The osteoinductive effect of controlled BMP-2 release is location-dependent

Abstract

The main challenge in BMP-2 based application lies in finding strategies that prolong its effective period, as it has a short biological half-life. Several BMP-2 release profiles have shown to enhance bone formation at various application sites. However, it remains to be determined which BMP-2 release profile best augments bone formation and whether this effect is location-dependent. Therefore, the aim of this study was to investigate the effect of BMP-2 release from oligo[(polyethylene glycol) fumarate] bis(2-(methacryloyloxy)ethyl) phosphate (OPF-BP) composites on the osteoinductive efficacy at ectopic versus orthotopic application. By varying the BMP-2 loading method, three different OPF-BP composites were created with varied release profiles. The composites were compared to unloaded OPF-BP as negative control, and to the clinically used Infuse® absorbable collagen sponge (ACS) as positive control. Bone formation was assessed by micro-computed tomography after 9 weeks of subcutaneous implantation and 3, 6, and 9 weeks of orthotopic implantation in rats (n=48). Whereas a BMP-2 burst release of >49% generated significantly more bone compared to sustained release (burst release <30%) at the subcutaneous implantation site, differential release did not affect bone formation at the orthotopic site. Furthermore, all BMP-2 containing OPF-BP composites showed significantly more bone formation compared to ACS in the orthotopic implantation site. In conclusion, this study clearly shows that the osteoinductive effect of different BMP-2 release profiles is location dependent. Additionally, more bone formation in OPF-BP compared to ACS at both application sites emphasizes the role of biomaterials as a scaffold to achieve proper bone tissue formation.