Bone tissue engineering: recent advances and challenges.

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.

[1]  Cato T Laurencin,et al.  The influence of side group modification in polyphosphazenes on hydrolysis and cell adhesion of blends with PLGA. , 2009, Biomaterials.

[2]  Alexis M Pietak,et al.  Magnesium and its alloys as orthopedic biomaterials: a review. , 2006, Biomaterials.

[3]  Cato T Laurencin,et al.  Novel polymer-synthesized ceramic composite-based system for bone repair: an in vitro evaluation. , 2004, Journal of biomedical materials research. Part A.

[4]  Margam Chandrasekaran,et al.  Rapid prototyping in tissue engineering: challenges and potential. , 2004, Trends in biotechnology.

[5]  Celso Matos,et al.  Treatment of osteonecrosis of the femoral head with implantation of autologous bone-marrow cells. A pilot study. , 2004, The Journal of bone and joint surgery. American volume.

[6]  Gordana Vunjak-Novakovic,et al.  Bone Tissue Engineering Using Human Mesenchymal Stem Cells: Effects of Scaffold Material and Medium Flow , 2004, Annals of Biomedical Engineering.

[7]  S. Gronthos,et al.  Perivascular Niche of Postnatal Mesenchymal Stem Cells in Human Bone Marrow and Dental Pulp , 2003, Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research.

[8]  G. Hosgood.  Wound healing. The role of platelet-derived growth factor and transforming growth factor beta. , 1993, Veterinary surgery : VS.

[9]  A. Jödicke,et al.  Autologous stem cells (adipose) and fibrin glue used to treat widespread traumatic calvarial defects: case report. , 2004, Journal of cranio-maxillo-facial surgery : official publication of the European Association for Cranio-Maxillo-Facial Surgery.

[10]  R. Holmes,et al.  Bone formation and implant degradation of coralline porous ceramics placed in bone and ectopic sites. , 1995, Journal of oral and maxillofacial surgery : official journal of the American Association of Oral and Maxillofacial Surgeons.

[11]  T. Webster,et al.  The effect of nanotopography on calcium and phosphorus deposition on metallic materials in vitro. , 2006, Biomaterials.

[12]  P. Robey.  Cell sources for bone regeneration: the good, the bad, and the ugly (but promising). , 2011, Tissue engineering. Part B, Reviews.

[13]  A. Khademhosseini,et al.  Hydrogels in Regenerative Medicine , 2009, Advanced materials.

[14]  Athanasios Mantalaris,et al.  The use of murine embryonic stem cells, alginate encapsulation, and rotary microgravity bioreactor in bone tissue engineering. , 2009, Biomaterials.

[15]  J F Connolly,et al.  Autologous marrow injection as a substitute for operative grafting of tibial nonunions. , 1991, Clinical orthopaedics and related research.

[16]  Helen H. Lu,et al.  Tissue Engineering Strategies for the Regeneration of Orthopedic Interfaces , 2010, Annals of Biomedical Engineering.

[17]  S. Vengallatore,et al.  Nanotechnology and Bone Healing , 2010, Journal of orthopaedic trauma.

[18]  J. Jansen,et al.  Multilineage differentiation potential of stem cells derived from human dental pulp after cryopreservation. , 2006, Tissue engineering.

[19]  R Cancedda,et al.  Repair of large bone defects with the use of autologous bone marrow stromal cells. , 2001, The New England journal of medicine.

[20]  J. Babensee,et al.  Macrophage and dendritic cell phenotypic diversity in the context of biomaterials. , 2011, Journal of biomedical materials research. Part A.

[21]  L. Nicolais,et al.  Effect of PMMA cement radical polymerisation on the inflammatory response , 2004, Journal of materials science. Materials in medicine.

[22]  Kristen A. Wieghaus,et al.  Sustained release of sphingosine 1-phosphate for therapeutic arteriogenesis and bone tissue engineering. , 2008, Biomaterials.

[23]  H. Kagami,et al.  Bone marrow stromal cells (bone marrow-derived multipotent mesenchymal stromal cells) for bone tissue engineering: basic science to clinical translation. , 2011, The international journal of biochemistry & cell biology.

[24]  A. Mikos,et al.  Delivery of plasmid DNA encoding bone morphogenetic protein-2 with a biodegradable branched polycationic polymer in a critical-size rat cranial defect model. , 2011, Tissue engineering. Part A.

[25]  Warren O Haggard,et al.  Composite chitosan/nano-hydroxyapatite scaffolds induce osteocalcin production by osteoblasts in vitro and support bone formation in vivo. , 2009, Tissue engineering. Part A.

[26]  I. Martin,et al.  Towards an intraoperative engineering of osteogenic and vasculogenic grafts from the stromal vascular fraction of human adipose tissue. , 2010, European cells & materials.

[27]  Jacqueline Alblas,et al.  The role of endothelial progenitor cells in prevascularized bone tissue engineering: development of heterogeneous constructs. , 2010, Tissue engineering. Part A.

[28]  G. Finerman,et al.  Regional gene therapy with a BMP‐2‐producing murine stromal cell line induces heterotopic and orthotopic bone formation in rodents , 1998, Journal of orthopaedic research : official publication of the Orthopaedic Research Society.

[29]  P. Bianco,et al.  Stem cells in tissue engineering , 2001, Nature.

[30]  Stan Gronthos,et al.  SHED: Stem cells from human exfoliated deciduous teeth , 2003, Proceedings of the National Academy of Sciences of the United States of America.

[31]  Junzo Tanaka,et al.  Application of perfusion culture system improves in vitro and in vivo osteogenesis of bone marrow-derived osteoblastic cells in porous ceramic materials. , 2003, Tissue engineering.

[32]  Paiyz E. Mikael,et al.  Functionalized Carbon Nanotube Composite Scaffolds for Bone Tissue Engineering: Prospects and Progress , 2011 .

[33]  C. Laurencin,et al.  In Vitro and In Vivo Evaluation of a Novel Polymer-Ceramic Composite Scaffold for Bone Tissue Engineering , 2006, 2006 International Conference of the IEEE Engineering in Medicine and Biology Society.

[34]  L G Griffith,et al.  Effect of pore size and void fraction on cellular adhesion, proliferation, and matrix deposition. , 2001, Tissue engineering.

[35]  M. Morra.  Biochemical modification of titanium surfaces: peptides and ECM proteins. , 2006, European cells & materials.

[36]  X Zhang,et al.  Bone induction by porous glass ceramic made from Bioglass (45S5). , 2001, Journal of biomedical materials research.

[37]  Cato T Laurencin,et al.  Optimally porous and biomechanically compatible scaffolds for large-area bone regeneration. , 2012, Tissue engineering. Part A.

[38]  H. Ohgushi,et al.  Tissue engineering approach to the treatment of bone tumors: three cases of cultured bone grafts derived from patients' mesenchymal stem cells. , 2006, Artificial organs.

