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

Abstract

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-2induced 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 125 I-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.

The bioelectrical properties of bone tissue

“…The major proteoglycans in bone tissue include biglycan, lumican, and osteoadherin. The abundance of negative charges present on glycosaminoglycan chains enable sequestration of Ca 2+ ions and various bioactive growth factors, as well as contributing to the overall negative charge of bone tissue, which is the reason why bone regeneration and healing is promoted when the natural electrical microenvironment at the defect site is recapitulated by negatively charged scaffold implants 64,65 …”

Osteo-inductive effect of piezoelectric stimulation from the poly(l-lactic acid) scaffolds

“…The ability of the piezoelectric charge of our films to induce cell migration was then studied using a transwell setup [ 28 , 29 ]. In this experiment, the cells were seeded on top of the transwell membrane while the PLLA scaffolds were placed in the receiving well ( Fig 2 .C.i ).…”

Hydrogel‐Based Growth Factor Delivery Platforms: Strategies and Recent Advances

“…[ 130 ] Among all BMPs, BMP‐2 and rhBMP‐2 are the most widely applied, and their incorporation into hydrogel systems for bone regeneration has been the focus of research in recent years. [ 131–154 ] Some basic studies investigating the effects of different variables of the delivery systems (e.g., BMP‐2 administration dose, [ 148,155–157 ] implantation site, [ 158 ] physical properties, [ 159–161 ] and crosslinking chemistry of the hydrogel matrices [ 132,162 ] ) on the therapeutic efficacy have also been reported. These studies may serve as references for improving BMP‐2 delivery in hydrogel systems for bone regeneration.…”