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

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 I-125-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. Impact Statement Biomaterials can play a dual role in bone regeneration: they enable local sustained delivery of growth factors, such as bone morphogenetic protein-2 (BMP-2), while they provide structural support as scaffold. By better imitating the properties of native bone tissue, scaffolds may be both osteoconductive and osteoinductive. The latter can be achieved by modifying the electrical charge of the surface. The present work uses tunable oligo[(polyethylene glycol) fumarate] hydrogel and demonstrates that negative charge enhances BMP-2-induced bone formation compared with neutral or positive charge. Altogether, this indicates that tissue-specific surface charge modifications of biomaterials hold great promise in the field of tissue regeneration.