Evaluation of recombinant human bone morphogenetic protein-2 on the repair of alveolar ridge defects in baboons.

BACKGROUND The objective of this study was to evaluate alveolar ridge augmentation following surgical implantation of recombinant human bone morphogenetic protein-2 (rhBMP-2) using two novel space-providing carrier technologies in the baboon (Papio anubis) model. METHODS Standardized alveolar ridge defects ( approximately 15 x 8 x 5 mm) were surgically produced in maxillary and mandibular edentulous areas in four baboons. The defect sites were implanted with rhBMP-2 (0.4 mg/mL) in a tricalcium phosphate/hydroxyapatite/ absorbable collagen sponge composite (TCP/HA/ACS) or calcium phosphate cement (alpha-BSM). Control treatments were TCP/HA/ACS and ?-BSM without rhBMP-2 and sham surgery. Stainless steel pins were placed at the mid-apical and coronal level of the defect sites to provide landmarks for clinical measurements pre- and post-implantation. Impressions were obtained pre- and postimplantation to determine changes in alveolar ridge volume. Radiographic registrations were obtained pre- and post-implantation. Block sections of the defect sites were harvested at week 16 postimplantation and processed for histometric analysis including new bone area and bone density. Statistical comparisons between treatments were made using a mixed effect generalized linear model using least squares estimation. RESULTS The carrier systems without rhBMP-2 provided a modest ridge augmentation. The addition of rhBMP-2 resulted in an almost 2-fold increase in alveolar ridge width, including a greater percentage of trabecular bone and a higher bone density compared to controls (P < or =0.05) without significant differences between the two rhBMP-2 protocols. CONCLUSIONS TCP/HA/ACS and alphaBSM appear to be suitable carrier technologies for rhBMP-2. Alveolar augmentation procedures using either technology combined with rhBMP-2, rather than stand-alone therapies, may provide clinically relevant augmentation of alveolar ridge defects for placement of endosseous dental implants.

[1]  C. Schnitzler,et al.  Histomorphometry of iliac crest trabecular bone in adult male baboons in captivity , 1993, Calcified Tissue International.

[2]  R. Nishimura,et al.  Long-term functional loading of dental implants in rhBMP-2 induced bone. A histologic study in the canine ridge augmentation model. , 2003, Clinical oral implants research.

[3]  J. Wozney,et al.  Periodontal Repair in Dogs: Evaluation of a Bioabsorbable Space-Providing Macro-Porous Membrane with Recombinant Human Bone Morphogenetic Protein-2. , 2003, Journal of periodontology.

[4]  J. Wozney,et al.  Effect of recombinant human bone morphogenetic protein-2 in dehiscence defects with non-submerged immediate implants: an experimental study in Cynomolgus monkeys. , 2003, Journal of periodontology.

[5]  J. Wozney,et al.  RhBMP-2/alphaBSM induces significant vertical alveolar ridge augmentation and dental implant osseointegration. , 2002, Clinical implant dentistry and related research.

[6]  J. Wozney,et al.  Effect of surgical implantation of recombinant human bone morphogenetic protein-2 in a bioabsorbable collagen sponge or calcium phosphate putty carrier in intrabony periodontal defects in the baboon. , 2002, Journal of periodontology.

[7]  J. Wozney,et al.  Bone repair following recombinant human bone morphogenetic protein-2 stimulated periodontal regeneration. , 2002, Journal of periodontology.

[8]  J. Wozney,et al.  Peri-implant bone regeneration using recombinant human bone morphogenetic protein-2 in a canine model: a dose-response study. , 2002, Journal of periodontal research.

[9]  J. Wozney,et al.  Effect of recombinant human bone morphogenetic protein-2/absorbable collagen sponge (rhBMP-2/ACS) on healing in 3-wall intrabony defects in dogs. , 2002, Journal of periodontology.

