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Background: Some practitioners are employing recombinant bone morphogenetic protein-2 (BMP-2) to reconstruct segmental mandible defects resulting from trauma and infection. This growth factor allows de novo bone regeneration and eliminates/reduces the need for bone grafting. The mandible is a composite tissue comprised of bone, teeth, and the inferior alveolar nerve (IAN), which provides sensation to the lower third of the face. Current methods of mandible reconstruction allow eventual dental restoration with osseointegrated implants, but do not commonly allow reconstruction of the IAN. The malleability of the BMP-2 carrier should allow a surgeon to encase a nerve repair with osteoinductive BMP-2 and reestablish bone and nerve continuity together. The feasibility of this reconstruction is unknown as there is little data to suggest what effect BMP-2 might have a regenerating nerve. We describe a novel model to investigate this interaction.
Methods: A one cm x 0.6 cm inferior boarder mandibulectomy was created in six adult male New Zealand White rabbits using a diamond burr. The IAN was identified and protected. A 5mm neurectomy was removed from the central portion of the exposed nerve, was reversed, and was utilized as a nerve autograft to reestablish continuity. Neurorrhaphies were executed with 10-0 nylon sutures utilizing an operating microscope. Bone defects were reconstructed differently in 3 groups (n=2). Group one utilized a 1.7x1.1cm acellular collagen sponge (ACS) soaked in 0.43mg/kg BMP-2. Group two included the same ACS soaked in lactated ringer solution, and group three received no bone reconstruction. The ACS was folded in half to recapitulate the lingual, buccal, and inferior cortices with the nerve repair sandwiched between the layers. This was held in place with 4-0 vicryl sutures. Animals underwent 1mm fine cut CT scans on post-op day 2 and six weeks post-op. The percent of bone defect healing for each animal was calculated using Amira 3D-imaging software. Animals were euthanized humanely after 6 weeks. The reconstructed nerve was harvested mesial to the anterior bone defect margin, embedded in epoxy and sectioned for nerve histomorphometry analysis after toluidine blue staining.
Results: Animals with BMP-2 bone reconstructions demonstrated a mean defect healing of 93.6%. Those with ACS healed 38.7% of the defect and the empty defects healed 58.5%. A single BMP-2 animal and an ACS animal have undergone nerve histomorphometry at a point 8mm from the second neurorrhaphy. The axon counts were 248 and 314, respectively. Fiber densities were 4973.1 and 5879.1 fibers/mm², and fiber widths were 2.8 and 3.1µm.
Conclusion: Our results indicate BMP-2 on an ACS can heal a mandibular boarder defect in rabbits. More interesting, early nerve regeneration was seen 8mm distal to the site of nerve repair beyond the reconstructed bone defect. More animals will studied to statistically prove if BMP-2 affects nerve regeneration, but we have shown BMP-2 is not prohibitive toward nerve growth, and composite tissue regeneration with BMP-2 and nerve grafting is a viable strategy for mandible repair. Future studies may investigate the feasibility of using nerve conduits or other vehicles for BMP-2 delivery in this system.