Mechanotherapy: revisiting physical therapy and recruiting mechanobiology for a new era in medicine

• A new definition of mechanotherapy is proposed.
• Mechanotherapies at the tissue, cellular, and molecular levels are described.
• Mechanobiology is recruited integrating biochemistry, mechanics, and clinical aspects.
• Mechanotherapy is a door to a new era of pharmacological and engineering interventions.

It has long been thought that the effectiveness and efficiency of physical therapy would improve if our understanding of the cell biology/biochemistry that participates in mechanics could be improved. Traditional physical therapy focuses primarily on rehabilitation, but recent developments in mechanobiology that illuminated the effects of physical forces on cells and tissues have led to the realization that the old therapy model should be updated. To achieve this here, the term mechanotherapy is proposed and recent studies showing how mechanotherapies target particular cells, molecules, and tissues are reviewed. These studies show how mechanical force modulates integrin-mediated processes and other mechanosensors such as gap junctions, hemichannels, primary cilia, transient receptor potential channels (cell targeting), and intracellular mechanosignaling pathways (molecule targeting). The role of mechanical force in various therapies, including microdeformation, shockwave, tissue expansion, distraction osteogenesis, and surgical tension reduction (tissue targeting) therapies, is reviewed. This review aims to jumpstart research into this field, which promises to generate a new era of viable and novel pharmacological and engineering interventions that can overcome human diseases.