Peptide-Functionalized Polyurethane Coatings Prepared via Grafting-To Strategy to Selectively Promote Endothelialization
Peptide-Functionalized Polyurethane Coatings Prepared via Grafting-To Strategy to Selectively Promote Endothelialization
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DOI：
10.1002/adhm.201700944
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发表时间：
2018-03-07
影响因子：
10
通讯作者：
Yang, Yi Yan
中科院分区：
文献类型：
--
作者：
Ding, Xin;Chin, Willy;Yang, Yi Yan
内皮化是在心血管植入物表面形成内皮细胞层，被认为是预防再狭窄（主要由于增殖的血管平滑肌细胞（SMC）的积聚导致血管再狭窄）和血栓形成的理想方法。在这项研究中，使用聚氨酯（PU）作为涂层平台与肽功能化，以提高植入物的内皮化的可能性进行了探索。PU是通过无金属有机催化聚合合成的，然后通过硫醇-烯反应与EC特异性REDV肽进行化学缀合。同时，PU的游离异氰酸酯基团允许共价接枝REDV官能化的PU（PU/REDV）以硅烷化植入材料（镍钛诺和PET）。PU/REDV涂层的肽接枝密度约为2 nmol cm（-2），选择性地容纳原代人脐静脉内皮细胞（HUVEC），并延缓原代人脐动脉平滑肌细胞（HUASMCs）的扩散。此外，PU/REDV涂层表面3 d内形成一层HUVECs，HUASMCs的增殖受到抑制。HUVECs和HUASMCs的共培养进一步证实了这种选择性。此外，PU/REDV涂层表面的血栓形成较少，如粘附血小板的数量和活性降低所证明的。因此，PU/REDV可用作心血管植入物的涂层，通过促进内皮化来防止再狭窄和血栓形成。
Endothelialization, formation of endothelial cells (ECs) layer on cardiovascular implant surface, is considered an ideal approach to prevent restenosis (renarrowing of blood vessel mainly due to the accumulation of proliferated vascular smooth muscle cells, SMCs) and thrombosis. In this study, the possibility of using polyurethane (PU) as a coating platform for functionalization with peptide to enhance endothelialization on implants is explored. PUs are synthesized through metal-free organocatalytic polymerization followed by chemical conjugation with an EC-specific REDV peptide through thiol-ene reaction. Meanwhile, the free isocyanate groups of PU allow for covalent grafting of REDV-functionalized PU (PU/REDV) to silanize implant materials (nitinol and PET). PU/REDV coating with peptide grafting density of approximate to 2 nmol cm(-2) selectively accommodates primary human umbilical vein ECs (HUVECs) and retards spreading of primary human umbilical artery SMCs (HUASMCs). In addition, a layer of HUVECs is formed within 3 d on PU/REDV-coated surfaces, while proliferation of HUASMCs is inhibited. The selectivity is further confirmed by coculture of HUVECs and HUASMCs. Moreover, the PU/REDV-coated surfaces are less thrombogenic as evidenced by reduced number and activity of adhered platelets. Therefore, PU/REDV can be potentially used as a coating of cardiovascular implants to prevent restenosis and thrombosis by promoting endothelialization.