differentiation along multiple mesenchymal lineages into...As part of implemented transition from University of Pittsburgh to Johns Hopkins University, we optimized our mesenchymal stem cell (MSC) isolation

  11. 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.

  12. 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.

  13. 3D printing of biomaterials with mussel-inspired nanostructures for tumor therapy and tissue regeneration.

    Science.gov (United States)

    Ma, Hongshi; Luo, Jian; Sun, Zhe; Xia, Lunguo; Shi, Mengchao; Liu, Mingyao; Chang, Jiang; Wu, Chengtie

    2016-12-01

    Primary bone cancer brings patients great sufferings. To deal with the bone defects resulted from cancer surgery, biomaterials with good bone-forming ability are necessary to repair bone defects. Meanwhile, in order to prevent possible tumor recurrence, it is essential that the remaining tumor cells around bone defects are completely killed. However, there are few biomaterials with the ability of both cancer therapy and bone regeneration until now. Here, we fabricated a 3D-printed bioceramic scaffold with a uniformly self-assembled Ca-P/polydopamine nanolayer surface. Taking advantage of biocompatibility, biodegradability and the excellent photothermal effect of polydopamine, the bifunctional scaffolds with mussel-inspired nanostructures could be used as a satisfactory and controllable photothermal agent, which effectively induced tumor cell death in vitro, and significantly inhibited tumor growth in mice. In addition, owing to the nanostructured surface, the prepared polydopamine-modified bioceramic scaffolds could support the attachment and proliferation of rabbit bone mesenchymal stem cells (rBMSCs), and significantly promoted the formation of new bone tissues in rabbit bone defects even under photothermal treatment. Therefore, the mussel-inspired nanostructures in 3D-printed bioceramic exhibited a remarkable capability for both cancer therapy and bone regeneration, offering a promising strategy to construct bifunctional biomaterials which could be widely used for therapy of tumor-induced tissue defects. Copyright © 2016 Elsevier Ltd. All rights reserved.

  14. Chitosan Composites for Bone Tissue Engineering—An Overview

    Directory of Open Access Journals (Sweden)

    Jayachandran Venkatesan

    2010-08-01

    Full Text Available Bone contains considerable amounts of minerals and proteins. Hydroxyapatite [Ca10(PO46(OH2] is one of the most stable forms of calcium phosphate and it occurs in bones as major component (60 to 65%, along with other materials including collagen, chondroitin sulfate, keratin sulfate and lipids. In recent years, significant progress has been made in organ transplantation, surgical reconstruction and the use of artificial protheses to treat the loss or failure of an organ or bone tissue. Chitosan has played a major role in bone tissue engineering over the last two decades, being a natural polymer obtained from chitin, which forms a major component of crustacean exoskeleton. In recent years, considerable attention has been given to chitosan composite materials and their applications in the field of bone tissue engineering due to its minimal foreign body reactions, an intrinsic antibacterial nature, biocompatibility, biodegradability, and the ability to be molded into various geometries and forms such as porous structures, suitable for cell ingrowth and osteoconduction. The composite of chitosan including hydroxyapatite is very popular because of the biodegradability and biocompatibility in nature. Recently, grafted chitosan natural polymer with carbon nanotubes has been incorporated to increase the mechanical strength of these composites. Chitosan composites are thus emerging as potential materials for artificial bone and bone regeneration in tissue engineering. Herein, the preparation, mechanical properties, chemical interactions and in vitro activity of chitosan composites for bone tissue engineering will be discussed.

  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. Pressure-activated microsyringe (PAM) fabrication of bioactive glass-poly(lactic-co-glycolic acid) composite scaffolds for bone tissue regeneration.

    Science.gov (United States)

    Mattioli-Belmonte, M; De Maria, C; Vitale-Brovarone, C; Baino, F; Dicarlo, M; Vozzi, G

    2017-07-01

    The aim of this work was the fabrication and characterization of bioactive glass-poly(lactic-co-glycolic acid) (PLGA) composite scaffolds mimicking the topological features of cancellous bone. Porous multilayer PLGA-CEL2 composite scaffolds were innovatively produced by a pressure-activated microsyringe (PAM) method, a CAD/CAM processing technique originally developed at the University of Pisa. In order to select the optimal formulations to be extruded by PAM, CEL2-PLGA composite films (CEL2 is an experimental bioactive SiO 2 -P 2 O 5 -CaO-MgO-Na 2 O-K 2 O glass developed at Politecnico di Torino) were produced and mechanically tested. The elastic modulus of the films increased from 30 to > 400 MPa, increasing the CEL2 amount (10-50 wt%) in the composite. The mixture containing 20 wt% CEL2 was used to fabricate 2D and 3D bone-like scaffolds composed by layers with different topologies (square, hexagonal and octagonal pores). It was observed that the increase of complexity of 2D topological structures led to an increment of the elastic modulus from 3 to 9 MPa in the composite porous monolayer. The elastic modulus of 3D multilayer scaffolds was intermediate (about 6.5 MPa) between the values of the monolayers with square and octagonal pores (corresponding to the lowest and highest complexity, respectively). MG63 osteoblast-like cells and periosteal-derived precursor cells (PDPCs) were used to assess the biocompatibility of the 3D bone-like scaffolds. A significant increase in cell proliferation between 48 h and 7 days of culture was observed for both cell phenotypes. Moreover, qRT-PCR analysis evidenced an induction of early genes of osteogenesis in PDPCs. Copyright © 2015 John Wiley & Sons, Ltd. Copyright © 2015 John Wiley & Sons, Ltd.

  17. 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

  18. Endurance Exercise Mobilizes Developmentally Early Stem Cells into Peripheral Blood and Increases Their Number in Bone Marrow: Implications for Tissue Regeneration

    OpenAIRE

    Marycz, Krzysztof; Mierzejewska, Katarzyna; Śmieszek, Agnieszka; Suszynska, Ewa; Malicka, Iwona; Kucia, Magda; Ratajczak, Mariusz Z.

    2016-01-01

    Endurance exercise has been reported to increase the number of circulating hematopoietic stem/progenitor cells (HSPCs) in peripheral blood (PB) as well as in bone marrow (BM). We therefore became interested in whether endurance exercise has the same effect on very small embryonic-like stem cells (VSELs), which have been described as a population of developmentally early stem cells residing in BM. Mice were run daily for 1 hour on a treadmill for periods of 5 days or 5 weeks. Human volunteers ...

  19. Bone tissue engineering scaffolding: computer-aided scaffolding techniques.

    Science.gov (United States)

    Thavornyutikarn, Boonlom; Chantarapanich, Nattapon; Sitthiseripratip, Kriskrai; Thouas, George A; Chen, Qizhi

    Tissue engineering is essentially a technique for imitating nature. Natural tissues consist of three components: cells, signalling systems (e.g. growth factors) and extracellular matrix (ECM). The ECM forms a scaffold for its cells. Hence, the engineered tissue construct is an artificial scaffold populated with living cells and signalling molecules. A huge effort has been invested in bone tissue engineering, in which a highly porous scaffold plays a critical role in guiding bone and vascular tissue growth and regeneration in three dimensions. In the last two decades, numerous scaffolding techniques have been developed to fabricate highly interconnective, porous scaffolds for bone tissue engineering applications. This review provides an update on the progress of foaming technology of biomaterials, with a special attention being focused on computer-aided manufacturing (Andrade et al. 2002) techniques. This article starts with a brief introduction of tissue engineering (Bone tissue engineering and scaffolds) and scaffolding materials (Biomaterials used in bone tissue engineering). After a brief reviews on conventional scaffolding techniques (Conventional scaffolding techniques), a number of CAM techniques are reviewed in great detail. For each technique, the structure and mechanical integrity of fabricated scaffolds are discussed in detail. Finally, the advantaged and disadvantage of these techniques are compared (Comparison of scaffolding techniques) and summarised (Summary).

  20. 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

  1. 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.

  2. 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.

  3. Computational model-informed design and bioprinting of cell-patterned constructs for bone tissue engineering.

    Science.gov (United States)

    Carlier, Aurélie; Skvortsov, Gözde Akdeniz; Hafezi, Forough; Ferraris, Eleonora; Patterson, Jennifer; Koç, Bahattin; Van Oosterwyck, Hans

    2016-05-17

    Three-dimensional (3D) bioprinting is a rapidly advancing tissue engineering technology that holds great promise for the regeneration of several tissues, including bone. However, to generate a successful 3D bone tissue engineering construct, additional complexities should be taken into account such as nutrient and oxygen delivery, which is often insufficient after implantation in large bone defects. We propose that a well-designed tissue engineering construct, that is, an implant with a specific spatial pattern of cells in a matrix, will improve the healing outcome. By using a computational model of bone regeneration we show that particular cell patterns in tissue engineering constructs are able to enhance bone regeneration compared to uniform ones. We successfully bioprinted one of the most promising cell-gradient patterns by using cell-laden hydrogels with varying cell densities and observed a high cell viability for three days following the bioprinting process. In summary, we present a novel strategy for the biofabrication of bone tissue engineering constructs by designing cell-gradient patterns based on a computational model of bone regeneration, and successfully bioprinting the chosen design. This integrated approach may increase the success rate of implanted tissue engineering constructs for critical size bone defects and also can find a wider application in the biofabrication of other types of tissue engineering constructs.

  4. TOPICAL REVIEW: Stem cell technology using bioceramics: hard tissue regeneration towards clinical application

    Science.gov (United States)

    Ohnishi, Hiroe; Oda, Yasuaki; Ohgushi, Hajime

    2010-02-01

    Mesenchymal stem cells (MSCs) are adult stem cells which show differentiation capabilities toward various cell lineages. We have already used MSCs for treatments of osteoarthritis, bone necrosis and bone tumor. For this purpose, culture expanded MSCs were combined with various ceramics and then implanted. Because of rejection response to allogeneic MSC implantation, we have utilized patients' own MSCs for the treatment. Bone marrow is a good cell source of MSCs, although the MSCs also exist in adipose tissue. When comparing osteogenic differentiation of these MSCs, bone marrow MSCs show more extensive bone forming capability than adipose MSCs. Thus, the bone marrow MSCs are useful for bone tissue regeneration. However, the MSCs show limited proliferation and differentiation capabilities that hindered clinical applications in some cases. Recent advances reveal that transduction of plural transcription factors into human adult cells results in generation of new type of stem cells called induced pluripotent stem cells (iPS cells). A drawback of the iPS cells for clinical applications is tumor formation after their in vivo implantation; therefore it is difficult to use iPS cells for the treatment. To circumvent the problem, we transduced a single factor of either SOX2 or NANOG into the MSCs and found high proliferation as well as osteogenic differentiation capabilities of the MSCs. The stem cells could be combined with bioceramics for clinical applications. Here, we summarize our recent technologies using adult stem cells in viewpoints of bone tissue regeneration.

  5. 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.

  6. Composite cell sheet for periodontal regeneration: crosstalk between different types of MSCs in cell sheet facilitates complex periodontal-like tissue regeneration.

    Science.gov (United States)

    Zhang, Hao; Liu, Shiyu; Zhu, Bin; Xu, Qiu; Ding, Yin; Jin, Yan

    2016-11-14

    Tissue-engineering strategies based on mesenchymal stem cells (MSCs) and cell sheets have been widely used for periodontal tissue regeneration. However, given the complexity in periodontal structure, the regeneration methods using a single species of MSC could not fulfill the requirement for periodontal regeneration. We researched the interaction between the periodontal ligament stem cells (PDLSCs) and jaw bone marrow-derived mesenchymal stem cells (JBMMSCs), and constructed a composite cell sheet comprising both of the above MSCs to regenerate complex periodontium-like structures in nude mice. Our results show that by co-culturing PDLSCs and JBMMSCs, the expressions of bone and extracellular matrix (ECM)-related genes and proteins were significantly improved in both MSCs. Further investigations showed that, compared to the cell sheet using PDLSCs or JBMMSCs, the composite stem cell sheet (CSCS), which comprises these two MSCs, expressed higher levels of bone- and ECM-related genes and proteins, and generated a composite structure more similar to the native periodontal tissue physiologically in vivo. In conclusion, our results demonstrate that the crosstalk between PDLSCs and JBMMSCs in cell sheets facilitate regeneration of complex periodontium-like structures, providing a promising new strategy for physiological and functional regeneration of periodontal tissue.

  7. 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

  8. Soft tissue aneurysmal bone cyst

    Energy Technology Data Exchange (ETDEWEB)

    Wang, X.L.; Gielen, J.L.; Delrue, F.; De Schepper, A.M.A. [Department of Radiology, Universitair Ziekenhuis Antwerpen (University of Antwerp), Wilrijkstraat 10, 2650, Edegem (Belgium); Salgado, R. [Department of Pathology, Universitair Ziekenhuis Antwerpen (University of Antwerp), Wilrijkstraat 10, 2650, Edegem (Belgium)

    2004-08-01

    A soft tissue aneurysmal bone cyst located in the right gluteus medius of a 21-year-old man is reported. On conventional radiography, the lesion demonstrated a spherically trabeculated mass with a calcific rim. On CT scan, it showed a well-organized peripheral calcification resembling a myositis ossificans. On MRI, it presented as a multilocular, cystic lesion with fluid-fluid levels. The lesion had no solid components except for intralesional septa. Although findings on imaging and histology were identical to those described in classical aneurysmal bone cyst, diagnosis was delayed because of lack of knowledge of this entity and its resemblance to the more familiar post-traumatic heterotopic ossification (myositis ossificans). (orig.)

  9. 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.

  10. Fabrication of micro/nanoporous collagen/dECM/silk-fibroin biocomposite scaffolds using a low temperature 3D printing process for bone tissue regeneration.

    Science.gov (United States)

    Lee, Hyeongjin; Yang, Gi Hoon; Kim, Minseong; Lee, JaeYoon; Huh, JunTae; Kim, GeunHyung

    2018-03-01

    Biomaterials must be biocompatible, biodegradable, and mechanically stable to be used for tissue engineering applications. Among various biomaterials, a natural-based biopolymer, collagen, has been widely applied in tissue engineering because of its outstanding biocompatibility. However, due to its low mechanical properties, collagen has been a challenge to build a desired/complex 3D porous structure with appropriate mechanical strength. To overcome this problem, in this study, we used a low temperature printing process to create a 3D porous scaffold consisting of collagen, decellularized extracellular matrix (dECM) to induce high cellular activities, and silk-fibroin (SF) to attain the proper mechanical strength. To show the feasibility of the scaffold, pre-osteoblast (MC3T3-E1) cells were grown on the fabricated scaffold. Various in vitro cellular activities (cell-viability, MTT assay, and osteogenic activity) for pure collagen, collagen/dECM, and collagen/SF/dECM scaffolds were compared. Copyright © 2017 Elsevier B.V. All rights reserved.

  11. Next Generation Tissue Engineering of Orthopedic Soft Tissue-to-Bone Interfaces

    Science.gov (United States)

    Boys, Alexander J.; McCorry, Mary Clare; Rodeo, Scott; Bonassar, Lawrence J.; Estroff, Lara A.

    2017-01-01

    Soft tissue-to-bone interfaces are complex structures that consist of gradients of extracellular matrix materials, cell phenotypes, and biochemical signals. These interfaces, called entheses for ligaments, tendons, and the meniscus, are crucial to joint function, transferring mechanical loads and stabilizing orthopedic joints. When injuries occur to connected soft tissue, the enthesis must be re-established to restore function, but due to structural complexity, repair has proven challenging. Tissue engineering offers a promising solution for regenerating these tissues. This prospective review discusses methodologies for tissue engineering the enthesis, outlined in three key design inputs: materials processing methods, cellular contributions, and biochemical factors. PMID:29333332

  12. 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.

  13. 3D-Printing Composite Polycaprolactone-Decellularized Bone Matrix Scaffolds for Bone Tissue Engineering Applications.

    Science.gov (United States)

    Rindone, Alexandra N; Nyberg, Ethan; Grayson, Warren L

    2017-05-11

    Millions of patients worldwide require bone grafts for treatment of large, critically sized bone defects from conditions such as trauma, cancer, and congenital defects. Tissue engineered (TE) bone grafts have the potential to provide a more effective treatment than current bone grafts since they would restore fully functional bone tissue in large defects. Most bone TE approaches involve a combination of stem cells with porous, biodegradable scaffolds that provide mechanical support and degrade gradually as bone tissue is regenerated by stem cells. 3D-printing is a key technique in bone TE that can be used to fabricate functionalized scaffolds with patient-specific geometry. Using 3D-printing, composite polycaprolactone (PCL) and decellularized bone matrix (DCB) scaffolds can be produced to have the desired mechanical properties, geometry, and osteoinductivity needed for a TE bone graft. This book chapter will describe the protocols for fabricating and characterizing 3D-printed PCL:DCB scaffolds. Moreover, procedures for culturing adipose-derived stem cells (ASCs) in these scaffolds in vitro will be described to demonstrate the osteoinductivity of the scaffolds.

  14. 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.

  15. 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....

