Recombinant human bone morphogenetic protein-2 is superior to demineralized bone matrix in repairing craniotomy defects in rats.

The purpose of this study was to measure bone-regenerative effects of recombinant human bone morphogenetic protein-2 (rhBMP-2) in rat calvarial critical-size defects (CSDs). CSDs (8 mm in diameter) were treated with either 1) 2.2 micrograms rhBMP-2 combined with insoluble collagenous bone matrix (ICBM), 2) 6.5 micrograms rhBMP-2 plus ICBM, 3) ICBM alone, or 4) demineralized bone matrix (DBM), for 7, 14, or 21 days. Multiple linear regression showed that rhBMP-2 had a significant time- and dose-dependent effect on bone regeneration (P < .05). After 7 days, new calcifying cartilage and remineralizing ICBM, with an occasional zone of new woven bone, was evident in defects treated with rhBMP-2/ICBM. By 14 days, both doses of rhBMP-2 reconstituted with ICBM had induced more bone formation than ICBM alone or DBM, and 6.5 micrograms was superior to 2.2 micrograms. There was no evidence of adverse cellular response. This study shows for the first time that rhBMP-2 could restore osseous form to a calvarial defect. In addition, osteoregeneration was accelerated by the higher dose of rhBMP-2.

[1]  H. Kleinman,et al.  Recombinant human bone morphogenetic protein 2B stimulates PC12 cell differentiation: potentiation and binding to type IV collagen , 1992, The Journal of cell biology.

[2]  H. Oppermann,et al.  Recombinant human osteogenic protein-1 (hOP-1) induces new bone formation in vivo with a specific activity comparable with natural bovine osteogenic protein and stimulates osteoblast proliferation and differentiation in vitro. , 1992, The Journal of biological chemistry.

[3]  V. Rosen,et al.  The BMP proteins in bone formation and repair. , 1992, Trends in genetics : TIG.

[4]  V. Rosen,et al.  Recombinant human bone morphogenetic protein-2 induces osteoblastic differentiation in W-20-17 stromal cells. , 1992, Endocrinology.

[5]  V. Rosen,et al.  Recombinant human bone morphogenetic protein-2 stimulates osteoblastic maturation and inhibits myogenic differentiation in vitro , 1991, The Journal of cell biology.

[6]  E. Wang,et al.  Bone morphogenetic protein-2 stimulates alkaline phosphatase activity and collagen synthesis in cultured osteoblastic cells, MC3T3-E1. , 1991, Biochemical and biophysical research communications.

[7]  V. Rosen,et al.  Identification of transforming growth factor beta family members present in bone-inductive protein purified from bovine bone. , 1990, Proceedings of the National Academy of Sciences of the United States of America.

[8]  J. Dasch,et al.  Immune responses to allogeneic and xenogeneic implants of collagen and collagen derivatives. , 1990, Clinical orthopaedics and related research.

[9]  V. Rosen,et al.  The non-osteogenic mouse pluripotent cell line, C3H10T1/2, is induced to differentiate into osteoblastic cells by recombinant human bone morphogenetic protein-2. , 1990, Biochemical and biophysical research communications.

[10]  A. Reddi,et al.  Repair of Calvarial Nonunions by Osteogenin, a Bone‐Inductive Protein , 1990, Plastic and reconstructive surgery.

[11]  H. Oppermann,et al.  Bovine osteogenic protein is composed of dimers of OP-1 and BMP-2A, two members of the transforming growth factor-beta superfamily. , 1990, The Journal of biological chemistry.

[12]  E. Drier,et al.  OP‐1 cDNA encodes an osteogenic protein in the TGF‐beta family. , 1990, The EMBO journal.

[13]  W. Larrabee,et al.  Demineralized bone. Implant resorption with long-term follow-up. , 1990, Archives of otolaryngology--head & neck surgery.

[14]  V. Rosen,et al.  Recombinant human bone morphogenetic protein induces bone formation. , 1990, Proceedings of the National Academy of Sciences of the United States of America.

[15]  G. Chen,et al.  Collaboration between Collagenous Matrix and Osteogenin Is Required for Bone Induction , 1990 .

[16]  F. Luyten,et al.  Purification and partial amino acid sequence of osteogenin, a protein initiating bone differentiation. , 1989, The Journal of biological chemistry.

[17]  V. Rosen,et al.  Novel regulators of bone formation: molecular clones and activities. , 1988, Science.

[18]  V. Rosen,et al.  Purification and characterization of other distinct bone-inducing factors. , 1988, Proceedings of the National Academy of Sciences of the United States of America.

[19]  N Muthukumaran,et al.  Isolation of osteogenin, an extracellular matrix-associated, bone-inductive protein, by heparin affinity chromatography. , 1987, Proceedings of the National Academy of Sciences of the United States of America.

[20]  D. Ousterhout.  Clinical Experience in Cranial and Facial Reconstruction with Demineralized Bone , 1985, Annals of plastic surgery.

[21]  A. Reddi,et al.  Homology of bone-inductive proteins from human, monkey, bovine, and rat extracellular matrix. , 1983, Proceedings of the National Academy of Sciences of the United States of America.

[22]  J. Glowacki,et al.  Treatment of jaw defects with demineralized bone implants. , 1982, Journal of oral and maxillofacial surgery : official journal of the American Association of Oral and Maxillofacial Surgeons.

[23]  J. Glowacki,et al.  APPLICATION OF THE BIOLOGICAL PRINCIPLE OF INDUCED OSTEOGENESIS FOR CRANIOFACIAL DEFECTS , 1981, The Lancet.

[24]  M. Urist,et al.  Excitation transfer in bone. Deleterious effects of cobalt 60 radiation-sterilization of bank bone. , 1974, Archives of surgery.

[25]  I. Scopp,et al.  Human bone induction by allogeneic dentin matrix. , 1972, Journal of periodontology.

[26]  Peter F. Davison,et al.  THE SEROLOGIC SPECIFICITY OF TROPOCOLLAGEN TELOPEPTIDES , 1967, The Journal of experimental medicine.

[27]  B. Boyan,et al.  Characterization of rat calvarial nonunion defects. , 1990, Acta anatomica.

[28]  J. Mellonig,et al.  The osteogenic potential of two human demineralized bone preparations using a xenogeneic model. , 1989, Journal of periodontology.

[29]  M. Hunkapiller,et al.  Purification of bovine bone morphogenetic protein by hydroxyapatite chromatography. , 1984, Proceedings of the National Academy of Sciences of the United States of America.

[30]  H. L. Ward,et al.  Decalcified, lyophilized bone allografts for use in human periodontal defects. , 1975, Journal of periodontology.

[31]  A. Reddi.  COLLAGENOUS BONE MATRIX AND GENE EXPRESSION IN FIBROBLASTS , 1975 .