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VEGF-Functionalized Polyelectrolyte Multilayers as Proangiogenic Prosthetic Coatings

机译:血管内皮生长因子功能的聚电解质多层作为促血管生成的修复涂层。

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摘要

Stimulation of transprosthetic vascularization represents an interesting strategy in implantology to allow rapid tissue integration and finally to avoid prosthetic rejection. To achieve this goal, we modified the surface of porous titanium implants with polyelectrolyte multilayer (PEM) films functionalized with vascular endothelial growth factor (VEGF). Among the two PEM systems investigated, poly(L-lysine)/poly(L-glutamic acid) (PLL/PGA) and poly(allylamine hydrochloride)/poly(sodium 4-styrenesulfonate) (PAH/PSS), the (PAH/PSS)_4 architecture was selected to functionalize porous titanium, both for its high efficiency to adsorb VEGF and for its biocompatibility toward endothelial cells. In an original way, we unambiguously demonstrated that VEGF adsorbed on (PAH/PSS)_4 maintains its bioactivity in vitro and stimulates endothelial cells proliferation. This effect was correlated with specific activation of intracellular signaling pathways induced by successive phosphorylation of the endothelial VEGF receptor VEGFR2 and mitogen-activated protein kinases (MAPK) ERK1/2. By clearly demonstrating the proangiogenic activity of the VEGF-PEM coating in vitro, the present study constitutes a first step toward in vivo application.
机译:跨假体血管化的刺激代表了一种有趣的策略,可以快速整合组织并最终避免假体排斥。为了实现此目标,我们用具有血管内皮生长因子(VEGF)功能的聚电解质多层(PEM)膜修饰了多孔钛植入物的表面。在研究的两个PEM系统中,聚(L-赖氨酸)/聚(L-谷氨酸)(PLL / PGA)和聚(盐酸烯丙胺)/聚(4-苯乙烯磺酸钠)(PAH / PSS),(PAH /选择PSS_4体系结构以功能化多孔钛,这是因为它能高效吸附VEGF,并且具有与内皮细胞的生物相容性。以一种原始的方式,我们明确地证明,吸附在(PAH / PSS)_4上的VEGF在体外可保持其生物活性并刺激内皮细胞增殖。这种作用与内皮细胞VEGF受体VEGFR2和有丝分裂原激活的蛋白激酶(MAPK)ERK1 / 2的连续磷酸化诱导的细胞内信号通路的特异性激活有关。通过清楚地证明VEGF-PEM涂层在体外的促血管生成活性,本研究构成了体内应用的第一步。

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