Biomaterial delivery of morphogens to mimic the natural healing cascade in bone.

[1]  C. Laurencin,et al.  Bone tissue engineering by gene delivery. , 2006, Advanced drug delivery reviews.

[2]  D. Mooney,et al.  Bone regeneration in a rat cranial defect with delivery of PEI-condensed plasmid DNA encoding for bone morphogenetic protein-4 (BMP-4) , 2005, Gene Therapy.

[3]  R. Guldberg,et al.  Role of hypoxia inducible factor-1α pathway in bone regeneration , 2008 .

[4]  Hyun Chul Lee,et al.  Remission in models of type 1 diabetes by gene therapy using a single-chain insulin analogue , 2000, Nature.

[5]  W. Sebald,et al.  Human bone morphogenetic protein 2 contains a heparin-binding site which modifies its biological activity. , 1996, European journal of biochemistry.

[6]  Britt Wildemann,et al.  Long‐term effects of local growth factor (IGF‐I and TGF‐β1) treatment on fracture healing . A safety study for using growth factors , 2004, Journal of orthopaedic research : official publication of the Orthopaedic Research Society.

[7]  Georg N Duda,et al.  Timely fracture-healing requires optimization of axial fixation stability. , 2007, The Journal of bone and joint surgery. American volume.

[8]  D. E. Ashhurst,et al.  The effect of exogenous transforming growth factor-beta 2 on healing fractures in the rabbit. , 1995, Bone.

[9]  William A. Pierce,et al.  Effect of Recombinant Human Bone Morphogenetic Protein‐2 on Fracture Healing in a Goat Tibial Fracture Model , 1998, Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research.

[10]  W. Taylor,et al.  Surgical Approach Influences Periprosthetic Femoral Bone Density , 2005, Clinical orthopaedics and related research.

[11]  A. Papavassiliou,et al.  Segmental bone defects: from cellular and molecular pathways to the development of novel biological treatments , 2010, Journal of cellular and molecular medicine.

[12]  M. Bostrom,et al.  Combination of Growth Factors Inhibits Bone Ingrowth in the Bone Harvest Chamber , 2001, Clinical orthopaedics and related research.

[13]  Rui L Reis,et al.  Carrageenan-based hydrogels for the controlled delivery of PDGF-BB in bone tissue engineering applications. , 2009, Biomacromolecules.

[14]  David J Mooney,et al.  Engineering RGD nanopatterned hydrogels to control preosteoblast behavior: a combined computational and experimental approach. , 2007, Biomaterials.

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

[16]  V. Devescovi,et al.  Growth factors in bone repair , 2008, La Chirurgia degli organi di movimento.

[17]  G. Duda,et al.  The early fracture hematoma and its potential role in fracture healing. , 2010, Tissue engineering. Part B, Reviews.

[18]  Daniel G. Anderson,et al.  Nanoliter-scale synthesis of arrayed biomaterials and application to human embryonic stem cells , 2004, Nature Biotechnology.

[19]  Salvatore Pernagallo,et al.  Polymer microarrays for cellular high-content screening. , 2011, Methods in molecular biology.

[20]  E. Schwarz,et al.  Stromal cell-derived factor 1/CXCR4 signaling is critical for the recruitment of mesenchymal stem cells to the fracture site during skeletal repair in a mouse model. , 2009, Arthritis and rheumatism.

[21]  N. Haas,et al.  Insulin-like growth factor-1 and transforming growth factor-beta1 accelerates osteotomy healing using polylactide-coated implants as a delivery system: a biomechanical and histological study in minipigs. , 2002, Bone.

[22]  David J Mooney,et al.  Polymers to direct cell fate by controlling the microenvironment. , 2007, Current opinion in biotechnology.

[23]  A. Nauta,et al.  Immunomodulatory properties of mesenchymal stromal cells. , 2007, Blood.

[24]  Masashi Suzuki,et al.  Engineering of an FGF–proteoglycan fusion protein with heparin-independent, mitogenic activity , 2000, Nature Biotechnology.

[25]  H. Seeherman,et al.  Bone consolidation is enhanced by rhBMP‐2 in a rabbit model of distraction osteogenesis , 2002, Journal of orthopaedic research : official publication of the Orthopaedic Research Society.

[26]  David J Mooney,et al.  Angiogenic effects of sequential release of VEGF-A165 and PDGF-BB with alginate hydrogels after myocardial infarction. , 2007, Cardiovascular research.

[27]  E H Schemitsch,et al.  Fracture vascularity and bone healing: a systematic review of the role of VEGF. , 2008, Injury.

[28]  Monya Baker,et al.  Tissue models: A living system on a chip , 2011, Nature.

[29]  G. Duda,et al.  Time kinetics of bone defect healing in response to BMP-2 and GDF-5 characterised by in vivo biomechanics. , 2011, European cells & materials.

[30]  Yoshihiro Ito,et al.  Covalently immobilized biosignal molecule materials for tissue engineering. , 2007, Soft matter.

[31]  David J. Mooney,et al.  Infection-Mimicking Materials to Program Dendritic Cells In Situ , 2008, Nature materials.

[32]  R Langer,et al.  Responsive polymeric delivery systems. , 2001, Advanced drug delivery reviews.

[33]  E. A. Cavalcanti-Adam,et al.  Surface immobilization of bone morphogenetic protein 2 via a self-assembled monolayer formation induces cell differentiation. , 2012, Acta biomaterialia.

