Rapid In Situ Endothelialization Of A Small Diameter Vascular Graft With Dual Modifications

Thrombosis and hyperplasia are the main causes for the failure of small diameter vascular grafts. One of the most effective approaches to solve these problems is to accelerate the post-implant endothelialization of the grafts.Nitric oxide(NO) could prevent acute thrombosis and hyperplasia through inhibiting the adhesion and activation of platelet as well as the proliferation of smooth muscle cells, and at the same time accelerate the endothelialization of blood-contact materials by promoting the survival and migration of endothelial cells. Endogenous NO donors in human blood decompose and release NO, and this progress could be accelerated by certain catalyst. REDV(Arg-Glu-Asp-Val) is a tetrapeptide derived from extracellular matrix and it selectively promotes the adhesion of endothelial cells without attracting other cells.In this work, a small diameter vascular graft with dual modifications was prepared and its property of rapid endothelialization was evaluated. First, a vascular graft matrix made of polycaprolactone was built by electrospinning and modified via layer-by-layer self-assembly with a NO donor decomposition catalyst organoselenium-immobilized polyethyleneimine(Se PEI) and REDV-grafted hyaluronic acid(HA). Then the properties and biological functions of the prepared materials were characterized and observed.The electrospun materials pre and post the immobilization of REDV were observed by scanning electron microscopy and proved to possess fine fiber morphology and high porosity. REDV immobilization was confirmed by fluorescence microscopy and X-ray photoelectron spectroscopy. Water contact angle measurement revealed that the deposition of Se PEI, HA and REDV improved the hydrophilicity of the matrix. The modified materials showed strong catalyzing capacity in catalytic NO generation experiment. Cytocompatibility of the modified material was satisfactory in fibroblast proliferation experiment. In endothelial cell adhesion experiment, the dual-modified material attracted more cells than control groups. In a co-culture system of endothelial cells and smooth muscle cells, the dual-modified material promoted the adhesion of endothelial cells while suppressed the adhesion and spread of smooth muscle cells, and hence raised the endothelial cell to smooth muscle cell ratio. Finally, the patency and endothelialization of dual modified vascular grafts were evaluated by implantation in rats. The results demonstrated that the modified grafts exhibited rapid endothelialization, showing a high endothelial coverage by endothelial cells with morphology similar to that of natural ones.In summary, the dual modifications proposed in this work could enhance the anti-thrombotic property and biological functions of the vascular graft material, and may provide a new strategy for the construction and modification of small diameter vascular grafts.