A polyurethane-based hydrophilic elastomer with multi-biological functions for small-diameter vascular grafts

Abstract

Thrombosis and intimal hyperplasia (IH) are two major problems faced by the small-diameter vascular grafts. Mimicking the native endothelium and physiological elasticity of blood vessels is considered an ideal strategy. Polyurethane (PU) is suitable for vascular grafts in mechanics because of its molecular designability and elasticity; however, it generally lacks the endothelium-like biofunctions and hydrophilicity. To solve this contradiction, a hydrophilic PU elastomer is developed by crosslinking the hydrophobic hard-segment chains containing diselenide with diaminopyrimidine-capped polyethylene glycol (PEG). In this network, the hydrophobic aggregation occurs underwater due to the uninterrupted hard-segment chains, leading to a significant self-enhancement in mechanics, which can be tailored to the elasticity similar to natural vessels by adjusting the crosslinking density. A series of in vitro studies confirm that the hydrophilicity of PEG and biological activities of aminopyrimidine and diselenide give the PU multi-biological functions similar to the native endothelium, including stable catalytic release of nitric oxide (NO) in the physiological level; anti-adhesion and anti-activation of platelets; inhibition of migration, adhesion, and proliferation of smooth muscle cells (SMCs); and antibacterial effect. In vivo studies further prove the good histocompatibility with both significant reduction in immune response and calcium deposition. STATEMENT OF SIGNIFICANCE: Constructing small-diameter vascular grafts similar to the natural vessels is considered an ideal method to solve the restenosis caused by thrombosis and intimal hyperplasia (IH). Because of the long-term stability, bulk modification is more suitable for implanted materials, however, how to achieve the biofunctions, hydrophilicity, and elasticity simultaneously is still a big challenge. In this work, a kind of polyurethane-based elastomer has been designed and prepared by crosslinking the functional long hard-segment chains with PEG soft segments. The underwater elasticity based on hydration-induced stiffening and the multi-biological functions similar to the native endothelium are compatible with natural vessels. Both in vitro and in vivo experiments demonstrate the potential of this PU as small-diameter vascular grafts.

Keywords: Biological functions; Diselenide; Hydration-induced stiffening; Hydrophilic polyurethane; Small-diameter vascular grafts.