Abstract
Antibody-mediated osseous regeneration (AMOR) has been introduced by our research group as a tissue engineering approach to capture of endogenous growth factors through the application of specific monoclonal antibodies (mAbs) immobilized on a scaffold. Specifically, anti-Bone Morphogenetic Protein- (BMP-) 2 mAbs have been demonstrated to be efficacious in mediating bone repair in a number of bone defects. The present study sought to investigate the application of AMOR for repair of mandibular continuity defect in nonhuman primates. Critical-sized mandibular continuity defects were created in Macaca fascicularis locally implanted with absorbable collagen sponges (ACS) functionalized with chimeric anti-BMP-2 mAb or isotype control mAb. 2D and 3D analysis of cone beam computed tomography (CBCT) imaging demonstrated increased bone density and volume observed within mandibular continuity defects implanted with collagen scaffolds functionalized with anti-BMP-2 mAb, compared with isotype-matched control mAb. Both CBCT imaging and histologic examination demonstrated de novo bone formation that was in direct apposition to the margins of the resected bone. It is hypothesized that bone injury may be necessary for AMOR. This is evidenced by de novo bone formation adjacent to resected bone margins, which may be the source of endogenous BMPs captured by anti-BMP-2 mAb, in turn mediating bone repair.
Highlights
Loss of mandibular bone due to congenital anomalies, trauma, infection, or tumor resection surgeries is a challenging clinical problem for reconstruction
To investigate the ability of the monoclonal antibodies (mAbs) to repair large critical-size craniofacial defects, 15 mm continuity defects were surgically created in the posterior mandible and the two segments were rigidly fixated with titanium reconstruction plates (Figure 1)
The 15 mm defect was filled with collagen scaffold functionalized with chimeric anti-Bone Morphogenetic Protein- (BMP-)2 mAb or isotypematched control mAb
Summary
Loss of mandibular bone due to congenital anomalies, trauma, infection, or tumor resection surgeries is a challenging clinical problem for reconstruction. It is well known that exogenous administration of recombinant human (rh) BMP-2 can initiate a healing cascade that mediates bone regeneration through the TGF-β/BMP signaling pathway [8] Owing to their substantial osteogenic properties, the US Food and Drug Administration (FDA) had approved rhBMP-2 and rhBMP-7 for clinical use [9, 10]. Application of exogenous growth factors has a number of drawbacks, including serious adverse effects which are occasionally fatal; recombinant growth factors have reduced biological activity, requiring high concentrations to be used in vivo and are associated with high costs [5, 11,12,13] These shortcomings have driven the quest for the development of alternative strategies. In the present study, we investigated the ability of chimeric anti-BMP-2 mAb to mediate repair of a critical-size mandibular continuity defect in a nonhuman primate model
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