Immunomodulatory extracellular matrix hydrogel induces tissue regeneration in a model of partial glossectomy

• Published in: Bioactive materials 2024-08, Vol.38, p.528-539
• Main Authors: Zelus, Emma I., Panduro, Aaron, Deshmukh, Isha, Grime, Jacqueline, Alperin, Marianna, Vahabzadeh-Hagh, Andrew M., Christman, Karen L.
• Format: Article
• Language: English
• Subjects: Atrophy; Biomaterial; Biomaterials; Biomedical materials; Cancer therapies; Chemotherapy; Denervation; Dysphagia; Extracellular matrix; Fibrosis; Gene expression; Head & neck cancer; Hydrogel; Hydrogels; Immune response; Immune system; Immunomodulation; Inflammation; Injuries; Investigations; Muscles; Musculoskeletal system; Oropharyngeal cancer; Partial glossectomy; Pathogenesis; Phenotypes; Regeneration (physiology); Scars; Skeletal muscle; Skeletal muscle regeneration; Standard of care; Stem cells; Swallowing; Tissue engineering; Tongue
• ISSN: 2452-199X; 2097-1192; 2452-199X
• DOI: 10.1016/j.bioactmat.2024.05.001

While oropharyngeal cancer treatment regimens, including surgical resection, irradiation, and chemotherapy, are effective at removing tumors, they lead to muscle atrophy, denervation, and fibrosis, contributing to the pathogenesis of oropharyngeal dysphagia – difficulty swallowing. Current standard of care of rehabilitative tongue strengthening and swallowing exercises is ineffective. Here, we evaluate an alternative approach utilizing an acellular and injectable biomaterial to preserve muscle content and reduce fibrosis of the tongue after injury. Skeletal muscle extracellular matrix (SKM) hydrogel is fabricated from decellularized porcine skeletal muscle tissue. A partial glossectomy injury in the rat is used to induce tongue fibrosis, and SKM hydrogels along with saline controls are injected into the site of scarring two weeks after injury. Tissues are harvested at 3 and 7 days post-injection for gene expression and immunohistochemical analyses, and at 4 weeks post-injection to evaluate histomorphological properties. SKM hydrogel reduces scar formation and improves muscle regeneration at the site of injury compared to saline. SKM additionally modulates the immune response towards an anti-inflammatory phenotype. This study demonstrates the immunomodulatory and tissue-regenerative capacity of an acellular and minimally invasive ECM hydrogel in a rodent model of tongue injury. [Display omitted] •ECM hydrogel injected in a model of tongue fibrosis to induce tissue regeneration.•ECM hydrogel reduces scar formation and improves muscle regeneration.•Pro-regenerative immunomodulation is involved in ECM hydrogel mechanism of action.•ECM hydrogel recruits pro-myogenic fibroadipogenic progenitors to site of injury.