  16. A comparative evaluation of freeze-dried bone allograft with and without bioabsorbable guided tissue regeneration membrane Healiguide® in the treatment of Grade II furcation defects: A clinical study

    Directory of Open Access Journals (Sweden)

    Deept Jain

    2015-01-01

    Full Text Available Background: Furcation defects represent one of the most demanding therapeutic challenges for periodontal therapy. Various treatment modalities have been tried with different success rates. The present study was undertaken to evaluate the efficacy of freeze-dried bone allograft (FDBA with and without bioabsorbable guided tissue regeneration (GTR membrane Healiguide® in the treatment of Grade II furcation defects. Materials and Methods: Ten patients with bilateral Grade II furcation defects were selected for the study. After phase I therapy, subjects were divided into two arms and treated in a split-mouth design. Ten defects were treated with FDBA alone in the control arm. Ten defects were treated with FDBA in conjunction with bioabsorbable GTR membrane Healiguide® in test arm. Clinical parameters like plaque index, gingival index, vertical probing depth, horizontal probing depth, and relative attachment level (RAL were assessed at baseline, 3 months, and 6 months postoperatively. Results: At 6 months, clinical improvement was seen in both the arms with mean pocket depth reduction of 1.2 ± 1.032 mm and 1.7 ± 0.948 mm and mean horizontal probing depth reduction being 2.1 ± 1.969 mm and 1.6 ± 1.264 mm in control and test arm, respectively. Both surgical procedures resulted in a statistically significant reduction in vertical and horizontal probing depths. Conclusion: Both the arms demonstrated a significant improvement in the probing depth, horizontal furcation depth, and RAL at 6 months postsurgery in the treatment of Grade II furcation defects. However, on the intergroup comparison, there was no statistically significant difference in the results achieved between two arms.

  17. 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

  18. In situ tissue regeneration: chemoattractants for endogenous stem cell recruitment.

    Science.gov (United States)

    Vanden Berg-Foels, Wendy S

    2014-02-01

    Tissue engineering uses cells, signaling molecules, and/or biomaterials to regenerate injured or diseased tissues. Ex vivo expanded mesenchymal stem cells (MSC) have long been a cornerstone of regeneration therapies; however, drawbacks that include altered signaling responses and reduced homing capacity have prompted investigation of regeneration based on endogenous MSC recruitment. Recent successful proof-of-concept studies have further motivated endogenous MSC recruitment-based approaches. Stem cell migration is required for morphogenesis and organogenesis during development and for tissue maintenance and injury repair in adults. A biomimetic approach to in situ tissue regeneration by endogenous MSC requires the orchestration of three main stages: MSC recruitment, MSC differentiation, and neotissue maturation. The first stage must result in recruitment of a sufficient number of MSC, capable of effecting regeneration, to the injured or diseased tissue. One of the challenges for engineering endogenous MSC recruitment is the selection of effective chemoattractant(s). The objective of this review is to synthesize and evaluate evidence of recruitment efficacy by reported chemoattractants, including growth factors, chemokines, and other more recently appreciated MSC chemoattractants. The influence of MSC tissue sources, cell culture methods, and the in vitro and in vivo environments is discussed. This growing body of knowledge will serve as a basis for the rational design of regenerative therapies based on endogenous MSC recruitment. Successful endogenous MSC recruitment is the first step of successful tissue regeneration.

  19. Piezoelectric smart biomaterials for bone and cartilage tissue engineering.

    Science.gov (United States)

    Jacob, Jaicy; More, Namdev; Kalia, Kiran; Kapusetti, Govinda

    2018-01-01

    Tissues like bone and cartilage are remodeled dynamically for their functional requirements by signaling pathways. The signals are controlled by the cells and extracellular matrix and transmitted through an electrical and chemical synapse. Scaffold-based tissue engineering therapies largely disturb the natural signaling pathways, due to their rigidity towards signal conduction, despite their therapeutic advantages. Thus, there is a high need of smart biomaterials, which can conveniently generate and transfer the bioelectric signals analogous to native tissues for appropriate physiological functions. Piezoelectric materials can generate electrical signals in response to the applied stress. Furthermore, they can stimulate the signaling pathways and thereby enhance the tissue regeneration at the impaired site. The piezoelectric scaffolds can act as sensitive mechanoelectrical transduction systems. Hence, it is applicable to the regions, where mechanical loads are predominant. The present review is mainly concentrated on the mechanism related to the electrical stimulation in a biological system and the different piezoelectric materials suitable for bone and cartilage tissue engineering.

  20. Biocompatibility and tissue regenerating capacity of crosslinked dermal sheep collagen

    NARCIS (Netherlands)

    van Wachem, P.B.; van Luyn, M.J.A.; Olde Damink, L.H.H.; Olde damink, L.H.H.; Dijkstra, Pieter J.; Feijen, Jan; Nieuwenhuis, P.

    1994-01-01

    The biocompatibility and tissue regenerating capacity of four crosslinked dermal sheep collagens (DSC) was studied. In vitro, the four DSC versions were found to be noncytotoxic or very low in cytoxicity. After subcutaneous implantation in rats, hexamethylenediisocyanatecrcrosslinked DSC (HDSC)

  1. Peptide based hydrogels for bone tissue engineering

    International Nuclear Information System (INIS)

    Ranny, H.R.; Schneider, J.P.

    2007-01-01

    Peptide hydrogels are potentially ideal scaffolds for tissue repair and regeneration due to their ability to mimic natural extra cellular matrix. The 20 amino acid peptide HPL8 (H2N- VKVKVKVKVDPP TKVKVKVKV-CONH2), has been shown to fold and self-assemble into a rigid hydrogel based on Environmental cues such as pH, salt, and temperature. Due to its environmental responsiveness, hydrogel assembly can be induced by cell culture media, allowing for 3D encapsulation of osteogenic cells. Initially, 20 cultures of MC3T3 cells proved that the hydrogel is nontoxic and sustains cellular attachment in the absence of serum proteins without altering the physical properties of the hydrogel. The cell-material structure relationship in normal and pathological conditions was further investigated by 3D encapsulation. Cell were viable for 3 weeks and grew in clonogenic spheroids. Characterization of the proliferation, differentiation and constitutive expression of various osteoblastic markers was performed using spectrophotometric methods. The well-defined, fibrillar nanostructure of the hydrogel directs the attachment and attachment and growth of osteoblast cells and dictates the mineralization of hydroxyapatite in a manner similar to bone. This study will enable control over the interaction of cellular systems with the peptide hydrogel with designs for biomedical applications of bone repair. (author)

  2. 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.

  3. 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, ...

  4. 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.

  5. 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.

  6. 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

  7. 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.

  8. 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)

  9. 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.

  10. 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.

  11. 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.

  12. Guided tissue regeneration for periodontal infra-bony defects.

    Science.gov (United States)

    Needleman, I G; Worthington, H V; Giedrys-Leeper, E; Tucker, R J

    2006-04-19

    Conventional treatment of destructive periodontal (gum) disease arrests the disease but does not usually regain the bone support or connective tissue lost in the disease process. Guided tissue regeneration (GTR) is a surgical procedure that specifically aims to regenerate the periodontal tissues when the disease is advanced and could overcome some of the limitations of conventional therapy. To assess the efficacy of GTR in the treatment of periodontal infra-bony defects measured against conventional surgery (open flap debridement (OFD)) and factors affecting outcomes. We conducted an electronic search of the Cochrane Oral Health Group Trials Register, MEDLINE and EMBASE up to April 2004. Handsearching included Journal of Periodontology, Journal of Clinical Periodontology, Journal of Periodontal Research and bibliographies of all relevant papers and review articles up to April 2004. In addition, we contacted experts/groups/companies involved in surgical research to find other trials or unpublished material or to clarify ambiguous or missing data and posted requests for data on two periodontal electronic discussion groups. Randomised, controlled trials (RCTs) of at least 12 months duration comparing guided tissue regeneration (with or without graft materials) with open flap debridement for the treatment of periodontal infra-bony defects. Furcation involvements and studies specifically treating aggressive periodontitis were excluded. Screening of possible studies and data extraction was conducted independently. The methodological quality of studies was assessed in duplicate using individual components and agreement determined by Kappa scores. Methodological quality was used in sensitivity analyses to test the robustness of the conclusions. The Cochrane Oral Health Group statistical guidelines were followed and the results expressed as mean differences (MD and 95% CI) for continuous outcomes and risk ratios (RR and 95% CI) for dichotomous outcomes calculated using

  13. 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.

  14. [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

  15. 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.

  16. Fibroblast growth factors: key players in regeneration and tissue repair.

    Science.gov (United States)

    Maddaluno, Luigi; Urwyler, Corinne; Werner, Sabine

    2017-11-15

    Tissue injury initiates a complex repair process, which in some organisms can lead to the complete regeneration of a tissue. In mammals, however, the repair of most organs is imperfect and results in scar formation. Both regeneration and repair are orchestrated by a highly coordinated interplay of different growth factors and cytokines. Among the key players are the fibroblast growth factors (FGFs), which control the migration, proliferation, differentiation and survival of different cell types. In addition, FGFs influence the expression of other factors involved in the regenerative response. Here, we summarize current knowledge on the roles of endogenous FGFs in regeneration and repair in different organisms and in different tissues and organs. Gaining a better understanding of these FGF activities is important for appropriate modulation of FGF signaling after injury to prevent impaired healing and to promote organ regeneration in humans. © 2017. Published by The Company of Biologists Ltd.

  17. Mesenchymal stem cells as a therapeutic tool in tissue and organ regeneration

    Directory of Open Access Journals (Sweden)

    Anna Bajek

    2011-01-01

    Full Text Available Tissue engineering is an interdisciplinary field that offers new opportunities for regeneration of diseased and damaged tissue with the use of many different cell types,including adult stem cells. In tissue engineering and regenerative medicine the most popular are mesenchymal stem cells (MSCs isolated from bone marrow. Bone marrow mesenchymal stem cells are a potential source of progenitor cells for osteoblasts, chondroblasts, adipocytes, skeletal muscles and cardiomyocytes. It has also been shown that these cells can differentiate into ecto- and endodermal cells, e.g. neuronal cells, glial cells, keratinocytes and hepatocytes. The availability of autologous MSCs, their proliferative potential and multilineage differentiation capacity make them an excellent tool for tissue engineering and regenerative medicine. The aim of this publication is to present characteristic and biological properties of mesenchymal stem cells isolated from bone marrow.

  18. 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

  19. 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

  20. [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.

  1. 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

  2. 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.

  3. 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.

  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. The Use of Endothelial Progenitor Cells for the Regeneration of Musculoskeletal and Neural Tissues

    Directory of Open Access Journals (Sweden)

    Naosuke Kamei

    2017-01-01

    Full Text Available Endothelial progenitor cells (EPCs derived from bone marrow and blood can differentiate into endothelial cells and promote neovascularization. In addition, EPCs are a promising cell source for the repair of various types of vascularized tissues and have been used in animal experiments and clinical trials for tissue repair. In this review, we focused on the kinetics of endogenous EPCs during tissue repair and the application of EPCs or stem cell populations containing EPCs for tissue regeneration in musculoskeletal and neural tissues including the bone, skeletal muscle, ligaments, spinal cord, and peripheral nerves. EPCs can be mobilized from bone marrow and recruited to injured tissue to contribute to neovascularization and tissue repair. In addition, EPCs or stem cell populations containing EPCs promote neovascularization and tissue repair through their differentiation to endothelial cells or tissue-specific cells, the upregulation of growth factors, and the induction and activation of endogenous stem cells. Human peripheral blood CD34(+ cells containing EPCs have been used in clinical trials of bone repair. Thus, EPCs are a promising cell source for the treatment of musculoskeletal and neural tissue injury.

  6. 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

  7. 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.

  8. 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

  9. 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

  10. 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)

  11. 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.

  12. 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.

  13. 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.

  14. P21 Deficiency Delays Regeneration of Skeletal Muscular Tissue

    OpenAIRE

    Chinzei, Nobuaki; Hayashi, Shinya; Ueha, Takeshi; Fujishiro, Takaaki; Kanzaki, Noriyuki; Hashimoto, Shingo; Sakata, Shuhei; Kihara, Shinsuke; Haneda, Masahiko; Sakai, Yoshitada; Kuroda, Ryosuke; Kurosaka, Masahiro

    2015-01-01

    The potential relationship between cell cycle checkpoint control and tissue regeneration has been indicated. Despite considerable research being focused on the relationship between p21 and myogenesis, p21 function in skeletal muscle regeneration remains unclear. To clarify this, muscle injury model was recreated by intramuscular injection of bupivacaine hydrochloride in the soleus of p21 knockout (KO) mice and wild type (WT) mice. The mice were sacrificed at 3, 14, and 28 days post-operation....

  15. 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.

  16. Image-Based, Fiber Guiding Scaffolds: A Platform for Regenerating Tissue Interfaces

    Science.gov (United States)

    Park, Chan Ho; Rios, Hector F.; Taut, Andrei D.; Padial-Molina, Miguel; Flanagan, Colleen L.; Pilipchuk, Sophia P.; Hollister, Scott J.

    2014-01-01

    In the oral and craniofacial complex, tooth loss is the most commonly acquired disfiguring injury. Among the most formidable challenges of reconstructing tooth-supporting osseous defects in the oral cavity is the regeneration of functional multi-tissue complexes involving bone, ligament, and tooth cementum. Furthermore, periodontal multi-tissue engineering with spatiotemporal orientation of the periodontal ligament (PDL) remains the most challenging obstacle for restoration of physiological loading and homeostasis. We report on the ability of a hybrid computer-designed scaffold—developed utilizing computed tomography—to predictably facilitate the regeneration and integration of dental supporting tissues. Here, we provide the protocol for rapid prototyping, manufacture, surgical implantation, and evaluation of dual-architecture scaffolds for controlling fiber orientation and facilitating morphogenesis of bone-ligament complexes. In contrast to conventional single-system methods of fibrous tissue formation, our protocol supports rigorous control of multi-compartmental scaffold architecture using computational scaffold design and manufacturing by 3D printing, as well as the evaluation of newly regenerated tissue physiology for clinical implementation. PMID:24188695

  17. 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.

  18. 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.

  19. 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

  20. Myocardial regeneration potential of adipose tissue-derived stem cells

    Energy Technology Data Exchange (ETDEWEB)

    Bai, Xiaowen, E-mail: baixw01@yahoo.com [Department of Molecular Pathology, The University of Texas M.D. Anderson Cancer Center, 1515 Holcombe, Houston, TX 77030 (United States); Alt, Eckhard, E-mail: ealt@mdanderson.org [Department of Molecular Pathology, The University of Texas M.D. Anderson Cancer Center, 1515 Holcombe, Houston, TX 77030 (United States)

    2010-10-22

    Research highlights: {yields} Various tissue resident stem cells are receiving tremendous attention from basic scientists and clinicians and hold great promise for myocardial regeneration. {yields} For practical reasons, human adipose tissue-derived stem cells are attractive stem cells for future clinical application in repairing damaged myocardium. {yields} This review summarizes the characteristics of cultured and freshly isolated stem cells obtained from adipose tissue, their myocardial regeneration potential and the, underlying mechanisms, and safety issues. -- Abstract: Various tissue resident stem cells are receiving attention from basic scientists and clinicians as they hold promise for myocardial regeneration. For practical reasons, adipose tissue-derived stem cells (ASCs) are attractive cells for clinical application in repairing damaged myocardium based on the following advantages: abundant adipose tissue in most patients and easy accessibility with minimally invasive lipoaspiration procedure. Several recent studies have demonstrated that both cultured and freshly isolated ASCs could improve cardiac function in animal model of myocardial infarction. The mechanisms underlying the beneficial effect of ASCs on myocardial regeneration are not fully understood. Growing evidence indicates that transplantation of ASCs improve cardiac function via the differentiation into cardiomyocytes and vascular cells, and through paracrine pathways. Paracrine factors secreted by injected ASCs enhance angiogenesis, reduce cell apoptosis rates, and promote neuron sprouts in damaged myocardium. In addition, Injection of ASCs increases electrical stability of the injured heart. Furthermore, there are no reported cases of arrhythmia or tumorigenesis in any studies regarding myocardial regeneration with ASCs. This review summarizes the characteristics of both cultured and freshly isolated stem cells obtained from adipose tissue, their myocardial regeneration potential, and the

  1. Designing the stem cell microenvironment for guided connective tissue regeneration.

    Science.gov (United States)

    Bogdanowicz, Danielle R; Lu, Helen H

    2017-12-01

    Adult mesenchymal stem cells (MSCs) are an attractive cell source for regenerative medicine because of their ability to self-renew and their capacity for multilineage differentiation and tissue regeneration. For connective tissues, such as ligaments or tendons, MSCs are vital to the modulation of the inflammatory response following acute injury while also interacting with resident fibroblasts to promote cell proliferation and matrix synthesis. To date, MSC injection for connective tissue repair has yielded mixed results in vivo, likely due to a lack of appropriate environmental cues to effectively control MSC response and promote tissue healing instead of scar formation. In healthy tissues, stem cells reside within a complex microenvironment comprising cellular, structural, and signaling cues that collectively maintain stemness and modulate tissue homeostasis. Changes to the microenvironment following injury regulate stem cell differentiation, trophic signaling, and tissue healing. Here, we focus on models of the stem cell microenvironment that are used to elucidate the mechanisms of stem cell regulation and inspire functional approaches to tissue regeneration. Recent studies in this frontier area are highlighted, focusing on how microenvironmental cues modulate MSC response following connective tissue injury and, more importantly, how this unique cell environment can be programmed for stem cell-guided tissue regeneration. © 2017 New York Academy of Sciences.

