A novel osteotropic biomaterial OG-PLG: Synthesis and in vitro release

Statins (e.g., simvastatin) have shown to induce expression of the bone morphogenic protein-2 gene in bone cells, but they are not used clinically because of a lack of a suitable delivery device. The overall objective is to develop optimized statin delivery devices for bone regeneration. The specific objective was to determine the effect of grafting statins to biodegradable poly[lactide-co-glycolide] (PLG) on release kinetics. Simvastatin was grafted to PLG (OG-PLG) and characterized using contact-angle measurements, attenuated total reflectance-Fourier transform infrared, and ultraviolet-visible spectroscopy to determine success of the synthesis. An ultraviolet-visible assay for measuring release of statins and degraded OG-PLG in media was also developed. In vitro release studies using films and scaffolds made with PLG, PLG blended with simvastatin (PLG + Sim), and OG-PLG (simvastatin grafted to PLG) blended into PLG at different concentrations showed that release rate of OG-PLG from films was significantly greater than that of PLG + Sim. However, release rate from scaffolds showed PLG + Sim to be significantly higher than that of OG-PLG. The diffusion-controlled release kinetics of simvastatin from PLG + Sim seems to be more heavily affected by device morphology, whereas the degradation-controlled release kinetics seem to be less affected. In short, release kinetics can be modulated by grafting statins to PLG.