[39]  H. Yamasaki,et al.  Osteogenic response to porous hydroxyapatite ceramics under the skin of dogs. , 1992, Biomaterials.

[40]  Ali Khademhosseini,et al.  Cultivation of Human Embryonic Stem Cells Without the Embryoid Body Step Enhances Osteogenesis In Vitro , 2006, Stem cells.

[41]  D L Butler,et al.  Functional tissue engineering: the role of biomechanics. , 2000, Journal of biomechanical engineering.

[42]  Buddy D. Ratner,et al.  Biomaterial topography alters healing in vivo and monocyte/macrophage activation in vitro. , 2010, Journal of biomedical materials research. Part A.

[43]  Cato T Laurencin,et al.  Induction of angiogenesis in tissue-engineered scaffolds designed for bone repair: A combined gene therapy–cell transplantation approach , 2008, Proceedings of the National Academy of Sciences.

[44]  D. L. Kaplan,et al.  Mechanical Stimulation Promotes Osteogenic Differentiation of Human Bone Marrow Stromal Cells on 3-D Partially Demineralized Bone Scaffolds In Vitro , 2004, Calcified Tissue International.

[45]  Ivan Martin,et al.  Bioreactor-based roadmap for the translation of tissue engineering strategies into clinical products. , 2009, Trends in biotechnology.

[46]  N. Ebraheim,et al.  Bone‐Graft Harvesting From Iliac and Fibular Donor Sites: Techniques and Complications , 2001, The Journal of the American Academy of Orthopaedic Surgeons.

[47]  R. Stewart,et al.  Induced Pluripotent Stem Cell Lines Derived from Human Somatic Cells , 2007, Science.

[48]  A. Aggeli,et al.  Self-assembling Peptide Scaffolds Promote Enamel Remineralization , 2007, Journal of dental research.

[49]  Antonios G Mikos,et al.  Formation of three-dimensional cell/polymer constructs for bone tissue engineering in a spinner flask and a rotating wall vessel bioreactor. , 2002, Journal of biomedical materials research.

[50]  S. Gronthos,et al.  Postnatal human dental pulp stem cells (DPSCs) in vitro and in vivo. , 2000, Proceedings of the National Academy of Sciences of the United States of America.

[51]  B. Frenkel,et al.  Leucine-rich amelogenin peptide induces osteogenesis by activation of the Wnt pathway. , 2009, Biochemical and biophysical research communications.

[52]  Byung-Soo Kim,et al.  A poly(lactide-co-glycolide)/hydroxyapatite composite scaffold with enhanced osteoconductivity. , 2007, Journal of biomedical materials research. Part A.

[53]  M. Hedrick,et al.  Plasticity of human adipose stem cells toward endothelial cells and cardiomyocytes , 2006, Nature Clinical Practice Cardiovascular Medicine.

[54]  D. Katti,et al.  Degradable polyphosphazene/poly(α-hydroxyester) blends: degradation studies , 2002 .

[55]  J. Mason,et al.  Gene-enhanced tissue engineering: applications for bone healing using cultured periosteal cells transduced retrovirally with the BMP-7 gene. , 1999, Annals of plastic surgery.

[56]  J. Hubbell,et al.  Fibronectin modulates macrophage adhesion and FBGC formation: the role of RGD, PHSRN, and PRRARV domains. , 2001, Journal of biomedical materials research.

[57]  D. Kaplan,et al.  Role of adult mesenchymal stem cells in bone tissue engineering applications: current status and future prospects. , 2005, Tissue engineering.

[58]  J. H. Kim,et al.  In vivo osteogenic differentiation of human adipose-derived stem cells in an injectable in situ-forming gel scaffold. , 2009, Tissue engineering. Part A.

[59]  J. Vacanti,et al.  A biodegradable nanofiber scaffold by electrospinning and its potential for bone tissue engineering. , 2003, Biomaterials.

[60]  H. Lorenz,et al.  Multilineage cells from human adipose tissue: implications for cell-based therapies. , 2001, Tissue engineering.

[61]  Helen H. Lu,et al.  Interface tissue engineering and the formulation of multiple-tissue systems. , 2006, Advances in biochemical engineering/biotechnology.

[62]  J. Jansen,et al.  In vivo evaluation of gene therapy vectors in ex vivo-derived marrow stromal cells for bone regeneration in a rat critical-size calvarial defect model. , 2003, Human gene therapy.

[63]  U. Ripamonti.  The induction of bone in osteogenic composites of bone matrix and porous hydroxyapatite replicas: an experimental study on the baboon (Papio ursinus). , 1991, Journal of oral and maxillofacial surgery : official journal of the American Association of Oral and Maxillofacial Surgeons.

[64]  Bindiya Patel,et al.  Adipose-derived stem cells: isolation, expansion and differentiation. , 2008, Methods.

[65]  Linda G Griffith,et al.  Engineering principles of clinical cell-based tissue engineering. , 2004, The Journal of bone and joint surgery. American volume.

[66]  C. V. van Blitterswijk,et al.  Osteogenecity of octacalcium phosphate coatings applied on porous metal implants. , 2003, Journal of biomedical materials research. Part A.

[67]  John B. Matson,et al.  Self‐Assembling Peptide Scaffolds for Regenerative Medicine , 2012 .

[68]  P. Soucacos,et al.  An update on recent advances in bone regeneration. , 2008, Injury.

[69]  R. Bizios,et al.  Engineering bone: challenges and obstacles , 2005, Journal of cellular and molecular medicine.

[70]  Vehid Salih,et al.  Stimulation of osteoblast responses to biomimetic nanocomposites of gelatin-hydroxyapatite for tissue engineering scaffolds. , 2005, Biomaterials.

[71]  F. Luyten,et al.  Multipotent mesenchymal stem cells from adult human synovial membrane. , 2001, Arthritis and rheumatism.

[72]  Anusuya Das,et al.  Evaluation of angiogenesis and osteogenesis. , 2011, Tissue engineering. Part B, Reviews.

[73]  Dominique P Pioletti,et al.  Biomechanics in bone tissue engineering , 2010, Computer methods in biomechanics and biomedical engineering.

[74]  J. Klein-Nulend,et al.  Osteogenesis versus chondrogenesis by BMP-2 and BMP-7 in adipose stem cells. , 2006, Biochemical and biophysical research communications.

[75]  J M Anderson,et al.  Influence of biomaterial surface chemistry on the apoptosis of adherent cells. , 2001, Journal of biomedical materials research.

[76]  Johnna S Temenoff,et al.  Engineering orthopedic tissue interfaces. , 2009, Tissue engineering. Part B, Reviews.

[77]  Gunasekaran Kumar,et al.  Morbidity at Bone Graft Donor Sites , 2014 .

[78]  Masashi Neo,et al.  In vivo evaluation of a porous hydroxyapatite/poly-DL-lactide composite for bone tissue engineering. , 2007, Journal of biomedical materials research. Part A.

