Incorporation of photo-carbon monoxide releasing materials into electrospun scaffolds for vascular tissue engineering

Hyper-proliferation of smooth muscle cells (SMCs) and a reduction in endothelial cell function are reasons for poor patency rates of current tissue engineered small-diameter vascular grafts. The controlled delivery of carbon monoxide (CO), a gasotransmitter involved in cell signaling, could improve vascular cell function in these grafts. Current CO releasing molecules (CORMs) can improve endothelialization of injured vessels with appropriate doses, but they still have limitations. The goal of this project was to generate a novel tissue engineered scaffold that includes a non-toxic and photoactivatable CORM. This is the first use of a CORM for tissue engineering. The results demonstrated that CORM-loaded, electrospun poly(epsilon-caprolactone) scaffolds can be photoactivated and release CO. The fluorescence that develops after CO release can be used to non-destructively track the extent of reaction. Further, activation can occur when both dry and incubated in cell culture conditions. However, incubation in serum protein-containing media decreases the time frame for activation, demonstrating the importance of testing the release profile in culture conditions. Rat SMCs were able to attach, grow, and express contractile SMC markers on activated CORM-loaded meshes and controls. Overall, these findings demonstrate that CORM-loaded electrospun scaffolds provide a promising delivery system for vascular tissue engineering.