Therapeutic Approaches to Skeletal Muscle Repair and Healing

Abstract

Context:Skeletal muscle is comprised of a highly organized network of cells, neurovascular structures, and connective tissue. Muscle injury is typically followed by a well-orchestrated healing response that consists of the following phases: inflammation, regeneration, and fibrosis. This review presents the mechanisms of action and evidence supporting the effectiveness of various traditional and novel therapies at each phase of the skeletal muscle healing process.Evidence Acquisition:Relevant published articles were identified using MEDLINE (1978-2013).Study Design:Clinical review.Level of Evidence:Level 3.Results:To facilitate muscle healing, surgical techniques involving direct suture repair, as well as the implantation of innovative biologic scaffolds, have been developed. Nonsteroidal anti-inflammatory drugs may be potentially supplanted by nitric oxide and curcumin in modulating the inflammatory pathway. Studies in muscle regeneration have identified stem cells, myogenic factors, and β-agonists capable of enhancing the regenerative capabilities of injured tissue. Furthermore, transforming growth factor-β1 (TGF-β1) and, more recently, myostatin and the rennin-angiotensin system have been implicated in fibrous tissue formation; several antifibrotic agents have demonstrated the ability to disrupt these systems.Conclusion:Effective repair of skeletal muscle after severe injury is unlikely to be achieved with a single intervention. For full functional recovery of muscle there is a need to control inflammation, stimulate regeneration, and limit fibrosis.Strength-of-Recommendation Taxonomy (SORT):B

RETURN TO PLAY: Where are we going? It is not a guessing game

“…Anatomical variability or different healing processes of connective tissues 12,13 (tendon, myotendon or fasciae 14 ) are important factors to define a muscle injury. 15 In this way has to be noted that the tendon healing 16 occurs in a very different way to muscle repair.…”

Effects of Low-level Laser Therapy on Muscle Repair in Rats with Chronic Alcohol Intake

“…Moreover, the activation of satellite cells and consequent expression of transcription factors such as MyoD and myogenin are mediated by cytokines released by inflammatory cells 22 . Danna et al 1 demonstrated the general phases of muscle regeneration and fibrosis, which are precipitated by a variety of cell types, cytokines, and growth factors. It is known that ethanol alters cytokine levels in a variety of tissues promoting alterations in the inflammatory response 24 .…”

“…Excessive consumption of alcohol is associated with different diseases of the brain, as well as other vital organs such as the heart, lung, liver, pancreas, and kidneys 1 . The immune system may be severely affected by the effects of alcohol on the different cellular components of the innate and/or adaptive system, with disruption of signaling pathways involved in initiation and control of the inflammatory response [2][3][4] .…”

TGF-β-driven downregulation of the Wnt/β-Catenin transcription factor TCF7L2/TCF4 in PDGFRα+fibroblasts

“…Thus, it is recognized that dysregulated TGF-β activity is a driver for reduced muscle regeneration, impaired tissue function and fibrosis (Mann et al, 2011; Pessina et al, 2015; Vidal et al, 2008). Interestingly, TGF-β inhibition improves the pathophysiology of MD (Accornero et al, 2014; Acuña et al, 2014; Ceco and McNally, 2013; Cohn et al, 2007; Danna et al, 2014). Mechanistically, TGF-β signaling stimulates FAPs and MSCs proliferation, extracellular matrix (ECM) production and myofibroblast differentiation (Contreras et al, 2019b; Hinz et al, 2007; Lemos et al, 2015; Uezumi et al, 2011).…”