  2. 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.

  3. Polydeoxyribonucleotides (PDRNs) From Skin to Musculoskeletal Tissue Regeneration via Adenosine A2AReceptor Involvement.

    Science.gov (United States)

    Veronesi, Francesca; Dallari, Dante; Sabbioni, Giacomo; Carubbi, Chiara; Martini, Lucia; Fini, Milena

    2017-09-01

    Polydeoxyribonucleotides (PDRNs) are low molecular weight DNA molecules of natural origin that stimulate cell migration and growth, extracellular matrix (ECM) protein production, and reduce inflammation. Most preclinical and clinical studies on tissue regeneration with PDRNs focused on skin, and only few are about musculoskeletal tissues. Starting from an overview on skin regeneration studies, through the analysis of in vitro, in vivo, and clinical studies (1990-2016), the present review aimed at defining the effects of PDRN and their mechanisms of action in the regeneration of musculoskeletal tissues. This would also help future researches in this area. A total of 29 studies were found by PubMed and www.webofknowledge.com searches: 20 were on skin (six in vitro, six in vivo, one vitro/vivo, seven clinical studies), while the other nine regarded bone (one in vitro, two in vivo, one clinical studies), cartilage (one in vitro, one vitro/vivo, two clinical studies), or tendon (one clinical study) tissues regeneration. PDRNs improved cell growth, tissue repair, ECM proteins, physical activity, and reduced pain and inflammation, through the activation of adenosine A 2A receptor. PDRNs are currently used for bone, cartilage, and tendon diseases, with a great variability regarding the PDRN dosage to be used in clinical practice, while the dosage for skin regeneration is well established. PDRNs are usually administered from a minimum of three to a maximum of five times and they act trough the activation of A 2A receptor. Further studies are advisable to confirm the effectiveness of PDRNs and to standardize the PDRN dose. J. Cell. Physiol. 232: 2299-2307, 2017. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  4. 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.

  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. Guiding tissue regeneration with ultrasound in vitro and in vivo

    Science.gov (United States)

    Dalecki, Diane; Comeau, Eric S.; Raeman, Carol H.; Child, Sally Z.; Hobbs, Laura; Hocking, Denise C.

    2015-05-01

    Developing new technologies that enable the repair or replacement of injured or diseased tissues is a major focus of regenerative medicine. This paper will discuss three ultrasound technologies under development in our laboratories to guide tissue regeneration both in vitro and in vivo. A critical obstacle in tissue engineering is the need for rapid and effective tissue vascularization strategies. To address this challenge, we are developing acoustic patterning techniques for microvascular tissue engineering. Acoustic radiation forces associated with ultrasound standing wave fields provide a rapid, non-invasive approach to spatially pattern cells in three dimensions without affecting cell viability. Acoustic patterning of endothelial cells leads to the rapid formation of microvascular networks throughout the volumes of three-dimensional hydrogels, and the morphology of the resultant microvessel networks can be controlled by design of the ultrasound field. A second technology under development uses ultrasound to noninvasively control the microstructure of collagen fibers within engineered tissues. The microstructure of extracellular matrix proteins provides signals that direct cell functions critical to tissue regeneration. Thus, controlling collagen microfiber structure with ultrasound provides a noninvasive approach to regulate the mechanical properties of biomaterials and control cellular responses. The third technology employs therapeutic ultrasound to enhance the healing of chronic wounds. Recent studies demonstrate increased granulation tissue thickness and collagen deposition in murine dermal wounds exposed to pulsed ultrasound. In summary, ultrasound technologies offer noninvasive approaches to control cell behaviors and extracellular matrix organization and thus hold great promise to advance tissue regeneration in vitro and in vivo.

  7. 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.

  8. 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.

  9. 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.

  10. 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.

  11. 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.

  12. Treatment strategy for guided tissue regeneration in various class II furcation defect: Case series

    Directory of Open Access Journals (Sweden)

    Pushpendra Kumar Verma

    2013-01-01

    Full Text Available Periodontal regeneration is a main aspect in the treatment of teeth affected by periodontitis. Periodontal regeneration in furcation areas is quite challenging, especially when it is in interproximal region. There are several techniques used alone or in combination considered to achieve periodontal regeneration, including the bone grafts or substitutes, guided tissue regeneration (GTR, root surface modification, and biological mediators. Many factors may account for variability in response to regenerative therapy in class II furcation. This case series describes the management of class II furcation defect in a mesial interproximal region of a maxillary tooth and other with a buccal class II furcation of mandibular tooth, with the help of surgical intervention including the GTR membrane and bone graft materials. This combined treatment resulted in healthy periodontium with a radiographic evidence of alveolar bone gain in both cases. This case series demonstrates that proper diagnosis, followed by removal of etiological factors and utilizing the combined treatment modalities will restore health and function of the tooth with the severe attachment loss.

  13. NONSPECIFIC INFECTIONS OF THE BONE TISSUE

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    Zoran Golubovic

    2002-11-01

    Full Text Available Osteomyelitis represents an inflammation of the bone tissue caused by microorganisms. The cause of the inflammation can be bacteria, viruses and parasites. The bone infections are divided into specific and nonspecific. Regarding the course they take, they can be of acute or chronic form. Nonspecific bone infections are analyzed, namely, hematogenic and exogenous osteomyelitis. The most frequent complications of osteomyelitis are bone infection recidivism, pathological fractures, infection penetration into the joint, malign tissue alteration and amyloidosis as a consequence of the chronic infection.

  14. Adipose stem cell tissue-engineered construct used to treat large anterior mandibular defect: a case report and review of the clinical application of good manufacturing practice-level adipose stem cells for bone regeneration.

    Science.gov (United States)

    Sándor, George K; Tuovinen, Veikko J; Wolff, Jan; Patrikoski, Mimmi; Jokinen, Jari; Nieminen, Elina; Mannerström, Bettina; Lappalainen, Olli-Pekka; Seppänen, Riitta; Miettinen, Susanna

    2013-05-01

    Large mandibular resection defects historically have been treated using autogenous bone grafts and reconstruction plates. However, a major drawback of large autogenous bone grafts is donor-site morbidity. This report describes the replacement of a 10-cm anterior mandibular ameloblastoma resection defect, reproducing the original anatomy of the chin, using a tissue-engineered construct consisting of β-tricalcium phosphate (β-TCP) granules, recombinant human bone morphogenetic protein-2 (BMP-2), and Good Manufacturing Practice-level autologous adipose stem cells (ASCs). Unlike prior reports, 1-step in situ bone formation was used without the need for an ectopic bone-formation step. The reconstructed defect was rehabilitated with a dental implant-supported overdenture. An additive manufactured medical skull model was used preoperatively to guide the prebending of patient-specific hardware, including a reconstruction plate and titanium mesh. A subcutaneous adipose tissue sample was harvested from the anterior abdominal wall of the patient before resection and simultaneous reconstruction of the parasymphysis. ASCs were isolated and expanded ex vivo over the next 3 weeks. The cell surface marker expression profile of ASCs was similar to previously reported results and ASCs were analyzed for osteogenic differentiation potential in vitro. The expanded cells were seeded onto a scaffold consisting of β-TCP and BMP-2 and the cell viability was evaluated. The construct was implanted into the parasymphyseal defect. Ten months after reconstruction, dental implants were inserted into the grafted site, allowing harvesting of bone cores. Histologic examination and in vitro analysis of cell viability and cell surface markers were performed and prosthodontic rehabilitation was completed. ASCs in combination with β-TCP and BMP-2 offer a promising construct for the treatment of large, challenging mandibular defects without the need for ectopic bone formation and allowing

  15. 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

  16. 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.

  17. Bioactive Sr(II/Chitosan/Poly(ε-caprolactone Scaffolds for Craniofacial Tissue Regeneration. In Vitro and In Vivo Behavior

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    Itzia Rodríguez-Méndez

    2018-03-01

    Full Text Available In craniofacial tissue regeneration, the current gold standard treatment is autologous bone grafting, however, it presents some disadvantages. Although new alternatives have emerged there is still an urgent demand of biodegradable scaffolds to act as extracellular matrix in the regeneration process. A potentially useful element in bone regeneration is strontium. It is known to promote stimulation of osteoblasts while inhibiting osteoclasts resorption, leading to neoformed bone. The present paper reports the preparation and characterization of strontium (Sr containing hybrid scaffolds formed by a matrix of ionically cross-linked chitosan and microparticles of poly(ε-caprolactone (PCL. These scaffolds of relatively facile fabrication were seeded with osteoblast-like cells (MG-63 and human bone marrow mesenchymal stem cells (hBMSCs for application in craniofacial tissue regeneration. Membrane scaffolds were prepared using chitosan:PCL ratios of 1:2 and 1:1 and 5 wt % Sr salts. Characterization was performed addressing physico-chemical properties, swelling behavior, in vitro biological performance and in vivo biocompatibility. Overall, the composition, microstructure and swelling degree (≈245% of scaffolds combine with the adequate dimensional stability, lack of toxicity, osteogenic activity in MG-63 cells and hBMSCs, along with the in vivo biocompatibility in rats allow considering this system as a promising biomaterial for the treatment of craniofacial tissue regeneration.

  18. Template-Mediated Biomineralization for Bone Tissue Engineering.

    Science.gov (United States)

    Leiendecker, Alexander; Witzleben, Steffen; Schulze, Margit; Tobiasch, Edda

    2017-01-01

    Template-mediated mineralization describes a research field of materials chemistry that deals with templates influencing product formation of foremost inorganic functional materials and composites. These templates are usually organic compounds - as far as molecules with natural origin are involved, the terminology "biomineralization" or "biomimetic mineralization: is used. The present review gives insight into recent developments in the research area of bone-tissue engineering with focus on chemical templates and cell-based approaches. The review is structured as follows: (1) a brief general overview about the principle of templating and recently used template materials, (2) important analytical methods, (3) examples of template-guided mineralization of various bone-related materials, (4) natural bone mineralization, (5) scaffolds for bone-tissue regeneration and (6) cell-based therapeutic approaches. For this purpose, a literature screening with emphasis on promising potential practical applications was performed. In particular, macromolecular structures and polymer composites with relation to naturally occurring compounds were favored. Priority was given to publications of the last five years. Although the present review does not cover the whole topic to full extent, it should provide information about current trends and the most promising approaches in the research area of bone-tissue engineering based on applications of organic templates/scaffolds as well as cell-based strategies. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  19. 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...

  20. MINIMALLY INVASIVE SINGLE FLAP APPROACH WITH CONNECTIVE TISSUE WALL FOR PERIODONTAL REGENERATION

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    Kamen Kotsilkov

    2017-09-01

    Full Text Available INTRODUCTION: The destructive periodontal diseases are among the most prevalent in the human population. In some cases, bony defects are formed during the disease progression, thus sustaining deep periodontal pockets. The reconstruction of these defects is usually done with the classical techniques of bone substitutes placement and guided tissue regeneration. The clinical and histological data from the recent years, however, demonstrate the relatively low regenerative potential of these techniques. The contemporary approaches for periodontal regeneration rely on minimally invasive surgical protocols, aimed at complete tissue preservation in order to achieve and maintain primary closure and at stimulating the natural regenerative potential of the periodontal tissues. AIM: This presentation demonstrates the application of a new, minimally invasive, single flap surgical technique for periodontal regeneration in a clinical case with periodontitis and a residual deep intrabony defect. MATERIALS AND METHODS: A 37 years old patient presented with chronic generalised periodontitis. The initial therapy led to good control of the periodontal infection with a single residual deep periodontal pocket medially at 11 due to a deep intrabony defect. A single flap approach with an enamel matrix derivate application and a connective tissue wall technique were performed. The proper primary closure was obtained. RESULT: One month after surgery an initial mineralisation process in the defect was detected. At the third month, a complete clinical healing was observed. The radiographic control showed finished bone mineralisation and periodontal space recreation. CONCLUSION: In the limitation of the presented case, the minimally invasive surgical approach led to complete clinical healing and new bone formation, which could be proof for periodontal regeneration.

  1. Cellular basis of tissue regeneration by omentum.

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    Shivanee Shah

    Full Text Available The omentum is a sheet-like tissue attached to the greater curvature of the stomach and contains secondary lymphoid organs called milky spots. The omentum has been used for its healing potential for over 100 years by transposing the omental pedicle to injured organs (omental transposition, but the mechanism by which omentum helps the healing process of damaged tissues is not well understood. Omental transposition promotes expansion of pancreatic islets, hepatocytes, embryonic kidney, and neurons. Omental cells (OCs can be activated by foreign bodies in vivo. Once activated, they become a rich source for growth factors and express pluripotent stem cell markers. Moreover, OCs become engrafted in injured tissues suggesting that they might function as stem cells.Omentum consists of a variety of phenotypically and functionally distinctive cells. To understand the mechanism of tissue repair support by the omentum in more detail, we analyzed the cell subsets derived from the omentum on immune and inflammatory responses. Our data demonstrate that the omentum contains at least two groups of cells that support tissue repair, immunomodulatory myeloid derived suppressor cells and omnipotent stem cells that are indistinguishable from mesenchymal stem cells. Based on these data, we propose that the omentum is a designated organ for tissue repair and healing in response to foreign invasion and tissue damage.

  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. 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.

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

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    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.

  5. Fibrogenic Cell Plasticity Blunts Tissue Regeneration and Aggravates Muscular Dystrophy

    Directory of Open Access Journals (Sweden)

    Patrizia Pessina

    2015-06-01

    Full Text Available Preservation of cell identity is necessary for homeostasis of most adult tissues. This process is challenged every time a tissue undergoes regeneration after stress or injury. In the lethal Duchenne muscular dystrophy (DMD, skeletal muscle regenerative capacity declines gradually as fibrosis increases. Using genetically engineered tracing mice, we demonstrate that, in dystrophic muscle, specialized cells of muscular, endothelial, and hematopoietic origins gain plasticity toward a fibrogenic fate via a TGFβ-mediated pathway. This results in loss of cellular identity and normal function, with deleterious consequences for regeneration. Furthermore, this fibrogenic process involves acquisition of a mesenchymal progenitor multipotent status, illustrating a link between fibrogenesis and gain of progenitor cell functions. As this plasticity also was observed in DMD patients, we propose that mesenchymal transitions impair regeneration and worsen diseases with a fibrotic component.

  6. Mechanochemical synthesis evaluation of nanocrystalline bone-derived bioceramic powder using for bone tissue engineering

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    Amirsalar Khandan

    2014-01-01

    Full Text Available Introduction: Bone tissue engineering proposes a suitable way to regenerate lost bones. Different materials have been considered for use in bone tissue engineering. Hydroxyapatite (HA is a significant success of bioceramics as a bone tissue repairing biomaterial. Among different bioceramic materials, recent interest has been risen on fluorinated hydroxyapatites, (FHA, Ca 10 (PO 4 6 F x (OH 2−x . Fluorine ions can promote apatite formation and improve the stability of HA in the biological environments. Therefore, they have been developed for bone tissue engineering. The aim of this study was to synthesize and characterize the FHA nanopowder via mechanochemical (MC methods. Materials and Methods: Natural hydroxyapatite (NHA 95.7 wt.% and calcium fluoride (CaF 2 powder 4.3 wt.% were used for synthesis of FHA. MC reaction was performed in the planetary milling balls using a porcelain cup and alumina balls. Ratio of balls to reactant materials was 15:1 at 400 rpm rotation speed. The structures of the powdered particles formed at different milling times were evaluated by X-ray diffraction (XRD, scanning electron microscopy (SEM and transmission electron microscopy (TEM. Results: Fabrication of FHA from natural sources like bovine bone achieved after 8 h ball milling with pure nanopowder. Conclusion: F− ion enhances the crystallization and mechanical properties of HA in formation of bone. The produced FHA was in nano-scale, and its crystal size was about 80-90 nm with sphere distribution in shape and size. FHA powder is a suitable biomaterial for bone tissue engineering.

