Periodontal repair in dogs: evaluation of a bioresorbable calcium phosphate cement (CeredexTM) as a carrier for rhBMP-2
Rachel G. Sorensen
Clinical Research & Development, Wyeth Research, Cambridge, MA, USA
Search for more papers by this authorUlf M. E. Wikesjö
Laboratory for Applied Periodontal and Craniofacial Regeneration, Department of Periodontology, Temple University School of Dentistry, Philadelphia, PA, USA
Search for more papers by this authorAtsuhiro Kinoshita
Section of Preventive Oral Health Care Science, Department of Oral Health Care Promotion, School of Oral Health Care Science, Faculty of Dentistry, Tokyo Medical and Dental University, Japan
Search for more papers by this authorJohn M. Wozney
Musculoskeletal Sciences, Wyeth Research, Cambridge, MA, USA
Search for more papers by this authorRachel G. Sorensen
Clinical Research & Development, Wyeth Research, Cambridge, MA, USA
Search for more papers by this authorUlf M. E. Wikesjö
Laboratory for Applied Periodontal and Craniofacial Regeneration, Department of Periodontology, Temple University School of Dentistry, Philadelphia, PA, USA
Search for more papers by this authorAtsuhiro Kinoshita
Section of Preventive Oral Health Care Science, Department of Oral Health Care Promotion, School of Oral Health Care Science, Faculty of Dentistry, Tokyo Medical and Dental University, Japan
Search for more papers by this authorJohn M. Wozney
Musculoskeletal Sciences, Wyeth Research, Cambridge, MA, USA
Search for more papers by this authorAbstract
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 ∼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.
References
- Blumenthal, N. M., Koh-Kunts, G., Alves, M. E. A. F., Miranda, D., Sorensen, R. G., Wozney, J. M. & Wikesjö, U. M. E. (2002) Effect of surgical implantation of recombinant human bone morphogenetic protein-2 in a bioabsorbable collagen sponge or a calcium phosphate putty carrier in intrabony periodontal defects in the baboon. Journal of Periodontology 73, 1494–1506.
- Choi, S.-H., Kim, C.-K., Cho, K.-S., Huh, J.-S., Sorensen, R. G., Wozney, J. M. & Wikesjö, U. M. E. (2002) Effect of recombinant human bone morphogenetic protein-2/absorbable collagen sponge (rhBMP-2/ACS) on healing in 3-wall intrabony defects in dogs. Journal of Periodontology 73, 63–72.
- Giannobile, W. V., Ryan, S., Shih, M.-S., Su, D. L., Kaplan, P. L. & Chan, T. C. K. (1998) Recombinant human osteogenic protein-1 (OP-1) stimulates periodontal wound healing in Class III furcation defects. Journal of Periodontology 69, 129–137.
- Haney, J. M., Nilvéus, R. E., McMillan, P. J. & Wikesjö, U. M. E. (1993) Periodontal repair in dogs: expanded polytetrafluoroethylene barrier membranes support wound stabilization and enhance bone regeneration. Journal of Periodontology 64, 883–890.
- Ishikawa, I., Kinoshita, A., Oda, S. & Roongruangphol, T. (1994) Regenerative therapy in periodontal diseases. Histological observations after implantation of rhBMP-2 in the surgically created periodontal defects in adult dogs. Dentistry in Japan 31, 141–146.
-
Ishikawa, K.,
Miyamoto, Y.,
Takechi, M.,
Toh, T.,
Kon, M.,
Nagayama, M. &
Asaoka, K. (1997) Non-decay type fast-setting calcium phosphate cement: hydroxyapatite putty containing an increased amount of sodium alginate.
Journal of Biomedical Materials Research
36, 393–399.
10.1002/(SICI)1097-4636(19970905)36:3<393::AID-JBM14>3.0.CO;2-F CAS PubMed Web of Science® Google Scholar
- Kim, C.-K., Cho, K.-S., Choi, S.-H., Prewett, A. & Wikesjö, U. M. E. (1998) Periodontal repair in dogs: effect of allogeneic freeze-dried demineralized bone matrix implants on alveolar bone and cementum regeneration. Journal of Periodontology 69, 26–33.
- Kinoshita, A., Oda, S., Takahashi, K., Yokota, S. & Ishikawa, I. (1997) Periodontal regeneration by application of rhBMP-2 to horizontal circumferential defects created by experimental periodontitis in beagle dogs. Journal of Periodontology 68, 103–109.
-
Knaack, D.,
Goad, M. E.,
Aiolova, M.,
Rey, C.,
Tofighi, A.,
Chakravarthy, P. &
Lee, D. D. (1998) Resorbable calcium phosphate bone substitute.
Journal of Biomedical Materials Research
43, 399–409.
10.1002/(SICI)1097-4636(199824)43:4<399::AID-JBM7>3.0.CO;2-J CAS PubMed Web of Science® Google Scholar
- Koo, K.-T., Polimeni, G., Qahash, M., Kim, C.-K. & Wikesjö, U. M. E. (in press) Periodontal repair in dogs: guided tissue regeneration enhances bone regeneration associated with a coral calcium carbonate implant. Journal of Clinical Periodontology.
