Skeletal Muscle Fibrosis: How Fibrotic Mechanisms Limit Muscle Regeneration After Injury
DOI:
https://doi.org/10.58445/rars.4216Keywords:
Skeletal Muscle Fibrosis, Muscle Regeneration, Muscle injuryAbstract
Skeletal muscle fibrosis is a dominant biological response that frequently limits effective regeneration following injury. While regenerative mechanisms exist, they are often suppressed by signaling pathways, immune responses, and extracellular changes. As a result, fibrosis commonly overrides regeneration leading to incomplete recovery. Further research is needed to overcome this problem despite the emerging solutions.
References
Awad, K., et al. “Innovations in Skeletal Muscle Regeneration: From Physiology to Bioengineering Approaches for Repair and Restoration.” Frontiers in Physiology, 2026, https://doi.org/10.3389/fphys.2026.1789642 .
Dewi, N. M., et al. “Targeted Therapy for Skeletal Muscle Fibrosis: Regulation of Myostatin, TGF-β, MMP, and TIMP to Maintain Extracellular Matrix Homeostasis.” Biologics: Targets and Therapy, vol. 19, 2025, pp. 213–229, https://doi.org/10.2147/BTT.S508221 .
Giannone, A. A., et al. “Deconstruction of Cellular Dynamics after Treatment of Volumetric Muscle Loss Injury with Extracellular Matrix.” npj Regenerative Medicine, 2025, https://doi.org/10.1038/s41536-025-00429-8 .
Gong, J., et al. “Molecular Mechanisms of Skeletal Muscle Fibrosis and Potential Targeted Therapeutic Strategies.” Frontiers in Immunology, vol. 17, 2026, article 1714238, https://doi.org/10.3389/fimmu.2026.1714238 .
Henze, H., et al. “Denervation Alters the Secretome of Myofibers and Thereby Affects Muscle Stem Cell Lineage Progression and Functionality.” npj Regenerative Medicine, vol. 9, 2024, article 10, https://doi.org/10.1038/s41536-024-00353-3 .
Højfeldt, G., et al. “The Repair Capacity Spectrum of Human Skeletal Muscle Injury from Sports to Surgical Trauma Settings.” The Journal of Physiology, vol. 603, no. 23, 2025, pp. 7441–7454, https://doi.org/10.1113/JP286507 .
Loreti, Matteo, and Alessandra Sacco. “The Jam Session between Muscle Stem Cells and the Extracellular Matrix in the Tissue Microenvironment.” npj Regenerative Medicine, 2022, https://doi.org/10.1038/s41536-022-00204-z .
Moiseeva, V., et al. “Senescence Atlas Reveals an Aged-Like Inflamed Niche That Blunts Muscle Regeneration.” Nature, 2023, https://doi.org/10.1038/s41586-022-05535-x.
Mottel, L. G., et al. “Immunomodulatory Biomaterials for Vascularized and Innervated Skeletal Muscle Repair.” Frontiers in Immunology, 2025, https://doi.org/10.3389/fimmu.2025.1657015 .
Parigi, M., et al. “Shining a Light on Skeletal Muscle Regeneration: Red Photobiomodulation Boosts Myoblast Differentiation In Vitro.” The FASEB Journal, vol. 39, no. 21, 2025, article e71107, https://doi.org/10.1096/fj.202502477R .
Qi, L., et al. “Advancements in Skeletal Muscle Tissue Engineering: Strategies for Repair and Regeneration of Skeletal Muscle beyond Self-Repair.” Regenerative Biomaterials, vol. 12, 2025, article rbaf050, https://doi.org/10.1093/rb/rbaf050.
Relaix, F., et al. “Perspectives on Skeletal Muscle Stem Cells.” Nature Communications, 2021, https://doi.org/10.1038/s41467-020-20760-6 .
Stepien, D. M., et al. “Tuning Macrophage Phenotype to Mitigate Skeletal Muscle Fibrosis.” The Journal of Immunology, vol. 204, no. 8, 2020, pp. 2203–2215, https://doi.org/10.4049/jimmunol.1900814 .
Szlachcikowska, D., et al. “Current Insights and Future Directions in Scar Management and Skin Regeneration.” International Journal of Molecular Sciences, vol. 26, no. 21, 2025, article 10636, https://doi.org/10.3390/ijms262110636 .
Theret, M., et al. “Evolving Roles of Muscle-Resident Fibro-Adipogenic Progenitors in Health, Regeneration, Neuromuscular Disorders, and Aging.” Frontiers in Physiology, vol. 12, 2021, article 673404, https://doi.org/10.3389/fphys.2021.673404 .
Wang, Z., et al. “Adipose Decellularized Matrix: A Promising Skeletal Muscle Tissue Engineering Material for Volume Muscle Loss.” Biomaterials Research, vol. 29, 2025, article 0174, https://doi.org/10.34133/bmr.0174 .
Yang, W., et al. “Research Progress on Scar-Free Healing.” Annals of Medicine, vol. 57, no. 1, 2025, article 2575109, https://doi.org/10.1080/07853890.2025.2575109 .
Downloads
Posted
Categories
License
Copyright (c) 2026 Research Archive of Rising Scholars
This work is licensed under a Creative Commons Attribution 4.0 International License.
