Periodontal repair in dogs: evaluation of a bioresorbable calcium phosphate cement (Ceredex) as a carrier for rhBMP-2.

BACKGROUND Recombinant human bone morphogenetic protein-2 (rhBMP-2) has been shown to induce clinically relevant bone formation for orthopedic, craniofacial, and oral indications. It appears critical, in particular for onlay indications, that the associated carrier technology exhibits structural integrity to offset compressive forces in support of rhBMP-2-induced bone formation. The objective of this study was to evaluate a calcium phosphate (CP) cement, Ceredex, as a candidate carrier for rhBMP-2 in a defect model with limited osteogenic potential. MATERIALS Bilateral, critical size, 6-mm, supra-alveolar, periodontal defects were created in six, adult, male, Hound Labrador mongrels. Three animals received rhBMP-2/Ceredex (rhBMP-2 at 0.20 and 0.40 mg/ml) in contralateral defect sites (implant volume/defect approximately 1 ml). One defect site in each of the three remaining animals received Ceredex without rhBMP-2 (control). The animals were euthanized at 12 weeks postsurgery for histologic and histometric analysis. RESULTS Mean induced bone height exceeded 80% of the defect height for supra-alveolar periodontal defects receiving rhBMP-2/Ceredex without major differences between rhBMP-2 concentrations compared with approximately 40% for the control. The newly formed bone, a mixture of lamellar and woven bone in fibrovascular tissue, circumscribed relatively large portions of the residual Ceredex biomaterial. Inflammatory lesions were associated with limited bone formation in some sites. From a periodontal perspective, sites receiving rhBMP-2/Ceredex exhibited increased cementum formation compared with control, but without a functionally oriented periodontal ligament, and increased ankylosis and root resorption. Control sites exhibited early wound failure and exposure, loss of the Ceredex biomaterial, and limited bone formation. CONCLUSIONS The Ceredex CP cement appears a potentially promising carrier technology for rhBMP-2 onlay indications. However, a slow resorption rate may prevent its wider use. This study does not support use of the rhBMP-2/Ceredex combination for periodontal indications.

[1]  J. Wozney,et al.  Periodontal repair in dogs: effect of recombinant human bone morphogenetic protein-12 (rhBMP-12) on regeneration of alveolar bone and periodontal attachment. , 2004, Journal of clinical periodontology.

[2]  H. Seeherman,et al.  rhBMP‐2 injected in a calcium phosphate paste (α‐BSM) accelerates healing in the rabbit ulnar osteotomy model , 2003, Journal of orthopaedic research : official publication of the Orthopaedic Research Society.

[3]  R. C. Thomson,et al.  Periodontal repair in dogs: space-providing ePTFE devices increase rhBMP-2/ACS-induced bone formation. , 2003, Journal of clinical periodontology.

[4]  R. C. Thomson,et al.  Periodontal repair in dogs: rhBMP-2 significantly enhances bone formation under provisions for guided tissue regeneration. , 2003, Journal of clinical periodontology.

[5]  J. Wozney,et al.  Space-providing expanded polytetrafluoroethylene devices define alveolar augmentation at dental implants induced by recombinant human bone morphogenetic protein 2 in an absorbable collagen sponge carrier. , 2003, Clinical implant dentistry and related research.

[6]  R. C. Thomson,et al.  Periodontal repair in dogs: gingival tissue occlusion, a critical requirement for GTR? , 2003, Journal of clinical periodontology.

[7]  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.

[8]  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.

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

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

[11]  J. Wozney,et al.  Clinical evaluation of recombinant human bone morphogenetic protein-2. , 2002, Clinical orthopaedics and related research.

[12]  J C Petit,et al.  Periodontal tissue regeneration by combined applications of recombinant human osteogenic protein-1 and bone morphogenetic protein-2. A pilot study in Chacma baboons (Papio ursinus). , 2001, European journal of oral sciences.