- Kuboki, Y., Sasaki, M., Saito, A., Takita, H. & Kato, H. (1998) Regeneration of periodontal ligament and cementum by BMP-applied tissue engineering. European Journal of Oral Sciences 106 (Suppl. 1), 197–203.
- Lee, D. D., Tofighi, A., Aiolova, M., Chakravarthy, P., Catalano, A., Majahad, A. & Knaack, D. (1999) Alpha-BSM: a biomimetic bone substitute and drug delivery vehicle. Clinical Orthopaedics and Related Research 367, S396–S405.
- Li, R. H., Bouxsein, M. L., Blake, C. A., D'Augusta, D., Li, X. J., Wozney, J. M. & Seeherman, H. J. (2003) rhBMP-2 injected in a calcium-phosphate paste (alpha-BSM) accelerates healing in the rabbit ulnar osteotomy model. Journal of Orthopaedic Research 21, 997–1004.
- Luna, L. G. (1992) Histologic Methods and Color Atlas of Special Stains and Tissue Artifacts. Gaithersburg, MD: American Histolab, Inc., Publications Division , p. 113.
- Ripamonti, U., Crooks, J., Petit, J. C. & Rueger, D. C. (2001) 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). European Journal of Oral Sciences 109, 241–248.
- Ripamonti, U., Heliotis, M., Rueger, D. C. & Sampath, T. K. (1996) Induction of cementogenesis by recombinant human osteogenic protein-1 (hop-1/bmp-7) in the baboon (Papio ursinus). Short communication. Archives of Oral Biology 41, 121–126.
- Ripamonti, U., Heliotis, M., Van Den Heever, B. & Reddi, A. H. (1994) Bone morphogenetic proteins induce periodontal regeneration in the baboon (Papio ursinus). Brief communication. Journal of Periodontal Research 29, 439–445.
- Schenk, R. K., Olah, A. J. & Herrmann, W. (1984) Preparation of calcified tissues for light microscopy. In: Methods of Calcified Tissue Preparation, eds. G. R. Dickson, pp. 1–42. Amsterdam: Elsevier Science Publishers BV.
- Schmitz, J. P., Hollinger, J. O. & Milam, S. B. (1999) Reconstruction of bone using calcium phosphate bone cements: a critical review. Journal of Oral and Maxillofacial Surgery 57, 1122–1126.
- Seeherman, H., Aiolova, M., Bouxsein, M. & Wozney, J. (2001) A single injection of rhBMP-2/calcium phosphate paste accelerates healing in a nonhuman primate osteotomy model. Transactions of the Annual Meeting of the Orthopaedic Research Society, 2001, San Francisco, CA.
- Seeherman, H., Li, R., Blake, C., Bouxsein, M., Cooper, J., Gavin, D., Li, J. & Wozney, J. (2002) A single injection of rhBMP-2/calcium phosphate paste given one week after surgery accelerates osteotomy healing by 50% in a non-human primate fibula osteotomy model. Transactions of the 48th Annual Meeting of the Orthopaedic Research Society, 2002, Dallas, TX.
- Selvig, K. A., Sorensen, R. G., Wozney, J. M. & Wikesjö, U. M. E. (2002) Bone repair following recombinant human bone morphogenetic protein-2 stimulated periodontal regeneration. Journal of Periodontology 73, 1020–1029.
- Sigurdsson, T. J., Hardwick, R., Bogle, G. C. & Wikesjö, U. M. E. (1994) Periodontal repair in dogs: space provision by reinforced ePTFE membranes enhances bone and cementum regeneration in large supraalveolar defects. Journal of Periodontology 65, 350–356.
- Sigurdsson, T. J., Lee, M. B., Kubota, K., Turek, T. J., Wozney, J. M. & Wikesjö, U. M. E. (1995) Periodontal repair in dogs: recombinant human bone morphogenetic protein-2 significantly enhances periodontal regeneration. Journal of Periodontology 66, 131–138.
- Sigurdsson, T. J., Nygaard, L., Tatakis, D. N., Fu, E., Turek, T. J., Jin, L., Wozney, J. M. & Wikesjö, U. M. E. (1996) Periodontal repair in dogs: evaluation of rhBMP-2 carriers. The International Journal of Periodontics and Restorative Dentistry 16, 525–537.
- Tatakis, D. N., Wikesjö, U. M. E., Razi, S. S., Sigurdsson, T. J., Lee, M. B., Nguyen, T., Ongpipattanakul, B. & Hardwick, R. (2000) Periodontal repair in dogs: effect of transforming growth factor-ß1 on alveolar bone and cementum regeneration. Journal of Clinical Periodontology 27, 698–704.
