Abstract
Endogenous molecular and cellular mediators modulate tissue repair and regeneration. We have recently described antibody mediated osseous regeneration (AMOR) as a novel strategy for bioengineering bone in rat calvarial defect. This entails application of anti-BMP-2 antibodies capable of in vivo capturing of endogenous osteogenic BMPs (BMP-2, BMP-4, and BMP-7). The present study sought to investigate the feasibility of AMOR in other animal models. To that end, we examined the efficacy of a panel of anti-BMP-2 monoclonal antibodies (mAbs) and a polyclonal Ab immobilized on absorbable collagen sponge (ACS) to mediate bone regeneration within rabbit calvarial critical size defects. After 6 weeks, de novo bone formation was demonstrated by micro-CT imaging, histology, and histomorphometric analysis. Only certain anti-BMP-2 mAb clones mediated significant in vivo bone regeneration, suggesting that the epitopes with which anti-BMP-2 mAbs react are critical to AMOR. Increased localization of BMP-2 protein and expression of osteocalcin were observed within defects, suggesting accumulation of endogenous BMP-2 and/or increased de novo expression of BMP-2 protein within sites undergoing bone repair by AMOR. Considering the ultimate objective of translation of this therapeutic strategy in humans, preclinical studies will be necessary to demonstrate the feasibility of AMOR in progressively larger animal models.
Highlights
Bioengineering strategies often use modulation of the extracellular environment to regulate cell fate and guide tissue differentiation
The ability of antiBMP-2 antibodies to accelerate in vivo bone regeneration and repair in rabbits was for the first time investigated (Figure 1)
A panel of anti-bone morphogenetic proteins (BMPs)-2 antibodies immobilized on absorbable collagen sponge was implanted within critical-sized calvarial defect in parietal bone of rabbits
Summary
Bioengineering strategies often use modulation of the extracellular environment to regulate cell fate and guide tissue differentiation. Tissue engineering approaches focus on either cells delivery to the tissue of interest, or scaffold-based delivery of signaling molecules to stimulate cell migration, differentiation, and regeneration [1,2,3,4,5] Bone healing requires both resident cells and endogenous bioactive molecules that are locally produced or brought into the circulation to the extracellular matrix (ECM) to activate the cascade of repair [6,7,8,9,10,11,12,13,14,15,16,17].
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