Endothelial Cell-Mediated Gene Delivery for In Situ Accelerated Endothelialization of a Vascular Graft.
Endothelial Cell-Mediated Gene Delivery for In Situ Accelerated Endothelialization of a Vascular Graft.
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内皮细胞介导的基因递送用于血管移植物的原位加速内皮化。
DOI：
10.1021/acsami.1c01869
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发表时间：
2021-03
期刊：
影响因子：
--
通讯作者：
Feng Yakai
中科院分区：
文献类型：
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作者：
Zhou Jiaying;Wang Meiyu;Wei Tingting;Bai Lingchuang;Zhao Jing;Wang Kai;Feng Yakai
小直径人工血管作为治疗血管疾病的急需器械，其高促凝性限制了其在临床上的应用。快速内皮化是构建抗血栓形成血管移植物内表面的一种有前途的方法。小直径血管移植物原位内皮细胞的粘附、迁移和增殖是快速内皮化的主要瓶颈。在此，我们创新性地制备了一种基于静电纺丝聚乳酸-己内酯共聚物和明胶的智能基因递送小口径血管移植物，用于快速原位内皮化。用EC粘附肽Arg-Glu-Asp-Val（REDV）和响应性基因传递系统共修饰移植物表面。REDV能选择性地将内皮细胞粘附在移植物表面，内皮细胞过表达的基质金属蛋白酶能有效地切割连接肽GPQGIWGQ-C，基因复合物智能地酶促释放，从而有效地转染内皮细胞。重要的是，由于生物素-抗生物素蛋白通过GPQGIWGQ-C肽接头与血管移植物内表面上的hepatocyte基因复合物相互作用，这种酶促释放基因表面已被证明是安全的，并且在血流中暂时稳定。它具有特异性地将EC粘附于表面并以高转染效率巧妙地将其转染的优点。共修饰的表面已被证明在体内加速管腔内皮化，这可能归因于REDV和有效基因转染的协同效应。特别是，智能和响应性基因释放表面将开辟一条新的途径，以提高血液接触装置的内皮化。
As an urgently needed device for vascular diseases, the small-diameter vascular graft is limited by high thrombogenicity in clinical applications. Rapid endothelialization is a promising approach to construct an antithrombogenic inner surface of the vascular graft. The main bottleneck for rapid endothelialization is the adhesion, migration, and proliferation of endothelial cells (ECs) in situ of the small-diameter vascular graft. Herein, we innovatively fabricated an intelligent gene delivery small-caliber vascular graft based on electrospun poly(lactic acid-co-caprolactone) and gelatin for rapid in situ endothelialization. The graft surface was co-modified with EC adhesive peptide of Arg-Glu-Asp-Val (REDV) and responsive gene delivery system. REDV can selectively adhere ECs onto the graft surface; subsequently, the overexpressed matrix metalloproteinase by ECs can effectively cleave the linker peptide GPQGIWGQ-C; and finally, the gene complexes were intelligently and enzymatically released from the graft surface, and thereby, the gene can efficiently transfect ECs. Importantly, this enzymatically releasing gene surface has been proven to be safe and temporarily stable in blood flow owing to the biotin-avidin interaction to immobilize gene complexes on the inner surface of vascular grafts through the GPQGIWGQ-C peptide linker. It has the advantage of specifically adhering the ECs to the surface and smartly transfecting them with high transfection efficiency. The co-modified surface has been demonstrated to accelerate the luminal endothelialization in vivo, which might be attributed to the synergistic effect of REDV and effective gene transfection. Particularly, the intelligent and responsive gene release surface will open a new avenue to enhance the endothelialization of blood-contacting devices.