  7. Carbon Nanoparticle Enhance Photoacoustic Imaging and Therapy for Bone Tissue Engineering

    Science.gov (United States)

    Talukdar, Yahfi

    Healing critical sized bone defects has been a challenge that led to innovations in tissue engineering scaffolds and biomechanical stimulations that enhance tissue regeneration. Carbon nanocomposite scaffolds have gained interest due to their enhanced mechanical properties. However, these scaffolds are only osteoconductive and not osteoinductive. Stimulating regeneration of bone tissue, osteoinductivity, has therefore been a subject of intense research. We propose the use of carbon nanoparticle enhanced photoacoustic (PA) stimulation to promote and enhance tissue regeneration in bone tissue-engineering scaffolds. In this study we test the feasibility of using carbon nanoparticles and PA for in vivo tissue engineering applications. To this end, we investigate 1) the effect of carbon nanoparticles, such as graphene oxide nanoplatelets (GONP), graphene oxide nano ribbons (GONR) and graphene nano onions (GNO), in vitro on mesenchymal stem cells (MSC), which are crucial for bone regeneration; 2) the use of PA imaging to detect and monitor tissue engineering scaffolds in vivo; and 3) we demonstrate the potential of carbon nanoparticle enhanced PA stimulation to promote tissue regeneration and healing in an in vivo rat fracture model. The results from these studies demonstrate that carbon nanoparticles such as GNOP, GONR and GNO do not affect viability or differentiation of MSCs and could potentially be used in vivo for tissue engineering applications. Furthermore, PA imaging can be used to detect and longitudinally monitor subcutaneously implanted carbon nanotubes incorporated polymeric nanocomposites in vivo. Oxygen saturation data from PA imaging could also be used as an indicator for tissue regeneration within the scaffolds. Lastly, we demonstrate that daily stimulation with carbon nanoparticle enhanced PA increases bone fracture healing. Rats stimulated for 10 minutes daily for two weeks showed 3 times higher new cortical bone BV/TV and 1.8 times bone mineral density

  8. 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.

  9. 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.

  10. 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.

  11. Drug delivery using composite scaffolds in the context of bone tissue engineering

    Science.gov (United States)

    Romagnoli, Cecilia; D’Asta, Federica; Brandi, Maria Luisa

    2013-01-01

    Summary Introduction Due to the disadvantages of the current bone autograft and allograft in many clinical condition in which bone regeneration is required in large quantity, engineered biomaterials combined with growth factors, such as bone morphogenetic protein-2 (BMP-2), have been demonstrated to be an effective approach in bone tissue engineering, since they can act both as a scaffold and as a drug delivery system to promote bone repair and regeneration. Area covered Recent advantages in the field of engineered scaffolds have been obtained from the investigation of composite scaffolds designed by the combination of bioceramics, especially hydroxyapatite (HA), and biodegradable polymers, such as poly (D,L-lactide-co-glycolide) (PLGA) and chitosan, in order to realize osteoconductive structures that can mimic the natural properties of bone tissue. Herein it is demonstrated that the incorporation of BMP-2 into different composite scaffolds, by encapsulation, absorption or entrapment, could be advantageous in terms of osteoinduction for new bone tissue engineered scaffolds as drug delivery systems and some of them should be further analyzed to optimized the drug release for future therapeutic applications. Expert opinion New design concepts and fabrication techniques represent novel challenges for further investigations about the development of scaffolds as a drug delivery system for bone tissue regeneration. PMID:24554923

  12. 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...

  13. 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

  14. 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.

  15. The materials used in bone tissue engineering

    Energy Technology Data Exchange (ETDEWEB)

    Tereshchenko, V. P., E-mail: tervp@ngs.ru; Kirilova, I. A.; Sadovoy, M. A.; Larionov, P. M. [Novosibirsk Research Institute of Traumatology and Orthopedics n.a. Ya.L. Tsivyan, Novosibirsk (Russian Federation)

    2015-11-17

    Bone tissue engineering looking for an alternative solution to the problem of skeletal injuries. The method is based on the creation of tissue engineered bone tissue equivalent with stem cells, osteogenic factors, and scaffolds - the carriers of these cells. For production of tissue engineered bone equivalent is advisable to create scaffolds similar in composition to natural extracellular matrix of the bone. This will provide optimal conditions for the cells, and produce favorable physico-mechanical properties of the final construction. This review article gives an analysis of the most promising materials for the manufacture of cell scaffolds. Biodegradable synthetic polymers are the basis for the scaffold, but it alone cannot provide adequate physical and mechanical properties of the construction, and favorable conditions for the cells. Addition of natural polymers improves the strength characteristics and bioactivity of constructions. Of the inorganic compounds, to create cell scaffolds the most widely used calcium phosphates, which give the structure adequate stiffness and significantly increase its osteoinductive capacity. Signaling molecules do not affect the physico-mechanical properties of the scaffold, but beneficial effect is on the processes of adhesion, proliferation and differentiation of cells. Biodegradation of the materials will help to fulfill the main task of bone tissue engineering - the ability to replace synthetic construct by natural tissues that will restore the original anatomical integrity of the bone.

  16. The materials used in bone tissue engineering

    Science.gov (United States)

    Tereshchenko, V. P.; Kirilova, I. A.; Sadovoy, M. A.; Larionov, P. M.

    2015-11-01

    Bone tissue engineering looking for an alternative solution to the problem of skeletal injuries. The method is based on the creation of tissue engineered bone tissue equivalent with stem cells, osteogenic factors, and scaffolds - the carriers of these cells. For production of tissue engineered bone equivalent is advisable to create scaffolds similar in composition to natural extracellular matrix of the bone. This will provide optimal conditions for the cells, and produce favorable physico-mechanical properties of the final construction. This review article gives an analysis of the most promising materials for the manufacture of cell scaffolds. Biodegradable synthetic polymers are the basis for the scaffold, but it alone cannot provide adequate physical and mechanical properties of the construction, and favorable conditions for the cells. Addition of natural polymers improves the strength characteristics and bioactivity of constructions. Of the inorganic compounds, to create cell scaffolds the most widely used calcium phosphates, which give the structure adequate stiffness and significantly increase its osteoinductive capacity. Signaling molecules do not affect the physico-mechanical properties of the scaffold, but beneficial effect is on the processes of adhesion, proliferation and differentiation of cells. Biodegradation of the materials will help to fulfill the main task of bone tissue engineering - the ability to replace synthetic construct by natural tissues that will restore the original anatomical integrity of the bone.

  17. Electrospun F18 Bioactive Glass/PCL—Poly (ε-caprolactone—Membrane for Guided Tissue Regeneration

    Directory of Open Access Journals (Sweden)

    Lucas Hidalgo Pitaluga

    2018-03-01

    Full Text Available Barrier membranes that are used for guided tissue regeneration (GTR therapy usually lack bioactivity and the capability to promote new bone tissue formation. However, the incorporation of an osteogenic agent into polymeric membranes seems to be the most assertive strategy to enhance their regenerative potential. Here, the manufacturing of composite electrospun membranes made of poly (ε-caprolactone (PCL and particles of a novel bioactive glass composition (F18 is described. The membranes were mechanically and biologically tested with tensile strength tests and tissue culture with MG-63 osteoblast-like cell line, respectively. The PCL-F18 composite membranes demonstrated no increased cytotoxicity and an enhanced osteogenic potential when compared to pure PCL membranes. Moreover, the addition of the bioactive phase increased the membrane tensile strength. These preliminary results suggested that these new membranes can be a strong candidate for small bone injuries treatment by GTR technique.

  18. [Mechanical strength and mechano-compatibility of tissue-engineered bones].

    Science.gov (United States)

    Tanaka, Shigeo

    2016-01-01

    Current artificial bones made of metals and ceramics may be replaced around a decade after implantation due to its low durability, which is brought on by a large difference from the host bone in mechanical properties, i.e., low mechano-compatibility. On the other hand, tissue engineering could be a solution with regeneration of bone tissues from stem cells in vitro. However, there are still some problems to realize exactly the same mechanical properties as those of real bone. This paper introduces the technical background of bone tissue engineering and discusses possible methods for installation of mechano-compatibility into a regenerative bone. At the end, future directions toward the realization of ideal mechano-compatible regenerative bone are proposed.

  19. Potential of Osteoblastic Cells Derived from Bone Marrow and Adipose Tissue Associated with a Polymer/Ceramic Composite to Repair Bone Tissue.

    Science.gov (United States)

    Freitas, Gileade P; Lopes, Helena B; Almeida, Adriana L G; Abuna, Rodrigo P F; Gimenes, Rossano; Souza, Lucas E B; Covas, Dimas T; Beloti, Marcio M; Rosa, Adalberto L

    2017-09-01

    One of the tissue engineering strategies to promote bone regeneration is the association of cells and biomaterials. In this context, the aim of this study was to evaluate if cell source, either from bone marrow or adipose tissue, affects bone repair induced by osteoblastic cells associated with a membrane of poly(vinylidene-trifluoroethylene)/barium titanate (PVDF-TrFE/BT). Mesenchymal stem cells (MSC) were isolated from rat bone marrow and adipose tissue and characterized by detection of several surface markers. Also, both cell populations were cultured under osteogenic conditions and it was observed that MSC from bone marrow were more osteogenic than MSC from adipose tissue. The bone repair was evaluated in rat calvarial defects implanted with PVDF-TrFE/BT membrane and locally injected with (1) osteoblastic cells differentiated from MSC from bone marrow, (2) osteoblastic cells differentiated from MSC from adipose tissue or (3) phosphate-buffered saline. Luciferase-expressing osteoblastic cells derived from bone marrow and adipose tissue were detected in bone defects after cell injection during 25 days without difference in luciferin signal between cells from both sources. Corroborating the in vitro findings, osteoblastic cells from bone marrow combined with the PVDF-TrFE/BT membrane increased the bone formation, whereas osteoblastic cells from adipose tissue did not enhance the bone repair induced by the membrane itself. Based on these findings, it is possible to conclude that, by combining a membrane with cells in this rat model, cell source matters and that bone marrow could be a more suitable source of cells for therapies to engineer bone.

  20. 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

  1. 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

  2. Tissue engineering bone using autologous progenitor cells in the peritoneum.

    Science.gov (United States)

    Shen, Jinhui; Nair, Ashwin; Saxena, Ramesh; Zhang, Cheng Cheng; Borrelli, Joseph; Tang, Liping

    2014-01-01

    Despite intensive research efforts, there remains a need for novel methods to improve the ossification of scaffolds for bone tissue engineering. Based on a common phenomenon and known pathological conditions of peritoneal membrane ossification following peritoneal dialysis, we have explored the possibility of regenerating ossified tissue in the peritoneum. Interestingly, in addition to inflammatory cells, we discovered a large number of multipotent mesenchymal stem cells (MSCs) in the peritoneal lavage fluid from mice with peritoneal catheter implants. The osteogenic potential of these peritoneal progenitor cells was demonstrated by their ability to easily infiltrate decalcified bone implants, produce osteocalcin and form mineralized bone in 8 weeks. Additionally, when poly(l-lactic acid) scaffolds loaded with bone morphogenetic protein-2 (a known osteogenic differentiation agent) were implanted into the peritoneum, signs of osteogenesis were seen within 8 weeks of implantation. The results of this investigation support the concept that scaffolds containing BMP-2 can stimulate the formation of bone in the peritoneum via directed autologous stem and progenitor cell responses.

  3. Endogenous Ion Dynamics in Cell Motility and Tissue Regeneration

    International Nuclear Information System (INIS)

    Özkucur, N; Perike, S; Epperlein, H H; Funk, R H W

    2011-01-01

    Directional cell migration is an essential process, including regeneration of tissues, wound healing, and embryonic development. Cells achieve persistent directional migration by polarizing the spatiotemporal components involved in the morphological polarity. Ion transporter proteins situated at the cell membrane generates small electric fields that can induce directional cell motility. Besides them, externally applied direct current electric fields induce similar kind of responses as cell orientation and directional migration. However, the bioelectric mechanisms that lead to cellular directedness are poorly understood. Therefore, understanding the bioelectric signaling cues can serve as a powerful modality in controlling the cell behaviour, which can contribute additional insights for development and regeneration.

  4. Bone tissue bioprinting for craniofacial reconstruction.

    Science.gov (United States)

    Datta, Pallab; Ozbolat, Veli; Ayan, Bugra; Dhawan, Aman; Ozbolat, Ibrahim T

    2017-11-01

    Craniofacial (CF) tissue is an architecturally complex tissue consisting of both bone and soft tissues with significant patient specific variations. Conditions of congenital abnormalities, tumor resection surgeries, and traumatic injuries of the CF skeleton can result in major deficits of bone tissue. Despite advances in surgical reconstruction techniques, management of CF osseous deficits remains a challenge. Due its inherent versatility, bioprinting offers a promising solution to address these issues. In this review, we present and analyze the current state of bioprinting of bone tissue and highlight how these techniques may be adapted to serve regenerative therapies for CF applications. Biotechnol. Bioeng. 2017;114: 2424-2431. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

  5. Promoting tissue regeneration by modulating the immune system.

    Science.gov (United States)

    Julier, Ziad; Park, Anthony J; Briquez, Priscilla S; Martino, Mikaël M

    2017-04-15

    The immune system plays a central role in tissue repair and regeneration. Indeed, the immune response to tissue injury is crucial in determining the speed and the outcome of the healing process, including the extent of scarring and the restoration of organ function. Therefore, controlling immune components via biomaterials and drug delivery systems is becoming an attractive approach in regenerative medicine, since therapies based on stem cells and growth factors have not yet proven to be broadly effective in the clinic. To integrate the immune system into regenerative strategies, one of the first challenges is to understand the precise functions of the different immune components during the tissue healing process. While remarkable progress has been made, the immune mechanisms involved are still elusive, and there is indication for both negative and positive roles depending on the tissue type or organ and life stage. It is well recognized that the innate immune response comprising danger signals, neutrophils and macrophages modulates tissue healing. In addition, it is becoming evident that the adaptive immune response, in particular T cell subset activities, plays a critical role. In this review, we first present an overview of the basic immune mechanisms involved in tissue repair and regeneration. Then, we highlight various approaches based on biomaterials and drug delivery systems that aim at modulating these mechanisms to limit fibrosis and promote regeneration. We propose that the next generation of regenerative therapies may evolve from typical biomaterial-, stem cell-, or growth factor-centric approaches to an immune-centric approach. Most regenerative strategies have not yet proven to be safe or reasonably efficient in the clinic. In addition to stem cells and growth factors, the immune system plays a crucial role in the tissue healing process. Here, we propose that controlling the immune-mediated mechanisms of tissue repair and regeneration may support

  6. 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

  7. Histological Features and Biocompatibility of Bone and Soft Tissue Substitutes in the Atrophic Alveolar Ridge Reconstruction

    Directory of Open Access Journals (Sweden)

    Carlo Maiorana

    2016-01-01

    Full Text Available The reconstruction of the atrophic alveolar ridges for implant placement is today a common procedure in dentistry daily practice. The surgical reconstruction provides for the optimization of the supporting bone for the implants and a restoration of the amount of keratinized gingiva for esthetic and functional reasons. In the past, tissue regeneration has been performed with autogenous bone and free gingival or connective tissue grafts. Nowadays, bone substitutes and specific collagen matrix allow for a complete restoration of the atrophic ridge without invasive harvesting procedures. A maxillary reconstruction of an atrophic ridge by means of tissue substitutes and its histological features are then presented.

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

    Science.gov (United States)

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

    2015-12-09

    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.

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

    Directory of Open Access Journals (Sweden)

    Qi Li

    2014-05-01

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

  10. 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...

  11. Nanostructured Biomaterials for Tissue Engineered Bone Tissue Reconstruction

    Directory of Open Access Journals (Sweden)

    Bressan Eriberto

    2012-01-01

    Full Text Available Bone tissue engineering strategies are emerging as attractive alternatives to autografts and allografts in bone tissue reconstruction, in particular thanks to their association with nanotechnologies. Nanostructured biomaterials, indeed, mimic the extracellular matrix (ECM of the natural bone, creating an artificial microenvironment that promotes cell adhesion, proliferation and differentiation. At the same time, the possibility to easily isolate mesenchymal stem cells (MSCs from different adult tissues together with their multi-lineage differentiation potential makes them an interesting tool in the field of bone tissue engineering. This review gives an overview of the most promising nanostructured biomaterials, used alone or in combination with MSCs, which could in future be employed as bone substitutes. Recent works indicate that composite scaffolds made of ceramics/metals or ceramics/polymers are undoubtedly more effective than the single counterparts in terms of osteoconductivity, osteogenicity and osteoinductivity. A better understanding of the interactions between MSCs and nanostructured biomaterials will surely contribute to the progress of bone tissue engineering.

  12. Role of pore size and morphology in musculo-skeletal tissue regeneration

    Energy Technology Data Exchange (ETDEWEB)

    Perez, Roman A., E-mail: romanp@dankook.ac.kr [Department of Nanobiomedical Science & BK21 PLUS NBM Global Research Center for Regenerative Medicine, Dankook University, Cheonan 330-714 (Korea, Republic of); Institute of Tissue Regeneration Engineering (ITREN), Dankook University, Cheonan 330-714 (Korea, Republic of); Mestres, Gemma [Department of Engineering Sciences, Uppsala University, Box 534, 751 21 Uppsala (Sweden)

    2016-04-01

    Biomaterials in the form of scaffolds hold great promise in the regeneration of diseased tissues. The scaffolds stimulate cellular adhesion, proliferation and differentiation. While the scaffold composition will dictate their biocompatibility, their porosity plays a key role in allowing proper cell penetration, nutrient diffusion as well as bone ingrowth. Porous scaffolds are processed with the help of a wide variety of techniques. Designing scaffolds with the appropriate porosity is a complex issue since this may jeopardize other physico-chemical properties. From a macroscopic point of view, parameters such as the overall architecture, pore morphology, interconnectivity and pore size distribution, have unique roles in allowing bone ingrowth to take place. From a microscopic perspective, the adsorption and retention of proteins in the microporosities of the material will dictate the subsequent cell adhesion. Therefore, the microstructure of the substrate can determine cell proliferation as well as the expression of specific osteogenic genes. This review aims at discussing the effect of micro- and macroporosity on the physico-chemical and biological properties of scaffolds for musculo-skeletal tissue regeneration. - Highlights: • Osteoconduction and osteoinduction of a biomaterial relies on its pattern of micro/macroporosity. • Size, morphology, distribution and interconnection of the pores influence both mechanical and biological properties. • Macroporosity (pores > 50 μm) determines cell colonization and therefore growth of vascular and bone tissue. • Micropores (< 50 μm) are crucial for proteins adsorption, which in turn can determine cell fate.

