Tetramethylpyrazine-derived polyurethane for improved hemocompatibility and rapid endothelialization.

Abstract

Thrombosis and intimal hyperplasia (IH) are the main factors affecting the long-term patency of small-diameter vascular grafts (SDVGs). Fabricating a confluent endothelial cell (EC) layer on surfaces with physiological elasticity to mimic vascular endothelium should be an effective strategy to prevent restenosis that is caused by thrombosis and IH. However, the vascular endothelialization process is time-consuming and always constrained by hemocompatibility of the vascular grafts, since excellent hemocompatibility could guarantee a sufficient time window for the endothelialization process. Tetramethylpyrazine (TMP)-derived polyurethane (PU) with improved hemocompatibility and accelerated endothelialization ability is synthesized by incorporating TMP moieties into PU backbones. Results show that TMP-contained PU films possess improved hemocompatibility by down-regulating platelet adhesion/activation and increasing the clotting time. Furthermore, the in vitro human umbilical vein endothelial cell (HUVEC) test demonstrates that the introduction of TMP can significantly promote HUVEC adhesion and proliferation, and thus accelerate luminal endothelialization of vascular grafts. Moreover, the TMP-containing PU films exhibit excellent biocompatibility especially for HUVECs, and their excellent, adjustable elasticity (1123%) guarantees compliance accommodation of vascular grafts. This newly synthesized TMP-containing material with multiple biological functions is expected to make up for the shortcomings of available SDVGs in clinical practice, and has significant potential in improving the long-term patency of SDVGs.