Exercise is Medicine. This phrase underscores the fact that physical and rehabilitative exercise is a widely recognized pillar in the management of chronic diseases. A multitude of tissues throughout the organism require mechanical loading to maintain homeostasis (i.e., mechanotherapy). While a number of in vitro and ex vivo studies have provided strong evidence for the regulation of cellular function through mechanotransductive signaling (i.e., the conversion of a mechanical stimulus into a chemical response), in vivo evidence is limited, and the mechanisms underlying clinically-relevant mechanotherapies are not completely understood.

What has impeded progress in clarifying how mechanical forces regulate tissue homeostasis in vivo? Technical challenges in the controlled application of mechanical forces in vivo is a key limiting factor. Traditional forms of rehabilitative exercise commonly used in animal studies, such as treadmill running, involves both mechanical and non-mechanical effects. This makes it difficult to disentangle the direct effects of mechanical stimulation with other physiologic responses, such as cardiovascular system alterations. This collection brings together a diverse array of systems and techniques that have been developed to study the underlying molecular mechanism of mechanical force on tissue homeostasis in vivo. We invite you to submit protocols that outline novel approaches for evaluating the impact of mechanical forces on tissue or organ homeostasis in vivo (including brain, spinal cord, peripheral nerve, spine, vasculature, skeletal muscle, tendon, ligament, bone, and articular cartilage). We believe that the dissemination of these new techniques will broaden design considerations for pre-clinical animal models and promote the development of clinically relevant in vivo mechanotherapy.