[79]  W C Hayes,et al.  Evolution of bone transplantation: molecular, cellular and tissue strategies to engineer human bone. , 1996, Biomaterials.

[80]  Laura A. Smith,et al.  The enhancement of human embryonic stem cell osteogenic differentiation with nano-fibrous scaffolding. , 2010, Biomaterials.

[81]  James M. Anderson,et al.  Foreign body reaction to biomaterials. , 2008, Seminars in immunology.

[82]  H. Takita,et al.  Pore size of porous hydroxyapatite as the cell-substratum controls BMP-induced osteogenesis. , 1997, Journal of biochemistry.

[83]  J. Arts,et al.  Bioactive and osteoinductive bone graft substitutes: definitions, facts and myths. , 2011, Injury.

[84]  V. Denaro,et al.  Platelet Rich Plasma and Tendinopathy: State of the Art , 2011, International journal of immunopathology and pharmacology.

[85]  Takatoshi Kinoshita,et al.  Dynamic reassembly of peptide RADA16 nanofiber scaffold. , 2005, Proceedings of the National Academy of Sciences of the United States of America.

[86]  Jeremy Mao,et al.  Bone tissue engineering and regeneration: from discovery to the clinic--an overview. , 2011, Tissue engineering. Part B, Reviews.

[87]  Antonios G Mikos,et al.  Harnessing and modulating inflammation in strategies for bone regeneration. , 2011, Tissue engineering. Part B, Reviews.

[88]  Eleftherios Tsiridis,et al.  Bone substitutes: an update. , 2005, Injury.

[89]  U. Ripamonti.  Osteoinduction in porous hydroxyapatite implanted in heterotopic sites of different animal models. , 1996, Biomaterials.

[90]  Huipin Yuan,et al.  Osteoinductive biomaterials: current knowledge of properties, experimental models and biological mechanisms. , 2011, European cells & materials.

[91]  Clemens A van Blitterswijk,et al.  Osteoconduction and osteoinduction of low-temperature 3D printed bioceramic implants. , 2008, Biomaterials.

[92]  Ayse B. Celil,et al.  Bone tissue engineering:recent advances and promising therapeutic agents , 2003, Expert opinion on biological therapy.

[93]  R. Klar,et al.  Synergistic induction of bone formation by hOP-1, hTGF-beta3 and inhibition by zoledronate in macroporous coral-derived hydroxyapatites. , 2010, Biomaterials.

[94]  J. Pak.  Autologous adipose tissue-derived stem cells induce persistent bone-like tissue in osteonecrotic femoral heads. , 2012, Pain physician.

[95]  M. Soleimani,et al.  Sinus augmentation using human mesenchymal stem cells loaded into a beta-tricalcium phosphate/hydroxyapatite scaffold. , 2008, Oral surgery, oral medicine, oral pathology, oral radiology, and endodontics.

[96]  M. Beatty,et al.  Human osteogenic protein-1 induces osteogenic differentiation of adipose-derived stem cells harvested from mice. , 2008, Archives of oral biology.

[97]  T. Webster,et al.  Nanotechnology and nanomaterials: Promises for improved tissue regeneration , 2009 .

[98]  R. Legeros,et al.  Properties of osteoconductive biomaterials: calcium phosphates. , 2002, Clinical orthopaedics and related research.

[99]  D. Katti,et al.  Degradable polyphosphazene/poly(alpha-hydroxyester) blends: degradation studies. , 2002, Biomaterials.

[100]  Cato T Laurencin,et al.  Human osteoblast-like cells in three-dimensional culture with fluid flow. , 2003, Biorheology.

[101]  Ivan Martin,et al.  Three‐Dimensional Perfusion Culture of Human Adipose Tissue‐Derived Endothelial and Osteoblastic Progenitors Generates Osteogenic Constructs with Intrinsic Vascularization Capacity , 2007, Stem cells.

[102]  A. Boccaccini,et al.  Biodegradable and bioactive porous polymer/inorganic composite scaffolds for bone tissue engineering. , 2006, Biomaterials.

[103]  V. Maquet,et al.  Polylactide macroporous biodegradable implants for cell transplantation. II. Preparation of polylactide foams by liquid-liquid phase separation. , 1996, Journal of biomedical materials research.

[104]  Ahmed El-Ghannam,et al.  Bone reconstruction: from bioceramics to tissue engineering , 2005, Expert review of medical devices.

[105]  T. Albert,et al.  Physical and monetary costs associated with autogenous bone graft harvesting. , 2003, American journal of orthopedics.

[106]  R. Reis,et al.  Design of nano- and microfiber combined scaffolds by electrospinning of collagen onto starch-based fiber meshes: a man-made equivalent of natural extracellular matrix. , 2011, Tissue engineering. Part A.

[107]  R. Maier,et al.  Differential monocyte/macrophage interleukin-1β production due to biomaterial topography requires the β2 integrin signaling pathway. , 2011, Journal of biomedical materials research. Part A.

[108]  Sanjin Zvonic,et al.  Immunophenotype of Human Adipose‐Derived Cells: Temporal Changes in Stromal‐Associated and Stem Cell–Associated Markers , 2006, Stem cells.

[109]  C. M. Agrawal,et al.  Fundamentals of biomechanics in tissue engineering of bone. , 2000, Tissue engineering.

[110]  P. Uggowitzer,et al.  Magnesium alloys for temporary implants in osteosynthesis: in vivo studies of their degradation and interaction with bone. , 2012, Acta biomaterialia.

[111]  Jeffrey M Karp,et al.  Mesenchymal stem cell homing: the devil is in the details. , 2009, Cell stem cell.

[112]  Arun K Gosain,et al.  A 1-year study of osteoinduction in hydroxyapatite-derived biomaterials in an adult sheep model: part I. , 2002, Plastic and reconstructive surgery.

[113]  J. Schantz,et al.  Cell guidance in tissue engineering: SDF-1 mediates site-directed homing of mesenchymal stem cells within three-dimensional polycaprolactone scaffolds. , 2007, Tissue engineering.

[114]  Charles P. Lin,et al.  Engineered cell homing. , 2011, Blood.

[115]  R. A. Forster,et al.  Alternatives to Autogenous Bone Graft: Efficacy and Indications , 1995, The Journal of the American Academy of Orthopaedic Surgeons.

[116]  D. Schmidt,et al.  Monocyte activation in response to polyethylene glycol hydrogels grafted with RGD and PHSRN separated by interpositional spacers of various lengths. , 2007, Journal of biomedical materials research. Part A.

[117]  C T Laurencin,et al.  Biodegradable polyphosphazenes for drug delivery applications. , 2003, Advanced drug delivery reviews.

[118]  Jeffrey A. Hubbell,et al.  Cell-Demanded Liberation of VEGF121 From Fibrin Implants Induces Local and Controlled Blood Vessel Growth , 2004, Circulation research.