[34]  A. Metters,et al.  Poly(ethylene glycol) hydrogels formed by conjugate addition with controllable swelling, degradation, and release of pharmaceutically active proteins. , 2005, Journal of controlled release : official journal of the Controlled Release Society.

[35]  L. Schmidt‐Mende,et al.  ZnO - nanostructures, defects, and devices , 2007 .

[36]  G. Finerman,et al.  Repair of segmental defects of the tibia with cancellous bone grafts augmented with human bone morphogenetic protein. A preliminary report. , 1988, Clinical orthopaedics and related research.

[37]  M. Pirela-Cruz,et al.  Management of Posttraumatic Segmental Bone Defects , 2004, The Journal of the American Academy of Orthopaedic Surgeons.

[38]  H. Uludaǧ,et al.  Carrier systems for bone morphogenetic proteins. , 1999, Clinical orthopaedics and related research.

[39]  M. Bostrom,et al.  Biosynthetic bone grafting. , 1999, Clinical orthopaedics and related research.

[40]  Jason E Gestwicki,et al.  Synthetic multivalent ligands as probes of signal transduction. , 2006, Angewandte Chemie.

[41]  G. Duda,et al.  Standard bone healing stages occur during delayed bone healing, albeit with a different temporal onset and spatial distribution of callus tissues. , 2010, Histology and histopathology.

[42]  N P Haas,et al.  Bone morphogenetic protein-2 coating of titanium implants increases biomechanical strength and accelerates bone remodeling in fracture treatment: a biomechanical and histological study in rats. , 2002, Bone.

[43]  John Greenman,et al.  A microfluidic device for tissue biopsy culture and interrogation , 2010 .

[44]  K. Lyons,et al.  Bone morphogenetic protein-2: biology and applications. , 1996, Clinical orthopaedics and related research.

[45]  Rui L. Reis,et al.  Incorporation of a sequential BMP-2/BMP-7 delivery system into chitosan-based scaffolds for bone tissue engineering. , 2009, Biomaterials.

[46]  J. Vacanti,et al.  Tissue engineering : Frontiers in biotechnology , 1993 .

[47]  L. Hofbauer,et al.  Clinical implications of the osteoprotegerin/RANKL/RANK system for bone and vascular diseases. , 2004, JAMA.

[48]  V. Rosen,et al.  Bone morphogenetic protein and bone morphogenetic protein gene family in bone formation and repair. , 1998, Clinical orthopaedics and related research.

[49]  G. Duda,et al.  Insights into Mesenchymal Stem Cell Aging: Involvement of Antioxidant Defense and Actin Cytoskeleton , 2009, Stem cells.

[50]  H. Ceylan,et al.  Surface-adhesive and osteogenic self-assembled peptide nanofibers for bioinspired functionalization of titanium surfaces , 2012 .

[51]  C. Kirker-Head,et al.  Potential applications and delivery strategies for bone morphogenetic proteins. , 2000, Advanced drug delivery reviews.

[52]  V. Hasırcı,et al.  Sequential BMP-2/BMP-7 delivery from polyester nanocapsules. , 2009, Journal of biomedical materials research. Part A.

[53]  P J Prendergast,et al.  Biophysical stimuli on cells during tissue differentiation at implant interfaces , 1997 .

[54]  Zhihe Zhao,et al.  Validation of β‐Actin Used as Endogenous Control for Gene Expression Analysis in Mechanobiology Studies , 2009, Stem cells.

[55]  David J Mooney,et al.  Controlled Growth Factor Delivery for Tissue Engineering , 2009, Advanced materials.

[56]  J. Buchowski,et al.  In reference to acute airway obstruction in cervical spinal procedures with bone morphogenetic proteins , 2011, The Laryngoscope.

[57]  L. Claes,et al.  Magnitudes of local stress and strain along bony surfaces predict the course and type of fracture healing. , 1998, Journal of biomechanics.

[58]  H. Tesluk,et al.  The Effects of Insulin-like Growth Factor-1 on Critical-Size Calvarial Defects in Sprague—Dawley Rats , 1993, Annals of plastic surgery.

[59]  Vivian H. Fan,et al.  Tethered Epidermal Growth Factor Provides a Survival Advantage to Mesenchymal Stem Cells , 2007, Stem cells.

[60]  D. Stewart,et al.  Effect of cell‐based VEGF gene therapy on healing of a segmental bone defect , 2009, Journal of orthopaedic research : official publication of the Orthopaedic Research Society.

[61]  Antonios G Mikos,et al.  Dose effect of dual delivery of vascular endothelial growth factor and bone morphogenetic protein-2 on bone regeneration in a rat critical-size defect model. , 2009, Tissue engineering. Part A.

[62]  B. Eppley,et al.  Allograft and Alloplastic Bone Substitutes: A Review of Science and Technology For the Craniomaxillofacial Surgeon , 2005, The Journal of craniofacial surgery.

[63]  R. F. Morgan,et al.  Insulinlike growth factor 1- and 2-augmented collagen gel repair of facial osseous defects. , 1999, Archives of otolaryngology--head & neck surgery.

[64]  P. Cuevas,et al.  Osteopromotion for cranioplasty: an experimental study in rats using acidic fibroblast growth factor. , 1997, Surgical neurology.

