Integrin binding to bioengineered hydrogel scaffolds is essential for tissue regrowth and regeneration, yet not all integrin binding can lead to tissue repair. Here, we show that through engineering hydrogel materials to promote α3/α5β1 integrin binding, we can promote the formation of a space-filling and mature vasculature compared with hydrogel materials that promote αvβ3 integrin binding. In vitro, α3/α5β1 scaffolds promoted endothelial cells to sprout and branch, forming organized extensive networks that eventually reached and anastomosed with neighbouring branches. In vivo, α3/α5β1 scaffolds delivering vascular endothelial growth factor (VEGF) promoted non-tortuous blood vessel formation and non-leaky blood vessels by 10 days post-stroke. In contrast, materials that promote αvβ3 integrin binding promoted endothelial sprout clumping in vitro and leaky vessels in vivo. This work shows that precisely controlled integrin activation from a biomaterial can be harnessed to direct therapeutic vessel regeneration and reduce VEGF-induced vascular permeability in vivo.

中文翻译：

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具有精确控制的整联蛋白活化作用的水凝胶决定了血管的形成方式和渗透性

整联蛋白与生物工程水凝胶支架的结合对于组织再生和再生至关重要，但并非所有整联蛋白结合都能导致组织修复。在这里，我们表明，通过工程的水凝胶材料，以促进α 3 / α 5β1整联蛋白结合，我们可以与促进水凝胶材料相比，促进一个空间填充的形成和成熟脉管系统α Vβ3整联蛋白结合。在体外，α 3 / α 5β1支架促进内皮细胞发芽和分支，形成有组织的广泛的网络，最终达到与邻近的分支吻合。在体内，α 3 / α卒中后10天，传递血管内皮生长因子（VEGF）的5β1支架促进了非曲折血管的形成和非渗漏的血管。相反，材料促进α Vβ3整联蛋白结合促进内皮芽结块体外中和渗漏血管体内。这项工作表明，可以利用从生物材料中精确控制的整联蛋白激活来指导治疗性血管再生并降低VEGF诱导的体内血管通透性。