[119]  Ulrich H. von Andrian,et al.  Stem Cell Trafficking in Tissue Development, Growth, and Disease , 2008, Cell.

[120]  H. Jung,et al.  Control of osteogenic differentiation and mineralization of human mesenchymal stem cells on composite nanofibers containing poly[lactic-co-(glycolic acid)] and hydroxyapatite. , 2010, Macromolecular bioscience.

[121]  O. Barbier,et al.  Bone allografts: What they can offer and what they cannot. , 2007, The Journal of bone and joint surgery. British volume.

[122]  D. Kaigler,et al.  Angiogenic and osteogenic potential of bone repair cells for craniofacial regeneration. , 2010, Tissue engineering. Part A.

[123]  S. Yamanaka,et al.  Induction of Pluripotent Stem Cells from Mouse Embryonic and Adult Fibroblast Cultures by Defined Factors , 2006, Cell.

[124]  S. Vukicevic,et al.  An EP2 receptor-selective prostaglandin E2 agonist induces bone healing , 2003, Proceedings of the National Academy of Sciences of the United States of America.

[125]  M. Kneževič,et al.  Bone tissue engineering with human stem cells , 2010, Stem Cell Research & Therapy.

[126]  A. Mikos,et al.  Effect of convection on osteoblastic cell growth and function in biodegradable polymer foam scaffolds. , 2001, Biomaterials.

[127]  B. Thiers.  Induction of Pluripotent Stem Cells from Adult Human Fibroblasts by Defined Factors , 2008 .

[128]  S. Badylak,et al.  A perivascular origin for mesenchymal stem cells in multiple human organs. , 2008, Cell stem cell.

[129]  Min Zhu,et al.  Human adipose tissue is a source of multipotent stem cells. , 2002, Molecular biology of the cell.

[130]  W A Morrison,et al.  Vascularisation of tissue-engineered grafts: the regulation of angiogenesis in reconstructive surgery and in disease states. , 2002, British journal of plastic surgery.

[131]  B. Baroli.  From natural bone grafts to tissue engineering therapeutics: Brainstorming on pharmaceutical formulative requirements and challenges. , 2009, Journal of pharmaceutical sciences.

[132]  D. Hutmacher,et al.  The correlation of pore morphology, interconnectivity and physical properties of 3D ceramic scaffolds with bone ingrowth. , 2009, Biomaterials.

[133]  C T Laurencin,et al.  Three-dimensional degradable porous polymer-ceramic matrices for use in bone repair. , 1996, Journal of biomaterials science. Polymer edition.

[134]  J. Polak,et al.  In vitro direct osteogenesis of murine embryonic stem cells without embryoid body formation. , 2008, Stem cells and development.

[135]  Leaf Huang,et al.  Nonviral gene therapy: promises and challenges , 2000, Gene Therapy.

[136]  Mara Riminucci,et al.  Bone Marrow Stromal Stem Cells: Nature, Biology, and Potential Applications , 2001, Stem cells.

[137]  J. D. de Bruijn,et al.  Heterotopic bone formation by nano-apatite containing poly(D,L-lactide) composites. , 2010, European cells & materials.

[138]  G. Sukhikh,et al.  Mesenchymal Stem Cells , 2002, Bulletin of Experimental Biology and Medicine.

[139]  Cato T. Laurencin,et al.  Bone-Graft Substitutes: Facts, Fictions, and Applications , 2001, The Journal of bone and joint surgery. American volume.

[140]  A. Lowman,et al.  Synthesis and characterization of an injectable hydrogel with tunable mechanical properties for soft tissue repair. , 2006, Biomacromolecules.

[141]  Rui L Reis,et al.  Bone tissue engineering: state of the art and future trends. , 2004, Macromolecular bioscience.

[142]  C. Laurencin,et al.  Differential analysis of peripheral blood‐ and bone marrow‐derived endothelial progenitor cells for enhanced vascularization in bone tissue engineering , 2012, Journal of orthopaedic research : official publication of the Orthopaedic Research Society.

[143]  E. Zussman,et al.  3-D Nanofibrous electrospun multilayered construct is an alternative ECM mimicking scaffold , 2008, Journal of materials science. Materials in medicine.

[144]  D. Kaplan,et al.  Porosity of 3D biomaterial scaffolds and osteogenesis. , 2005, Biomaterials.

[145]  Byung-Soo Kim,et al.  In vivo bone formation from human embryonic stem cell-derived osteogenic cells in poly(d,l-lactic-co-glycolic acid)/hydroxyapatite composite scaffolds. , 2008, Biomaterials.

[146]  K. Hochedlinger,et al.  Cell type of origin influences the molecular and functional properties of mouse induced pluripotent stem cells , 2010, Nature Biotechnology.

[147]  J M Anderson,et al.  Biomaterial surface chemistry dictates adherent monocyte/macrophage cytokine expression in vitro. , 2002, Cytokine.

[148]  R Borojevic,et al.  Characterization of a bovine collagen-hydroxyapatite composite scaffold for bone tissue engineering. , 2003, Biomaterials.

[149]  G. Vunjak‐Novakovic,et al.  Tissue engineered bone grafts: biological requirements, tissue culture and clinical relevance. , 2008, Current stem cell research & therapy.

[150]  J. Polak,et al.  Embryonic stem cells , 2002, The Journal of pathology.

[151]  Cato T. Laurencin,et al.  Nanotechnology and orthopedics: a personal perspective. , 2009, Wiley interdisciplinary reviews. Nanomedicine and nanobiotechnology.

[152]  Stephen B Doty,et al.  In vivo evaluation of a multiphased scaffold designed for orthopaedic interface tissue engineering and soft tissue-to-bone integration. , 2008, Journal of biomedical materials research. Part A.

[153]  F. Carinci,et al.  A New Population of Human Adult Dental Pulp Stem Cells: A Useful Source of Living Autologous Fibrous Bone Tissue (LAB) , 2005, Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research.

[154]  Yusuf Khan,et al.  Bone graft substitutes , 2006, Expert review of medical devices.

[155]  Cato T. Laurencin,et al.  Nanostructured Scaffolds for Bone Tissue Engineering , 2011 .

[156]  Galip Akay,et al.  The enhancement of osteoblast growth and differentiation in vitro on a peptide hydrogel-polyHIPE polymer hybrid material. , 2005, Biomaterials.

[157]  Ashok K. Goel,et al.  Percutaneous bone marrow grafting for the treatment of tibial non-union. , 2005, Injury.

[158]  Yaokai Gan,et al.  The clinical use of enriched bone marrow stem cells combined with porous beta-tricalcium phosphate in posterior spinal fusion. , 2008, Biomaterials.

[159]  Toshitaka Nakamura,et al.  Prostaglandin E2 receptor (EP4) selective agonist (ONO-4819.CD) accelerates bone repair of femoral cortex after drill-hole injury associated with local upregulation of bone turnover in mature rats. , 2004, Bone.

