ETD

• collagen–fibrin biomaterials
• hydrogels
• myogenic differentiation
• skeletal muscle tissue engineering
• viscoelasticity

Skeletal muscle tissue engineering represents a promising strategy to address the limited regenerative capacity of muscle tissue after severe damage. In this work, hydrogel-based constructs were developed as biomimetic matrices able to support myoblast viability, organization, and maturation within a three-dimensional environment. The study focused on the optimization of natural polymer-based formulations combining biological compatibility, structural stability, and mechanical properties relevant for skeletal muscle applications. Hydrogel degradation was evaluated by monitoring the residual mass over time, while the mechanical behavior was investigated through Dynamic Mechanical Analysis, with particular attention to the viscoelastic properties of the constructs. Cellular response was assessed by evaluating cell viability and metabolic activity through LIVE/DEAD and PrestoBlue assays, while myogenic differentiation was investigated by immunostaining. The results showed that hydrogel composition strongly influences construct stability and cell organization, highlighting the importance of both biochemical and biomechanical cues in guiding cell–matrix interactions. Overall, this work provides a basis for the development of mechanically responsive hydrogel platforms for skeletal muscle tissue engineering and future stimulation-based approaches.