[65]  D. Möbest,et al.  Differentiation of osteoblasts in three-dimensional culture in processed cancellous bone matrix: quantitative analysis of gene expression based on real-time reverse transcription-polymerase chain reaction. , 2005, Tissue engineering.

[66]  S. Mitragotri,et al.  Ultrasound-induced cavitation: applications in drug and gene delivery , 2006, Expert opinion on drug delivery.

[67]  L. Deguzman,et al.  Combination of bone marrow and TGF-beta1 augment the healing of critical-sized bone defects. , 1998, Journal of pharmaceutical sciences.

[68]  Abraham J. Verbout,et al.  Growth factor interactions in bone regeneration. , 2010, Tissue engineering. Part B, Reviews.

[69]  A. Metters,et al.  Hydrogels in controlled release formulations: network design and mathematical modeling. , 2006, Advanced drug delivery reviews.

[70]  Michael J Yaszemski,et al.  Effect of local sequential VEGF and BMP-2 delivery on ectopic and orthotopic bone regeneration. , 2009, Biomaterials.

[71]  David J Mooney,et al.  VEGF Scaffolds Enhance Angiogenesis and Bone Regeneration in Irradiated Osseous Defects , 2006, Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research.

[72]  Y. Shimabukuro,et al.  Recombinant human basic fibroblast growth factor (bFGF) stimulates periodontal regeneration in class II furcation defects created in beagle dogs. , 2003, Journal of periodontal research.

[73]  Jeffrey Bonadio,et al.  Localized, direct plasmid gene delivery in vivo: prolonged therapy results in reproducible tissue regeneration , 1999, Nature Medicine.

[74]  Y. Izumi,et al.  Effectable application of vascular endothelial growth factor to critical sized rat calvaria defects. , 2010, Oral surgery, oral medicine, oral pathology, oral radiology, and endodontics.

[75]  E. Verpoorte,et al.  Microfluidics Enables Small-Scale Tissue-Based Drug Metabolism Studies with Scarce Human Tissue , 2011, Journal of laboratory automation.

[76]  Thomas A Einhorn,et al.  Fracture healing as a post‐natal developmental process: Molecular, spatial, and temporal aspects of its regulation , 2003, Journal of cellular biochemistry.

[77]  Antonios G Mikos,et al.  Dual delivery of an angiogenic and an osteogenic growth factor for bone regeneration in a critical size defect model. , 2008, Bone.

[78]  S. Goldstein,et al.  Stimulation of new bone formation by direct transfer of osteogenic plasmid genes. , 1996, Proceedings of the National Academy of Sciences of the United States of America.

[79]  Georg N. Duda,et al.  Inflammatory phase of bone healing initiates the regenerative healing cascade , 2011, Cell and Tissue Research.

[80]  Robert E Guldberg,et al.  Spatiotemporal Delivery Strategies for Promoting Musculoskeletal Tissue Regeneration , 2009, Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research.

[81]  A. Reddi,et al.  Complete regeneration of bone in the baboon by recombinant human osteogenic protein-1 (hOP-1, bone morphogenetic protein-7). , 1996, Growth factors.

[82]  J. L. Santos,et al.  Non-viral gene delivery to mesenchymal stem cells: methods, strategies and application in bone tissue engineering and regeneration. , 2011, Current gene therapy.

[83]  J Bonadio,et al.  Tissue engineering via local gene delivery: update and future prospects for enhancing the technology. , 2000, Advanced drug delivery reviews.

[84]  V. Pillay,et al.  Novel Modulation of Drug Delivery Using Binary Zinc-Alginate-Pectinate Polyspheres for Zero-Order Kinetics Over Several Days: Experimental Design Strategy to Elucidate the Crosslinking Mechanism , 2005, Drug development and industrial pharmacy.

[85]  D. Wells,et al.  Gene Therapy Progress and Prospects: Electroporation and other physical methods , 2004, Gene Therapy.

[86]  Bradley K Weiner,et al.  A critical review of recombinant human bone morphogenetic protein-2 trials in spinal surgery: emerging safety concerns and lessons learned. , 2011, The spine journal : official journal of the North American Spine Society.

[87]  M. Costa,et al.  The clinical use of platelet-rich plasma in the promotion of bone healing: a systematic review. , 2009, Injury.

[88]  Sundeep Khosla,et al.  Receptor activator of nuclear factor kappaB ligand and osteoprotegerin regulation of bone remodeling in health and disease. , 2008, Endocrine reviews.

[89]  P. Fratzl,et al.  Designing biomimetic scaffolds for bone regeneration: why aim for a copy of mature tissue properties if nature uses a different approach? , 2010 .

[90]  Georg N Duda,et al.  Mechanical induction of critically delayed bone healing in sheep: radiological and biomechanical results. , 2008, Journal of biomechanics.

[91]  S. Goldstein,et al.  In vivo nonviral delivery factors to enhance bone repair. , 2000, Clinical orthopaedics and related research.

[92]  A. Burstein,et al.  The healing of segmental bone defects induced by demineralized bone matrix. A radiographic and biomechanical study. , 1984, The Journal of bone and joint surgery. American volume.

[93]  Thomas A Einhorn,et al.  Differential Temporal Expression of Members of the Transforming Growth Factor β Superfamily During Murine Fracture Healing , 2002, Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research.

[94]  F. Nociti,et al.  Platelet-derived growth factor/insulin-like growth factor-1 combination and bone regeneration around implants placed into extraction sockets: a histometric study in dogs. , 2000, Implant dentistry.

