Shan Yaping, Jia Bing, Ye Ming, Shen Hua, Chen Weicheng, Zhang Huifeng
Department of Cardiovascular Center, Children's Hospital of Fudan University, Shanghai, China.
Artif Organs. 2018 Aug;42(8):824-834. doi: 10.1111/aor.13131. Epub 2018 Apr 18.
Expanded polytetrafluoroethylene (ePTFE) prosthetic valves have been widely used in clinical applications in Asian countries. However, these valves still have limits with regard to thrombosis, neointimal hyperplasia, restenosis, and valvar vegetation. The achievement of in situ endothelialization on implant materials is a promising way to overcome those limits. Here, heparin/collagen multilayers were fabricated on ePTFE films via a layer-by-layer (LBL) self-assembly technique, and then, the endothelial cell (EC) adhesive peptide sequence Arg-Glu-Asp-Val (REDV) was immobilized on the multilayers. After modification with the heparin/collagen multilayers with or without REDV peptide, less platelet activation and aggregation were observed, the blood coagulation time was increased, and the hemolysis rate was decreased compared to that on pristine ePTFE films. The REDV-functionalized ePTFE films positively impacted early EC adhesion, later cell proliferation and cell activity. The EC barrier was confirmed to be successfully achieved on the functionalized ePTFE film surface in vitro. The successful assembly of the REDV-functionalized heparin/collagen multilayer on ePTFE films improved the blood compatibility, anticoagulant properties, and cell compatibility of the films in vitro, and thus, represents a candidate approach for applications requiring quick in situ endothelialization in vivo.
膨体聚四氟乙烯(ePTFE)人工瓣膜已在亚洲国家的临床应用中广泛使用。然而,这些瓣膜在血栓形成、新生内膜增生、再狭窄和瓣膜赘生物方面仍存在局限性。在植入材料上实现原位内皮化是克服这些局限性的一种有前景的方法。在此,通过层层(LBL)自组装技术在ePTFE膜上制备了肝素/胶原蛋白多层膜,然后将内皮细胞(EC)黏附肽序列精氨酸-谷氨酸-天冬氨酸-缬氨酸(REDV)固定在多层膜上。在用含或不含REDV肽的肝素/胶原蛋白多层膜修饰后,与原始ePTFE膜相比,观察到血小板活化和聚集减少,凝血时间延长,溶血率降低。REDV功能化的ePTFE膜对早期EC黏附、后期细胞增殖和细胞活性有积极影响。在体外证实功能化的ePTFE膜表面成功实现了EC屏障。REDV功能化的肝素/胶原蛋白多层膜在ePTFE膜上的成功组装改善了膜在体外的血液相容性、抗凝性能和细胞相容性,因此,代表了一种在体内需要快速原位内皮化的应用的候选方法。