{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,12]],"date-time":"2026-09-12T11:07:52Z","timestamp":1789211272872,"version":"build-2803163510"},"reference-count":50,"publisher":"SAGE Publications","license":[{"start":{"date-parts":[[2026,1,7]],"date-time":"2026-01-07T00:00:00Z","timestamp":1767744000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"funder":[{"DOI":"10.13039\/100000069","name":"National Institute of Arthritis and Musculoskeletal and Skin Diseases","doi-asserted-by":"crossref","award":["1R01AR067744-01"],"award-info":[{"award-number":["1R01AR067744-01"]}],"id":[{"id":"10.13039\/100000069","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000090","name":"Congressionally Directed Medical Research Programs","doi-asserted-by":"crossref","award":["W81XWH-19-DMRDPRMFRA-DM190593P2"],"award-info":[{"award-number":["W81XWH-19-DMRDPRMFRA-DM190593P2"]}],"id":[{"id":"10.13039\/100000090","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Tissue Engineering Part A"],"abstract":"<jats:p>Volumetric muscle loss (VML) is characterized as the loss of muscle tissue that exceeds the muscle\u2019s self-repair mechanism, resulting in incomplete restoration of muscle mass and function. Existing treatment modalities, including muscle grafts or autologous muscle transfers, are limited by constraints such as tissue availability and donor site morbidity. Moreover, the inadequate recovery of muscle may lead to fibrosis within the VML site, impeding the process of muscle regeneration and resulting in permanent deficits. Emerging therapeutics, such as hydrogels, show promise in addressing the limitations of current therapeutics and have the potential to significantly reduce fibrosis and facilitate the restoration of muscle form and function following VML injury and repair. This study evaluated the therapeutic potential of repairing a 30% VML injury in the rat tibialis anterior muscle with engineered skeletal muscle units (SMUs), alone, and in combination with a hyaluronic acid-based hydrogel (HyA-HG). Following 1- or 3-months post-implantation, muscle structure and function were assessed. The results indicated that the incorporation of HyA-HG in combination with our SMUs resulted in improvements in force production for VML injuries repaired for 1 month. However, over extended recovery periods (3 months), sustained superior improvements in muscle function with the combination therapy were not observed compared with the repair with just an SMU. Moreover, histological analyses revealed that muscle treated with SMUs and HyA-HG exhibited a greater cross-sectional area and force production in the early stages of recovery (1-month post-surgery) compared with untreated VML sites or those treated with HyA-HG only. However, after 3 months, muscle mass and force production in all experimental groups reached comparable levels, suggesting a transient benefit of the combination therapy. Our findings highlight the potential of HyA-HG and SMU combination therapy to enhance early functional recovery following VML.<\/jats:p>","DOI":"10.1177\/19373341251410209","type":"journal-article","created":{"date-parts":[[2025,12,29]],"date-time":"2025-12-29T17:19:23Z","timestamp":1767028763000},"update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":0,"title":["Repairing Volumetric Muscle Loss with Skeletal Muscle Units and Hyaluronic Acid Hydrogel in Rats"],"prefix":"10.1177","author":[{"given":"Eileen Y.","family":"Su","sequence":"first","affiliation":[{"name":"Department of Molecular and Integrative Physiology, University of Michigan, Ann Arbor, Michigan, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emmanuel E.","family":"Vega-Soto","sequence":"additional","affiliation":[{"name":"Department of Molecular and Integrative Physiology, University of Michigan, Ann Arbor, Michigan, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stoyna