Department of Chemical Engineering, University of Waterloo, 200 University Avenue West, Waterloo, ON N2L 3G1, Canada.
Department of Biomedical Engineering, Oregon Health & Science University, Portland, OR 97239, USA.
Biomaterials. 2020 Aug;249:120011. doi: 10.1016/j.biomaterials.2020.120011. Epub 2020 Apr 1.
The performance of clinical synthetic small diameter vascular grafts remains disappointing due to the fast occlusion caused by thrombosis and intimal hyperplasia formation. Poly(vinyl alcohol) (PVA) hydrogels have tunable mechanical properties and a low thrombogenic surface, which suggests its potential value as a small diameter vascular graft material. However, PVA does not support cell adhesion and thus requires surface modification to encourage endothelialization. This study presents a modification of PVA with fucoidan. Fucoidan is a sulfated polysaccharide with anticoagulant and antithrombotic properties, which was shown to potentially increase endothelial cell adhesion and proliferation. By mixing fucoidan with PVA and co-crosslinked by sodium trimetaphosphate (STMP), the modification was achieved without sacrificing mechanical properties. Endothelial cell adhesion and monolayer function were significantly enhanced by the fucoidan modification. In vitro and ex-vivo studies showed low platelet adhesion and activation and decreased thrombin generation with fucoidan modified PVA. The modification proved to be compatible with gamma sterilization. In vivo evaluation of fucoidan modified PVA grafts in rabbits exhibited increased patency rate, endothelialization, and reduced intimal hyperplasia formation. The fucoidan modification presented here benefited the development of PVA vascular grafts and can be adapted to other blood contacting surfaces.
由于血栓形成和内膜增生导致快速闭塞，临床合成小直径血管移植物的性能仍然不尽如人意。聚乙烯醇（PVA）水凝胶具有可调节的机械性能和低血栓形成表面，这表明其作为小直径血管移植物材料具有潜在价值。然而，PVA 不支持细胞黏附，因此需要进行表面改性以促进内皮化。本研究提出了一种用褐藻聚糖进行 PVA 的改性。褐藻聚糖是一种具有抗凝和抗血栓形成特性的硫酸多糖，已被证明可以潜在地增加内皮细胞黏附和增殖。通过将褐藻聚糖与 PVA 混合并由三聚磷酸钠（STMP）共同交联，可以在不牺牲机械性能的情况下实现改性。褐藻聚糖改性显著增强了内皮细胞的黏附和单层功能。体外和体内研究表明，褐藻聚糖改性的 PVA 具有低血小板黏附和激活以及降低凝血酶生成的作用。该改性被证明与γ射线灭菌相容。在兔体内评估褐藻聚糖改性的 PVA 移植物的实验中，表现出增加的通畅率、内皮化和减少的内膜增生形成。本文提出的褐藻聚糖改性有利于 PVA 血管移植物的发展，并可以适应其他与血液接触的表面。
