Interpenetrating Polymer Network Hydrogels of Gelatin and Poly(ethylene glycol) as an Engineered 3D Tumor Microenvironment

An emerging trend in cancer research is to develop engineered tumor models using bio-inspired biomaterials that can mimic the native tumor microenvironment. Although various bio-inspired hydrogels have been utilized, it is still challenging to develop advanced polymeric hydrogel materials that can more accurately reconstruct critical aspects of the native tumor microenvironment. Herein, we present interpenetrating polymer network (IPN) hydrogels composed of thiolated gelatin and tyramine-conjugated poly(ethylene glycol), which form IPN hydrogels via horseradish peroxidase-mediated dual cross-linking reactions. We demonstrate that the IPN hydrogels exhibit independently controllable physicochemical properties. Also, the IPN hydrogels show resistance to the proteolytic enzymes and cytocompatibility for long-term culture of human fibrosarcoma (HT1080) cells. Moreover, we utilize the engineered tumor construct as a platform to evaluate the effect of matrix stiffness on cancer cell proliferation and drug resistance against the anticancer drug 5-fluorouracil as a model drug. In conclusion, we suggest that our IPN hydrogel is a promising material to study cancer biology and to screen innovative therapeutic agents for better clinical outcomes.