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Impaired muscle regeneration remains the main culprit for unsatisfactory surgical outcomes. However, there is a lack of study on how different surgical manipulations affect lip muscle regeneration, limiting efforts to seek effective interventions.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>In this study, we established a rat lip surgery model where the orbicularis oris muscle was injured by manipulations including dissection, transection and stretch. The effect of each technique on muscle regeneration was examined by histological analysis of myogenesis and fibrogenesis. The impact of tensile force was further investigated by the in vitro application of mechanical strain on cultured myoblasts. Transcriptome profiling of muscle satellite cells from different surgical groups was performed to figure out the key factors mediating muscle fibrosis, followed by therapeutic intervention to improve muscle regeneration after lip surgeries.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Evaluation of lip muscle regeneration till 56\u00a0days after injury revealed that the stretch group resulted in the most severe muscle fibrosis (<jats:italic>n<\/jats:italic>\u00a0=\u00a06, fibrotic area 48.9% in the stretch group, <jats:italic>P<\/jats:italic>\u00a0&lt;\u00a00.001, and 25.1% in the dissection group, <jats:italic>P<\/jats:italic>\u00a0&lt;\u00a00.001). There was the lowest number of Pax7\u2010positive nuclei at Days 3 and 7 in the stretch group (<jats:italic>n<\/jats:italic>\u00a0=\u00a06, <jats:italic>P<\/jats:italic>\u00a0&lt;\u00a00.001, <jats:italic>P<\/jats:italic>\u00a0&lt;\u00a00.001), indicating impaired satellite cell expansion. Myogenesis was impaired in both the transection and stretch groups, as evidenced by the delayed peak of centrally nucleated myofibers and embryonic MyHC. Meanwhile, the stretch group had the highest percentage of Pdgfra<jats:sup>+<\/jats:sup> fibro\u2010adipogenic progenitors infiltrated area at Days 3, 7 and 14 (<jats:italic>n<\/jats:italic>\u00a0=\u00a06, <jats:italic>P<\/jats:italic>\u00a0=\u00a00.003, <jats:italic>P<\/jats:italic>\u00a0=\u00a00.006, <jats:italic>P<\/jats:italic>\u00a0=\u00a00.037). Cultured rat lip muscle myoblasts exhibited impaired myotube formation and fusion capacity when exposed to a high magnitude (\u03b5\u00a0=\u00a02688\u00a0\u03bc strain) of mechanical strain (<jats:italic>n<\/jats:italic>\u00a0=\u00a03, <jats:italic>P<\/jats:italic>\u00a0=\u00a00.014, <jats:italic>P<\/jats:italic>\u00a0=\u00a00.023). RNA\u2010seq analysis of satellite cells isolated from different surgical groups demonstrated that interleukin\u201010 was the key regulator in muscle fibrosis. Administration of recombinant human Wnt7a, which can inhibit the expression of interleukin\u201010 in cultured satellite cells (<jats:italic>n<\/jats:italic>\u00a0=\u00a03, <jats:italic>P<\/jats:italic>\u00a0=\u00a00.041), exerted an ameliorating effect on orbicularis oris muscle fibrosis after stretching injury in surgical lip repair.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Tensile force proved to be the most detrimental manoeuvre for post\u2010operative lip muscle regeneration, despite its critical role in correcting lip and nose deformities. Adjunctive biotherapies to regulate the interleukin\u201010\u2010mediated inflammatory process could facilitate lip muscle regeneration under conditions of high surgical tensile force.<\/jats:p><\/jats:sec>","DOI":"10.1002\/jcsm.13584","type":"journal-article","created":{"date-parts":[[2024,10,1]],"date-time":"2024-10-01T08:40:15Z","timestamp":1727772015000},"page":"2497-2508","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Tensile force impairs lip muscle regeneration under the regulation of interleukin\u201010"],"prefix":"10.1002","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7523-3891","authenticated-orcid":false,"given":"Xu","family":"Cheng","sequence":"first","affiliation":[{"name":"State Key Laboratory of Oral Diseases, National Center for Stomatology, National Clinical Research Center for Oral Diseases West China Hospital of Stomatology, Sichuan University  Chengdu China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jinfeng","family":"Dou","sequence":"additional","affiliation":[{"name":"Department of Oral and Maxillofacial Surgery, State Key Laboratory of Oral Diseases, National Center for Stomatology, National Clinical Research Center for Oral Diseases West China Hospital of Stomatology, Sichuan University  Chengdu China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jinggui","family":"Li","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Oral Diseases, National Center for Stomatology, National Clinical Research Center for Oral Diseases West China Hospital of Stomatology, Sichuan University  Chengdu China"},{"name":"Department of Oral and Craniomaxillofacial Surgery Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine  Shanghai China"},{"name":"Shanghai Key Laboratory of Stomatology, National Center for Stomatology, National Clinical Research Center for Oral Diseases College of Stomatology, Shanghai Jiao Tong University  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yixuan","family":"Huang","sequence":"additional","affiliation":[{"name":"Department of Oral and Maxillofacial Surgery, State Key Laboratory of Oral Diseases, National Center for Stomatology, National Clinical Research Center for Oral Diseases West China Hospital of Stomatology, Sichuan University  Chengdu China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5100-2485","authenticated-orcid":false,"given":"Bing","family":"Shi","sequence":"additional","affiliation":[{"name":"Department of Oral and Maxillofacial Surgery, State Key Laboratory of Oral Diseases, National Center for Stomatology, National Clinical Research Center for Oral Diseases West China Hospital of Stomatology, Sichuan University  Chengdu 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