Regenerative rehabilitation: Navigating the gap between preclinical promises and clinical realities for treating trauma-induced volumetric muscle loss

Regenerative rehabilitation is an emerging interdisciplinary field that combines regenerative medicine principles with rehabilitation science to improve recovery in musculoskeletal trauma cases such as volumetric muscle loss (VML). This article reviews preclinical and clinical studies, aiming to bridge the gap between these domains, summarize recent advancements and identify areas for further exploration. The review delves into preclinical studies, which explore the potential of regenerative approaches, including cellular and acellular scaffolds, to augment exercise-based rehabilitation. These studies demonstrate that regenerative rehabilitation can aid in functional recovery post-VML through various mechanisms such as modulation of fibrosis, angiogenesis, myogenesis and innervation. However, the approach in clinical studies differs significantly, involving diverse exercise therapy regimens both before and after surgical interventions. To date, only acellular extracellular matrix scaffolds have been combined with physical therapy in VML-injured patients, resulting in modest improvements in functional recovery. The field of regenerative rehabilitation is nascent but has seen noteworthy progress, with ample room for improvement. This article also highlights the need for closer collaboration between researchers in the fields of tissue engineering, orthopaedic surgery and physical therapy to improve recovery outcomes following traumatic muscle injuries. (Figure presented.).