Modulating smooth muscle cell response by the release of TGF beta 2 from tubular scaffolds for vascular tissue engineering

摘要

Tissue engineering has gained considerable attention in the development of small diameter tissue engineered vascular grafts (TEVGs) for treating coronary heart disease. A properly designed acellular and biodegradable TEVG must encourage the infiltration and growth of vascular smooth muscle cells (SMCs). Our group has previously shown that increasing levels of TGF beta 2 can differentially modulate SMC migration and proliferation. In this study, tubular electrospun scaffolds loaded with TGF beta 2 were fabricated using various ratios of gelatin/polycaprolactone (PCL), resulting in scaffolds with porous nano-woven architecture suitable for tissue ingrowth. Scaffold morphology, degradation rate, TGF beta 2 release kinetics, and bioactivity were assessed. TGF beta 2 was successfully integrated into the electrospun biomaterial that resulted in a differential release profile depending on the gelatin/PCL ratio over the course of 42 days. Higher TGF beta 2 elution was obtained in scaffolds with higher gelatin content, which may be related to the biodegradation of gelatin in culture media. The biological activity of the released TGF beta 2 was evaluated by its ability to affect SMC proliferation as a function of its concentration. SMCs seeded on TGF beta 2-loaded scaffolds also showed higher densities and infiltration after 5 days in culture as compared to scaffolds without TGF beta 2. Our results demonstrate that the ratio of synthetic and natural polymers in electrospun blends can be used to tune the release of TGF beta 2. This method can be used to intelligently modulate the SMC response in gelatin/PCL scaffolds making the TGF beta 2-loaded conduits attractive for cardiovascular tissue engineering applications.