Primate mandibular reconstruction with prefabricated, vascularized tissue-engineered bone flaps and recombinant human bone morphogenetic protein-2 implanted in situ

Several studies have validated successful mandibular reconstruction with prefabricated tissue-engineered bone flaps and recombinant human bone morphogenetic protein-2 (rhBMP-2) implanted in situ. Whether rhBMP-2 applied with the prefabrication technique enables faster ossification of mandibular defects than rhBMP-2 applied in situ is unknown. We aimed to compare mandibular reconstruction with prefabricated, vascularized tissue-engineered bone flaps with rhBMP-2 and rhBMP-2 applied in situ in primates (Rhesus monkey). We also compared the use of the carriers demineralized freeze-dried bone allograft (DFDBA) and coralline hydroxyapatite (CHA) for applying rhBMP-2. After computed tomography of the monkey head, custom meshes were made, loaded with rhBMP-2-incorporated DFDBA or CHA, and implanted in the latissimus dorsi muscle. Meanwhile, contralateral segmental mandibular defects were created, and custom meshes loaded with DFDBA, CHA, or rhBMP-2-incooperated DFDBA and CHA were implanted in situ. Thirteen weeks later, the bone flaps with rhBMP-2-incorporated DFDBA or CHA were transferred to repair segmental mandibular defects. The meshes loaded with DFDBA or CHA alone showed no bone regeneration 13 weeks after implantation in latissimus dorsi muscle. Radiography, angiography and histological analysis were used to evaluate the repair and vascularization of the implant. Segmental mandibular defects were successfully restored with prefabricated bone flaps and rhBMP-2-incorporated CHA in situ, but other segmental mandibular defects remained with rhBMP-2-incorporated DFDBA, DFDBA and CHA in situ. Moreover, mandibles reconstructed with rhBMP-2-incorporated CHA bone flaps revealed more regenerated and homogeneous bone formation than did other reconstructions. The study suggested that the prefabrication technique induced better mandibular reconstruction and bone regeneration in quantity and quality.