- Trombelli, L., Lee, M. B., Promsudthi, A., Guglielmoni, P. G. & Wikesjö, U. M. E. (1999) Periodontal repair in dogs: histologic observations of guided tissue regeneration with a prostaglandin E1 analog/methacrylate composite. Journal of Clinical Periodontology 26, 381–387.
- Valentin-Opran, A., Wozney, J., Csimma, C., Lilly, L. & Riedel, G. E. (2002) Clinical evaluation of recombinant human bone morphogenetic protein-2. Clinical Orthopaedics and Related Research 395, 110–120.
- Wikesjö, U. M. E., Guglielmoni, P. G., Promsudthi, A., Cho, K.-S., Trombelli, L., Selvig, K. A., Jin, L. & Wozney, J. M. (1999) Periodontal repair in dogs: effect of rhBMP-2 concentration on regeneration of alveolar bone and periodontal attachment. Journal of Clinical Periodontology 26, 392–400.
- Wikesjö, U. M. E., Kean, C. J. C. & Zimmerman, G. J. (1994) Periodontal repair in dogs: supraalveolar defect models for evaluation of safety and efficacy of periodontal reconstructive therapy. Journal of Periodontology 65, 1151–1157.
- Wikesjö, U. M. E., Lim, W. H., Razi, S. S., Sigurdsson, T. J., Lee, M. B., Tatakis, D. N. & Hardwick, W. R. (2003e) Periodontal repair in dogs: a bioresorbable calcium carbonate coral implant enhances space provision for alveolar bone regeneration in conjunction with guided tissue regeneration. Journal of Periodontology 74, 955–962.
- Wikesjö, U. M. E., Lim, W. H., Thomson, R. C., Cook, A. D., Wozney, J. M. & Hardwick, W. R. (2003d) Periodontal repair in dogs: evaluation of a bioresorbable space-providing macro-porous membrane with recombinant human bone morphogenetic protein-2. Journal of Periodontology 74, 635–647.
- Wikesjö, U. M. E., Lim, W. H., Thomson, R. C. & Hardwick, W. R. (2003c) Periodontal repair in dogs: gingival tissue exclusion, a critical requirement for guided tissue regeneration? Journal of Clinical Periodontology 30, 655–664.
- Wikesjö, U. M. E. & Nilvéus, R. (1991) Periodontal repair in dogs: healing patterns in large circumferential periodontal defects. Journal of Clinical Periodontology 18, 49–59.
- Wikesjö, U. M. E., Qahash, M., Thomson, R. C., Cook, A. D., Rohrer, M. D., Wozney, J. M. & Hardwick, W. R. (2003b) Space-providing expanded polytetrafluoroethylene devices define alveolar augmentation at dental implants induced by recombinant human bone morphogenetic protein-2. Clinical Implant Dentistry and Related Research 5, 112–123.
- Wikesjö, U. M. E., Razi, S. S., Sigurdsson, T. J., Tatakis, D. N., Lee, M. B., Ongpipattanakul, B., Nguyen, T. & Hardwick, R. (1998) Periodontal repair in dogs: effect of recombinant human transforming growth factor-beta1 on guided tissue regeneration. Journal of Clinical Periodontology 25, 475–481.
- Wikesjö, U. M. E. & Selvig, K. A. (1999) Periodontal wound healing and regeneration. Periodontology 2000 19, 21–39.
- Wikesjö, U. M. E., Sorensen, R. G., Kinoshita, A., Li, X. J. & Wozney, J. M. (2004) Periodontal repair in dogs: effect of rhBMP-12 on regeneration of alveolar bone and periodontal attachment. A pilot study. Journal of Clinical Periodontology 31, 662–670.
-
Wikesjö, U. M. E.,
Sorensen, R. G.,
Kinoshita, A. &
Wozney, J. M. (2002) rhBMP-2/α-BSM® induces significant vertical alveolar ridge augmentation and dental implant osseointegration.
Clinical Implant Dentistry and Related Research
4, 173–181.
10.1111/j.1708-8208.2002.tb00169.x Google Scholar
- Wikesjö, U. M. E., Sorensen, R. G. & Wozney, J. M. (2001) Augmentation of alveolar bone and dental implant osseointegration: clinical implications of studies with rhBMP-2. A comprehensive review. The Journal of Bone and Joint Surgery. American Volume 83-A (Suppl. 1, Part 2), S136–S145.
- Wikesjö, U. M. E., Xiropaidis, A. V., Thomson, R. C., Cook, A. D., Selvig, K. A. & Hardwick, W. R. (2003a) Periodontal repair in dogs: space-providing ePTFE devices increase rhBMP-2/ACS induced bone formation. Journal of Clinical Periodontology 30, 715–725.
- Wikesjö, U. M. E., Xiropaidis, A. V., Thomson, R. C., Cook, A. D., Selvig, K. A. & Hardwick, W. R. (2003f) Periodontal repair in dogs: rhBMP-2 significantly enhances bone formation under provisions for guided tissue regeneration. Journal of Clinical Periodontology 30, 705–714.
Citing Literature
