Abstract
Biomaterials are widely used as scaffolds for tissue engineering. We have developed a strategy for bone tissue engineering that entails application of immobilized anti-BMP-2 monoclonal antibodies (mAbs) to capture endogenous BMPs in vivo and promote antibody-mediated osseous regeneration (AMOR). The purpose of the current study was to compare the efficacy of immobilization of a specific murine anti-BMP-2 mAb on three different types of biomaterials and to evaluate their suitability as scaffolds for AMOR. Anti-BMP-2 mAb or isotype control mAb was immobilized on titanium (Ti) microbeads, alginate hydrogel, and ACS. The treated biomaterials were surgically implanted in rat critical-sized calvarial defects. After 8 weeks, de novo bone formation was assessed using micro-CT and histomorphometric analyses. Results showed de novo bone regeneration with all three scaffolds with immobilized anti-BMP-2 mAb, but not isotype control mAb. Ti microbeads showed the highest volume of bone regeneration, followed by ACS. Alginate showed the lowest volume of bone. Localization of BMP-2, -4, and -7 antigens was detected on all 3 scaffolds with immobilized anti-BMP-2 mAb implanted in calvarial defects. Altogether, these data suggested a potential mechanism for bone regeneration through entrapment of endogenous BMP-2, -4, and -7 proteins leading to bone formation using different types of scaffolds via AMOR.
Highlights
The goal of bone tissue engineering is the regeneration of a construct that matches the physical and biological properties of the natural bone tissue and reestablishes function [1]
Anti-bone morphogenetic proteins (BMPs)-2 and isotype control monoclonal antibodies (mAbs) were diluted with plain phosphate-buffered saline (PBS) at 25 μg/mL and immobilized on each of the scaffolds according to the protocol previously reported by Freire et al, 2011
We report here on the application of immobilized murine anti-BMP-2 mAb to three different types of biomaterial to investigate their ability to mediate antibody-mediated osseous regeneration (AMOR)
Summary
The goal of bone tissue engineering is the regeneration of a construct that matches the physical and biological properties of the natural bone tissue and reestablishes function [1]. Osteoconductive graft materials such as allografts, xenografts, and alloplastic material have limited ability to repair large defects, due to their inherent inability to initiate bone formation. For these reasons, alternative bone regeneration treatment modalities are desirable. Bone tissue engineering aims to combine biomaterial scaffolds, cells, and molecular signals that can mediate tissue regeneration, matching the physical and biological properties of the natural tissue [3,4,5]
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