Development of bioactive polyurethaneureas to support endothelialization

Abstract

Vascular diseases are responsible for the majority of deaths in the United States. Synthetic materials have been developed for blood vessel substitutes but not suitable for small diameter vascular applications such as coronary artery bypass grafting (CABG). Polyurethaneureas (PUU) have been widely used for biomedical applications due to their excellent mechanical properties and relatively good biocompatibility. However, like other synthetic materials, they are generally thrombogenic on exposure to blood. Endothelialization of synthetic grafts is a good strategy to improve graft patency. However, the graft patency is dependent on retention of endothelial cells on exposure to physiological shear stress. In this study, we developed bioactive polyurethaneureas to support endothelialization. First, we have demonstrated that endothelial cell behaviors could be altered by the surface YIGSR peptide concentrations. Bioactive polyurethanureas (PUUYIGSR) have been developed by incorporating YIGSR peptide sequences into polymer main chain, and improved endothelialization has been observed on the surface. In addition, PEG- and YIGSR-modified polyurethaneureas (PUUYIGSR-PEG) have been developed, and enhanced endothelialization and improved thromboresistance have been obtained simultaneously. Our bulk modification strategy allowed us to fabricate microporous scaffolds without interfering bioactivity of incorporated peptide sequences. Microporous scaffolds have been also used as a carrier of vascular endothelial growth factor (VEGF). The synergistic effects of peptide sequences, microporous structure, and incorporated VEGF on endothelialization have been observed. Additionally, nitric oxide (NO) releasing polyurethanes (PUBD-NO) have been developed by incorporating NO donor into the polymer main chain. NO was successfully released from the PUBD-NO in controlled manner and reduced platelet adhesion and smooth muscle cell proliferation but improved endothelialization proliferation.