Hydrogels with precisely controlled integrin activation dictate vascular patterning and permeability

Journal Article (Journal Article)

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.

Full Text

Duke Authors

Cited Authors

  • Li, S; Nih, LR; Bachman, H; Fei, P; Li, Y; Nam, E; Dimatteo, R; Carmichael, ST; Barker, TH; Segura, T

Published Date

  • September 1, 2017

Published In

Volume / Issue

  • 16 / 9

Start / End Page

  • 953 - 961

PubMed ID

  • 28783156

Pubmed Central ID

  • PMC5809173

Electronic International Standard Serial Number (EISSN)

  • 1476-4660

International Standard Serial Number (ISSN)

  • 1476-1122

Digital Object Identifier (DOI)

  • 10.1038/nmat4954

Citation Source

  • Scopus