Design, development, and benchmarking of a mechanical platform integrated with 3D bioprinting: application to skeletal muscle regeneration

The development of engineered muscle constructs for regenerative medicine and in-vitro models for pharmacological testing and musculoskeletal disease research has received significant attention in recent years. Achieving these goals requires replicating the 3D structure of muscle tissue and applying external stimuli to enhance muscle cell differentiation facing the challenges presented by the complexity of muscle tissue in-vivo. While Bioprinting (BioP) shows promise in producing 3D tissue structures, there is a lack of research on the mechanical stimulation of these 3D bioprinted constructs. Novel approaches are required to address this knowledge gap, including 1) applying mechanical stimulation to the 3D bioprinted construct and 2) integrating the BioP phase into the stimulation device. For this reason, the present work proposes the design, manufacturing, and benchmarking of a BioP-integrated mechanical platform that can mechanically stimulate a 3D muscle model directly printed within the bioreactor. The study involves three primary phases. The first phase includes the design and development of elastic supports suitable for BioP and long-term cell culture. In the second phase, numerical tools will be used to design a Smart Petri Dish (SPD) containing the stimulation mechanism as well as the final cyclic mechanical platform. Finally, the third phase of the study will involve the in-vitro validation of the proposed platform in terms of transmission of the mechanical stimulation to the 3D construct, integration of the BioP step, and the biological effect of dynamic culture on muscle cells. In conclusion, prototypes are now available of a cutting-edge mechanical platform that integrates the 3D BioP phase and is capable of stimulating 3D biological constructs for applications in the field of muscle tissue engineering.