  13. Photosensitive materials and potential of photocurrent mediated tissue regeneration.

    Science.gov (United States)

    Jin, Guorui; Prabhakaran, Molamma P; Liao, Susan; Ramakrishna, Seeram

    2011-02-07

    Photocurrent therapy with participation of light and electrical stimulations could be an innovative and promising approach in regenerative medicine, especially for skin and nerve regeneration. Photocurrent is generated when light irradiates on a photosensitive device, and with more and more types of photosensitive materials being synthesized, photocurrent could be applied for enhanced regeneration of tissue. Photosensitive scaffolds such as composite poly (3-hexylthiophene)/polycaprolactone (P3HT/PCL) nanofibers are fabricated by electrospinning process in our lab for skin regeneration in presence of applied photocurrent. This review article discuss on the various in vitro, in vivo and clinical studies that utilized the principle of 'electrotherapy' and 'phototherapy' for regenerative medicine and evaluates the potential application of photocurrent in regenerative medicine. We conclude that photocurrent therapy will play an important role in regenerative medicine. Copyright © 2010 Elsevier B.V. All rights reserved.

  14. Immobilization of Murine Anti-BMP-2 Monoclonal Antibody on Various Biomaterials for Bone Tissue Engineering

    Directory of Open Access Journals (Sweden)

    Sahar Ansari

    2014-01-01

    Full Text Available Biomaterials are widely used as scaffolds for tissue engineering. We have developed a strategy for bone tissue engineering that entails application of immobilized anti-BMP-2 monoclonal antibodies (mAbs to capture endogenous BMPs in vivo and promote antibody-mediated osseous regeneration (AMOR. The purpose of the current study was to compare the efficacy of immobilization of a specific murine anti-BMP-2 mAb on three different types of biomaterials and to evaluate their suitability as scaffolds for AMOR. Anti-BMP-2 mAb or isotype control mAb was immobilized on titanium (Ti microbeads, alginate hydrogel, and ACS. The treated biomaterials were surgically implanted in rat critical-sized calvarial defects. After 8 weeks, de novo bone formation was assessed using micro-CT and histomorphometric analyses. Results showed de novo bone regeneration with all three scaffolds with immobilized anti-BMP-2 mAb, but not isotype control mAb. Ti microbeads showed the highest volume of bone regeneration, followed by ACS. Alginate showed the lowest volume of bone. Localization of BMP-2, -4, and -7 antigens was detected on all 3 scaffolds with immobilized anti-BMP-2 mAb implanted in calvarial defects. Altogether, these data suggested a potential mechanism for bone regeneration through entrapment of endogenous BMP-2, -4, and -7 proteins leading to bone formation using different types of scaffolds via AMOR.

  15. 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.

  16. The (re)generation of splenic tissue

    Science.gov (United States)

    Hovius, J W R; Verberne, H J; Bennink, R J; Blok, W L

    2010-01-01

    A 48-year-old man with a history of a traumatic splenic rupture followed by splenectomy at the age of 5 years was referred to the outpatient clinic with markedly elevated liver enzymes. He was diagnosed with alcoholic liver cirrhosis. Ultrasound of the upper abdomen revealed hepatomegaly and suggested a central mass in the liver. Subsequent MRI of the abdomen did not show a hepatic mass, but revealed multiple intraperitoneal and retroperitoneal ovoid structures with a maximum diameter of 3 cm. A peripheral blood smear did not reveal Howell-Jolly bodies suggesting intact splenic function. The diagnosis splenosis—that is, autotransplantation of splenic tissue after iatrogenic/traumatic rupture of the spleen—was considered and confirmed by SPECT-CT with technetium-99m (99mTc) labelled heat-denatured autologous red blood cells. PMID:22778202

  17. 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.

  18. 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.

  19. 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.

  20. Efficacy of Connective Tissue with and without Periosteum in Regeneration of Intrabony Defects

    Directory of Open Access Journals (Sweden)

    Vahid Esfahanian

    2014-12-01

    Full Text Available Background and aims. Connective tissue grafts with and without periosteum is used in regenerative treatments of bone and has demonstrated successful outcomes in previous investigations. The aim of present study was to evaluate the effec-tiveness of connective tissue graft with and without periosteum in regeneration of intrabony defects. Materials and methods. In this single-blind randomized split-mouth clinical trial, 15 pairs of intrabony defects in 15 pa-tients with moderate to advanced periodontitis were treated by periosteal connective tissue graft + ABBM (test group or non-periosteal connective tissue graft + ABBM (control group. Probing pocket depth, clinical attachment level, free gingi-val margin position, bone crestal position, crest defect depth and defect depth to stent were measured at baseline and after six months by surgical re-entry. Data was analyzed by Student’s t-test and paired t-tests (α=0.05. Results. Changes in clinical parameters after 6 months in the test and control groups were as follows: mean of PPD reduc-tion: 3.1±0.6 (P<0.0001; 2.5±1.0 mm (P<0.0001, CAL gain: 2.3±0.9 (P<0.0001; 2.2±1.0 mm (P<0.0001, bone fill: 2.2±0.7 mm (P<0.0001; 2.2±0.7 mm (P<0.0001, respectively. No significant differences in the position of free gingival margin were observed during 6 months compared to baseline in both groups. Conclusion. Combinations of periosteal connective tissue graft + ABBM and non-periosteal connective tissue graft + ABBM were similarly effective in treating intrabony defects without any favor for any group. Connective tissue and perio-steum can be equally effective in regeneration of intrabony defects.

  1. 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...

  2. Biomimetic extracellular matrix mediated somatic stem cell differentiation: applications in dental pulp tissue regeneration.

    Science.gov (United States)

    Ravindran, Sriram; George, Anne

    2015-01-01

    Dental caries is one of the most widely prevalent infectious diseases in the world. It affects more than half of the world's population. The current treatment for necrotic dental pulp tissue arising from dental caries is root canal therapy. This treatment results in loss of tooth sensitivity and vitality making it prone for secondary infections. Over the past decade, several tissue-engineering approaches have attempted regeneration of the dental pulp tissue. Although several studies have highlighted the potential of dental stem cells, none have transitioned into a clinical setting owing to limited availability of dental stem cells and the need for growth factor delivery systems. Our strategy is to utilize the intact ECM of pulp cells to drive lineage specific differentiation of bone marrow derived mesenchymal stem cells. From a clinical perspective, pulp ECM scaffolds can be generated using cell lines and patient specific somatic stem cells can be used for regeneration. Our published results have shown the feasibility of using pulp ECM scaffolds for odontogenic differentiation of non-dental mesenchymal cells. This focused review discusses the issues surrounding dental pulp tissue regeneration and the potential of our strategy to overcome these issues.

  3. Biomimetic Extracellular Matrix Mediated Somatic Stem Cell Differentiation: Applications in Dental Pulp Tissue Regeneration.

    Directory of Open Access Journals (Sweden)

    Sriram eRavindran

    2015-04-01

    Full Text Available Dental caries is one of the most widely prevalent infectious diseases in the world. It affects more than half of the world’s population. The current treatment for necrotic dental pulp tissue arising from dental caries is root canal therapy. This treatment results in loss of tooth sensitivity and vitality making it prone for secondary infections. Over the past decade, several tissue-engineering approaches have attempted regeneration of the dental pulp tissue. Although several studies have highlighted the potential of dental stem cells, none have transitioned into a clinical setting owing to limited availability of dental stem cells and the need for growth factor delivery systems. Our strategy is to utilize the intact ECM of pulp cells to drive lineage specific differentiation of bone marrow derived mesenchymal stem cells. From a clinical perspective, pulp ECM scaffolds can be generated using cell lines and patient specific somatic stem cells can be used for regeneration. Our published results have shown the feasibility of using pulp ECM scaffolds for odontogenic differentiation of non-dental mesenchymal cells. This focused review discusses the issues surrounding dental pulp tissue regeneration and the potential of our strategy to overcome these issues.

  4. Dental Pulp Stem Cells as a multifaceted tool for bioengineering and the regeneration of craniomaxillofacial tissues

    Directory of Open Access Journals (Sweden)

    Maitane eAurrekoetxea

    2015-10-01

    Full Text Available Dental pulp stem cells, or DPSC, are neural crest-derived cells with an outstanding capacity to differentiate along multiple cell lineages of interest for cell therapy. In particular, highly efficient osteo/dentinogenic differentiation of DPSC can be achieved using simple in vitro protocols, making these cells a very attractive and promising tool for the future treatment of dental and periodontal diseases. Among craniomaxillofacial organs, the tooth and salivary gland are two such cases in which complete regeneration by tissue engineering using DPSC appears to be possible, as research over the last decade has made substantial progress in experimental models of partial or total regeneration of both organs, by cell recombination technology. Moreover, DPSC seem to be a particularly good choice for the regeneration of nerve tissues, including injured or transected cranial nerves. In this context, the oral cavity appears to be an excellent testing ground for new regenerative therapies using DPSC. However, many issues and challenges need yet to be addressed before these cells can be employed in clinical therapy. In this review, we point out some important aspects on the biology of DPSC with regard to their use for the reconstruction of different craniomaxillofacial tissues and organs, with special emphasis on cranial bones, nerves, teeth, and salivary glands. We suggest new ideas and strategies to fully exploit the capacities of DPSC for bioengineering of the aforementioned tissues.

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

    Directory of Open Access Journals (Sweden)

    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.

  6. The Evaluation of the Possibilities of Using PLGA Co-Polymer and Its Composites with Carbon Fibers or Hydroxyapatite in the Bone Tissue Regeneration Process – in Vitro and in Vivo Examinations

    Science.gov (United States)

    Cieślik, Magdalena; Mertas, Anna; Morawska-Chochólł, Anna; Sabat, Daniel; Orlicki, Rajmund; Owczarek, Aleksander; Król, Wojciech; Cieślik, Tadeusz

    2009-01-01

    Synthetic polymers belonging to the aliphatic polyester group have become highly promising biomaterials for reconstructive medicine. The purpose of the present work is a biological evaluation of lactide-glycolide co-polymer (PLGA) and its composites with carbon fibers (PLGA+CF) or hydroxyapatite (PLGA+HA). The cytotoxicity of the evaluated materials towards hFOB 1.19 human osteoblast-like cells was assessed. Moreover, during the one-year contact of the assessed materials with living osseous tissue, the progress of bone formation was analyzed and the accompanying process of the materials’ degradation was evaluated. The materials under evaluation proved to be biocompatible. PMID:19742134

  7. The Evaluation of the Possibilities of Using PLGA Co-Polymer and Its Composites with Carbon Fibers or Hydroxyapatite in the Bone Tissue Regeneration Process – in Vitro and in Vivo Examinations

    Directory of Open Access Journals (Sweden)

    Tadeusz Cieślik

    2009-07-01

    Full Text Available Synthetic polymers belonging to the aliphatic polyester group have become highly promising biomaterials for reconstructive medicine. The purpose of the present work is a biological evaluation of lactide-glycolide co-polymer (PLGA and its composites with carbon fibers (PLGA+CF or hydroxyapatite (PLGA+HA. The cytotoxicity of the evaluated materials towards hFOB 1.19 human osteoblast-like cells was assessed. Moreover, during the one-year contact of the assessed materials with living osseous tissue, the progress of bone formation was analyzed and the accompanying process of the materials’ degradation was evaluated. The materials under evaluation proved to be biocompatible.

  8. Bioactive glasses beyond bone and teeth: emerging applications in contact with soft tissues.

    Science.gov (United States)

    Miguez-Pacheco, Valentina; Hench, Larry L; Boccaccini, Aldo R

    2015-02-01

    The applications of bioactive glasses (BGs) have to a great extent been related to the replacement, regeneration and repair of hard tissues, such as bone and teeth, and there is an extensive bibliography documenting the role of BGs as bone replacement materials and in bone tissue engineering applications. Interestingly, many of the biochemical reactions arising from the contact of BGs with bodily fluids, in particular the local increase in concentration of various ions at the glass-tissue interface, are also relevant to mechanisms involved in soft tissue regeneration. An increasing number of studies report on the application of BGs in contact with soft tissues, aiming at exploiting the well-known bioactive properties of BGs in soft tissue regeneration and wound healing. This review focuses on research, sometimes involving preliminary in vitro studies but also in vivo evidence, that demonstrates the suitability of BGs in contact with tissues outside the skeletal system, which includes studies investigating vascularization, wound healing and cardiac, lung, nerve, gastrointestinal, urinary tract and laryngeal tissue repair using BGs in various forms of particulates, fibers and nanoparticles with and without polymer components. Potentially active mechanisms of interaction of BGs and soft tissues based on the surface bioreactivity of BGs and on biomechanical stimuli affecting the soft tissue-BG collagenous bonding are discussed based on results in the literature. Copyright © 2014 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

  9. 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)

  10. 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.

  11. From natural bone grafts to tissue engineering therapeutics: Brainstorming on pharmaceutical formulative requirements and challenges.

    Science.gov (United States)

    Baroli, Biancamaria

    2009-04-01

    Tissue engineering is an emerging multidisciplinary field of investigation focused on the regeneration of diseased or injured tissues through the delivery of appropriate molecular and mechanical signals. Therefore, bone tissue engineering covers all the attempts to reestablish a normal physiology or to speed up healing of bone in all musculoskeletal disorders and injuries that are lashing modern societies. This article attempts to give a pharmaceutical perspective on the production of engineered man-made bone grafts that are described as implantable tissue engineering therapeutics, and to highlight the importance of understanding bone composition and structure, as well as osteogenesis and bone healing processes, to improve the design and development of such implants. In addition, special emphasis is given to pharmaceutical aspects that are frequently minimized, but that, instead, may be useful for formulation developments and in vitro/in vivo correlations.

  12. Tissue Microarray Analysis Applied to Bone Diagenesis

    OpenAIRE

    Barrios Mello, Rafael; Regis Silva, Maria Regina; Seixas Alves, Maria Teresa; Evison, Martin; Guimarães, Marco Aurélio; Francisco, Rafaella Arrabaça; Dias Astolphi, Rafael; Miazato Iwamura, Edna Sadayo

    2017-01-01

    Taphonomic processes affecting bone post mortem are important in forensic, archaeological and palaeontological investigations. In this study, the application of tissue microarray (TMA) analysis to a sample of femoral bone specimens from 20 exhumed individuals of known period of burial and age at death is described. TMA allows multiplexing of subsamples, permitting standardized comparative analysis of adjacent sections in 3-D and of representative cross-sections of a large number of specimens....

  13. 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.

  14. In vitro aging of mineralized collagen-based composite as guided tissue regeneration membrane

    International Nuclear Information System (INIS)

    Pan, S.X.; Li, Y.; Feng, H.L.; Bai, W.; Gu, Y.Y.

    2006-01-01

    The technique of guided tissue regeneration (GTR) has been developed for the regeneration of periodontal tissues, bone around natural teeth and dental implants. The aim of this study is to investigate the biodegradability and mechanic behavior of a novel mineralized nano-hydroxyapatite/collagen/poly (lactic acid) (nHAC/PLA) composite as GTR membrane in vitro. The elastic modulus and maximum tensile strength of GTR film samples with different nHAC/PLA ratio were measured to get an optimal nHAC/PLA ratio. Thermogravimetric analysis was conducted to evaluate the change of the inorganic component in the samples during the process of in vitro aging. Morphology of samples was checked by using scanning electron microscopy. On the basis of the above results, it can be concluded that the GTR membranes maintained integrity and the original appearance throughout the 1-month in vitro aging. There is an active dissolution and deposition process of crystals which is propitious to the bone formation on the surface of the composite membrane. The optimal nHAC/PLA ratio of the novel membrane is 0.4:1. For a longer period of bone repair, PLA with higher molecular weight should be chosen as the scaffold for the GTR membrane

  15. Application of stem cells derived from the periodontal ligament or gingival tissue sources for tendon tissue regeneration.

