In this study, a process is presented for modifying human decellularized extracellular matrix (dECM) chemically and integrating it into a hybrid-hydrogel system that is dynamically tunable and contains a poly(ethylene glycol)-α methacrylate (PEGαMA) backbone. By incorporating intact, tissue-derived dECM, key biochemical properties of human tissue were recapitulated while taking advantage of dual-stage photopolymerization techniques to mimic the dynamic increase in microenvironmental stiffness observed during fibrotic progression in human organs. The incorporation of dECM altered key network properties of the hydrogels, including increasing the swelling ratio, average molecular weight between crosslinks, and mesh size, while decreasing the average shear modulus of the resulting hybrid-hydrogels. These findings advance our knowledge of the biomolecular networks that form within hybrid-hydrogels. This completely human phototunable hybrid-hydrogel system allows researchers to regulate and disentangle the biochemical modifications that occur during fibrotic pathogenesis from the resulting increases in stiffness, allowing for the study of the dynamic cell−matrix interactions that perpetuate fibrotic diseases.

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