[13]  U. Wikesjö,et al.  Periodontal repair in dogs: effect of transforming growth factor-beta 1 on alveolar bone and cementum regeneration. , 2000, Journal of clinical periodontology.

[14]  P. Chakravarthy,et al.  alpha-BSM: a biomimetic bone substitute and drug delivery vehicle. , 1999, Clinical orthopaedics and related research.

[15]  J. Hollinger,et al.  Reconstruction of bone using calcium phosphate bone cements: a critical review. , 1999, Journal of oral and maxillofacial surgery : official journal of the American Association of Oral and Maxillofacial Surgeons.

[16]  L. Trombelli,et al.  Periodontal repair in dogs: histologic observations of guided tissue regeneration with a prostaglandin E1 analog/methacrylate composite. , 1999, Journal of clinical periodontology.

[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]  K. Selvig,et al.  Periodontal wound healing and regeneration. , 1999, Periodontology 2000.

[19]  C. Rey,et al.  Resorbable calcium phosphate bone substitute. , 1998, Journal of biomedical materials research.

[20]  U. Wikesjö,et al.  Periodontal repair in dogs: effect of recombinant human transforming growth factor-beta1 on guided tissue regeneration. , 1998, Journal of clinical periodontology.

[21]  W. Giannobile,et al.  Recombinant human osteogenic protein-1 (OP-1) stimulates periodontal wound healing in class III furcation defects. , 1998, Journal of periodontology.

[22]  K. Asaoka,et al.  Non-decay type fast-setting calcium phosphate cement: hydroxyapatite putty containing an increased amount of sodium alginate. , 1997, Journal of biomedical materials research.

[23]  I. Ishikawa,et al.  Periodontal regeneration by application of recombinant human bone morphogenetic protein-2 to horizontal circumferential defects created by experimental periodontitis in beagle dogs. , 1997, Journal of periodontology.

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

[25]  J. Wozney,et al.  Periodontal repair in dogs: recombinant human bone morphogenetic protein-2 significantly enhances periodontal regeneration. , 1995, Journal of periodontology.

[26]  U. Wikesjö,et al.  Periodontal repair in dogs: supraalveolar defect models for evaluation of safety and efficacy of periodontal reconstructive therapy. , 1994, Journal of periodontology.

[27]  A. Reddi,et al.  Bone morphogenetic proteins induce periodontal regeneration in the baboon (Papio ursinus) , 1994, Journal of periodontal research.

[28]  U. Wikesjö,et al.  Periodontal repair in dogs: space provision by reinforced ePTFE membranes enhances bone and cementum regeneration in large supraalveolar defects. , 1994, Journal of periodontology.

[29]  P. McMillan,et al.  Periodontal repair in dogs: expanded polytetrafluoroethylene barrier membranes support wound stabilization and enhance bone regeneration. , 1993, Journal of periodontology.

[30]  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.

[31]  P C Amadio,et al.  Repetitive stress injury. , 2001, The Journal of bone and joint surgery. American volume.

[32]  H. Takita,et al.  Regeneration of periodontal ligament and cementum by BMP-applied tissue engineering. , 1998, European journal of oral sciences.

[33]  U. Wikesjö,et al.  Periodontal repair in dogs: effect of allogenic freeze-dried demineralized bone matrix implants on alveolar bone and cementum regeneration. , 1998, Journal of periodontology.

[34]  M. Heliotis,et al.  Induction of cementogenesis by recombinant human osteogenic protein-1 (hop-1/bmp-7) in the baboon (Papio ursinus). , 1996, Archives of oral biology.

[35]  I. Ishikawa Regenerative therapy in periodontal diseases. Histological observations after implantation of rhBMP-2 in the surgically created periodontal defects in adult dogs , 1994 .

[36]  U. Wikesjö,et al.  Periodontal repair in dogs. Healing patterns in large circumferential periodontal defects. , 1991, Journal of clinical periodontology.