Modified fibrin hydrogels stimulate angiogenesis in vivo: Potential application to increase perfusion of ischemic tissues

The lack of angiogenesis in ischemic tissues is a major health problem and many studies aim to explore strategies to locally increase blood perfusion. Our approach is to use covalently modified fibrin-based hydrogels as a matrix that induces endothelial cell survival in vitro and angiogenesis in vivo. Fibrin hydrogels were covalently modified by L1Ig6, a specific receptor for cell survival integrin αvβ3 that is expressed on angiogenic endothelial cells. In addition, L1Ig6-modified matrices were filled with growth factors VEGF-A₁₆₅ or bFGF. These hydrogels were applied on growing shell-free chicken chorioallantoic membranes (CAMs) and the developing vasculature was found to be increased by ∼50%. Moreover, the increase in αv-integrin levels in the CAMs underlying the hydrogel implants were investigated and found to be increased by ∼40% and ∼100%, respectively, after CAM stimulation with L1Ig6 alone or in combination with growth factors VEGF-A₁₆₅ and bFGF. Therefore, modified fibrin hydrogels provide an interesting way to design an implant that can be introduced at the site of ischemia, and provides a scaffold and release system for growth factors that induce specific tissue responses.