[95]  J. Poser,et al.  Novel formulation of fibroblast growth factor‐2 in a hyaluronan gel accelerates fracture healing in nonhuman primates , 1999, Journal of orthopaedic research : official publication of the Orthopaedic Research Society.

[96]  T. Clemens,et al.  Mesenchymal stem cells expressing osteogenic and angiogenic factors synergistically enhance bone formation in a mouse model of segmental bone defect. , 2010, Molecular therapy : the journal of the American Society of Gene Therapy.

[97]  David J Mooney,et al.  Quantitative assessment of scaffold and growth factor‐mediated repair of critically sized bone defects , 2007, Journal of orthopaedic research : official publication of the Orthopaedic Research Society.

[98]  J. Hollinger,et al.  A Bone Regeneration Study: Transforming Growth Factor‐β1 and Its Delivery , 1996 .

[99]  Michael J Yaszemski,et al.  Non-invasive monitoring of BMP-2 retention and bone formation in composites for bone tissue engineering using SPECT/CT and scintillation probes. , 2009, Journal of controlled release : official journal of the Controlled Release Society.

[100]  Kenneth M. Yamada,et al.  Taking Cell-Matrix Adhesions to the Third Dimension , 2001, Science.

[101]  David J. Mooney,et al.  Non-viral gene delivery regulated by stiffness of cell adhesion substrates , 2005, Nature materials.

[102]  D. Muscolo,et al.  Massive allograft use in orthopedic oncology. , 2006, The Orthopedic clinics of North America.

[103]  P. Aspenberg,et al.  CDMP‐2 induces bone or tendon‐like tissue depending on mechanical stimulation , 2002, Journal of orthopaedic research : official publication of the Orthopaedic Research Society.

[104]  Guangzhi Wang,et al.  Optimal delivery systems for bone morphogenetic proteins in orthopedic applications should model initial tissue repair structures by using a heparin-incorporated fibrin-fibronectin matrix. , 2008, Medical hypotheses.

[105]  Byung-Soo Kim,et al.  Enhancement of ectopic bone formation by bone morphogenetic protein-2 released from a heparin-conjugated poly(L-lactic-co-glycolic acid) scaffold. , 2007, Biomaterials.

[106]  David J Mooney,et al.  An alginate-based hybrid system for growth factor delivery in the functional repair of large bone defects. , 2011, Biomaterials.

[107]  W. Sufan,et al.  Alginate hydrogel linked with synthetic oligopeptide derived from BMP-2 allows ectopic osteoinduction in vivo. , 2000, Journal of biomedical materials research.

[108]  K. Ohya,et al.  Bone regeneration by modified gene-activated matrix: effectiveness in segmental tibial defects in rats. , 2006, Tissue engineering.

[109]  D J Mooney,et al.  Alginate hydrogels as synthetic extracellular matrix materials. , 1999, Biomaterials.

[110]  S. Parikh.  Bone graft substitutes: past, present, future. , 2002, Journal of postgraduate medicine.

[111]  Bong Geun Chung,et al.  High-throughput screening of cell responses to biomaterials. , 2008, European journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences.

[112]  K W Anderson,et al.  Cell-interactive Alginate Hydrogels for Bone Tissue Engineering , 2001, Journal of dental research.

[113]  M. Becker,et al.  Synergistic enhancement of human bone marrow stromal cell proliferation and osteogenic differentiation on BMP-2-derived and RGD peptide concentration gradients. , 2011, Acta biomaterialia.

[114]  Thomas Mittlmeier,et al.  Bone morphogenetic protein-2 application by a poly(D,L-lactide)-coated interbody cage: in vivo results of a new carrier for growth factors. , 2002, Journal of neurosurgery.

[115]  Robert Langer,et al.  Biomaterial microarrays: rapid, microscale screening of polymer-cell interaction. , 2005, Biomaterials.

[116]  N. Peppas,et al.  Factors influencing drug and protein transport and release from ionic hydrogels , 1995 .

[117]  Hollinger,et al.  Sustained release emphasizing recombinant human bone morphogenetic protein-2. , 1998, Advanced drug delivery reviews.

[118]  J. Miyazaki,et al.  Simple strategy for bone regeneration with a BMP-2/7 gene expression cassette vector. , 2009, Biochemical and biophysical research communications.

[119]  David J. Mooney,et al.  Growth Factors, Matrices, and Forces Combine and Control Stem Cells , 2009, Science.

[120]  David J. Mooney,et al.  DNA delivery from polymer matrices for tissue engineering , 1999, Nature Biotechnology.

[121]  Fa-Ming Chen,et al.  In vitro cellular responses to scaffolds containing two microencapulated growth factors. , 2009, Biomaterials.

[122]  H. Redmond,et al.  Is human fracture hematoma inherently angiogenic , 2000 .

[123]  C Perka,et al.  Segmental bone repair by tissue-engineered periosteal cell transplants with bioresorbable fleece and fibrin scaffolds in rabbits. , 2000, Biomaterials.

[124]  M J Yaszemski,et al.  Polymer concepts in tissue engineering. , 1998, Journal of biomedical materials research.

[125]  Christina Eckhardt,et al.  Vascular Endothelial Growth Factor Gene‐Activated Matrix (VEGF165‐GAM) Enhances Osteogenesis and Angiogenesis in Large Segmental Bone Defects , 2005, Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research.

