Chemical modification of human decellularized extracellular matrix for incorporation into phototunable hybrid-hydrogel models of tissue fibrosis

There is a critical need to engineer model systems that better recapitulate the spatial and temporal changes in the fibrotic extracellular microenvironment and enable study of the cellular and molecular alterations that occur during pathogenesis. Here, we present a process for chemically modifying human decellularized extracellular matrix (dECM) and incorporating it into a dynamically tunable hybrid-hydrogel system containing a poly(ethylene glycol)-alpha methacrylate (PEGαMA) backbone.

Following modification and characterization, an off-stoichiometry thiol-ene Michael addition reaction resulted in hybrid-hydrogels with mechanical properties that could be tuned to recapitulate many healthy tissue types. Next, photoinitiated, free-radical homopolymerization of excess α-methacrylates increased crosslinking density and hybrid-hydrogel elastic modulus to mimic a fibrotic microenvironment. The incorporation of dECM into the PEGαMAhydrogel decreased the elastic modulus and, relative to fully synthetic hydrogels, increased the swelling ratio, the average molecular weight between crosslinks, and the mesh size of hybrid-hydrogel networks.