S.","family":"Novakova","sequence":"additional","affiliation":[{"name":"Department of Molecular and Integrative Physiology, University of Michigan, Ann Arbor, Michigan, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anouk R.","family":"Killaars","sequence":"additional","affiliation":[{"name":"Departments of Bioengineering and Materials Science &amp; Engineering, University of California, Berkeley, California, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kevin E.","family":"Healy","sequence":"additional","affiliation":[{"name":"Departments of Bioengineering and Materials Science &amp; Engineering, University of California, Berkeley, California, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"George J.","family":"Christ","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering, University of Virginia, Charlottesville, Virginia, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lisa M.","family":"Larkin","sequence":"additional","affiliation":[{"name":"Department of Molecular and Integrative Physiology, University of Michigan, Ann Arbor, Michigan, USA."},{"name":"Department of Biomedical Engineering, University of Michigan, Ann Arbor, Michigan, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","published-online":{"date-parts":[[2026,1,7]]},"reference":[{"key":"e_1_3_4_2_2","doi-asserted-by":"publisher","DOI":"10.1682\/JRRD.2014.07.0165"},{"key":"e_1_3_4_3_2","doi-asserted-by":"publisher","DOI":"10.1002\/jor.22730"},{"key":"e_1_3_4_4_2","doi-asserted-by":"publisher","DOI":"10.3390\/biomedicines9050564"},{"key":"e_1_3_4_5_2","doi-asserted-by":"publisher","DOI":"10.1159\/000443925"},{"key":"e_1_3_4_6_2","doi-asserted-by":"publisher","DOI":"10.5435\/00124635-201102001-00007"},{"key":"e_1_3_4_7_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-017-13306-2"},{"key":"e_1_3_4_8_2","doi-asserted-by":"publisher","DOI":"10.1155\/2018\/1984879"},{"key":"e_1_3_4_9_2","doi-asserted-by":"publisher","DOI":"10.1055\/s-0036-1583301"},{"key":"e_1_3_4_10_2","doi-asserted-by":"publisher","DOI":"10.1089\/ten.TEA.2021.0137"},{"key":"e_1_3_4_11_2","doi-asserted-by":"publisher","DOI":"10.1021\/acsbiomaterials.0c01751"},{"key":"e_1_3_4_12_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.actbio.2018.11.030"},{"key":"e_1_3_4_13_2","doi-asserted-by":"publisher","DOI":"10.1089\/ten.TEA.2016.0458"},{"key":"e_1_3_4_14_2","doi-asserted-by":"publisher","DOI":"10.1089\/ten.TEA.2016.0457"},{"key":"e_1_3_4_15_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.actbio.2013.12.019"},{"key":"e_1_3_4_16_2","doi-asserted-by":"publisher","DOI":"10.1039\/C2SM06463D"},{"key":"e_1_3_4_17_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.mtbio.2022.100453"},{"key":"e_1_3_4_18_2","doi-asserted-by":"publisher","DOI":"10.1089\/ten.TEA.2014.0060"},{"key":"e_1_3_4_19_2","doi-asserted-by":"publisher","DOI":"10.1007\/s40883-020-00175-x"},{"key":"e_1_3_4_20_2","doi-asserted-by":"publisher","DOI":"10.1007\/s40883-018-0078-7"},{"key":"e_1_3_4_21_2","doi-asserted-by":"publisher","DOI":"10.1089\/ten.TEA.2019.0288"},{"key":"e_1_3_4_22_2","doi-asserted-by":"publisher","DOI":"10.1089\/ten.TEA.2021.0187"},{"key":"e_1_3_4_23_2","doi-asserted-by":"publisher","DOI":"10.1089\/ten.TEA.2023.0240"},{"key":"e_1_3_4_24_2","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2015.00201"},{"key":"e_1_3_4_25_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.matbio.2018.08.008"},{"key":"e_1_3_4_26_2","doi-asserted-by":"publisher","DOI":"10.3390\/biom11101518"},{"key":"e_1_3_4_27_2","doi-asserted-by":"publisher","DOI":"10.1007\/s40883-019-00117-2"},{"key":"e_1_3_4_28_2","doi-asserted-by":"crossref","DOI":"10.17226\/25801","volume-title":"Guide for the care and use of laboratory animals","author":"Institute of Laboratory Animal Resources (U.S.). 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