[126]  B. Ratner,et al.  The engineering of biomaterials exhibiting recognition and specificity , 1996, Journal of molecular recognition : JMR.

[127]  R. Weissleder,et al.  Cell-specific targeting of nanoparticles by multivalent attachment of small molecules , 2005, Nature Biotechnology.

[128]  Maryam Tabrizian,et al.  Delivery of recombinant bone morphogenetic proteins for bone regeneration and repair. Part A: Current challenges in BMP delivery , 2009, Biotechnology Letters.

[129]  David W. Rowe,et al.  Live-animal tracking of individual haematopoietic stem/progenitor cells in their niche , 2009, Nature.

[130]  K. Yaremchuk,et al.  Acute airway obstruction in cervical spinal procedures with bone morphogenetic proteins , 2010, The Laryngoscope.

[131]  Paula T Hammond,et al.  Tunable dual growth factor delivery from polyelectrolyte multilayer films. , 2011, Biomaterials.

[132]  C. Yellowley,et al.  Hypoxic regulation of mesenchymal stem cell migration: the role of RhoA and HIF‐1α , 2011, Cell biology international.

[133]  R E Guldberg,et al.  Analyzing bone, blood vessels, and biomaterials with microcomputed tomography. , 2003, IEEE engineering in medicine and biology magazine : the quarterly magazine of the Engineering in Medicine & Biology Society.

[134]  David J Mooney,et al.  Cell delivery mechanisms for tissue repair. , 2008, Cell stem cell.

[135]  Takaaki Tanaka,et al.  Repair of segmental bone defects in rabbit tibiae using a complex of beta-tricalcium phosphate, type I collagen, and fibroblast growth factor-2. , 2006, Biomaterials.

[136]  L. Claes,et al.  Bone formation in a long bone defect model using a platelet-rich plasma-loaded collagen scaffold. , 2006, Biomaterials.

[137]  Francesca Ungaro,et al.  Controlled drug delivery in tissue engineering. , 2008, Advanced drug delivery reviews.

[138]  David J Mooney,et al.  Mimicking nature by codelivery of stimulant and inhibitor to create temporally stable and spatially restricted angiogenic zones , 2010, Proceedings of the National Academy of Sciences.

[139]  Georg N Duda,et al.  Endochondral ossification in vitro is influenced by mechanical bending. , 2007, Bone.

[140]  M. Liebergall,et al.  Nucleofection-based ex vivo nonviral gene delivery to human stem cells as a platform for tissue regeneration. , 2006, Tissue engineering.

[141]  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.

[142]  J. Pohl,et al.  A preliminary report on the effect of dimeric rhGDF-5 and its monomeric form rhGDF-5C465A on bone healing of rat cranial defects. , 2009, Journal of cranio-maxillo-facial surgery : official publication of the European Association for Cranio-Maxillo-Facial Surgery.

[143]  Hanna Parnas,et al.  Mathematical modeling and optimization of drug delivery from intratumorally injected microspheres. , 2005, Clinical cancer research : an official journal of the American Association for Cancer Research.

[144]  S. Kadiyala,et al.  Culture-expanded, bone marrow-derived mesenchymal stem cells can regenerate a critical-sized segmental bone defect , 1997 .

[145]  Jason A Burdick,et al.  Delivery of osteoinductive growth factors from degradable PEG hydrogels influences osteoblast differentiation and mineralization. , 2002, Journal of controlled release : official journal of the Controlled Release Society.

[146]  R. Oreffo,et al.  Gene delivery in bone tissue engineering: progress and prospects using viral and nonviral strategies. , 2004, Tissue engineering.

[147]  David J Mooney,et al.  Temporally regulated delivery of VEGF in vitro and in vivo. , 2006, Journal of biomedical materials research. Part A.

[148]  Johnny Huard,et al.  Synergistic enhancement of bone formation and healing by stem cell-expressed VEGF and bone morphogenetic protein-4. , 2002, The Journal of clinical investigation.

[149]  J. Lee,et al.  Osteoprogenitor cells within skeletal muscle , 2000, Journal of orthopaedic research : official publication of the Orthopaedic Research Society.

[150]  A. Caplan.  New era of cell-based orthopedic therapies. , 2009, Tissue engineering. Part B, Reviews.

[151]  D. Davy,et al.  The effect of osteogenin (a bone morphogenetic protein) on the formation of bone in orthotopic segmental defects in rats. , 1994, The Journal of bone and joint surgery. American volume.

[152]  David J Mooney,et al.  Integrated approach to designing growth factor delivery systems , 2007, FASEB journal : official publication of the Federation of American Societies for Experimental Biology.

[153]  B P F Lelieveldt,et al.  Optical advances in skeletal imaging applied to bone metastases. , 2011, Bone.

[154]  Dennis R. Carter,et al.  Mechanobiology of Skeletal Regeneration , 1998, Clinical orthopaedics and related research.

[155]  Shigeru Kobayashi,et al.  Bone formation on apatite-coated titanium with incorporated BMP-2/heparin in vivo. , 2009, Oral surgery, oral medicine, oral pathology, oral radiology, and endodontics.

[156]  Jörg A Auer,et al.  Localized insulin-like growth factor I delivery to enhance new bone formation. , 2003, Bone.

[157]  D. Puleo,et al.  In vitro effects of combined and sequential delivery of two bone growth factors. , 2004, Biomaterials.

