BONE MORPHOGENETIC PROTEIN PROMOTES VASCULARIZATION AND OSTEOINDUCTION IN PREFORMED HYDROXYAPATITE IN THE RABBIT

Early reconstruction of large osseous defects in children is often del ayed due to limited availability of autogenous bone graft donor sites. With the advent of growth factors, osteoinductive proteins, and deliv ery matrices, it is possible to fabricate new bone at extraskeletal si tes. Due to their own blood supply, adequate bony volume, and decrease d resorption, vascularized bone flaps have demonstrated greater succes s in restoring large bony defects compared with nonvascularized bone g rafts. The purpose of this study is to prefabricate a vascularized bon e flap in the immature-age rabbit using the auricularis anterior muscl e as a muscle pedicle. Sixteen female New Zealand White rabbits, 2.0 t o 2.5 kg, were divided into two groups. Group 1 contained 8 animals th at had T-shaped, 10 x 6 x 4-mm hydroxyapatite (HA) implants combined w ith 100-mu g bovine-derived bone morphogenetic protein (BMP) placed su praperiosteally and fixed deep to the auricularis anterior muscle. Imp lants with HA alone were placed in the same animal and secured to the contralateral auricularis anterior muscle. Group 2 contained 8 animals that had HA/BMP placed subperiosteally and fixed deep to the auricula ris anterior muscle, while implants with HA alone were secured in the same animal to the contralateral auricularis anterior muscle. In each group, 4 animals were sacrificed at 4 and 8 weeks. The animals underwe nt randomized bilateral carotid artery injection with micropaque bariu m suspension just prior to sacrifice to help maintain vascularity. At harvest the implants and surrounding muscle and cranium were removed e n bloc. New bone formation in the HA implants was examined by using ro utine histology and scanning electron microscopic backscattering image (quantitative) analysis. Microradiographs were performed on represent ative specimens. At 4 weeks postimplantation, backscattering analysis in the subperiosteal HA/BMP showed a mean 17.1% bone ingrowth vs. 11.3 % of HA alone (p < 0.05). Supraperiosteal HA/BMP showed a mean 12.9% b one ingrowth vs. 0% of HA alone (p < 0.05). At 8 weeks, backscatter an alysis of supraperiosteal HA/BMP showed a mean 19.33% bone ingrowth vs . 0% of HA alone (p < 0.05). Subperiosteal HA/BMP showed a mean 22% bo ne ingrowth vs, 20.85% of HA alone. This was the only group that did n ot have statistically significant results. Implant histology demonstra ted woven bone within the interstices of HA/BMP placed either supra- o r subperiosteally. In the HA-alone implants placed supraperiosteally, fibrovascular ingrowth was seen without any evidence of bone formation . In the HA-alone implant placed subperiosteally, woven bone was seen at the calvarium-implant junction. Microradiographs also demonstrated vascularization and bone formation similar to that seen on scanning el ectron microscopy. BMP-treated specimens appeared to have slightly gre ater vascularity than the nontreated specimens. The greatest bone form ation occurred with the HA/BMP implant placed subperiosteally in the i mmature rabbit. Furthermore, these results demonstrate the potential p refabrication of vascularized bone flaps as early as 4 to 8 weeks. The clinical advantage of HA permits the surgeon to design osseous flaps that are customized in shape, fill all contour defects, and have littl e resorptive properties. Such prefabricated bone with an axial blood s upply may allow for ultimate transfer as a pedicle or free flap to rec onstruct osseous defects in children.