Macrophysiologic Roles of a Delivery System for Vulnerary Factors Needed for Bone Regeneration

Traditional histology identifies three components of bone: cells, an extracellular mineralized organic matrix, and a lymphatic-vascular component. Specialized bone cells known as osteoblasts promote bone regeneration. Clinically, this property has been exploited by surgeons with autografts and bank bone preparations to restore deficient form and function to almost every aspect of the skeleton. Unfortunately, these therapies can be inadequate for patients with panskeletal trauma. Therefore, a suitable alternative may be a laboratory-derived product consisting of a vulnerary factor and delivery system. The integration of a laboratory-engineered product in an osseous wound environment is a formidable challenge demanding a keen appreciation of the product's macrophysiologic roles in wound healing biology. Consequently, the purposes for this paper are 1) to define briefly macrophysiology relevant to a delivery system for vulnerary molecules and bone regeneration; 2) to review a key family of bone regenerating molecules, the bone morphogenetic proteins (BMPs); and 3) to relate delivery system engineering with bone regeneration.

[1]  Y. Ma,et al.  Time responses of cancellous and cortical bones to sciatic neurectomy in growing female rats. , 1996, Bone.

[2]  E. Shore,et al.  Bone morphogenetic proteins and C-FOS: early signals in endochondral bone formation. , 1996, Bone.

[3]  M Browne,et al.  Use of Bone Morphogenetic Protein-2 in the Rabbit Ulnar Nonunion Model , 1996, Clinical orthopaedics and related research.

[4]  L. Cima,et al.  In vitro cell response to differences in poly-L-lactide crystallinity. , 1996, Journal of biomedical materials research.

[5]  T. Suda,et al.  Bone morphogenetic protein-2 does not alter the differentiation pathway of committed progenitors of osteoblasts and chondroblasts , 1996, Cell and Tissue Research.

[6]  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.

[7]  K. Leong,et al.  Poly(L-lactic acid) foams with cell seeding and controlled-release capacity. , 1996, Journal of biomedical materials research.

[8]  D E Ingber,et al.  Cell shape, cytoskeletal mechanics, and cell cycle control in angiogenesis. , 1995, Journal of biomechanics.

[9]  K. Miyazono,et al.  Enhanced expression of type I receptors for bone morphogenetic proteins during bone formation , 1995, Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research.

[10]  B. Hogan,et al.  Bone morphogenetic protein-4 is required for mesoderm formation and patterning in the mouse. , 1995, Genes & development.

[11]  T A Einhorn,et al.  Enhancement of fracture-healing. , 1995, The Journal of bone and joint surgery. American volume.

[12]  A. Weiland,et al.  Immunolocalization and expression of bone morphogenetic proteins 2 and 4 in fracture healing , 1995, Journal of orthopaedic research : official publication of the Orthopaedic Research Society.

[13]  S D Cook,et al.  Effect of recombinant human osteogenic protein-1 on healing of segmental defects in non-human primates. , 1995, The Journal of bone and joint surgery. American volume.

[14]  D. Carey,et al.  Expression of bone morphogenetic protein‐6 messenger RNA in bovine growth plate chondrocytes of different size , 1995, Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research.

[15]  C. Tabin,et al.  Sonic hedgehog and Fgf-4 act through a signaling cascade and feedback loop to integrate growth and patterning of the developing limb bud , 1994, Cell.

[16]  D. Duboule,et al.  How to make a limb? , 1994, Science.

[17]  J. Hollinger,et al.  Osseous regeneration in the rat calvarium using novel delivery systems for recombinant human bone morphogenetic protein-2 (rhBMP-2). , 1994, Journal of biomedical materials research.

[18]  J. Hollinger,et al.  Recombinant human bone morphogenetic protein-2 is superior to demineralized bone matrix in repairing craniotomy defects in rats. , 1994, Journal of biomedical materials research.

[19]  R. Tuan,et al.  Surface composition of orthopaedic implant metals regulates cell attachment, spreading, and cytoskeletal organization of primary human osteoblasts in vitro. , 1994, Clinical orthopaedics and related research.

[20]  R. Raghow,et al.  The role of extracellular matrix in postinflammatory wound healing and fibrosis , 1994, FASEB journal : official publication of the Federation of American Societies for Experimental Biology.

[21]  D E Ingber,et al.  Control of cytoskeletal mechanics by extracellular matrix, cell shape, and mechanical tension. , 1994, Biophysical journal.

[22]  S. Cook,et al.  The effect of recombinant human osteogenic protein-1 on healing of large segmental bone defects. , 1994, The Journal of bone and joint surgery. American volume.

