Abstract
Background
Massive frozen stocked allogeneic bone grafts are often used to reconstruct large bone defects caused by trauma or tumor resections. However, the long-term failure rate of such massive allografts was reported to be 25% because of infection, fracture, and nonunion. In this study, we evaluated the ability of a recombinant human bone morphogenetic protein (rhBMP)-2-retaining paste to promote the osteogenic potential of frozen stocked allogeneic bone grafts to repair intercalated femoral shaft defects in a rat model.
Methods
After confirming the transplantation intolerance between two rat strains (Wistar and Lewis) by skin transplantation from Lewis rats to Wistar rats, an 8-mm-long bone segment was removed from the Wistar rats, and a frozen stocked allograft coated with the rhBMP-2-retaining paste from the Lewis rats was placed into the defect and subjected to intramedullary fixation with an 18-gauge injection needle pin. The allografted femurs were evaluated by radiographic, histologic, and biomechanical examinations at specified time points.
Results
The results revealed successful repair of critical-size cortical bone defects by implanting frozen stocked allografts coated with the rhBMP-2-retaining synthetic biodegradable carrier paste from an immunologically intolerant host.
Conclusions
This experimental study suggest that allogeneic bone grafting in combination with rhBMP-2 and its local delivery system may represent an innovative approach to the reconstruction of bone defects.
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References
Donati D, Di Liddo M, Zavatta M, Manfrini M, Bacci G, Picci P, Capanna R, Mercuri M. Massive bone allograft reconstruction in high-grade osteosarcoma. Clin Orthop Relat Res. 2000;377:186–94.
Gazdag AR, Lane JM, Glaser D, Forster RA. Alternatives to autogenous bone graft: efficacy and indications. J Am Acad Orthop Surg. 1995;3:1–8.
Caldroa P, Donati D, Capanna R, Di Liddo M, Benassi MS, Campanacci DA, Sangiorgi L, Zavatta M, Picci P. A histomorphologic study of explants of massive allografts: preliminary results. Chir Org Mov. 1995;80:191–205.
Enneking WF, Campanacci DA. Retrieved human allografts: a clinicopathological study. J Bone Jt Surg Am. 2001;83-A:971–86.
Berrey BH, Lord CF, Gebhardt MC, Mankin HJ. Fractures of allografts. Frequency, treatment, and end-results. J Bone Jt Surg Am. 1990;72:825–33.
Anand N, Hamilton JF, Perri B, Miraliakbar H, Goldstein T. Cantilever TLIF with structural allograft and RhBMP2 for correction and maintenance of segmental sagittal lordosis: long-term clinical, radiographic, and functional outcome. Spine (Phila Pa 1976). 2006;31:E748–53.
Salkeld SL, Patron LP, Barrack RL, Cook SD. The effect of osteogenic protein-1 on the healing of segmental bone defects treated with autograft or allograft bone. J Bone Jt Surg Am. 2001;83-A:803–16.
Cheng H, Jiang W, Phillips FM, Haydon RC, Peng Y, Zhou L, Luu HH, An N, Breyer B, Vanichakarn P, Szatkowski JP, Park JY, He TC. Osteogenic activity of the fourteen types of human bone morphogenetic proteins (BMPs). J Bone Jt Surg Am. 2003;85-A:1544–52.
Yasko AW, Lane JM, Fellinger EJ, Rosen V, Wozney JM, Wang EA. The healing of segmental bone defects, induced by recombinant human bone morphogenetic protein (rhBMP-2). A radiographic, histological, and biomechanical study in rats. J Bone Jt Surg Am. 1992;74:659–70.
Bong MR, Capla EL, Egol KA, Sorkin AT, Distefano M, Buckle R, Chandler RW, Koval KJ. Osteogenic protein-1 (bone morphogenic protein-7) combined with various adjuncts in the treatment of humeral diaphyseal nonunions. Bull Hosp Jt Dis. 2005;63:20–3.
Taguchi S, Namikawa T, Ieguchi M, Takaoka K. Reconstruction of bone defects using rhBMP-2-coated devitalized bone. Clin Orthop Relat Res. 2007;461:162–9.
