Establishing the Basis for Mechanobiology-Based Physical Therapy Protocols to Potentiate Cellular Healing and Tissue Regeneration

Abstract

Life is mechanobiological: mechanical stimuli play a pivotal role in the formation of structurally and functionally appropriate body templates through mechanobiologically-driven cellular and tissue re/modeling. The body responds to mechanical stimuli engendered through physical movement in an integrated fashion, internalizing and transferring forces from organ, through tissue and cellular length scales. In the context of rehabilitation and therapeutic outcomes, such mechanical stimuli are referred to as mechanotherapy. Physical therapists use mechanotherapy and mechanical interventions, e.g., exercise therapy and manual mobilizations, to restore function and treat disease and/or injury. While the effect of directed movement, such as in physical therapy, is well documented at the length scale of the body and its organs, a number of recent studies implicate its integral effect in modulating cellular behavior and subsequent tissue adaptation. Yet the link between movement biomechanics, physical therapy, and subsequent cellular and tissue mechanoadaptation is not well established in the literature. Here we review mechanoadaptation in the context of physical therapy, from organ to cell scale mechanotransduction and cell to organ scale extracellular matrix genesis and re/modeling. We suggest that physical therapy can be developed to harness the mechanosensitivity of cells and tissues, enabling prescriptive definition of physical and mechanical interventions to enhance tissue genesis, healing, and rehabilitation.

Bioinspired Technologies to Connect Musculoskeletal Mechanobiology to the Person for Training and Rehabilitation

“…However, integrating experimental results with whole-body-, tissue-, and cell-level computational models, and using these models to modulate physical behavior to affect musculoskeletal tissue health remains challenging (Erdemir et al, 2015 ). In a recent narrative review, Ng et al ( 2017 ) proposed physical therapy to enhance and promote tissue regeneration, linking external mechanical stimuli to tissue mechanobiology. In line with Ng et al ( 2017 ), we describe an approach to deterministically quantify the link between physical behavior and tissue mechanobiology, inspired by integration of biomedical technologies (i.e., wearable devices, contemporary motion capture, and medical imaging) coupled to computational models of joints and musculoskeletal tissues.…”

Pressure‐induced mesenchymal stem cell osteogenesis is dependent on intermediate filament remodeling

“…Therefore, the objective of this study is to investigate whether pressure transients associated with the bone marrow micromechanical environment can elicit an osteogenic response in MSCs and to determine whether these effects are mediated by the cell cytoskeleton. The ability to discern and induce cytoskeletal changes to manipulate stem cell lineage commitment would be a powerful tool, both for the determination of bone metabolic disorders, in addition to applications in tissue engineering strategies, and the development of mechanotherapies as an anabolic treatment for bone-loss diseases (33)(34)(35).…”

Mechanomics Approaches to Understand Cell Behavior in Context of Tissue Neogenesis, During Prenatal Development and Postnatal Healing

“…Displacements and/or stresses and strains measured in the experimental models noted above serve as inputs for the analytical and/or computational FIGURE 1 | Multiscale and multidisciplinary approaches to mechanomics. (A) Mechanoadaptation of tissues and organs aligns closely with mechanoadaptation at a cellular level, since cells manufacture the structural proteins making up the extracellular tissue matrix and the matrix in turn modulates how exogenous mechanical signals are transferred to cells and their nuclei, after (Ng et al, 2017), used with permission. (B) A recently updated first map of the mechanome includes data points from a number of labs in which volume and shape changing stresses were mapped against time and lineage commitment was noted by the shape of the data point, after (Anderson and Knothe Tate, 2007a;Ng et al, 2017), used with permission.…”