    Science.gov (United States)

    Moshaverinia, Alireza; Xu, Xingtian; Chen, Chider; Ansari, Sahar; Zadeh, Homayoun H; Snead, Malcolm L; Shi, Songtao

    2014-03-01

    Tendon injuries are often associated with significant dysfunction and disability due to tendinous tissue's very limited self-repair capacity and propensity for scar formation. Dental-derived mesenchymal stem cells (MSCs) in combination with appropriate scaffold material present an alternative therapeutic option for tendon repair/regeneration that may be advantageous compared to other current treatment modalities. The MSC delivery vehicle is the principal determinant for successful implementation of MSC-mediated regenerative therapies. In the current study, a co-delivery system based on TGF-β3-loaded RGD-coupled alginate microspheres was developed for encapsulating periodontal ligament stem cells (PDLSCs) or gingival mesenchymal stem cells (GMSCs). The capacity of encapsulated dental MSCs to differentiate into tendon tissue was investigated in vitro and in vivo. Encapsulated dental-derived MSCs were transplanted subcutaneously into immunocompromised mice. Our results revealed that after 4 weeks of differentiation in vitro, PDLSCs and GMSCs as well as the positive control human bone marrow mesenchymal stem cells (hBMMSCs) exhibited high levels of mRNA expression for gene markers related to tendon regeneration (Scx, DCn, Tnmd, and Bgy) via qPCR measurement. In a corresponding in vivo animal model, ectopic neo-tendon regeneration was observed in subcutaneous transplanted MSC-alginate constructs, as confirmed by histological and immunohistochemical staining for protein markers specific for tendons. Interestingly, in our quantitative PCR and in vivo histomorphometric analyses, PDLSCs showed significantly greater capacity for tendon regeneration than GMSCs or hBMMSCs (P cell sources for tendon engineering. PDLSCs and GMSCs encapsulated in TGF-β3-loaded RGD-modified alginate microspheres are promising candidates for tendon regeneration. Copyright © 2013 Elsevier Ltd. All rights reserved.

  16. Tissue-Engineered Tendon for Enthesis Regeneration in a Rat Rotator Cuff Model

    Directory of Open Access Journals (Sweden)

    Michael J. Smietana

    2017-06-01

    Full Text Available Healing of rotator cuff (RC injuries with current suture or augmented scaffold techniques fails to regenerate the enthesis and instead forms a weaker fibrovascular scar that is prone to subsequent failure. Regeneration of the enthesis is the key to improving clinical outcomes for RC injuries. We hypothesized that the utilization of our tissue-engineered tendon to repair either an acute or a chronic full-thickness supraspinatus tear would regenerate a functional enthesis and return the biomechanics of the tendon back to that found in native tissue. Engineered tendons were fabricated from bone marrow-derived mesenchymal stem cells utilizing our well-described fabrication technology. Forty-three rats underwent unilateral detachment of the supraspinatus tendon followed by acute (immediate or chronic (4 weeks retracted repair by using either our engineered tendon or a trans-osseous suture technique. Animals were sacrificed at 8 weeks. Biomechanical and histological analyses of the regenerated enthesis and tendon were performed. Statistical analysis was performed by using a one-way analysis of variance with significance set at p < 0.05. Acute repairs using engineered tendon had improved enthesis structure and lower biomechanical failures compared with suture repairs. Chronic repairs with engineered tendon had a more native-like enthesis with increased fibrocartilage formation, reduced scar formation, and lower biomechanical failure compared with suture repair. Thus, the utilization of our tissue-engineered tendon showed improve enthesis regeneration and improved function in chronic RC repairs compared with suture repair. Clinical Significance: Our engineered tendon construct shows promise as a clinically relevant method for repair of RC injuries.

  17. Pericytes at the intersection between tissue regeneration and pathology.

    Science.gov (United States)

    Birbrair, Alexander; Zhang, Tan; Wang, Zhong-Min; Messi, Maria Laura; Mintz, Akiva; Delbono, Osvaldo

    2015-01-01

    Perivascular multipotent cells, pericytes, contribute to the generation and repair of various tissues in response to injury. They are heterogeneous in their morphology, distribution, origin and markers, and elucidating their molecular and cellular differences may inform novel treatments for disorders in which tissue regeneration is either impaired or excessive. Moreover, these discoveries offer novel cellular targets for therapeutic approaches to many diseases. This review discusses recent studies that support the concept that pericyte subtypes play a distinctive role in myogenesis, neurogenesis, adipogenesis, fibrogenesis and angiogenesis.

  18. 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.

  19. In vitro evaluation of electrospun chitosan mats crosslinked with genipin as guided tissue regeneration barrier membranes

    Science.gov (United States)

    Norowski, Peter Andrew, Jr.

    Guided tissue regeneration (GTR) is a surgical technique commonly used to exclude bacteria and soft tissues from bone graft sites in oral/maxillofacial bone graft sites by using a barrier membrane to maintain the graft contour and space. Current clinical barrier membrane materials based on expanded polytetrafluoroethylene (ePTFE) and bovine type 1 collagen are non-ideal and experience a number of disadvantages including membrane exposure, bacterial colonization/biofilm formation and premature degradation, all of which result in increased surgical intervention and poor bone regeneration. These materials do not actively participate in tissue regeneration, however bioactive materials, such as chitosan, may provide advantages such as the ability to stimulate wound healing and de novo bone formation. Our hypothesis is that electrospun chitosan GTR membranes will support cell attachment and growth but prevent cell infiltration/penetration of membrane, demonstrate in vitro degradation predictive of 4--6 month in vivo functionality, and will deliver antibiotics locally to prevent/inhibit periopathogenic complications. To test this hypothesis a series of chitosan membranes were electrospun, in the presence or absence of genipin, a natural crosslinking agent, at concentrations of 5 and 10 mM. These membranes were characterized by scanning electron microscopy, tensile testing, suture pullout testing, Fourier transform infrared spectroscopy, X-ray diffraction, and gel permeation chromatography, and in vitro biodegradation for diameter/morphology of fibers, membrane strengths, degree of crosslinking, crystallinity, molecular weight, and degradation kinetics, respectively. Cytocompability of membranes was evaluated in osteoblastic, fibroblastic and monocyte cultures. The activity of minocycline loaded and released from the membranes was determined in zone of inhibition tests using P. gingivalis microbe. The results demonstrated that genipin crosslinking extended the in vitro

  20. P21 deficiency delays regeneration of skeletal muscular tissue.

    Science.gov (United States)

    Chinzei, Nobuaki; Hayashi, Shinya; Ueha, Takeshi; Fujishiro, Takaaki; Kanzaki, Noriyuki; Hashimoto, Shingo; Sakata, Shuhei; Kihara, Shinsuke; Haneda, Masahiko; Sakai, Yoshitada; Kuroda, Ryosuke; Kurosaka, Masahiro

    2015-01-01

    The potential relationship between cell cycle checkpoint control and tissue regeneration has been indicated. Despite considerable research being focused on the relationship between p21 and myogenesis, p21 function in skeletal muscle regeneration remains unclear. To clarify this, muscle injury model was recreated by intramuscular injection of bupivacaine hydrochloride in the soleus of p21 knockout (KO) mice and wild type (WT) mice. The mice were sacrificed at 3, 14, and 28 days post-operation. The results of hematoxylin-eosin staining and immunofluorescence of muscle membrane indicated that muscle regeneration was delayed in p21 KO mice. Cyclin D1 mRNA expression and both Ki-67 and PCNA immunohistochemistry suggested that p21 deficiency increased cell cycle and muscle cell proliferation. F4/80 immunohistochemistry also suggested the increase of immune response in p21 KO mice. On the other hand, both the mRNA expression and western blot analysis of MyoD, myogenin, and Pax7 indicated that muscular differentiation was delayed in p21KO mice. Considering these results, we confirmed that muscle injury causes an increase in cell proliferation. However, muscle differentiation in p21 KO mice was inhibited due to the low expression of muscular synthesis genes, leading to a delay in the muscular regeneration. Thus, we conclude that p21 plays an important role in the in vivo healing process in muscular injury.

  1. P21 deficiency delays regeneration of skeletal muscular tissue.

    Directory of Open Access Journals (Sweden)

    Nobuaki Chinzei

    Full Text Available The potential relationship between cell cycle checkpoint control and tissue regeneration has been indicated. Despite considerable research being focused on the relationship between p21 and myogenesis, p21 function in skeletal muscle regeneration remains unclear. To clarify this, muscle injury model was recreated by intramuscular injection of bupivacaine hydrochloride in the soleus of p21 knockout (KO mice and wild type (WT mice. The mice were sacrificed at 3, 14, and 28 days post-operation. The results of hematoxylin-eosin staining and immunofluorescence of muscle membrane indicated that muscle regeneration was delayed in p21 KO mice. Cyclin D1 mRNA expression and both Ki-67 and PCNA immunohistochemistry suggested that p21 deficiency increased cell cycle and muscle cell proliferation. F4/80 immunohistochemistry also suggested the increase of immune response in p21 KO mice. On the other hand, both the mRNA expression and western blot analysis of MyoD, myogenin, and Pax7 indicated that muscular differentiation was delayed in p21KO mice. Considering these results, we confirmed that muscle injury causes an increase in cell proliferation. However, muscle differentiation in p21 KO mice was inhibited due to the low expression of muscular synthesis genes, leading to a delay in the muscular regeneration. Thus, we conclude that p21 plays an important role in the in vivo healing process in muscular injury.

  2. Preparation of dexamethasone-loaded biphasic calcium phosphate nanoparticles/collagen porous composite scaffolds for bone tissue engineering.

    Science.gov (United States)

    Chen, Ying; Kawazoe, Naoki; Chen, Guoping

    2018-02-01

    Although bone is regenerative, its regeneration capacity is limited. For bone defects beyond a critical size, further intervention is required. As an attractive strategy, bone tissue engineering (bone TE) has been widely investigated to repair bone defects. However, the rapid and effective bone regeneration of large non-healing defects is still a great challenge. Multifunctional scaffolds having osteoinductivity and osteoconductivity are desirable to fasten functional bone tissue regeneration. In the present study, biomimetic composite scaffolds of collagen and biphasic calcium phosphate nanoparticles (BCP NPs) with a controlled release of dexamethasone (DEX) and the controlled pore structures were prepared for bone TE. DEX was introduced in the BCP NPs during preparation of the BCP NPs and hybridized with collagen scaffolds, which pore structures were controlled by using pre-prepared ice particulates as a porogen material. The composite scaffolds had well controlled and interconnected pore structures, high mechanical strength and a sustained release of DEX. The composite scaffolds showed good biocompatibility and promoted osteogenic differentiation of hMSCs when used for three-dimensional culture of human bone marrow-derived mesenchymal stem cells. Subcutaneous implantation of the composite scaffolds at the dorsa of athymic nude mice demonstrated that they facilitated the ectopic bone tissue regeneration. The results indicated the DEX-loaded BCP NPs/collagen composite scaffolds had high potential for bone TE. Scaffolds play a crucial role for regeneration of large bone defects. Biomimetic scaffolds having the same composition of natural bone and a controlled release of osteoinductive factors are desirable for promotion of bone regeneration. In this study, composite scaffolds of collagen and biphasic CaP nanoparticles (BCP NPs) with a controlled release nature of dexamethasone (DEX) were prepared and their porous structures were controlled by using ice particulates

  3. 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.

  4. In vitro evaluation of hydroxyapatite-chitosan-gelatin composite membrane in guided tissue regeneration.

    Science.gov (United States)

    Hunter, Kimberly T; Ma, Teng

    2013-04-01

    Resorbable biomaterials have been investigated as barrier membranes to compartmentalize the periodontal defects while selectively guiding osteoprogenitor cell proliferation and bone tissue expansion. Hydroxyapatite (H), chitosan (C), and gelatin (G) have chemical similarity to the structural components of natural bone and their composites have been tested as bone scaffolds. Human mesenchymal stem or stromal cells (hMSCs) are inducible osteoprogenitors and are responsible for bone tissue repair and regeneration. In this study, the dynamic interactions of hMSC with composite hydroxyapatite-chitosan-gelatin (HCG) membranes were investigated. The association of HCG formed a biodegradable membrane with ~60 wt % water and an initial stiffness of ~20 kPa. Preconditioning in serum-containing media resulted in the formation nanopores in the HCG membranes and the increase of extracellular matrix (ECM) protein adsorption. Expression of integrin α(2)β(1) and α(5)β(1) coincided with ECM enrichment, suggesting the enhanced cell-ECM interactions. The elevated expression of bone marker proteins and genes in the HCG membranes suggests the progression of hMSC osteogenic differentiation in the absence of chemical induction. The results showed that the HCG membranes possess sufficient mechanical and structural properties to function as a barrier membrane, and that the adsorbed ECM proteins effectively functionalized the HCG membranes and promoted hMSC osteogenic differentiation. Copyright © 2012 Wiley Periodicals, Inc.

  5. Recent developments in scaffold-guided cartilage tissue regeneration.

    Science.gov (United States)

    Liao, Jinfeng; Shi, Kun; Ding, Qiuxia; Qu, Ying; Luo, Feng; Qian, Zhiyong

    2014-10-01

    Articular cartilage repair is one of the most challenging problems in biomedical engineering because the regenerative capacity of cartilage is intrinsically poor. The lack of efficient treatment modalities motivates researches into cartilage tissue engineering such as combing cells, scaffolds and growth factors. In this review we summarize the current developments on scaffold systems available for cartilage tissue engineering. The factors that are critical to successfully design an ideal scaffold for cartilage regeneration were discussed. Then we present examples of selected material types (natural polymers and synthetic polymers) and fabricated forms of the scaffolds (three-dimensional scaffolds, micro- or nanoparticles, and their composites). In the end of review, we conclude with an overview of the ways in which biomedical nanotechnology is widely applied in cartilage tissue engineering, especially in the design of composite scaffolds. This review attempts to provide recommendations on the combination of qualities that would produce the ideal scaffold system for cartilage tissue engineering.

  6. 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.

  7. 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

  8. 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.

  9. 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.

  10. 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.

  11. Multimodal-3D imaging based on μMRI and μCT techniques bridges the gap with histology in visualization of the bone regeneration process.

    Science.gov (United States)

    Sinibaldi, R; Conti, A; Sinjari, B; Spadone, S; Pecci, R; Palombo, M; Komlev, V S; Ortore, M G; Tromba, G; Capuani, S; Guidotti, R; De Luca, F; Caputi, S; Traini, T; Della Penna, S

    2018-03-01

    Bone repair/regeneration is usually investigated through X-ray computed microtomography (μCT) supported by histology of extracted samples, to analyse biomaterial structure and new bone formation processes. Magnetic resonance imaging (μMRI) shows a richer tissue contrast than μCT, despite at lower resolution, and could be combined with μCT in the perspective of conducting non-destructive 3D investigations of bone. A pipeline designed to combine μMRI and μCT images of bone samples is here described and applied on samples of extracted human jawbone core following bone graft. We optimized the coregistration procedure between μCT and μMRI images to avoid bias due to the different resolutions and contrasts. Furthermore, we used an Adaptive Multivariate Clustering, grouping homologous voxels in the coregistered images, to visualize different tissue types within a fused 3D metastructure. The tissue grouping matched the 2D histology applied only on 1 slice, thus extending the histology labelling in 3D. Specifically, in all samples, we could separate and map 2 types of regenerated bone, calcified tissue, soft tissues, and/or fat and marrow space. Remarkably, μMRI and μCT alone were not able to separate the 2 types of regenerated bone. Finally, we computed volumes of each tissue in the 3D metastructures, which might be exploited by quantitative simulation. The 3D metastructure obtained through our pipeline represents a first step to bridge the gap between the quality of information obtained from 2D optical microscopy and the 3D mapping of the bone tissue heterogeneity and could allow researchers and clinicians to non-destructively characterize and follow-up bone regeneration. Copyright © 2017 John Wiley & Sons, Ltd.

  12. Autologous adipose tissue-derived stem cells induce persistent bone-like tissue in osteonecrotic femoral heads.

    Science.gov (United States)

    Pak, Jaewoo

    2012-01-01

    Osteonecrosis, also known as avascular necrosis, of the femoral head is a debilitating disorder that commonly affects 30- to 50-year-old individuals. Currently, definitive treatment is limited to total hip replacement. However, recent studies have demonstrated bone regeneration in the femoral head after the infusion of bone marrow-derived mesenchymal stem cells. In addition, local injection of adipose tissue-derived stem cells has been shown to regenerate medullary bone-like tissue 3 months after treatment. However, there have been no long-term follow-up studies on humans treated with adipose tissue-derived stem cells for osteonecrosis. To determine if treatment with adipose tissue-derived stem cells and platelet-rich plasma leads to the regeneration of medullary bone-like tissue and long-term reduction of hip pain in patients with femoral head osteonecrosis. This report of two clinical cases was in compliance with the Declaration of Helsinki. Also, the Korean Food and Drug Administration has allowed the use of adipose tissue-derived stem cells (ADSCs) in medical treatments since 2009. To obtain ADSCs, lipoaspirates were obtained from lower abdominal subcutaneous adipose tissue. The stromal vascular fraction was separated from the lipoaspirates by centrifugation after treatment with collagenase. The stem-cell-containing stromal vascular fraction was mixed with calcium chloride-activated platelet rich plasma and hyaluronic acid, and this mixture was then injected into the diseased hip. The affected hip was reinjected with calcium chloride-activated platelet rich plasma weekly for 4 weeks. Patients were subjected to pre- and post-treatment magnetic resonance imaging (MRI) scans. Two patients (34- and 39-year-old men) with femoral head osteonecrosis and severe hip pain were treated with adipose-derived stem cells. The MRI scans of the affected hip in both patients showed segmental areas of low signal intensity (T1 axial views) in the subchondral bones with a "double

  13. 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.