Rokahr KL, Sharland AF, Sun J, Wang C, Sheil AG, Yan Y, McCaughan GW, Bishop GA. Paradoxical early immune activation during acceptance of liver allografts compared with rejection of skin grafts in a rat model of transplantation. Immunology. 1998;95:257–63.
Shimizu H, Takahashi M, Kaneko T, Murakami T, Hakamata Y, Kudou S, Kishi T, Fukuchi K, Iwanami S, Kuriyama K, Yasue T, Enosawa S, Matsumoto K, Takeyoshi I, Morishita Y, Kobayashi E. KRP-203, a novel synthetic immunosuppressant, prolongs graft survival and attenuates chronic rejection in rat skin and heart allografts. Circulation. 2005;111:222–9.
Murakami N, Saito N, Takahashi J, Ota H, Horiuchi H, Nawata M, Okada T, Nozaki K, Takaoka K. Repair of a proximal femoral bone defect in dogs using a porous surfaced prosthesis in combination with recombinant BMP-2 and a synthetic polymer carrier. Biomaterials. 2003;24:2153–9.
Yuehuei H. Animal models of bone defect repair. Boca Raton: CRC; 1999.
Lee FY, Storer S, Hazan EJ, Gebhardt MC, Mankin HJ. Repair of bone allograft fracture using bone morphogenetic protein-2. Clin Orthop Relat Res. 2002;397:119–26.
Murnaghan M, McIlmurray L, Mushipe MT, Li G. Time for treating bone fracture using rhBMP-2: a randomised placebo controlled mouse fracture trial. J Orthop Res. 2005;23:625–31.
Pluhar GE, Manley PA, Heiner JP, Vanderby R, Seeherman HJ, Markel MD. The effect of recombinant human bone morphogenetic protein-2 on femoral reconstruction with an intercalary allograft in a dog model. J Orthop Res. 2001;19:308–17.
Boden SD, Kang J, Sandhu H, Heller JG. Use of recombinant human bone morphogenetic protein-2 to achieve posterolateral lumbar spine fusion in humans: a prospective, randomized clinical pilot trial: 2002 Volvo Award in clinical studies. Spine (Phila Pa 1976). 2002;27:2662–73.
Burkus JK, Sandhu HS, Gornet MF, Longley MC. Use of rhBMP-2 in combination with structural cortical allografts: clinical and radiographic outcomes in anterior lumbar spinal surgery. J Bone Jt Surg Am. 2005;87:1205–12.
Kato M, Toyoda H, Namikawa T, Hoshino M, Terai H, Miyamoto S, Takaoka K. Optimized use of a biodegradable polymer as a carrier material for the local delivery of recombinant human bone morphogenetic protein-2 (rhBMP-2). Biomaterials. 2006;27:2035–41.
Saito N, Okada T, Horiuchi H, Murakami N, Takahashi J, Nawata M, Ota H, Nozaki K, Takaoka K. A biodegradable polymer as a cytokine delivery system for inducing bone formation. Nat Biotechnol. 2001;19:332–5.
Saito N, Takaoka K. New synthetic biodegradable polymers as BMP carriers for bone tissue engineering. Biomaterials. 2003;24:2287–93.
Matsushita N, Terai H, Okada T, Nozaki K, Inoue H, Miyamoto S, Takaoka K. A new bone-inducing biodegradable porous beta-tricalcium phosphate. J Biomed Mater Res A. 2004;70:450–8.
McClellan JW, Mulconrey DS, Forbes RJ, Fullmer N. Vertebral bone resorption after transforaminal lumbar interbody fusion with bone morphogenetic protein (rhBMP-2). J Spinal Disord Tech. 2006;19:483–6.
Acknowledgments
The authors would like to thank Ms K. Hata for her technical assistance.
Conflict of interest
The authors declare that they have no conflict of interest. The authors did not receive and will not receive any benefits or funding from any commercial party related directly or indirectly to the subject of this article.
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Yasuda, H., Yano, K., Wakitani, S. et al. Repair of critical long bone defects using frozen bone allografts coated with an rhBMP-2-retaining paste. J Orthop Sci 17, 299–307 (2012). https://doi.org/10.1007/s00776-012-0196-x
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DOI: https://doi.org/10.1007/s00776-012-0196-x