Photo/thermo-sensitive chitosan and gelatin-based interpenetrating polymer network for mimicking muscle tissue extracellular matrix

The dynamic interplay between extracellular matrix (ECM), its 3D architecture and resident cells plays a pivotal role in cell behavior influencing essential processes like proliferation, migration, and differentiation. Matrix-based 3D culture systems have emerged as valuable tools to model organ and tissue interactions <i>in vitro</i>. A 3D matrix analog must possess high biocompatibility and fully reproduce the characteristics of the native tissue in terms of mechanical properties. In this regard, interpenetrating polymer networks (IPNs) are particularly attractive because of the high tunability of their physicochemical properties. In this study, a chitosan (Ch) and modified gelatin (GelMA) IPN with a sol-gel transition triggered by two external physical stimuli, UV light and temperature, was designed to mimic the muscle tissue ECM in terms of mechanical stiffness. The system was deeply characterized demonstrating to support not only the growth and viability of muscle cells embedded within the hydrogel, but also cell differentiation toward muscle phenotype.