[158]  H. Frost,et al.  A determinant of bone architecture. The minimum effective strain. , 1983, Clinical orthopaedics and related research.

[159]  R Langer,et al.  Novel approach to fabricate porous sponges of poly(D,L-lactic-co-glycolic acid) without the use of organic solvents. , 1996, Biomaterials.

[160]  G N Duda,et al.  Mechanobiology of bone healing and regeneration: in vivo models , 2010, Proceedings of the Institution of Mechanical Engineers. Part H, Journal of engineering in medicine.

[161]  T. Steffen,et al.  Porous tricalcium phosphate and transforming growth factor used for anterior spine surgery , 2001, European Spine Journal.

[162]  E. Rodríguez‐Merchán,et al.  Nonunion: general principles and experimental data. , 2004, Clinical orthopaedics and related research.

[163]  T A Einhorn,et al.  The cell and molecular biology of fracture healing. , 1998, Clinical orthopaedics and related research.

[164]  Vasif Hasirci,et al.  Sequential growth factor delivery from complexed microspheres for bone tissue engineering. , 2008, Biomaterials.

[165]  Jay R Lieberman,et al.  The role of growth factors in the repair of bone. Biology and clinical applications. , 2002, The Journal of bone and joint surgery. American volume.

[166]  D. Mooney,et al.  Targeted delivery of nanoparticles to ischemic muscle for imaging and therapeutic angiogenesis. , 2011, Nano letters.

[167]  Georg N Duda,et al.  Insight into the molecular pathophysiology of delayed bone healing in a sheep model. , 2010, Tissue engineering. Part A.

[168]  D. Graves,et al.  Impaired Fracture Healing in the Absence of TNF‐α Signaling: The Role of TNF‐α in Endochondral Cartilage Resorption , 2003 .

[169]  A. Aono,et al.  Potent ectopic bone-inducing activity of bone morphogenetic protein-4/7 heterodimer. , 1995, Biochemical and biophysical research communications.

[170]  D. Mooney,et al.  Alginate: properties and biomedical applications. , 2012, Progress in polymer science.

[171]  N. Gallay,et al.  The In Vitro Migration Capacity of Human Bone Marrow Mesenchymal Stem Cells: Comparison of Chemokine and Growth Factor Chemotactic Activities , 2007, Stem cells.

[172]  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.

[173]  David J Mooney,et al.  New materials for tissue engineering: towards greater control over the biological response. , 2008, Trends in biotechnology.

[174]  C. Ackert-Bicknell,et al.  Marrow fat and the bone microenvironment: developmental, functional, and pathological implications. , 2009, Critical reviews in eukaryotic gene expression.

[175]  G. Duda,et al.  Locally applied osteogenic predifferentiated progenitor cells are more effective than undifferentiated mesenchymal stem cells in the treatment of delayed bone healing. , 2009, Tissue engineering. Part A.

[176]  H Willenegger,et al.  [Primary and secondary healing of bone fractures]. , 1971, Der Chirurg; Zeitschrift fur alle Gebiete der operativen Medizen.

[177]  Eben Alsberg,et al.  Dual growth factor delivery and controlled scaffold degradation enhance in vivo bone formation by transplanted bone marrow stromal cells. , 2004, Bone.

[178]  G. Schmidmaier,et al.  Sequential release kinetics of two (gentamicin and BMP-2) or three (gentamicin, IGF-I and BMP-2) substances from a one-component polymeric coating on implants. , 2011, Journal of controlled release : official journal of the Controlled Release Society.

[179]  C. R. Howlett,et al.  Effect of platelet-derived growth factor on tibial osteotomies in rabbits. , 1994, Bone.

[180]  S. Bauer,et al.  Covalent functionalization of TiO2 nanotube arrays with EGF and BMP-2 for modified behavior towards mesenchymal stem cells. , 2011, Integrative biology : quantitative biosciences from nano to macro.

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

[182]  J. Hubbell,et al.  Synthetic biomaterials as instructive extracellular microenvironments for morphogenesis in tissue engineering , 2005, Nature Biotechnology.

[183]  Georg N Duda,et al.  Instability prolongs the chondral phase during bone healing in sheep. , 2006, Bone.

[184]  L. Tagliabue,et al.  Application of rhBMP-7 and platelet-rich plasma in the treatment of long bone non-unions: a prospective randomised clinical study on 120 patients. , 2008, Injury.

[185]  D. Heymann,et al.  Mechanisms of bone repair and regeneration. , 2009, Trends in molecular medicine.

[186]  H. Redmond,et al.  Vascular endothelial growth factor stimulates bone repair by promoting angiogenesis and bone turnover , 2002, Proceedings of the National Academy of Sciences of the United States of America.

[187]  Jae-Hyung Jang,et al.  Gene delivery from polymer scaffolds for tissue engineering , 2004, Expert review of medical devices.

[188]  D. Hutmacher,et al.  Spatiotemporal delivery of bone morphogenetic protein enhances functional repair of segmental bone defects. , 2011, Bone.

[189]  Yoshihiro Ito,et al.  Peptide immobilized on gold particles enhances cell growth , 2008, Cytotechnology.

[190]  David J. Mooney,et al.  Polymeric Growth Factor Delivery Strategies for Tissue Engineering , 2003, Pharmaceutical Research.