[23]  H. Steenfos,et al.  Growth factors and wound healing. , 1994, Scandinavian journal of plastic and reconstructive surgery and hand surgery.

[24]  K. Takaoka,et al.  Transient and localized expression of bone morphogenetic protein 4 messenger RNA during fracture healing , 1994, Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research.

[25]  N. Copeland,et al.  Limb alterations in brachypodism mice due to mutations in a new member of the TGFβ-superfamily , 1994, Nature.

[26]  C. Tickle On making a skeleton , 1994, Nature.

[27]  S. Cook,et al.  Recombinant human bone morphogenetic protein-7 induces healing in a canine long-bone segmental defect model. , 1994, Clinical orthopaedics and related research.

[28]  J. Wozney,et al.  Expression of bone morphogenetic protein messenger RNAs by normal rat and human prostate and prostate cancer cells , 1994, The Prostate.

[29]  G. Gross,et al.  Expression of human bone morphogenetic proteins-2 or -4 in murine mesenchymal progenitor C3H10T1/2 cells induces differentiation into distinct mesenchymal cell lineages. , 1993, DNA and cell biology.

[30]  Haralson Ma Extracellular matrix and growth factors: an integrated interplay controlling tissue repair and progression to disease. , 1993, Laboratory investigation; a journal of technical methods and pathology.

[31]  R Langer,et al.  Laminated three-dimensional biodegradable foams for use in tissue engineering. , 1993, Biomaterials.

[32]  D E Ingber,et al.  Preparation of poly(glycolic acid) bonded fiber structures for cell attachment and transplantation. , 1993, Journal of biomedical materials research.

[33]  Mark E. Bolander,et al.  Regulation of Fracture Repair by Growth Factors , 1992, Proceedings of the Society for Experimental Biology and Medicine. Society for Experimental Biology and Medicine.

[34]  Richard O. Hynes,et al.  Integrins: Versatility, modulation, and signaling in cell adhesion , 1992, Cell.

[35]  E. Wang,et al.  Mandibular reconstruction with a recombinant bone-inducing factor. Functional, histologic, and biomechanical evaluation. , 1991, Archives of otolaryngology--head & neck surgery.

[36]  H. Kleinman,et al.  Interaction of osteogenin, a heparin binding bone morphogenetic protein, with type IV collagen. , 1990, The Journal of biological chemistry.

[37]  L. Wolpert Positional information revisited. , 1989, Development.

[38]  J O Hollinger,et al.  Biodegradable bone repair materials. Synthetic polymers and ceramics. , 1986, Clinical orthopaedics and related research.

[39]  J O Hollinger,et al.  The critical size defect as an experimental model for craniomandibulofacial nonunions. , 1986, Clinical orthopaedics and related research.

[40]  M. Urist,et al.  The bone induction principle. , 1967, Clinical orthopaedics and related research.

[41]  J. Black,et al.  Biological performance of materials : fundamentals of biocompatibility , 1999 .

[42]  J H Brekke,et al.  A rationale for delivery of osteoinductive proteins. , 1996, Tissue engineering.

[43]  C. Bünger,et al.  Bone morphogenetic protein-2 but not bone morphogenetic protein-4 and -6 stimulates chemotactic migration of human osteoblasts, human marrow osteoblasts, and U2-OS cells. , 1996, Bone.

[44]  K. Leong,et al.  Poly(α-hydroxy acids). Carriers for bone morphogenetic proteins , 1996 .

[45]  G. Stein,et al.  The influence of type I collagen on the development and maintenance of the osteoblast phenotype in primary and passaged rat calvarial osteoblasts: modification of expression of genes supporting cell growth, adhesion, and extracellular matrix mineralization. , 1995, Experimental cell research.

[46]  Jeffrey O. Hollinger,et al.  Biomedical applications of synthetic biodegradable polymers , 1995 .

[47]  D. Kingsley,et al.  The TGF-beta superfamily: new members, new receptors, and new genetic tests of function in different organisms. , 1994, Genes & development.

[48]  D. Kingsley,et al.  What do BMPs do in mammals? Clues from the mouse short-ear mutation. , 1994, Trends in genetics : TIG.

[49]  E. Wang,et al.  Bone morphogenetic protein-2 causes commitment and differentiation in C3H10T1/2 and 3T3 cells. , 1993, Growth factors.

[50]  J O Hollinger,et al.  The critical size defect as an experimental model to test bone repair materials. , 1990, The Journal of craniofacial surgery.