Bone Regeneration Using rhBMP-2 Induction in Hemimandibulectomy Type Defects of Elderly Sub-Human Primates

Abstract

Our previous work has shown that total osseous reconstruction of large discontinuity hemimandibulectomy, critical-sized defects can be achieved easily in 8-year-old Macaca fascicularis monkeys (Boyne 1996). However the literature has indicated that animal aging decreases the BMP induction of stem cells in rats and in other rodent species. It was necessarily important that the rhBMP-2 be demonstrated in non-human primates to determine if this reduction in effectiveness also existed in the higher animals phylogenetically. The purpose of this study was to operate aged non-human primates duplicating the model used in middle-aged animals to demonstrate regeneration of hemimandibulectomy defects. This age group could be extrapolated to the 80-year-old clinic patient. Six non-human primates aged 20 years were rendered edentulous posteriorly and the mandibles allowed to heal. Three months postoperatively bilateral hemimandibulectomies were performed. The defects received BMP in a collagen sponge (Helistat) using a dose level of 0.75 mg of rhBMP-2. After the manner previously reported by Boyne (1996, 1999), at the end of four months the surgical sites were exposed by mucoperiosteal flap demonstrating complete regeneration of the critical-sized defects. The animals received two dental implants in restored areas. The implants were brought into function approximately four months later, and were allowed to function for eight months in all cases. The results indicate that the regeneration of mandibular critical-sized defects by the use of rhBMP-2 in aged animals is comparable to that of the middle-aged group. This study indicates that aged non-human primates, chronologically comparable to 80-year-old humans, respond as favorably to rhBMP-2 as do the middle-aged animals. Extrapolating the results to the clinical level, one would expect that rhBMP-2 would produce a comparable result in the regeneration of large hemimandibulectomy-type defects in clinical human patients.

Mandibular bone repair by implantation of rhBMP-2 in a slow release carrier of polylactic acid—An experimental study in rats

“…Collagen, collagen/HA/TCP, anorganic bovine bone, hyaluronic acid, PLA/PGA coated gelatine sponges and PGLA beads have been employed with various doses of either rhBMP-2, rhBMP4 or rhBMP7 [33][34][35][36][37][38][39] All carriers of these studies had been soak-loaded with their respective BMP solution, in one study rhBMP-2 was suspended in PGLA/dioxane solution and freeze-dried for implantation [40].…”

The role of topical simvastatin on bone regeneration: A systematic review

“…However, the use of BMPs entails some problems such as their short life, storage and handling difficulties, inefficiency in the recognition of target cells, and high cost. This has hampered their popularization in bone regeneration procedures (6). …”

Bases teóricas y aplicación clínica de las proteínas morfogenéticas óseas en cirugía maxilofacial

“…The BMPs have been successfully used in primates to restore bisected mandibles and critical bone defects, 1,2 repair alveolar fissures, 3 and induce bone formation in the maxillary sinus before implant placement. 4 The clinical application of the BMP includes repairing facial, alveolar, and mandible bone defects.…”

“…3 La restauración de la actividad biológica después de la extracción disociativa y reconstrucción de la PMO con matriz de colágeno insoluble indica que los componentes de la matriz extracelular ósea actúan como un vehículo para la expresión funcional de las PMO. 2,9 Algunas investigaciones han demostrado que el colágeno de la matriz ósea proporciona un sustrato óptimo para el reclutamiento y adhesión de células progenitoras y la posterior proliferación y diferenciación en osteoblastos. 1, 2 La fundamentación de la matriz de colá-geno en el desarrollo y diferenciación ha sido manifestado tempranamente, 8 demostrando que la matriz de colágeno puede prevenir la difusión prematura en la implantación quirúrgica, 2, 9 y puede proteger la PMO de proteólisis no específica.…”