Fibrosis of skeletal muscle is a hallmark of muscular dystrophies, aging, and severe muscle injuries. The excessive deposition of fibrous tissue impairs muscle function, affects muscle fiber regeneration after injury, and increases muscle susceptibility to re-injury. (Mahdy, 2019)
Traumatic injury is often sufficient to disrupt the regenerative capacity of skeletal muscle, and the resulting fibrosis remains often overlooked sequelae of pathologic healing. Muscle strain proves the most frequent sports injury whereby the extent of muscle fibrosis corresponds to the severity of the injury. In addition to physical trauma, thermal and ionizing radiation are sufficient to disrupt muscle regeneration. (Cholok et al, 2017) If tissue injury persists, as in severe muscular dystrophies, the repair process becomes uncontrolled leading to the substitution of myofibers by a non-functional mass of fibrotic tissue. (Serrano, 2010)
The healing response after muscle trauma can result in regeneration, degeneration with fibrosis and fatty replacement, or disordered tissue proliferation as seen in myositis ossificans. (Flores et al, 2018)
Muscle fibrosis involves the production of several growth factors, cytokines, and proteolytic enzymes and is strictly associated to inflammatory processes. Moreover, fibrosis causes profound changes in tissue properties, including increased stiffness and density, lower pH, and oxygenation. (Bersini et al, 2018)
Mahdy MAA. Skeletal muscle fibrosis: an overview. Cell Tissue Res. 2019 Mar;375(3):575-588. doi: 10.1007/s00441-018-2955-2. Epub 2018 Nov 12. PMID: 30421315.
Cholok D, Lee E, Lisiecki J, Agarwal S, Loder S, Ranganathan K, Qureshi AT, Davis TA, Levi B. Traumatic muscle fibrosis: From pathway to prevention. J Trauma Acute Care Surg. 2017 Jan;82(1):174-184. doi: 10.1097/TA.0000000000001290. PMID: 27787441; PMCID: PMC5177464.
Serrano AL, Muñoz-Cánoves P. Regulation and dysregulation of fibrosis in skeletal muscle. Exp Cell Res. 2010 Nov 1;316(18):3050-8. doi: 10.1016/j.yexcr.2010.05.035. Epub 2010 Jun 4. PMID: 20570674.
Flores DV, Mejía Gómez C, Estrada-Castrillón M, Smitaman E, Pathria MN. MR Imaging of Muscle Trauma: Anatomy, Biomechanics, Pathophysiology, and Imaging Appearance. Radiographics. 2018 Jan-Feb;38(1):124-148. doi: 10.1148/rg.2018170072. Epub 2017 Dec 8. PMID: 29220207.
Bersini S, Gilardi M, Mora M, Krol S, Arrigoni C, Candrian C, Zanotti S, Moretti M. Tackling muscle fibrosis: From molecular mechanisms to next generation engineered models to predict drug delivery. Adv Drug Deliv Rev. 2018 Apr;129:64-77. doi: 10.1016/j.addr.2018.02.009. Epub 2018 Mar 5. PMID: 29518415.