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基质结合型血管内皮生长因子的软聚电解质多层膜对内皮细胞单层的血管内皮功能的改善。

Improved Endothelial Function of Endothelial Cell Monolayer on the Soft Polyelectrolyte Multilayer Film with Matrix-Bound Vascular Endothelial Growth Factor.

机构信息

MOE Key Laboratory of Macromolecule Synthesis and Functionalization, Department of Polymer Science and Engineering, Zhejiang University , Hangzhou 310027, China.

出版信息

ACS Appl Mater Interfaces. 2016 Jun 15;8(23):14357-66. doi: 10.1021/acsami.6b01870. Epub 2016 Jun 6.

Abstract

Endothelialization on the vascular implants is of great importance for prevention of undesired postimplantation symptoms. However, endothelial dysfunction of regenerated endothelial cell (EC) monolayer has been frequently observed, leading to severe complications, such as neointimal hyperplasia, late thrombosis, and neoatherosclerosis. It has significantly impeded long-term success of the therapy. So far, very little attention has been paid on endothelial function of EC monolayer. Bioinspired by the microenvironment of the endothelium in a blood vessel, this study described a soft polyelectrolyte multilayer film (PEM) through layer-by-layer assembly of poly(l-lysine) (PLL) and hyaluronan (HA). The (PLL/HA) PEM was chemically cross-linked and further incorporated with vascular endothelial growth factor. It demonstrated that this approach could promote EC adhesion and proliferation, further inducing formation of EC monolayer. Further, improved endothelial function of the EC monolayer was achieved as shown with the tighter integrity, higher production of nitric oxide, and expression level of endothelial function related genes, compared to EC monolayers on traditional substrates with high stiffness (e.g., glass, tissue culture polystyrene, and stainless steel). Our findings highlighted the influence of substrate stiffness on endothelial function of EC monolayer, giving a new strategy in the surface design of vascular implants.

摘要

血管植入物的内皮化对于预防植入后不良症状非常重要。然而,再生内皮细胞(EC)单层的内皮功能障碍经常被观察到,导致严重的并发症,如新生内膜增生、晚期血栓形成和新动脉粥样硬化。这极大地阻碍了治疗的长期成功。到目前为止,很少有人关注 EC 单层的内皮功能。受血管内皮微环境的启发,本研究通过层层组装聚(L-赖氨酸)(PLL)和透明质酸(HA)来描述软聚电解质多层膜(PEM)。(PLL/HA)PEM 经过化学交联,并进一步掺入血管内皮生长因子。结果表明,与传统高刚性基底(如玻璃、组织培养聚苯乙烯和不锈钢)相比,这种方法可以促进 EC 的黏附和增殖,进一步诱导 EC 单层的形成。进一步的研究表明,与传统高刚性基底相比,EC 单层的内皮功能得到了改善,表现为完整性更紧密、一氧化氮的产生量更高、与内皮功能相关基因的表达水平更高。我们的研究结果强调了基底刚度对 EC 单层内皮功能的影响,为血管植入物的表面设计提供了新的策略。

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