[160]  Markus Rudin,et al.  Three-dimensional co-cultures of osteoblasts and endothelial cells in DegraPol foam: histological and high-field magnetic resonance imaging analyses of pre-engineered capillary networks in bone grafts. , 2011, Tissue engineering. Part A.

[161]  Fotios Papadimitrakopoulos,et al.  Biomaterials/Tissue Interactions: Possible Solutions to Overcome Foreign Body Response , 2010, The AAPS Journal.

[162]  S. Nukavarapu,et al.  Design, fabrication and in vitro evaluation of a novel polymer‐hydrogel hybrid scaffold for bone tissue engineering , 2014, Journal of tissue engineering and regenerative medicine.

[163]  D. Mooney,et al.  Hydrogels for tissue engineering. , 2001, Chemical reviews.

[164]  Joshua R Porter,et al.  Biodegradable poly(epsilon-caprolactone) nanowires for bone tissue engineering applications. , 2009, Biomaterials.

[165]  Matthew Shaw,et al.  Healos and Bone Marrow Aspirate Used for Lumbar Spine Fusion: A Case Controlled Study Comparing Healos With Autograft , 2006, Spine.

[166]  R. Jain.  Normalization of Tumor Vasculature: An Emerging Concept in Antiangiogenic Therapy , 2005, Science.

[167]  Y. Ikada,et al.  Polymer-hydroxyapatite composites for biodegradable bone fillers. , 1986, Biomaterials.

[168]  O. Mei-Dan,et al.  The Role of Platelet-rich Plasma in Rotator Cuff Repair , 2011, Sports medicine and arthroscopy review.

[169]  F. Papadimitrakopoulos,et al.  Dexamethasone-loaded poly(lactic-co-glycolic) acid microspheres/poly(vinyl alcohol) hydrogel composite coatings for inflammation control. , 2004, Diabetes technology & therapeutics.

[170]  G. Papaccio,et al.  Methods for the Identification, Characterization and Banking of Human DPSCs: Current Strategies and Perspectives , 2011, Stem Cell Reviews and Reports.

[171]  Casey K Chan,et al.  Stem cell homing in musculoskeletal injury. , 2011, Biomaterials.

[172]  R Langer,et al.  Dynamic Cell Seeding of Polymer Scaffolds for Cartilage Tissue Engineering , 1998, Biotechnology progress.

[173]  Anna Spagnoli,et al.  Regenerative Effects of Transplanted Mesenchymal Stem Cells in Fracture Healing , 2009, Stem cells.

[174]  L. Roden,et al.  The induction of bone formation by coral-derived calcium carbonate/hydroxyapatite constructs. , 2009, Biomaterials.

[175]  Pamela Habibovic,et al.  Osteoinductive biomaterials—properties and relevance in bone repair , 2007, Journal of tissue engineering and regenerative medicine.

[176]  Scott J Hollister,et al.  Scaffold translation: barriers between concept and clinic. , 2011, Tissue engineering. Part B, Reviews.

[177]  P. Proussaefs,et al.  Platelet-rich plasma application in sinus graft surgery: Part I--Background and processing techniques. , 2001, The Journal of oral implantology.

[178]  Banwart Jc,et al.  Iliac crest bone graft harvest donor site morbidity. A statistical evaluation. , 1995 .

[179]  J. Nicholas.  THE ORTHOPAEDIC RESEARCH SOCIETY , 1963 .

[180]  Andrea Bagno,et al.  Electrospun scaffolds of self-assembling peptides with poly(ethylene oxide) for bone tissue engineering. , 2011, Acta biomaterialia.

[181]  Syam P. Nukavarapu,et al.  Optimal scaffold design and effective progenitor cell identification for the regeneration of vascularized bone , 2011, 2011 Annual International Conference of the IEEE Engineering in Medicine and Biology Society.

[182]  J. Gimble,et al.  Surface protein characterization of human adipose tissue‐derived stromal cells , 2001, Journal of cellular physiology.

[183]  Miya Ishihara,et al.  Bone formation using human adipose tissue-derived stromal cells and a biodegradable scaffold. , 2006, Journal of biomedical materials research. Part B, Applied biomaterials.

[184]  Pierre Hardouin,et al.  Biomaterial challenges and approaches to stem cell use in bone reconstructive surgery. , 2004, Drug discovery today.

[185]  Maurilio Marcacci,et al.  Stem cells associated with macroporous bioceramics for long bone repair: 6- to 7-year outcome of a pilot clinical study. , 2007, Tissue engineering.

[186]  J. Davies,et al.  Engineering three-dimensional bone tissue in vitro using biodegradable scaffolds: investigating initial cell-seeding density and culture period. , 2000, Journal of biomedical materials research.

[187]  J. Fox,et al.  Autogeneic anterior cruciate ligament (ACL) anterior reconstruction of the knee. A review. , 1985, Clinical orthopaedics and related research.

[188]  T. Desai,et al.  Aligned arrays of biodegradable poly(epsilon-caprolactone) nanowires and nanofibers by template synthesis. , 2007, Nano letters.

[189]  Tejal A Desai,et al.  Influence of engineered titania nanotubular surfaces on bone cells. , 2007, Biomaterials.

[190]  Fa-Ming Chen,et al.  Homing of endogenous stem/progenitor cells for in situ tissue regeneration: Promises, strategies, and translational perspectives. , 2011, Biomaterials.

[191]  I. Martin,et al.  Platelet lysate as a serum substitute for 2D static and 3D perfusion culture of stromal vascular fraction cells from human adipose tissue. , 2009, Tissue engineering. Part A.

[192]  U. Ripamonti,et al.  The morphogenesis of bone in replicas of porous hydroxyapatite obtained from conversion of calcium carbonate exoskeletons of coral. , 1991, The Journal of bone and joint surgery. American volume.

[193]  H. Gruber,et al.  Adipose-Derived Stem Cells: Characterization and Current Application in Orthopaedic Tissue Repair , 2009, Experimental biology and medicine.

[194]  J T Czernuszka,et al.  Collagen-hydroxyapatite composites for hard tissue repair. , 2006, European cells & materials.

[195]  S. Shi,et al.  Dental pulp tissue engineering with stem cells from exfoliated deciduous teeth. , 2008, Journal of endodontics.

[196]  J. Babensee,et al.  Differential effects of agarose and poly(lactic-co-glycolic acid) on dendritic cell maturation. , 2006, Journal of biomedical materials research. Part A.

[197]  K. Popat,et al.  Bone tissue engineering: A review in bone biomimetics and drug delivery strategies , 2009, Biotechnology progress.

[198]  Antonios G. Mikos,et al.  Fluid flow increases mineralized matrix deposition in 3D perfusion culture of marrow stromal osteoblasts in a dose-dependent manner , 2002, Proceedings of the National Academy of Sciences of the United States of America.