[191]  H. Vandenburgh,et al.  The role of multifunctional delivery scaffold in the ability of cultured myoblasts to promote muscle regeneration. , 2011, Biomaterials.

[192]  M. Somerman,et al.  Growth factors regulate expression of osteoblast-associated genes. , 1999, Journal of periodontology.

[193]  Y. Jin,et al.  Induction of new bone by ceramic bovine bone with recombinant human bone morphogenetic protein 2 and transforming growth factor beta. , 1998, International journal of oral and maxillofacial surgery.

[194]  M. Vallet‐Regí,et al.  Immobilization and bioactivity evaluation of FGF-1 and FGF-2 on powdered silicon-doped hydroxyapatite and their scaffolds for bone tissue engineering , 2011, Journal of materials science. Materials in medicine.

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

[196]  Chao Wan,et al.  The hypoxia-inducible factor alpha pathway couples angiogenesis to osteogenesis during skeletal development. , 2007, The Journal of clinical investigation.

[197]  David J Mooney,et al.  Upregulation of bone cell differentiation through immobilization within a synthetic extracellular matrix. , 2007, Biomaterials.

[198]  J. Ong,et al.  Experimental studies on bone induction using low-molecular-weight poly (DL-lactide-co-glycolide) as a carrier for recombinant human bone morphogenetic protein-2. , 2002, Journal of biomedical materials research.

[199]  Nastaran Zahir,et al.  Death in the third dimension: apoptosis regulation and tissue architecture. , 2004, Current opinion in genetics & development.

[200]  M. Swiontkowski,et al.  Bone-graft substitutes , 1999, The Lancet.

[201]  Satoru Kidoaki,et al.  Time-programmed dual release formulation by multilayered drug-loaded nanofiber meshes. , 2010, Journal of controlled release : official journal of the Controlled Release Society.

[202]  S. Goodman,et al.  Modulating osteogenesis of mesenchymal stem cells by modifying growth factor availability. , 2010, Cytokine.

[203]  Stefaan C. De Smedt,et al.  “Programmed Polymeric Devices” for Pulsed Drug Delivery , 2004, Pharmaceutical Research.

[204]  Renjing Liu,et al.  Myogenic progenitors contribute to open but not closed fracture repair , 2011, BMC musculoskeletal disorders.

[205]  David J. Mooney,et al.  Controlled growth factor release from synthetic extracellular matrices , 2000, Nature.

[206]  L. Claes,et al.  Early dynamization by reduced fixation stiffness does not improve fracture healing in a rat femoral osteotomy model , 2009, Journal of orthopaedic research : official publication of the Orthopaedic Research Society.

[207]  Reine Bareille,et al.  Influences of vascularization and osteogenic cells on heterotopic bone formation within a madreporic ceramic in rats. , 2003, Plastic and reconstructive surgery.

[208]  R. Weissleder,et al.  Imaging in the era of molecular oncology , 2008, Nature.

[209]  T. Gaber,et al.  Hypoxia inducible factor (HIF) in rheumatology: low O2! See what HIF can do! , 2005, Annals of the rheumatic diseases.

[210]  R. Schugar,et al.  Small molecules in stem cell self-renewal and differentiation , 2008, Gene Therapy.

[211]  M. Maeda,et al.  Continuous Administration of Basic Fibroblast Growth Factor (FGF-2) Accelerates Bone Induction on Rat Calvaria— An Application of a New Drug Delivery System , 1998, Journal of dental research.

[212]  J. Welsh,et al.  Ligand-induced transformation by a noninternalizing epidermal growth factor receptor. , 1990, Science.

[213]  Ann Sandison,et al.  Comparison of the Vascularity of Fasciocutaneous Tissue and Muscle for Coverage of Open Tibial Fractures , 2009, Plastic and reconstructive surgery.

[214]  Deenu Kanjickal,et al.  Modeling of drug release from polymeric delivery systems--a review. , 2004, Critical reviews in therapeutic drug carrier systems.

[215]  Britt Wildemann,et al.  Synergistic effect of IGF-I and TGF-ß1 on fracture healing in ratsSingle versus combined application of IGF-I and TGF-ß1 , 2003, Acta orthopaedica Scandinavica.

[216]  Y. Ikada,et al.  Promoted bone healing at a rabbit skull gap between autologous bone fragment and the surrounding intact bone with biodegradable microspheres containing transforming growth factor-beta1. , 2000, Tissue engineering.

[217]  L Claes,et al.  [Mechanical modification of callus healing]. , 2000, Der Chirurg; Zeitschrift fur alle Gebiete der operativen Medizen.

[218]  Ralph Müller,et al.  Repair of bone defects using synthetic mimetics of collagenous extracellular matrices , 2003, Nature Biotechnology.

[219]  B L Currier,et al.  Biological activity of rhBMP-2 released from PLGA microspheres. , 2000, Journal of biomechanical engineering.

[220]  N. Demertzis,et al.  Reconstruction of tibia defects by ipsilateral vascularized fibula transposition , 2008, Archives of Orthopaedic and Trauma Surgery.

[221]  Y. M. Lee,et al.  The bone regenerative effect of platelet-derived growth factor-BB delivered with a chitosan/tricalcium phosphate sponge carrier. , 2000, Journal of periodontology.

[222]  Thomas A Einhorn,et al.  The biology of fracture healing. , 2011, Injury.

[223]  N. Epstein,et al.  Pros, cons, and costs of INFUSE in spinal surgery , 2011, Surgical neurology international.

