Deciphering the relative roles of matrix metalloproteinase- and plasmin-mediated matrix degradation during capillary morphogenesis using engineered hydrogels.

ABSTRACT: Extracellular matrix (ECM) remodeling is essential for the process of capillary morphogenesis. Here we employed synthetic poly(ethylene glycol) (PEG) hydrogels engineered with proteolytic specificity to either matrix metalloproteinases (MMPs), plasmin, or both to investigate the relative contributions of MMP- and plasmin-mediated ECM remodeling to vessel formation in a 3D-model of capillary self-assembly analogous to vasculogenesis. We first demonstrated a role for both MMP- and plasmin-mediated mechanisms of ECM remodeling in an endothelial-fibroblast co-culture model of vasculogenesis in fibrin hydrogels using inhibitors of MMPs and plasmin. When this co-culture model was employed in engineered PEG hydrogels with selective protease sensitivity, we observed robust capillary morphogenesis

SUBMITTER: Beamish JA 

PROVIDER: S-EPMC6699943 | biostudies-literature | 2019 Nov

REPOSITORIES: biostudies-literature