[10]  T. Sigurdsson,et al.  Alveolar ridge augmentation with rhBMP-2 and bone-to-implant contact in induced bone. , 2001, The International journal of periodontics & restorative dentistry.

[11]  S. Shabahang,et al.  An evaluation of bone induction delivery materials in conjunction with root-form implant placement. , 2001, The International journal of periodontics & restorative dentistry.

[12]  J. Wozney,et al.  Hyaluronan supports recombinant human bone morphogenetic protein-2 induced bone reconstruction of advanced alveolar ridge defects in dogs. A pilot study. , 2001, Journal of periodontology.

[13]  M. Block,et al.  Bone gap healing in the dog using recombinant human bone morphogenetic protein-2. , 2000, Journal of oral and maxillofacial surgery : official journal of the American Association of Oral and Maxillofacial Surgeons.

[14]  U. Wikesjö,et al.  Ridge augmentation following implantation of recombinant human bone morphogenetic protein-2 in the dog. , 2000, Journal of periodontology.

[15]  Blumenthal Nm,et al.  The use of demineralized freeze-dried bone-glycoprotein matrix grafts in treating baboon periodontal infrabony defects. , 2000 .

[16]  S. Shabahang,et al.  Evaluation of the long-term effect of function on rhBMP-2 regenerated hemimandibulectomy defects. , 1999, The British journal of oral & maxillofacial surgery.

[17]  J. Wozney,et al.  Periodontal repair in dogs: effect of rhBMP-2 concentration on regeneration of alveolar bone and periodontal attachment. , 1999, Journal of clinical periodontology.

[18]  J. Wozney,et al.  Recombinant human bone morphogenetic protein-2 stimulation of bone formation around endosseous dental implants. , 1999, Journal of periodontology.

[19]  M. Taylor,et al.  Maxillary sinus augmentation in the non-human primate: a comparative radiographic and histologic study between recombinant human osteogenic protein-1 and natural bone mineral. , 1998, Journal of periodontology.

[20]  P. Boyne,et al.  Human recombinant BMP-2 in osseous reconstruction of simulated cleft palate defects. , 1998, The British journal of oral & maxillofacial surgery.

[21]  M. Bošković,et al.  Bone formation and reosseointegration in peri-implantitis defects following surgical implantation of rhBMP-2. , 1997, The International journal of oral & maxillofacial implants.

[22]  J. Wozney,et al.  Bone formation and osseointegration stimulated by rhBMP-2 following subantral augmentation procedures in nonhuman primates. , 1997, The International journal of oral & maxillofacial implants.

[23]  E. Fu,et al.  Bone morphogenetic protein-2 for peri-implant bone regeneration and osseointegration. , 1997, Clinical oral implants research.

[24]  J. Wozney,et al.  Periodontal repair in dogs: evaluation of rhBMP-2 carriers. , 1996, The International journal of periodontics & restorative dentistry.

[25]  P. Boyne Animal studies of application of rhBMP-2 in maxillofacial reconstruction. , 1996, Bone.

[26]  C. Kirker-Head,et al.  Bone formation in the goat maxillary sinus induced by absorbable collagen sponge implants impregnated with recombinant human bone morphogenetic protein-2. , 1996, The International journal of periodontics & restorative dentistry.

[27]  L. Gandini,et al.  Non-human primate models for testing the efficacy and safety of periodontal regeneration procedures. , 1994, Journal of periodontology.

[28]  K. Selvig Discussion: animal models in reconstructive therapy. , 1994, Journal of periodontology.

[29]  H. Greenwell,et al.  Doxycycline-tricalcium phosphate composite graft facilitates osseous healing in advanced periodontal furcation defects. , 1991, Journal of periodontology.

[30]  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.

[31]  T. Karring,et al.  Guided tissue regeneration following treatment of recession-type defects in the monkey. , 1990, Journal of periodontology.

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

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

[34]  Seibert Js Reconstruction of deformed, partially edentulous ridges, using full thickness onlay grafts. Part I. Technique and wound healing. , 1983 .