Loss of skeletal muscle tissue caused by traumatic injury or damage due to myopathies produces a deficit of muscle function for which there is still no clinical treatment. Transplantation of myogenic cells, themselves or combined with materials, has been proposed to increase the regenerative capacity of skeletal muscle but it is hampered by many limitations, such as low cell survival and engraftment or immunological reaction and low biocompatibility of the exogenous materials. Recently, myoblast sheet engineering, obtained with thermoresponsive culture dishes, has attracted attention as a new technique for muscle damage treatment. For this purpose, a series of thermoresponsive hydrogels, constituted by poly(N-isopropylacrylamide-co-2-hydroxyethylmethacrylate) [p(NIPAAM-co-HEMA)] were synthesized by a simple and inexpensive free-radical polymerization of the two co-monomers with a redox initiator. Different ratios of N-isopropylacrylamide (NIPAAm) and 2-hydroxyethylmethacrylate (HEMA) have been examined to evaluate the effects on physicochemical, mechanical and optical hydrogel properties. The murine muscle cell line C2C12 has been exploited to test the cytotoxicity of the thermoresponsive hydrogels, depending on different synthesis conditions. In this study, we have identified a thermoresponsive hydrogel that allows cell adhesion and viability, together with the detachment of viable sheet of muscle cells, giving the chance to develop further applications for muscle damage and disease. Copyright © 2014 John Wiley & Sons, Ltd.