Capillary morphogenesis in PEG-collagen hydrogels

A wide variety of hydrogels have been explored as 3D culture platforms and for applications in tissue engineering. Hydrogels formed from natural extracellular matrix (ECM) proteins readily support the formation of vasculature in vitro, but only a handful of hydrogels composed of synthetic materials have shown anything comparable. This relative lack of synthetic material options has hindered efforts to better understand how ECM cues direct vascularization. We developed a biosynthetic hydrogel consisting of polyethylene glycol diacrylamide conjugated to macromolecular type-I collagen. Through their acrylamide-based crosslinks, these materials allow for independent control of physical properties and bulk ligand concentration. These hydrogels exhibited hydrolytic stability, but the collagen component retained its susceptibility to enzymatic remodeling. Photoencapsulation of endothelial cells and fibroblasts within this hydrogel material and their subsequent co-culture led to the formation of capillary vessel-like networks with well-defined hollow lumens. Capillary formation was prevented by inhibiting matrix metalloproteinase (MMP) activity, recapitulating the MMP-dependence of vascularization observed in natural hydrogels. These findings validate the utility of this material platform to decipher how the ECM regulates capillary morphogenesis and to support the formation of vascularized tissue constructs for potential applications in regenerative medicine.