Hydrogels with precisely controlled integrin activation dictate vascular patterning and permeability.

ABSTRACT: 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 ?3/?5?1 integrin binding, we can promote the formation of a space-filling and mature vasculature compared with hydrogel materials that promote ?v?3 integrin binding. In vitro, ?3/?5?1 scaffolds promoted endothelial cells to sprout and branch, forming organized extensive networks that eventually reached and anastomosed with neighbouring branches. In vivo, ?3/?5?1 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 ?v?3 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.

SUBMITTER: Li S 

PROVIDER: S-EPMC5809173 | biostudies-literature | 2017 Sep

REPOSITORIES: biostudies-literature