Effect of Biomaterial Electrical Charge on Bone Morphogenetic Protein-2-Induced In Vivo Bone Formation

摘要

Biomaterials that act as both protein delivery vehicle and scaffold can improve the safety and efficacy of bone morphogenetic protein-2 (BMP-2) for clinical applications. However, the optimal scaffold characteristics are not known. The osteoinductive and osteoconductive capacity of a fixed electrically charged surface is thus far unexplored. Therefore, in this study, we aim to investigate the effect of different electrical states on BMP-2-induced bone formation in oligo[(polyethylene glycol) fumarate] (OPF) hydrogels. Neutral, negatively, or positively charged scaffolds were fabricated using unmodified OPF (neutral charge), sodium methacrylate crosslinked OPF (negative charge), or [2-(methacryloyloxy) ethyl] trimethylammonium chloride crosslinked OPF (positive charge), respectively. To allow investigation of surface charge for different BMP-2 release rates, three BMP-2 release profiles were generated by protein encapsulation into poly(lactic-co-glycolic acid) microspheres and/or adsorption on the OPF composite. Release of radiolabeled 125I-BMP-2 was analyzed in vitro and in vivo and bone formation was assessed after 9 weeks of subcutaneous implantation in rats. Negatively charged OPF generated significantly more bone formation compared with neutral and positively charged OPF. This effect was seen for all three loading methods and subsequent BMP-2 release profiles. Along with charge modifications, a more sustained release of BMP-2 improved overall bone formation in OPF composites. Overall, this study clearly shows that negative charge enhances bone formation compared with neutral and positive charge in OPF composites.