title: Bone morphogenetic protein 2–mediated mandible reconstruction successfully heals bony defects but inhibits concurrent inferior alveolar nerve grafting: a rabbit experimental model.
abstract: BACKGROUND
  Bone morphogenetic protein 2 (BMP-2) has been used to reconstruct mandibular defects. An elegant addition to this reconstruction method would be incorporation of a nerve graft wrapped in a BMP-2 carrier to reconstitute the inferior alveolar nerve (IAN) and restore sensation to the lower face. We developed a rabbit model to determine the effect BMP-2 has on nerve regeneration following neurorrhaphy.
  
  
  METHODS
  An inferior border mandibulectomy was created in 16 adult New Zealand white rabbits. The IAN was protected, divided, and repaired with either primary neurorrhaphy or reverse autografts. Bone defects were treated with no treatment controls (n = 2), absorbable collagen sponge (ACS) (vehicle controls) (n = 7), and ACS soaked in BMP-2 (treatment group) (n = 7). Animals underwent computed tomography (CT) 2 days and 6 weeks postoperatively. The percent bone defect healing was calculated using Amira 3D imaging software. At 6 weeks, IANs were harvested mesial to the reconstruction and were evaluated with toluidine blue histology to identify myelinated axons. Reconstructed mandible segments were evaluated with micro-CT and hematoxylin-eosin histology.
  
  
  RESULTS
  Bone morphogenetic protein 2-treated animals demonstrated significantly more bone healing than did the ACS and empty defect groups (82%, 38%, 44%, respectively; P < 0.01). One hundred percent of ACS-treated nerves (n = 4) demonstrated axon regrowth, whereas only 25% of BMP-2-treated nerves (n = 4) did. Micro-CT and histology showed BMP-2 caused bone growth around the IAN, but regenerated bone infiltrated the repair site and created a physical barrier to axon growth.
  
  
  CONCLUSIONS
  Bone morphogenetic protein 2 can successfully heal bone defects in the rabbit mandible, but ectopic bone growth can inhibit IAN recovery after repair. Level of Evidence: Not gradable.
authors.forename: S Alex
authors.initials: SA
authors.lastname: Rottgers
authors.forename: James J
authors.initials: JJ
authors.lastname: Cray
authors.forename: Darren M
authors.initials: DM
authors.lastname: Smith
authors.forename: Mark P
authors.initials: MP
authors.lastname: Mooney
authors.forename: Joseph E
authors.initials: JE
authors.lastname: Losee
authors.forename: Greg M
authors.initials: GM
authors.lastname: Cooper
mesh_terms: D000818:Animals; D001369:Axons / Q000187:drug effects; D055396:Bone Morphogenetic Protein 2 / Q000627:therapeutic use*; D001861:Bone Regeneration / Q000187:drug effects*; D003094:Collagen; D004396:Coloring Agents; D004195:Disease Models, Animal; D007091:Image Processing, Computer-Assisted / Q000379:methods; D021621:Imaging, Three-Dimensional / Q000379:methods; D008334:Mandible / Q000187:drug effects / Q000601:surgery; D008336:Mandibular Diseases / Q000601:surgery*; D008340:Mandibular Nerve / Q000187:drug effects* / Q000601:surgery; D009413:Nerve Fibers, Myelinated / Q000187:drug effects; D009416:Nerve Regeneration / Q000187:drug effects*; D010012:Osteogenesis / Q000187:drug effects; D011817:Rabbits; D019651:Plastic Surgery Procedures / Q000379:methods*; D054457:Tissue Scaffolds; D014048:Tolonium Chloride; D014057:Tomography, X-Ray Computed / Q000379:methods; D061221:Trigeminal Nerve Injuries / Q000601:surgery; D014945:Wound Healing / Q000187:drug effects; D055114:X-Ray Microtomography / Q000379:methods
chemical_list: D055396:Bone Morphogenetic Protein 2; D004396:Coloring Agents; D014048:Tolonium Chloride; D003094:Collagen