[199]  P. Hernigou,et al.  The use of percutaneous autologous bone marrow transplantation in nonunion and avascular necrosis of bone. , 2005, The Journal of bone and joint surgery. British volume.

[200]  H R Allcock,et al.  Novel polyphosphazene/poly(lactide-co-glycolide) blends: miscibility and degradation studies. , 1997, Biomaterials.

[201]  F. Shapiro,et al.  Bone development and its relation to fracture repair. The role of mesenchymal osteoblasts and surface osteoblasts. , 2008, European cells & materials.

[202]  Moustapha Kassem,et al.  Effect of dynamic 3-D culture on proliferation, distribution, and osteogenic differentiation of human mesenchymal stem cells. , 2008, Journal of biomedical materials research. Part A.

[203]  W. Mutschler,et al.  Hypoxia in static and dynamic 3D culture systems for tissue engineering of bone. , 2008, Tissue engineering. Part A.

[204]  Kamran Kaveh,et al.  Bone grafting and bone graft substitutes , 2010 .

[205]  G. Churchill,et al.  Characterization of human embryonic stem cell lines by the International Stem Cell Initiative , 2007, Nature Biotechnology.

[206]  V. Jansson,et al.  Bone formation in coralline hydroxyapatite. Effects of pore size studied in rabbits. , 1994, Acta orthopaedica Scandinavica.

[207]  Dong Yeon Lee,et al.  Mobilization of endothelial progenitor cells in fracture healing and distraction osteogenesis. , 2008, Bone.

[208]  D. Wendt,et al.  The role of bioreactors in tissue engineering. , 2004, Trends in biotechnology.

[209]  P. Ma,et al.  Engineering new bone tissue in vitro on highly porous poly(alpha-hydroxyl acids)/hydroxyapatite composite scaffolds. , 2001, Journal of biomedical materials research.

[210]  Marc A. Asher,et al.  Iliac Crest Bone Graft Harvest Donor Site Morbidity: A Statistical Evaluation , 1995, Spine.

[211]  S. Doty,et al.  Thrombin peptide (TP508) promotes fracture repair by up‐regulating inflammatory mediators, early growth factors, and increasing angiogenesis , 2005, Journal of orthopaedic research : official publication of the Orthopaedic Research Society.

[212]  L. Applegate,et al.  Bone regeneration and stem cells , 2011, Journal of cellular and molecular medicine.

[213]  Paul H Wooley,et al.  Promotion of osteogenesis in tissue‐engineered bone by pre‐seeding endothelial progenitor cells‐derived endothelial cells , 2008, Journal of orthopaedic research : official publication of the Orthopaedic Research Society.

[214]  J. Pak.  Regeneration of human bones in hip osteonecrosis and human cartilage in knee osteoarthritis with autologous adipose-tissue-derived stem cells: a case series , 2011, Journal of medical case reports.

[215]  Byung-Soo Kim,et al.  In vivo bone formation following transplantation of human adipose-derived stromal cells that are not differentiated osteogenically. , 2008, Tissue engineering. Part A.

[216]  Rozalia Dimitriou,et al.  Bone regeneration: current concepts and future directions , 2011, BMC medicine.

[217]  三澤 治夫.  PuraMatrix facilitates bone regeneration in bone defects of calvaria in mice , 2007 .

[218]  V. Sikavitsas,et al.  Biomaterials and bone mechanotransduction. , 2001, Biomaterials.

[219]  Peter X Ma,et al.  Nano-fibrous scaffolding promotes osteoblast differentiation and biomineralization. , 2007, Biomaterials.

[220]  X. Zhang,et al.  Osseous substance formation induced in porous calcium phosphate ceramics in soft tissues. , 1994, Biomaterials.

[221]  A. Piattelli,et al.  Human Dental Pulp Stem Cells Hook into Biocoral Scaffold Forming an Engineered Biocomplex , 2011, PloS one.

[222]  Moncy V. Jose,et al.  Aligned PLGA/HA nanofibrous nanocomposite scaffolds for bone tissue engineering. , 2009, Acta biomaterialia.

[223]  Cato T Laurencin,et al.  Nanobiomaterial applications in orthopedics , 2007, Journal of orthopaedic research : official publication of the Orthopaedic Research Society.

[224]  C. Semino.  Self-assembling Peptides: From Bio-inspired Materials to Bone Regeneration , 2008, Journal of dental research.

[225]  C. V. van Blitterswijk,et al.  Influence of octacalcium phosphate coating on osteoinductive properties of biomaterials , 2004, Journal of materials science. Materials in medicine.

[226]  F. Claas,et al.  Isolation of Mesenchymal Stem Cells of Fetal or Maternal Origin from Human Placenta , 2004, Stem cells.

[227]  Ying Yang,et al.  Tissue engineering: a new take-off using nanofiber-based scaffolds. , 2007, The Journal of craniofacial surgery.

[228]  H. Kronenberg,et al.  Developmental regulation of the growth plate , 2003, Nature.

[229]  J. A. Cooper,et al.  Tissue engineering: orthopedic applications. , 1999, Annual review of biomedical engineering.

[230]  M. Marei,et al.  Regeneration of dentine/pulp-like tissue using a dental pulp stem cell/poly(lactic-co-glycolic) acid scaffold construct in New Zealand white rabbits. , 2008, Australian endodontic journal : the journal of the Australian Society of Endodontology Inc.

[231]  Shaoyi Jiang,et al.  Reduced foreign body reaction to implanted biomaterials by surface treatment with oriented osteopontin , 2008, Journal of biomaterials science. Polymer edition.

[232]  M. Jäger,et al.  Safety of autologous bone marrow aspiration concentrate transplantation: initial experiences in 101 patients , 2009, Orthopedic reviews.

[233]  M. Jäger,et al.  Bone marrow concentrate: a novel strategy for bone defect treatment. , 2009, Current stem cell research & therapy.

[234]  C. Colnot.  Cell sources for bone tissue engineering: insights from basic science. , 2011, Tissue engineering. Part B, Reviews.

[235]  J. Jansen,et al.  Effect of varied release kinetics of the osteogenic thrombin peptide TP508 from biodegradable, polymeric scaffolds on bone formation in vivo. , 2005, Journal of biomedical materials research. Part A.

[236]  Jeroen Rouwkema,et al.  Vascularization in tissue engineering. , 2008, Trends in biotechnology.

[237]  C. D. Reyes,et al.  Bio-adhesive Surfaces to Promote Osteoblast Differentiation and Bone Formation , 2005, Journal of dental research.

[238]  A. Abbas,et al.  Human peripheral blood derived mesenchymal stem cells demonstrate similar characteristics and chondrogenic differentiation potential to bone marrow derived mesenchymal stem cells , 2012, Journal of orthopaedic research : official publication of the Orthopaedic Research Society.