  14. 3-Dimensional cell-laden nano-hydroxyapatite/protein hydrogels for bone regeneration applications

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    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.

  15. 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

  16. 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.

  17. Improved repair of bone defects with prevascularized tissue-engineered bones constructed in a perfusion bioreactor.

    Science.gov (United States)

    Li, De-Qiang; Li, Ming; Liu, Pei-Lai; Zhang, Yuan-Kai; Lu, Jian-Xi; Li, Jian-Min

    2014-10-01

    Vascularization of tissue-engineered bones is critical to achieving satisfactory repair of bone defects. The authors investigated the use of prevascularized tissue-engineered bone for repairing bone defects. The new bone was greater in the prevascularized group than in the non-vascularized group, indicating that prevascularized tissue-engineered bone improves the repair of bone defects. [Orthopedics. 2014; 37(10):685-690.]. Copyright 2014, SLACK Incorporated.

  18. 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.

  19. 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

  20. Additive Biomanufacturing : An Advanced Approach for Periodontal Tissue Regeneration

    NARCIS (Netherlands)

    Carter, Sarah-Sophia D; Vaquette, Cedryck; Ivanovski, Saso; Hutmacher, Dietmar W; Malda, Jos

    2016-01-01

    Periodontitis is defined as a chronic inflammatory condition, characterized by destruction of the periodontium, composed of hard (i.e. alveolar bone and cementum) and soft tissues (i.e. gingiva and periodontal ligament) surrounding and supporting the teeth. In severe cases, reduced periodontal

  1. Additive Biomanufacturing : An Advanced Approach for Periodontal Tissue Regeneration

    NARCIS (Netherlands)

    Carter, Sarah Sophia D.; Costa, Pedro F.; Vaquette, Cedryck; Ivanovski, Saso; Hutmacher, Dietmar W.; Malda, Jos

    2017-01-01

    Periodontitis is defined as a chronic inflammatory condition, characterized by destruction of the periodontium, composed of hard (i.e. alveolar bone and cementum) and soft tissues (i.e. gingiva and periodontal ligament) surrounding and supporting the teeth. In severe cases, reduced periodontal

  2. Concept and strategies of bone tissue engineering

    Directory of Open Access Journals (Sweden)

    Đorđević Ljubiša B.

    2016-01-01

    Full Text Available In contemporary clinical practice bone substitutes such as implants are used in reconstructive orthopedics and maxillofacial surgery. Judging from physical and chemical properties each implant has some advantages and disadvantages. The idea of bone tissue engineering is to simulate the formation of bone to implants as carriers in combination with osteogenic cells and osteo-stimulative factors (osteoinduction. The design of the implant itself in terms of the chosen carrier with its own characteristics, the type of cells that have been implanted, the type and combination of stimulative factors play an important role in the behavior of the implanted material within a body. Tissue engineering looks promising, however a lot of obstacles have to be surmounted in order to consider it a proper alternative.

  3. Novel monoclonal antibodies to study tissue regeneration in planarians.

    Science.gov (United States)

    Ross, Kelly G; Omuro, Kerilyn C; Taylor, Matthew R; Munday, Roma K; Hubert, Amy; King, Ryan S; Zayas, Ricardo M

    2015-01-21

    Planarians are an attractive model organism for studying stem cell-based regeneration due to their ability to replace all of their tissues from a population of adult stem cells. The molecular toolkit for planarian studies currently includes the ability to study gene function using RNA interference (RNAi) and observe gene expression via in situ hybridizations. However, there are few antibodies available to visualize protein expression, which would greatly enhance analysis of RNAi experiments as well as allow further characterization of planarian cell populations using immunocytochemistry and other immunological techniques. Thus, additional, easy-to-use, and widely available monoclonal antibodies would be advantageous to study regeneration in planarians. We have created seven monoclonal antibodies by inoculating mice with formaldehyde-fixed cells isolated from dissociated 3-day regeneration blastemas. These monoclonal antibodies can be used to label muscle fibers, axonal projections in the central and peripheral nervous systems, two populations of intestinal cells, ciliated cells, a subset of neoblast progeny, and discrete cells within the central nervous system as well as the regeneration blastema. We have tested these antibodies using eight variations of a formaldehyde-based fixation protocol and determined reliable protocols for immunolabeling whole planarians with each antibody. We found that labeling efficiency for each antibody varies greatly depending on the addition or removal of tissue processing steps that are used for in situ hybridization or immunolabeling techniques. Our experiments show that a subset of the antibodies can be used alongside markers commonly used in planarian research, including anti-SYNAPSIN and anti-SMEDWI, or following whole-mount in situ hybridization experiments. The monoclonal antibodies described in this paper will be a valuable resource for planarian research. These antibodies have the potential to be used to better understand

  4. Regeneration of the skin and muscle tissue in rainbow trout (Oncorhynchus mykiss) following mechanical injury

    DEFF Research Database (Denmark)

    Ingerslev, Hans-Christian; Nielsen, Michael Engelbrecht

    Mechanical injury induced by needles penetrating the skin and underlying muscle tissue in rainbow trout (Oncorhynchus mykiss) was used as a model to study the initial phase(s) of tissue regeneration. Tissue regeneration in humans is characterised by four phases; hemostatis, inflammation, prolifer......Mechanical injury induced by needles penetrating the skin and underlying muscle tissue in rainbow trout (Oncorhynchus mykiss) was used as a model to study the initial phase(s) of tissue regeneration. Tissue regeneration in humans is characterised by four phases; hemostatis, inflammation...

  5. Aberrant innate immune activation following tissue injury impairs pancreatic regeneration.

    Directory of Open Access Journals (Sweden)

    Alexandra E Folias

    Full Text Available Normal tissue architecture is disrupted following injury, as resident tissue cells become damaged and immune cells are recruited to the site of injury. While injury and inflammation are critical to tissue remodeling, the inability to resolve this response can lead to the destructive complications of chronic inflammation. In the pancreas, acinar cells of the exocrine compartment respond to injury by transiently adopting characteristics of progenitor cells present during embryonic development. This process of de-differentiation creates a window where a mature and stable cell gains flexibility and is potentially permissive to changes in cellular fate. How de-differentiation can turn an acinar cell into another cell type (such as a pancreatic β-cell, or a cell with cancerous potential (as in cases of deregulated Kras activity is of interest to both the regenerative medicine and cancer communities. While it is known that inflammation and acinar de-differentiation increase following pancreatic injury, it remains unclear which immune cells are involved in this process. We used a combination of genetically modified mice, immunological blockade and cellular characterization to identify the immune cells that impact pancreatic regeneration in an in vivo model of pancreatitis. We identified the innate inflammatory response of macrophages and neutrophils as regulators of pancreatic regeneration. Under normal conditions, mild innate inflammation prompts a transient de-differentiation of acinar cells that readily dissipates to allow normal regeneration. However, non-resolving inflammation developed when elevated pancreatic levels of neutrophils producing interferon-γ increased iNOS levels and the pro-inflammatory response of macrophages. Pancreatic injury improved following in vivo macrophage depletion, iNOS inhibition as well as suppression of iNOS levels in macrophages via interferon-γ blockade, supporting the impairment in regeneration and the

  6. Spatial regulation of controlled bioactive factor delivery for bone tissue engineering

    Science.gov (United States)

    Samorezov, Julia E.; Alsberg, Eben

    2015-01-01

    Limitations of current treatment options for critical size bone defects create a significant clinical need for tissue engineered bone strategies. This review describes how control over the spatiotemporal delivery of growth factors, nucleic acids, and drugs and small molecules may aid in recapitulating signals present in bone development and healing, regenerating interfaces of bone with other connective tissues, and enhancing vascularization of tissue engineered bone. State-of-the-art technologies used to create spatially controlled patterns of bioactive factors on the surfaces of materials, to build up 3D materials with patterns of signal presentation within their bulk, and to pattern bioactive factor delivery after scaffold fabrication are presented, highlighting their applications in bone tissue engineering. As these techniques improve in areas such as spatial resolution and speed of patterning, they will continue to grow in value as model systems for understanding cell responses to spatially regulated bioactive factor signal presentation in vitro, and as strategies to investigate the capacity of the defined spatial arrangement of these signals to drive bone regeneration in vivo. PMID:25445719

  7. 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.

  8. 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.

  9. 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

  10. 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...

  11. 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

  12. 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

  13. Stem Cell Therapy in Wound Healing and Tissue Regeneration

    Directory of Open Access Journals (Sweden)

    Anna Meiliana

    2016-08-01

    a novel approach to many diseases. SUMMARY: Wound healing therapies continue to rapidly evolve, with advances in basic science and engineering research heralding the development of new therapies, as well as ways to modify existing treatments. Stem cell-based therapy is one of the most promising therapeutic concepts for wound healing. Advances in stem cell biology have enabled researchers and clinicians alike with access to cells capable of actively modulating the healing response.  KEYWORDS: wound healing, tissue regeneration, stem cells therapy

  14. Recent Developments of Functional Scaffolds for Craniomaxillofacial Bone Tissue Engineering Applications

    Directory of Open Access Journals (Sweden)

    Yukihiko Kinoshita

    2013-01-01

    Full Text Available Autogenous bone grafting remains a gold standard for the reconstruction critical-sized bone defects in the craniomaxillofacial region. Nevertheless, this graft procedure has several disadvantages such as restricted availability, donor-site morbidity, and limitations in regard to fully restoring the complicated three-dimensional structures in the craniomaxillofacial bone. The ultimate goal of craniomaxillofacial bone reconstruction is the regeneration of the physiological bone that simultaneously fulfills both morphological and functional restorations. Developments of tissue engineering in the last two decades have brought such a goal closer to reality. In bone tissue engineering, the scaffolds are fundamental, elemental and mesenchymal stem cells/osteoprogenitor cells and bioactive factors. A variety of scaffolds have been developed and used as spacemakers, biodegradable bone substitutes for transplanting to the new bone, matrices of drug delivery system, or supporting structures enhancing adhesion, proliferation, and matrix production of seeded cells according to the circumstances of the bone defects. However, scaffolds to be clinically completely satisfied have not been developed yet. Development of more functional scaffolds is required to be applied widely to cranio-maxillofacial bone defects. This paper reviews recent trends of scaffolds for crania-maxillofacial bone tissue engineering, including our studies.

  15. 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.

  16. 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.

  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. 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. Fibronectin in tissue regeneration : timely disassembly of the scaffold is necessary to complete the build

    NARCIS (Netherlands)

    Stoffels, Josephine M. J.; Zhao, Chao; Baron, Wia

    2013-01-01

    Tissue injury initiates extracellular matrix molecule expression, including fibronectin production by local cells and fibronectin leakage from plasma. To benefit tissue regeneration, fibronectin promotes opsonization of tissue debris, migration, proliferation, and contraction of cells involved in

  20. The synergistic effect of bone forming peptide-1 and endothelial progenitor cells to promote vascularization of tissue engineered bone.

    Science.gov (United States)

    Wang, Huaixi; Cheng, Hao; Tang, Xiangyu; Chen, Jingyuan; Zhang, Jun; Wang, Wei; Li, Wenkai; Lin, Guanlin; Wu, Hua; Liu, Chaoxu

    2018-04-01

    Large segmental bone defect repair remains a challenge in orthopedic surgeries. The tissue engineered bone graft will be a promising approach if vascularization of the graft is realized. In this study, beta-tricalcium phosphate (β-TCP) scaffold incorporated with bone forming peptide-1 (BFP-1) was fabricated. Endothelial progenitor cells (EPCs) were introduced as well. We investigated the effect of BFP-1 on the proliferation, differentiation, and angiogenic functions of EPCs. Additionally, segmental femur bone defect was created in rabbits. Prevascularized β-TCP scaffold was constructed and implanted into the bone defect. The vascularization and bone formation were evaluated after 4 and 12 weeks. The results showed that BFP-1 promoted the angiogenesis of EPCs through activating the activin receptor-like kinase-1/Smad pathway. The prevascularized tissue engineered bone graft enhanced capillary vessel in-growth and new bone formation. Significantly higher values of vascularization and radiographic grading scores were observed in groups involving EPCs and BFP-1, compared to β-TCP scaffold alone. In conclusion, the synergy between EPCs and BFP-1 improved the vascularization and new bone regeneration, which has great potentials in clinical applications. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 106A: 1008-1021, 2018. © 2017 Wiley Periodicals, Inc.

  1. 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.

  2. 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.

  3. Engineering Cell Fate for Tissue Regeneration by In Vivo Transdifferentiation.

    Science.gov (United States)

    de Lázaro, I; Kostarelos, K

    2016-02-01

    Changes in cell identity occur in adult mammalian organisms but are rare and often linked to disease. Research in the last few decades has thrown light on how to manipulate cell fate, but the conversion of a particular cell type into another within a living organism (also termed in vivo transdifferentiation) has only been recently achieved in a limited number of tissues. Although the therapeutic promise of this strategy for tissue regeneration and repair is exciting, important efficacy and safety concerns will need to be addressed before it becomes a reality in the clinical practice. Here, we review the most relevant in vivo transdifferentiation studies in adult mammalian animal models, offering a critical assessment of this potentially powerful strategy for regenerative medicine.

  4. Fibroblast growth factors as tissue repair and regeneration therapeutics

    Directory of Open Access Journals (Sweden)

    Quentin M. Nunes

    2016-01-01

    Full Text Available Cell communication is central to the integration of cell function required for the development and homeostasis of multicellular animals. Proteins are an important currency of cell communication, acting locally (auto-, juxta-, or paracrine or systemically (endocrine. The fibroblast growth factor (FGF family contributes to the regulation of virtually all aspects of development and organogenesis, and after birth to tissue maintenance, as well as particular aspects of organism physiology. In the West, oncology has been the focus of translation of FGF research, whereas in China and to an extent Japan a major focus has been to use FGFs in repair and regeneration settings. These differences have their roots in research history and aims. The Chinese drive into biotechnology and the delivery of engineered clinical grade FGFs by a major Chinese research group were important enablers in this respect. The Chinese language clinical literature is not widely accessible. To put this into context, we provide the essential molecular and functional background to the FGF communication system covering FGF ligands, the heparan sulfate and Klotho co-receptors and FGF receptor (FGFR tyrosine kinases. We then summarise a selection of clinical reports that demonstrate the efficacy of engineered recombinant FGF ligands in treating a wide range of conditions that require tissue repair/regeneration. Alongside, the functional reasons why application of exogenous FGF ligands does not lead to cancers are described. Together, this highlights that the FGF ligands represent a major opportunity for clinical translation that has been largely overlooked in the West.

  5. Radiographic outcomes following treatment of intrabony defect with guided tissue regeneration in aggressive periodontitis.

    Science.gov (United States)

    Rakmanee, Thanasak; Griffiths, Gareth S; Auplish, Gita; Darbar, Ulpee; Petrie, Aviva; Olsen, Irwin; Donos, Nikolaos

    2016-07-01

    This study reports the radiographic analysis of a split-mouth, single-blinded, randomised controlled clinical trial which was designed to compare the efficacy of simplified papilla preservation flap (SPPF) with or without guided tissue regeneration (GTR) in patients with aggressive periodontitis (AgP). Eighteen AgP patients who had similar bilateral intrabony defects were treated. In all patients, the defects presented with radiographic evidence of an intrabony defect ≥3 and ≥5 mm of periodontal pocket depths (PPD). The surgical procedures included access for root instrumentation using SPPF alone (control) or, after debridement, a placement of resorbable GTR membrane (test). The standardised radiographic assessments were carried out at pre-surgical baseline and at 6 and 12 month post-surgery. Radiographic linear measurements and subtraction radiography were used as the method of analysis. Both treatments showed significant improvements in linear radiographic bone fill and defect resolution at 6 and 12 months, compared to baseline. The 12-month subtraction radiography at the GTR sites showed a significant improvement compared to the 6-month outcomes. Both therapies were effective in the treatment of intrabony defects in AgP patients although no significant differences between them could be demonstrated. The finding that the bone fill and resolution of the defect at the GTR sites were significantly higher at 12 months than at 6 months after treatment indicates that bone regeneration is still an ongoing process at 6 months post-surgery. Radiographic assessment of periodontal regeneration should be carried out at 12 months post-surgery in order to evaluate the complete healing of the bony defect.

  6. 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.

  7. 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

  8. 3D Printing of Scaffolds for Tissue Regeneration Applications

    Science.gov (United States)

    Do, Anh-Vu; Khorsand, Behnoush; Geary, Sean M.; Salem, Aliasger K.

