Intersection of Mechanobiology and Musculoskeletal Regenerative Rehabilitation

Thesis (Ph.D.)--University of Washington, 2021Mechanical stimuli play an essential role in the formation of structurally and functionally appropriate cellular and tissue modeling/remodeling. Musculoskeletal system responds to mechanical stimuli through physical movement in an integrated fashion, transferring forces from tissue to cellular and molecular scales. In the context of rehabilitation, mechanical stimuli are referred to as mechanotherapy and physical therapists use them to treat musculoskeletal disease and/or injury, with the goal to modulate cellular behavior and subsequent tissue adaptation. However, the link between mechanotherapy and subsequent cellular and tissue mechanoadaptation is not well established in the literature. To address this, first, recent literature on how mechanotherapies such as exercise training, stretching, electrical stimulation, and shockwave might activate mechanotransductive and metabolic signaling pathways were evaluated. Although there is sufficient evidence on the regulation of these signaling pathways; however, there is insufficient data on the mechanism of activation of these pathways following mechanotherapy in aged, diseased, and injured skeletal muscle tissues. In the second research study, mechanical stimulation in the form of passive stretch was used to develop in vitro skeletal muscle injury model. Then, the model was applied to both normal and Duchenne Muscular Dystrophy (DMD) skeletal muscle fibers to induce passive stretch-induced injury, and the acute biochemical responses of cytoplasmic and myofibrillar proteins to the selected stretch protocol were measured. The preliminary findings indicated that muscle fibers in DMD were more susceptible to the passive stretch-induced injury protocol than normal. Lastly, in the clinical regenerative rehabilitation pilot study, feasibility and short-term efficacy of rehabilitation program after regenerative therapies was assessed to harness the mechanosensitivity of chondrocyte and better facilitate tissue healing and regeneration. The initial findings demonstrated that the rehabilitation program was clinically meaningful across most Knee injury and Osteoarthritis Outcome Score (KOOS) subscales between 2- and 3-months post-injection in both treatment groups. Future randomized clinical trials are needed to fully understand the role of mechanical stimulation of chondrocyte to facilitate the repair and regeneration following regenerative therapies in knee degenerative joint disorders