[224]  L. Xing,et al.  Functions of RANKL/RANK/OPG in bone modeling and remodeling. , 2008, Archives of biochemistry and biophysics.

[225]  Vladimir Volloch,et al.  Bone morphogenetic protein-2 decorated silk fibroin films induce osteogenic differentiation of human bone marrow stromal cells. , 2004, Journal of biomedical materials research. Part A.

[226]  Georg N Duda,et al.  Differential regulation of blood vessel formation between standard and delayed bone healing , 2009, Journal of orthopaedic research : official publication of the Orthopaedic Research Society.

[227]  Stuart B Goodman,et al.  The sequential expression profiles of growth factors from osteoprogenitors [correction of osteroprogenitors] to osteoblasts in vitro. , 2007, Tissue engineering.

[228]  Lutz Claes,et al.  Mechanical characterization of external fixator stiffness for a rat femoral fracture model , 2009, Journal of orthopaedic research : official publication of the Orthopaedic Research Society.

[229]  C. Bosch,et al.  Recombinant Transforming Growth Factor‐β1 Induces Endochondral Bone in the Baboon and Synergizes with Recombinant Osteogenic Protein‐1 (Bone Morphogenetic Protein‐7) to Initiate Rapid Bone Formation , 1997, Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research.

[230]  R. Guldberg,et al.  A Perspective: Engineering Periosteum for Structural Bone Graft Healing , 2008, Clinical orthopaedics and related research.

[231]  T. Einhorn,et al.  Impaired Intramembranous Bone Formation during Bone Repair in the Absence of Tumor Necrosis Factor-Alpha Signaling , 2001, Cells Tissues Organs.

[232]  D J Mooney,et al.  Regulating Bone Formation via Controlled Scaffold Degradation , 2003, Journal of dental research.

[233]  Y. Ito,et al.  Protein-free cell culture on an artificial substrate with covalently immobilized insulin. , 1996, Proceedings of the National Academy of Sciences of the United States of America.

[234]  Charles A Gersbach,et al.  Virus-based gene therapy strategies for bone regeneration. , 2007, Biomaterials.

[235]  G. Pelled,et al.  Ultrasound-based nonviral gene delivery induces bone formation in vivo , 2008, Gene Therapy.

[236]  M. Schütz,et al.  Cyclic strain disrupts endothelial network formation on Matrigel. , 2009, Microvascular research.

[237]  K. Kozloff,et al.  Near‐infrared fluorescent probe traces bisphosphonate delivery and retention in vivo , 2010, Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research.

[238]  Christopher B. Rives,et al.  Plasmid delivery in vivo from porous tissue-engineering scaffolds: transgene expression and cellular transfection. , 2005, Molecular therapy : the journal of the American Society of Gene Therapy.

[239]  G. Duda,et al.  Fracture healing is accelerated in the absence of the adaptive immune system , 2010, Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research.

[240]  E. Brogi,et al.  Therapeutic angiogenesis. A single intraarterial bolus of vascular endothelial growth factor augments revascularization in a rabbit ischemic hind limb model. , 1994, The Journal of clinical investigation.

[241]  G. Duda,et al.  Mechanical stimulation of the pro-angiogenic capacity of human fracture haematoma: involvement of VEGF mechano-regulation. , 2010, Bone.

[242]  G. Duda,et al.  Characterization of a rat osteotomy model with impaired healing , 2008, BMC musculoskeletal disorders.

[243]  G. Duda,et al.  A 5-mm femoral defect in female but not in male rats leads to a reproducible atrophic non-union , 2010, Archives of Orthopaedic and Trauma Surgery.

[244]  Richard O C Oreffo,et al.  Bone tissue engineering: hope vs hype. , 2002, Biochemical and biophysical research communications.

[245]  J. Wozney,et al.  Implantation of recombinant human bone morphogenetic proteins with biomaterial carriers: A correlation between protein pharmacokinetics and osteoinduction in the rat ectopic model. , 2000, Journal of biomedical materials research.

[246]  D. Marsh,et al.  Concepts of fracture union, delayed union, and nonunion. , 1998, Clinical orthopaedics and related research.

[247]  A. Mikos,et al.  TGF-&bgr;1 Release from Biodegradable Polymer Microparticles: Its Effects on Marrow Stromal Osteoblast Function , 2001, The Journal of bone and joint surgery. American volume.

[248]  S. Glassman,et al.  Adverse Effects Associated With High-Dose Recombinant Human Bone Morphogenetic Protein-2 Use in Anterior Cervical Spine Fusion , 2006, Spine.

[249]  Y. Izumi,et al.  Recombinant human growth/differentiation factor-5 (rhGDF-5) induced bone formation in murine calvariae. , 2006, Journal of periodontal research.

[250]  G. Pelled,et al.  Applications of gene therapy and adult stem cells in bone bioengineering. , 2006, Regenerative medicine.

[251]  N. Peppas,et al.  Present and future applications of biomaterials in controlled drug delivery systems. , 1981, Biomaterials.

[252]  P. Kostenuik,et al.  Osteoprotegerin: a physiological and pharmacological inhibitor of bone resorption. , 2001, Current pharmaceutical design.

[253]  Yoshihisa Suzuki,et al.  Accelerated bone repair with the use of a synthetic BMP-2-derived peptide and bone-marrow stromal cells. , 2005, Journal of biomedical materials research. Part A.