[239]  K. Satomura,et al.  Circulating Skeletal Stem Cells , 2001, The Journal of cell biology.

[240]  J. Jansen,et al.  Scaffold mesh size affects the osteoblastic differentiation of seeded marrow stromal cells cultured in a flow perfusion bioreactor. , 2005, Journal of biomedical materials research. Part A.

[241]  M. Richards,et al.  Comparative Evaluation of Various Human Feeders for Prolonged Undifferentiated Growth of Human Embryonic Stem Cells , 2003, Stem cells.

[242]  James M. Anderson,et al.  The topographical effect of electrospun nanofibrous scaffolds on the in vivo and in vitro foreign body reaction. , 2009, Journal of biomedical materials research. Part A.

[243]  Antonios G Mikos,et al.  Biomimetic materials for tissue engineering. , 2003, Biomaterials.

[244]  X. Sherry Liu,et al.  Engineering anatomically shaped human bone grafts , 2009, Proceedings of the National Academy of Sciences.

[245]  B. Alman,et al.  Heal thyself: using endogenous regeneration to repair bone. , 2011, Tissue engineering. Part B, Reviews.

[246]  N. Fazzalari,et al.  Bone fracture and bone fracture repair , 2011, Osteoporosis International.

[247]  M. Kassem,et al.  The Human Umbilical Cord Blood: A Potential Source for Osteoblast Progenitor Cells , 2003, Calcified Tissue International.

[248]  Cato T Laurencin,et al.  Miscibility and in vitro osteocompatibility of biodegradable blends of poly[(ethyl alanato) (p-phenyl phenoxy) phosphazene] and poly(lactic acid-glycolic acid). , 2008, Biomaterials.

[249]  M. Gebhardt,et al.  Infection in bone allografts. Incidence, nature, and treatment. , 1988, The Journal of bone and joint surgery. American volume.

[250]  S. Gronthos,et al.  Adult Human Dental Pulp Stem Cells Differentiate Toward Functionally Active Neurons Under Appropriate Environmental Cues , 2008, Stem cells.

[251]  Stephen B Doty,et al.  Development of controlled matrix heterogeneity on a triphasic scaffold for orthopedic interface tissue engineering. , 2006, Tissue engineering.

[252]  George P McCabe,et al.  Extracellular matrix bioscaffolds for orthopaedic applications. A comparative histologic study. , 2006, The Journal of bone and joint surgery. American volume.

[253]  P. Netti,et al.  Effect of micro- and macroporosity of bone tissue three-dimensional-poly(epsilon-caprolactone) scaffold on human mesenchymal stem cells invasion, proliferation, and differentiation in vitro. , 2010, Tissue engineering. Part A.

[254]  Jan Feijen,et al.  Preparation of interconnected highly porous polymeric structures by a replication and freeze-drying process. , 2003, Journal of biomedical materials research. Part B, Applied biomaterials.

[255]  Xing‐dong Zhang,et al.  Osteoinduction by calcium phosphate biomaterials , 1998, Journal of materials science. Materials in medicine.

[256]  D. Kuik,et al.  Effect of tissue-harvesting site on yield of stem cells derived from adipose tissue: implications for cell-based therapies , 2008, Cell and Tissue Research.

[257]  W. Mutschler,et al.  Tissue engineering for bone defect healing: an update on a multi-component approach. , 2008, Injury.

[258]  Ke Yang,et al.  In vivo evaluation of biodegradable magnesium alloy bone implant in the first 6 months implantation. , 2009, Journal of biomedical materials research. Part A.

[259]  Josep A Planell,et al.  Simulation of tissue differentiation in a scaffold as a function of porosity, Young's modulus and dissolution rate: application of mechanobiological models in tissue engineering. , 2007, Biomaterials.

[260]  M. S. Park,et al.  Accelerated bonelike apatite growth on porous polymer/ceramic composite scaffolds in vitro. , 2006, Tissue engineering.

[261]  M. Goldman,et al.  A study of the clinical incidence of infection in the use of banked allograft bone. , 1981, The Journal of bone and joint surgery. American volume.

[262]  E. Mäkelä,et al.  Percutaneous bone grafting in the treatment of the delayed union and non-union of tibial fractures. , 2002, Injury.

[263]  S L Weissman,et al.  The clinical use of combined xenografts of bone and autologous red marrow. A preliminary report. , 1978, The Journal of bone and joint surgery. British volume.

[264]  D. Mooney,et al.  Polymeric system for dual growth factor delivery , 2001, Nature Biotechnology.

[265]  Yingzi Yang.  Skeletal morphogenesis during embryonic development. , 2009, Critical reviews in eukaryotic gene expression.

[266]  Zhou Yu-zhen.  Characterization and culture of human embryonic stem cells , 2012 .

[267]  S. Soker,et al.  Osteogenic differentiation of human amniotic fluid-derived stem cells induced by bone morphogenetic protein-7 and enhanced by nanofibrous scaffolds. , 2010, Biomaterials.

[268]  R. Marchant,et al.  Design and synthesis of biomimetic hydrogel scaffolds with controlled organization of cyclic RGD peptides. , 2009, Bioconjugate chemistry.

[269]  A. Mikos,et al.  Growing new organs. , 1999, Scientific American.

[270]  J. Klein-Nulend,et al.  Stem cells from adipose tissue allow challenging new concepts for regenerative medicine. , 2007, Tissue engineering.

[271]  M. Sampaolesi,et al.  Human postnatal dental pulp cells co-differentiate into osteoblasts and endotheliocytes: a pivotal synergy leading to adult bone tissue formation , 2007, Cell Death and Differentiation.

[272]  E. Place,et al.  Complexity in biomaterials for tissue engineering. , 2009, Nature materials.

[273]  B. Heng,et al.  Comparison of osteogenesis of human embryonic stem cells within 2D and 3D culture systems , 2008, Scandinavian journal of clinical and laboratory investigation.

[274]  C. Laurencin,et al.  Miscibility of bioerodible polyphosphazene/poly(lactide-co-glycolide) blends. , 2007, Biomacromolecules.

[275]  H. V. von Recum,et al.  Endothelial stem cells and precursors for tissue engineering: cell source, differentiation, selection, and application. , 2008, Tissue engineering. Part B, Reviews.

[276]  Jun-Beom Park.  The use of hydrogels in bone-tissue engineering. , 2011, Medicina oral, patologia oral y cirugia bucal.

[277]  Syam P Nukavarapu,et al.  Short-term and long-term effects of orthopedic biodegradable implants. , 2011, Journal of long-term effects of medical implants.

[278]  J. Kinney,et al.  Repair of rabbit segmental defects with the thrombin peptide, TP508 , 2004, Journal of orthopaedic research : official publication of the Orthopaedic Research Society.

[279]  G. Bowlin,et al.  Modulation of murine innate and acquired immune responses following in vitro exposure to electrospun blends of collagen and polydioxanone. , 2009, Journal of biomedical materials research. Part A.