    2015-01-01

    The current need for organ and tissue replacement, repair and regeneration for patients is continually growing such that supply is not meeting the high demand primarily due to a paucity of donors as well as biocompatibility issues that lead to immune rejection of the transplant. In an effort to overcome these drawbacks, scientists working in the field of tissue engineering and regenerative medicine have investigated the use of scaffolds as an alternative to transplantation. These scaffolds are designed to mimic the extracellular matrix (ECM) by providing structural support as well as promoting attachment, proliferation, and differentiation with the ultimate goal of yielding functional tissues or organs. Initial attempts at developing scaffolds were problematic and subsequently inspired a growing interest in 3D printing as a mode for generating scaffolds. Utilizing three-dimensional printing (3DP) technologies, ECM-like scaffolds can be produced with a high degree of complexity and precision, where fine details can be included at a micron level. In this review, we discuss the criteria for printing viable and functional scaffolds, scaffolding materials, and 3DP technologies used to print scaffolds for tissue engineering. A hybrid approach, employing both natural and synthetic materials, as well as multiple printing processes may be the key to yielding an ECM-like scaffold with high mechanical strength, porosity, interconnectivity, biocompatibility, biodegradability, and high processability. Creating such biofunctional scaffolds could potentially help to meet the demand by patients for tissues and organs without having to wait or rely on donors for transplantation. PMID:26097108

  9. 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.

  10. Nano-hydroxyapatite composite biomaterials for bone tissue engineering--a review.

    Science.gov (United States)

    Venkatesan, Jayachandran; Kim, Se-Kwon

    2014-10-01

    In recent years, significant development has been achieved in the construction of artificial bone with ceramics, polymers and metals. Nano-hydroxyapatite (nHA) is widely used bioceramic material for bone graft substitute owing to its biocompatibility and osteoconductive properties. nHA with chitin, chitosan, collagen, gelatin, fibrin, polylactic acid, polycaprolactone, poly(lactic-co-glycolic) acid, polyamide, polyvinyl alcohol, polyurethane and polyhydroxybutyrate based composite scaffolds have been explored in the present review for bone graft substitute. This article further reviews the preparative methods, chemical interaction, biocompatibiity, biodegradation, alkaline phosphatase activity, mineralization effect, mechanical properties and delivery of nHA-based nanocomposites for bone tissue regeneration. The nHA based composite biomaterials proved to be promising biomaterials for bone tissue engineering.

  11. Immunotherapy for Bone and Soft Tissue Sarcomas

    Directory of Open Access Journals (Sweden)

    Takenori Uehara

    2015-01-01

    Full Text Available Although multimodal therapies including surgery, chemotherapy, and radiotherapy have improved clinical outcomes of patients with bone and soft tissue sarcomas, the prognosis of patients has plateaued over these 20 years. Immunotherapies have shown the effectiveness for several types of advanced tumors. Immunotherapies, such as cytokine therapies, vaccinations, and adoptive cell transfers, have also been investigated for bone and soft tissue sarcomas. Cytokine therapies with interleukin-2 or interferons have limited efficacy because of their cytotoxicities. Liposomal muramyl tripeptide phosphatidylethanolamine (L-MTP-PE, an activator of the innate immune system, has been approved as adjuvant therapeutics in combination with conventional chemotherapy in Europe, which has improved the 5-year overall survival of patients. Vaccinations and transfer of T cells transduced to express chimeric antigen receptors have shown some efficacy for sarcomas. Ipilimumab and nivolumab are monoclonal antibodies designed to inhibit immune checkpoint mechanisms. These antibodies have recently been shown to be effective for patients with melanoma and also investigated for patients with sarcomas. In this review, we provide an overview of various trials of immunotherapies for bone and soft tissue sarcomas, and discuss their potential as adjuvant therapies in combination with conventional therapies.

  12. 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

  13. Development of a Novel Tissue Engineering Strategy Towards Whole Limb Regeneration

    National Research Council Canada - National Science Library

    Laurencin, Cato T

    2008-01-01

    .... In contrast to the bottom up approach of limb regeneration that relies on blastema formation outgrowth and cell dedifferentiation as seen in amphibians and lower vertebrates tissue engineering...

  14. 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

  15. Tissue absence initiates regeneration through follistatin-mediated inhibition of activin signaling.

    Science.gov (United States)

    Gaviño, Michael A; Wenemoser, Danielle; Wang, Irving E; Reddien, Peter W

    2013-09-10

    Regeneration is widespread, but mechanisms that activate regeneration remain mysterious. Planarians are capable of whole-body regeneration and mount distinct molecular responses to wounds that result in tissue absence and those that do not. A major question is how these distinct responses are activated. We describe a follistatin homolog (Smed-follistatin) required for planarian regeneration. Smed-follistatin inhibition blocks responses to tissue absence but does not prevent normal tissue turnover. Two activin homologs (Smed-activin-1 and Smed-activin-2) are required for the Smed-follistatin phenotype. Finally, Smed-follistatin is wound-induced and expressed at higher levels following injuries that cause tissue absence. These data suggest that Smed-follistatin inhibits Smed-Activin proteins to trigger regeneration specifically following injuries involving tissue absence and identify a mechanism critical for regeneration initiation, a process important across the animal kingdom. DOI:http://dx.doi.org/10.7554/eLife.00247.001.

  16. 3D Printing of Scaffolds for Tissue Regeneration Applications.

    Science.gov (United States)

    Do, Anh-Vu; Khorsand, Behnoush; Geary, Sean M; Salem, Aliasger K

    2015-08-26

    The current need for organ and tissue replacement, repair, and regeneration for patients is continually growing such that supply is not meeting demand primarily due to a paucity of donors as well as biocompatibility issues leading to immune rejection of the transplant. In order to overcome these drawbacks, scientists have investigated the use of scaffolds as an alternative to transplantation. These scaffolds are designed to mimic the extracellular matrix (ECM) by providing structural support as well as promoting attachment, proliferation, and differentiation with the ultimate goal of yielding functional tissues or organs. Initial attempts at developing scaffolds were problematic and subsequently inspired an interest in 3D printing as a mode for generating scaffolds. Utilizing three-dimensional printing (3DP) technologies, ECM-like scaffolds can be produced with a high degree of complexity, where fine details can be included at a micrometer level. In this Review, the criteria for printing viable and functional scaffolds, scaffolding materials, and 3DP technologies used to print scaffolds for tissue engineering are discussed. Creating biofunctional scaffolds could potentially help to meet the demand by patients for tissues and organs without having to wait or rely on donors for transplantation. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  17. A review of fibrin and fibrin composites for bone tissue engineering.

    Science.gov (United States)

    Noori, Alireza; Ashrafi, Seyed Jamal; Vaez-Ghaemi, Roza; Hatamian-Zaremi, Ashraf; Webster, Thomas J

    2017-01-01

    Tissue engineering has emerged as a new treatment approach for bone repair and regeneration seeking to address limitations associated with current therapies, such as autologous bone grafting. While many bone tissue engineering approaches have traditionally focused on synthetic materials (such as polymers or hydrogels), there has been a lot of excitement surrounding the use of natural materials due to their biologically inspired properties. Fibrin is a natural scaffold formed following tissue injury that initiates hemostasis and provides the initial matrix useful for cell adhesion, migration, proliferation, and differentiation. Fibrin has captured the interest of bone tissue engineers due to its excellent biocompatibility, controllable biodegradability, and ability to deliver cells and biomolecules. Fibrin is particularly appealing because its precursors, fibrinogen, and thrombin, which can be derived from the patient's own blood, enable the fabrication of completely autologous scaffolds. In this article, we highlight the unique properties of fibrin as a scaffolding material to treat bone defects. Moreover, we emphasize its role in bone tissue engineering nanocomposites where approaches further emulate the natural nanostructured features of bone when using fibrin and other nanomaterials. We also review the preparation methods of fibrin glue and then discuss a wide range of fibrin applications in bone tissue engineering. These include the delivery of cells and/or biomolecules to a defect site, distributing cells, and/or growth factors throughout other pre-formed scaffolds and enhancing the physical as well as biological properties of other biomaterials. Thoughts on the future direction of fibrin research for bone tissue engineering are also presented. In the future, the development of fibrin precursors as recombinant proteins will solve problems associated with using multiple or single-donor fibrin glue, and the combination of nanomaterials that allow for the

  18. 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

  19. 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.

  20. 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.

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

    Directory of Open Access Journals (Sweden)

    Sabrina Pappalardo

    2013-10-01

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

  2. 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.

  3. 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

  4. 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

  5. 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.

  6. 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.

  7. 3D-Printed Bioactive Ca3SiO5Bone Cement Scaffolds with Nano Surface Structure for Bone Regeneration.

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    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.

  8. Organ and plantlet regeneration of Menyanthes trifoliata through tissue culture

    Directory of Open Access Journals (Sweden)

    Urszula Adamczyk-Rogozińska

    2014-01-01

    Full Text Available The conditions for the regeneration of plants through organogenesis from callus tissues of Menyanthes trifoliata are described. The shoot multiplication rate was affected by basal culture media, the type and concentration of cytokinin and subculture number. The best response was obtained when caulogenic calli were cultured on the modified Schenk and Hildebrandt medium (SH-M containing indole-3-acetic acid (IAA 0,5 mg/l and 6-benzyladenine (BA 1 mg/l or zeatin (2 mg/l. Under these conditions ca 7 shoots (mostly 1 cm or more in length per culture in the 5th and 6th passages could be developed. In older cultures (after 11-12 passages there was a trend for more numerous but shorter shoot formation. All regenerated shoots could be rooted on the SH-M medium supplemented with 0.5 mg/l IAA within 6 weeks; 80% of in vitro rooted plantlets survived their transfer to soil.

  9. Bone tissue response to experimental zirconia implants.

    Science.gov (United States)

    Mihatovic, Ilja; Golubovic, Vladimir; Becker, Jürgen; Schwarz, Frank

    2017-03-01

    This study seeks to assess the bone tissue response at experimental zirconia implants in comparison with titanium implants by means of descriptive histology and histomorphometry in a dog model. Experimental zirconia implants with three different surface roughnesses (Z1  Z2 30.1 % > Z3 28.9 % > Z1 25.1 %, p > 0.05, unpaired t test, respectively). A provisional matrix was evident at all implant surfaces. At 14 days, percentages of BIC increased in all groups (tBIC: Ti 62.1 % > Z3 69.2 %  Z1 42.3 %; nBIC: Z3 58.9 % > Ti 52.2 % > Z2 35.1 % > Z1 32.5 %). Two implants, one of group Z1 and one of group Z2, were lost. At 10 weeks, 13 of 18 zirconia implants were lost, equally distributed between all three surface modifications. The remaining implants revealed increased BIC values (tBIC: Z3 69.5 % > Ti 58.5 % > Z1 49.7 % > Z2 37.1 %; nBIC: Z3 57.2 % > Ti 46.5 % > Z1 32.3 % > Z2 29.3 %). Histomorphometrical analysis showed comparable mean BIC values in all groups at all healing periods without showing statistical differences (p > 0.05, unpaired t test, respectively). The bone tissue response throughout the healing periods was characterized by a constant bone remodeling accompanied by resorption of old bone in favor of new bone formation at both titanium and zirconia implants. Surface roughness had a positive effect on BIC, although not showing statistical significance. Due to the poor survival rate, the experimental zirconia implants investigated may not be suitable for clinical use. Zirconia has been introduced as an alternative biomaterial for dental implants. A profound knowledge about the bone tissue response at zirconia implant surfaces is necessary as it plays an important role for proper osseointegration and long-term stability.

  10. Successful surgical management of palatogingival groove using platelet-rich fibrin and guided tissue regeneration: A novel approach

    Directory of Open Access Journals (Sweden)

    J V Karunakaran

    2017-01-01

    Full Text Available Palatogingival groove also known as radicularlingual groove is a developmental anomaly involving the lingual surface of the maxillary incisors. They are inconspicuous, funnel-shaped, extend for varying distances on root surface and occur due to infolding of the hertwigs epithelial root sheath. This encourages adherence of microorganisms and plaque to levels significant for pathological changes resulting in endodontic and periodontal lesions. The variations in anatomy of the tooth as a cause of pulp necrosis in teeth of anterior maxillary segment should be considered by the clinician when other etiological factors are ruled out. Recognition of palatogingival groove is critical, especially because of its diagnostic complexity and the problems that may arise if it is not properly interpreted and treated. Regeneration is a new emerging approach in endodontics. Choukroun et al. were among the pioneers for using platelet-rich fibrin (PRF to improve bone healing. PRF is rich in platelet cytokines and growth factors. Numerous techniques have been used to eliminate or seal the groove and regenerate endodontic and periodontal tissues. In this case report of two cases, a novel combination therapy involving ultrasonics, blend of PRF with bone graft, guided tissue regeneration membrane was used in the treatment of a palatogingival groove with an endoperio lesion to ensure arrest of disease progression and promote regeneration. The groove was cleaned and prepared ultrasonically and sealed with a bioactive dentin substitute.

  11. Tissue Microarray Analysis Applied to Bone Diagenesis.

    Science.gov (United States)

    Mello, Rafael Barrios; Silva, Maria Regina Regis; Alves, Maria Teresa Seixas; Evison, Martin Paul; Guimarães, Marco Aurelio; Francisco, Rafaella Arrabaca; Astolphi, Rafael Dias; Iwamura, Edna Sadayo Miazato

    2017-01-04

    Taphonomic processes affecting bone post mortem are important in forensic, archaeological and palaeontological investigations. In this study, the application of tissue microarray (TMA) analysis to a sample of femoral bone specimens from 20 exhumed individuals of known period of burial and age at death is described. TMA allows multiplexing of subsamples, permitting standardized comparative analysis of adjacent sections in 3-D and of representative cross-sections of a large number of specimens. Standard hematoxylin and eosin, periodic acid-Schiff and silver methenamine, and picrosirius red staining, and CD31 and CD34 immunohistochemistry were applied to TMA sections. Osteocyte and osteocyte lacuna counts, percent bone matrix loss, and fungal spheroid element counts could be measured and collagen fibre bundles observed in all specimens. Decalcification with 7% nitric acid proceeded more rapidly than with 0.5 M EDTA and may offer better preservation of histological and cellular structure. No endothelial cells could be detected using CD31 and CD34 immunohistochemistry. Correlation between osteocytes per lacuna and age at death may reflect reported age-related responses to microdamage. Methodological limitations and caveats, and results of the TMA analysis of post mortem diagenesis in bone are discussed, and implications for DNA survival and recovery considered.

  12. Impact of Age on Human Adipose Stem Cells for Bone Tissue Engineering.

    Science.gov (United States)

    Dufrane, Denis

    2017-09-01

    Bone nonunion is a pathological condition in which all bone healing processes have stopped, resulting in abnormal mobility between 2 bone segments. The incidence of bone-related injuries will increase in an aging population, leading to such injuries reaching epidemic proportions. Tissue engineering and cell therapy using mesenchymal stem cells (MSCs) have raised the possibility of implanting living tissue for bone reconstruction. Bone marrow was first proposed as the source of stem cells for bone regeneration. However, as the quantity of MSCs in the bone marrow decreases, the capacity of osteogenic differentiation of bone marrow stem cells is also impaired by the donor's age in terms of reduced MSC replicative capacity; an increased number of apoptotic cells; formation of colonies positive for alkaline phosphatase; and decreases in the availability, growth potential, and temporal mobilization of MSCs for bone formation in case of fracture. Adipose-derived stem cells (ASCs) demonstrate several advantages over those from bone marrow, including a less invasive harvesting procedure, a higher number of stem cell progenitors from an equivalent amount of tissue harvested, increased proliferation and differentiation capacities, and better angiogenic and osteogenic properties in vivo. Subcutaneous native adipose tissue was not affected by the donor's age in terms of cellular senescence and yield of ASC isolation. In addition, a constant mRNA level of osteocalcin and alkaline phosphatase with a similar level of matrix mineralization of ASCs remained unaffected by donor age after osteogenic differentiation. The secretome of ASCs was also unaffected by age when aiming to promote angiogenesis by vascular endothelial growth factor (VEGF) release in hypoxic conditions. Therefore, the use of adipose cells for bone tissue engineering is not limited by the donor's age from the isolation of stem cells up to the manufacturing of a complex osteogenic graft.

  13. Use of the carbon dioxide laser in guided tissue regeneration wound healing in the beagle dog

    Science.gov (United States)

    Rossmann, Jeffrey A.; Parlar, Ates; Abdel-Ghaffar, Khaled A.; El-Khouli, Amr M.; Israel, Michael

    1996-04-01

    The concept of guided tissue regeneration (GTR) allowing cells from the periodontal ligament and alveolar bone to repopulate the treated root surface has shown the ability to obtain periodontal new attachment. Healing studies have also shown that conventional GTR therapy still does not exclude all the epithelium. This epithelial proliferation apically interferes with the establishment of the new connective tissue attachment to the root surface. The objective of this research study was to examine whether controlled de-epithelialization with the carbon dioxide laser during the healing phase after periodontal surgery, would retard the apical migration of the epithelium and thereby enhance the results obtained through guided tissue regeneration. Eight beagle dogs were used, the experimental side received de-epithelialization with the CO2 laser in conjunction with flap reflection and surgically created buccal osseous defects. Selected defects on each side were treated with ePTFE periodontal membranes. The laser de-epithelialization was repeated every 10 days until removal of the membranes. The control side received the same surgical treatment without laser application. This experimental design allowed histologic study of the new attachment obtained in defects treated with flap debridement with or without laser de-epithelialization and with or without ePTFE membranes. A statistical analysis was performed on the histometric data from 48 teeth in the 8 dogs after 4 months of healing. The results showed significant amounts of new attachment obtained from all four treatment modalities with no statistically significant differences for any one treatment. However, the trend towards enhanced