Recent and Future Strategies of Mechanotherapy for Tissue Regenerative Rehabilitation.

Mechanotherapy, the application of various mechanical forces on injured or diseased tissue, is a viable option for tissue regenerative rehabilitation. Recent advances in tissue engineering (i.e., engineered materials and 3D printing) and soft-robotic technologies have enabled systematic and controlled studies to demonstrate the therapeutic impacts of mechanical stimulation on severely injured tissue. Along with innovation in actuation systems, improvements in analysis methods uncovering cellular and molecular landscapes during tissue regeneration under mechanical loading expand our understanding of how mechanical cues are translated into specific biological responses (i.e., stem cell self-renewal and differentiation, immune responses, etc.). Moving forward, the development of diversified actuation systems that are mechanically tissue friendly, easily scalable, and capable of delivering various modes of loading and monitoring functional biomarkers will facilitate systematic and controlled preclinical and clinical studies. Combining these future actuation systems with single-cell resolution analysis of cellular and molecular markers will enable detailed knowledge of underlying biological responses, and optimization of mechanotherapy protocols for specific tissues/injuries. These advancements will enable diverse mechanotherapy therapies in the future.