[280]  H. Chambers,et al.  Complications of iliac crest bone graft harvesting. , 1996, Clinical orthopaedics and related research.

[281]  Martin Ehrbar,et al.  Cell‐demanded release of VEGF from synthetic, biointeractive cell‐ingrowth matrices for vascularized tissue growth , 2003, FASEB journal : official publication of the Federation of American Societies for Experimental Biology.

[282]  Cato T Laurencin,et al.  Quantitative analysis of three-dimensional fluid flow in rotating bioreactors for tissue engineering. , 2004, Journal of biomedical materials research. Part A.

[283]  I. Marzi,et al.  Endothelial progenitor cells and mesenchymal stem cells seeded onto beta-TCP granules enhance early vascularization and bone healing in a critical-sized bone defect in rats. , 2010, Tissue engineering. Part A.

[284]  Miqin Zhang,et al.  Calcium phosphate-chitosan composite scaffolds for bone tissue engineering. , 2003, Tissue engineering.

[285]  R. Quigg,et al.  TP508 accelerates fracture repair by promoting cell growth over cell death. , 2007, Biochemical and biophysical research communications.

[286]  M. McPherson,et al.  Recombinant self-assembling peptides as biomaterials for tissue engineering , 2010, Biomaterials.

[287]  K. Ueda,et al.  Tissue Engineering Skin Flaps: Which Vascular Carrier, Arteriovenous Shunt Loop or Arteriovenous Bundle, Has More Potential for Angiogenesis and Tissue Generation? , 2003, Plastic and reconstructive surgery.

[288]  M. Yoshinari,et al.  In vitro study of collagen coating of titanium implants for initial cell attachment. , 2002, Dental materials journal.

[289]  Yingjun Wang,et al.  Poly(lactide-co-glycolide)/hydroxyapatite nanofibrous scaffolds fabricated by electrospinning for bone tissue engineering , 2011, Journal of materials science. Materials in medicine.

[290]  S. Yamanaka,et al.  Induction of pluripotent stem cells from fibroblast cultures , 2007, Nature Protocols.

[291]  D. Mooney,et al.  Combined Angiogenic and Osteogenic Factor Delivery Enhances Bone Marrow Stromal Cell‐Driven Bone Regeneration , 2004, Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research.

[292]  Cato T Laurencin,et al.  Biomedical Applications of Biodegradable Polymers. , 2011, Journal of polymer science. Part B, Polymer physics.

[293]  C. Chung,et al.  The evaluation of the correlation between histomorphometric analysis and micro-computed tomography analysis in AdBMP-2 induced bone regeneration in rat calvarial defects , 2011, Journal of periodontal & implant science.

[294]  Jung-Woog Shin,et al.  Fabrication and characterization of novel nano- and micro-HA/PCL composite scaffolds using a modified rapid prototyping process. , 2008, Journal of biomedical materials research. Part A.

[295]  Craig L Duvall,et al.  3D imaging of tissue integration with porous biomaterials. , 2008, Biomaterials.

[296]  Stuart R Stock,et al.  Bone regeneration mediated by biomimetic mineralization of a nanofiber matrix. , 2010, Biomaterials.

[297]  D P Pioletti,et al.  How plate positioning impacts the biomechanics of the open wedge tibial osteotomy; A finite element analysis , 2005, Computer methods in biomechanics and biomedical engineering.

[298]  T. Desai,et al.  Aligned Arrays of Biodegradable Poly(ε-caprolactone) Nanowires and Nanofibers by Template Synthesis , 2007 .

[299]  W. Kao,et al.  In vivo modulation of host response and macrophage behavior by polymer networks grafted with fibronectin-derived biomimetic oligopeptides: the role of RGD and PHSRN domains. , 2001, Biomaterials.

[300]  H. Wong,et al.  A biodegradable polymer-based coating to control the performance of magnesium alloy orthopaedic implants. , 2010, Biomaterials.

[301]  Z. Xiong,et al.  Skeletal repair in rabbits using a novel biomimetic composite based on adipose‐derived stem cells encapsulated in collagen I gel with PLGA‐β‐TCP scaffold , 2009, Journal of orthopaedic research : official publication of the Orthopaedic Research Society.

[302]  Frank Witte,et al.  The history of biodegradable magnesium implants: a review. , 2010, Acta biomaterialia.

[303]  Peter X Ma,et al.  Phase separation, pore structure, and properties of nanofibrous gelatin scaffolds. , 2009, Biomaterials.

[304]  J O Hollinger,et al.  Options for tissue engineering to address challenges of the aging skeleton. , 2000, Tissue engineering.

[305]  Warren L Grayson,et al.  Bone tissue engineering bioreactors: a role in the clinic? , 2012, Tissue engineering. Part B, Reviews.

[306]  Cato T Laurencin,et al.  Polyphosphazene/nano-hydroxyapatite composite microsphere scaffolds for bone tissue engineering. , 2008, Biomacromolecules.

[307]  P. Neuenschwander,et al.  DegraPol-foam: a degradable and highly porous polyesterurethane foam as a new substrate for bone formation. , 2000, Artificial organs.

[308]  Peter X Ma,et al.  Structure and properties of nano-hydroxyapatite/polymer composite scaffolds for bone tissue engineering. , 2004, Biomaterials.

[309]  D. Kohane,et al.  Engineering vascularized skeletal muscle tissue , 2005, Nature Biotechnology.

[310]  Austin G Smith,et al.  Osteogenic and chondrogenic differentiation of embryonic stem cells in response to specific growth factors. , 2005, Bone.

[311]  K. Dai,et al.  Osteoblastogenesis regulation signals in bone remodeling , 2012, Osteoporosis International.

[312]  Matthias P Lutolf,et al.  Biopolymeric delivery matrices for angiogenic growth factors. , 2003, Cardiovascular pathology : the official journal of the Society for Cardiovascular Pathology.

[313]  J M Polak,et al.  Differentiation of osteoblasts and in vitro bone formation from murine embryonic stem cells. , 2001, Tissue engineering.

[314]  R. Guaschino,et al.  Not every PRP‐gel is born equal Evaluation of growth factor availability for tissues through four PRP‐gel preparations: Fibrinet®, RegenPRP‐Kit®, Plateltex® and one manual procedure , 2009, Vox sanguinis.

[315]  J. Babensee,et al.  Differential levels of dendritic cell maturation on different biomaterials used in combination products. , 2005, Journal of biomedical materials research. Part A.

[316]  C A van Blitterswijk,et al.  3D fiber-deposited scaffolds for tissue engineering: influence of pores geometry and architecture on dynamic mechanical properties. , 2006, Biomaterials.

[317]  P. Farlie,et al.  Bone regeneration in a rabbit critical-sized skull defect using autologous adipose-derived cells. , 2008, Tissue engineering. Part A.