Small diameter expanded polytetrafluoroethylene vascular graft with differentiated inner and outer biomacromolecules for collaborative endothelialization, anti-thrombogenicity and anti-inflammation

Without differentiated inner and outer biological function, expanded polytetrafluoroethylene (ePTFE) small-diameter (<6 mm) artificial blood vessels would fail in vivo due to foreign body rejection, thrombosis, and hyperplasia. In order to synergistically promote endothelialization, anti-thrombogenicity, and anti-inflammatory function, we modified the inner and outer surface of ePTFE, respectively, by grafting functional biomolecules, such as heparin and epigallocatechin gallate (EGCG), into the inner surface and polyethyleneimine and rapamycin into the outer surface via layer-by-layer self-assembly. Fourier-transform infrared spectroscopy showed the successful incorporation of EGCG, heparin, and rapamycin. The collaborative release profile of heparin and rapamycin lasted for 42 days, respectively. The inner surface promoted human umbilical vein endothelial cells (HUVECs) adhesion and growth and that the outer surface inhibited smooth muscle cells growth and proliferation. The modified ePTFE effectively regulated the differentiation behavior of RAW264.7, inhibited the expression of proinflammatory mediator TNF-α, and up-regulated the expression of anti-inflammatory genes Arg1 and Tgfb-1. The ex vivo circulation results indicated that the occlusions and total thrombus weight of modified ePTFE was much lower than that of the thrombus formed on the ePTFE, presenting good anti-thrombogenic properties. Hence, the straightforward yet efficient synergistic surface functionalization approach presented a potential resolution for the prospective clinical application of small-diameter ePTFE blood vessel grafts.