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具有内皮细胞选择性的贻贝启发式三嵌段功能蛋白涂层用于内皮化。

Mussel-inspired triblock functional protein coating with endothelial cell selectivity for endothelialization.

作者信息

Zheng Weiwei, Liu Min, Qi Haishan, Wen Chiyu, Zhang Chen, Mi Jiali, Zhou Xiao, Zhang Lei, Fan Daidi

机构信息

Department of Biochemical Engineering, School of Chemical Engineering and Technology, Tianjin University, Tianjin 300072, PR China; Key Laboratory of Systems Bioengineering (Ministry of Education), PR China; Collaborative Innovation Center of Chemical Science and Engineering (Tianjin): School of Chemical Engineering and Technology, Frontier Science Center for Synthetic Biology and Key Laboratory of Systems Bioengineering (MOE), Tianjin University, Tianjin 300072, PR China.

Department of Biochemical Engineering, School of Chemical Engineering and Technology, Tianjin University, Tianjin 300072, PR China; Key Laboratory of Systems Bioengineering (Ministry of Education), PR China; Collaborative Innovation Center of Chemical Science and Engineering (Tianjin): School of Chemical Engineering and Technology, Frontier Science Center for Synthetic Biology and Key Laboratory of Systems Bioengineering (MOE), Tianjin University, Tianjin 300072, PR China.

出版信息

J Colloid Interface Sci. 2020 Sep 15;576:68-78. doi: 10.1016/j.jcis.2020.04.116. Epub 2020 May 4.

Abstract

Surface modification of biomaterials for rapid endothelialization is a promising approach for improving long-term patency of artificial vascular grafts (e.g. polytetrafluoroethylene, PTFE) with small-caliber vascular (<6 mm). However, surfaces modified with traditional strategies using hydrophilic polymers may be excessively hydrophilic to limit endothelial cell adhesion and formation of confluent endothelial lining. In this study, a triblock functional protein cofp-MZY/R was fabricated with cell selectivity of endothelial cells (ECs) over smooth muscle cells (SMCs) for endothelialization on PTFE. This rational designed triblock protein consisted of mussel-inspired domain, zwitterionic polypeptide and bioactive peptides (YIGSR and REDV), in which Dopa was efficiently obtained with residue-specificity in vivo. The triblock protein could facilely form coating on PTFE surface and the resulting protein coating exhibited moderate nonspecific resistance of protein and platelets. Together with bioactive peptides tail, it was available for cell attachment on surfaces. As protein material, this coating displayed remarkable biocompatibility through cytotoxicity and hemolysis measurements. Moreover, cellular behavior assay demonstrated that triblock protein coating could selectively promote adhesion, proliferation and migration of ECs rather than SMCs. This mussel-inspired triblock functional protein coating indicated a promising strategy for endothelialization of artificial vascular grafts.

摘要

对生物材料进行表面改性以实现快速内皮化,是改善小口径血管(<6mm)人工血管移植物(如聚四氟乙烯,PTFE)长期通畅性的一种有前景的方法。然而,使用亲水性聚合物的传统策略修饰的表面可能过于亲水,从而限制内皮细胞的粘附和融合内皮衬里的形成。在本研究中,制备了一种三嵌段功能蛋白cofp-MZY/R,其对内皮细胞(ECs)具有相对于平滑肌细胞(SMCs)的细胞选择性,用于在PTFE上实现内皮化。这种合理设计的三嵌段蛋白由贻贝启发结构域、两性离子多肽和生物活性肽(YIGSR和REDV)组成,其中多巴在体内以残基特异性有效获得。该三嵌段蛋白能够在PTFE表面轻松形成涂层,所得蛋白涂层对蛋白质和血小板表现出适度的非特异性抗性。连同生物活性肽尾,它可用于细胞在表面的附着。作为蛋白质材料,通过细胞毒性和溶血测量,该涂层显示出显著的生物相容性。此外,细胞行为分析表明,三嵌段蛋白涂层可以选择性地促进ECs而非SMCs的粘附、增殖和迁移。这种贻贝启发的三嵌段功能蛋白涂层为人工血管移植物的内皮化指明了一种有前景的策略。

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