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

作　　者：Emma I.Zelus Aaron Panduro Isha Deshmukh Jacqueline Grime Marianna Alperin Andrew M.Vahabzadeh-Hagh Karen L.Christman 

机构地区：[1]Shu Chien-Gene Lay Department of Bioengineering,UC San Diego,9500 Gilman Dr.MC 0412,La Jolla,CA,92093-0412,USA [2]Department of Obstetrics,Gynecology,and Reproductive Sciences,Division of Female Pelvic Medicine and Reconstructive Surgery,UC San Diego School of Medicine,9300 Campus Point,MC 7433,La Jolla,CA,92037-7433,USA [3]Department of Otolaryngology-Head&Neck Surgery,UC San Diego School of Medicine,9300 Campus Point,MC 7400,La Jolla,CA,92037-7400,USA [4]Sanford Consortium for Regenerative Medicine,2880 Torrey Pines Scenic Drive,La Jolla,CA,92037,USA [5]Sanford Stem Cell Institute,2880 Torrey Pines Scenic Drive,La Jolla,CA,92037,USA

出　　处：《Bioactive Materials》2024年第8期528-539,共12页生物活性材料（英文）

基　　金：Funding provided by the UCSD Galvanizing Engineering in Medicine Program.The authors would like to thank the UC San Diego Stem Cell Genomics Core at the Sanford Consortium for Regenerative Medicine for assistance with RNA sequencing and analysis.

摘　　要：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.

关 键 词：Extracellular matrix Biomaterial HYDROGEL Skeletal muscle regeneration Partial glossectomy DYSPHAGIA Immunomodulation 

分 类 号：R318[医药卫生—生物医学工程] TQ427.26[医药卫生—基础医学]