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Human umbilical cord mesenchymal stem cells\u2010 (HuMSCs\u2010) based therapy has shown promising results in the treatment of intrauterine adhesions (IUA). In this study, we aimed to construct a HuMSCs\u2010seeded silk fibroin small\u2010intestinal submucosa (SF\u2010SIS) scaffold and evaluate its ability to repair the damaged endometrium in an IUA mouse model. <jats:italic>Methods<\/jats:italic>. To identify the functional effect of HuMSCs\u2010SF\u2010SIS scaffolds on the repair of damaged endometrium, a mouse IUA model was established. Uterine morphology and fibrosis were evaluated by hematoxylin\u2010eosin staining and Masson staining. CircRNA sequencing, real\u2010time PCR, and RNA fluorescence in situ hybridization were used to screen and verify the potential circRNAs involved in the repair of damaged endometrium by HuMSCs. Real\u2010time integrated cellular measurement of oxygen consumption rate was performed using the Seahorse XF24 Extracellular Flux Analyzer. The potential downstream miRNAs and proteins of circRNAs were analyzed by dual\u2010luciferase reporter assay and western blot. <jats:italic>Results<\/jats:italic>. HuMSCs\u2010SF\u2010SIS not only increased the number of glands but also reduced the ulcer area in the IUA model. circPTP4A2 was elevated in the HuMSCs seeded on the SF\u2010SIS scaffolds and was targeted by miR\u2010330\u20105p\u2010PDK2. It also stabilized the mitochondrial metabolism of HuMSCs. Moreover, miR\u2010330\u20105p was found to inhibit PDK2 expression through the 3\u2009<jats:sup>\u2032<\/jats:sup> UTR target region. A rescue experiment further showed that circPTP4A2\u2010miR\u2010330\u20105p\u2010PDK2 signaling was critical to HuMSCs\u2010SF\u2010SIS in decreasing the fibrosis area and increasing the number of glands in the IUA model. <jats:italic>Conclusion<\/jats:italic>. We demonstrated that circPTP4A2 was elevated in HuMSCs\u2010seeded on SF\u2010SIS scaffolds and stabilized the mitochondrial metabolism through miR\u2010330\u20105p\u2010PDK2 signaling, which contributes to endometrial repair progression. These findings demonstrate that HuMSCs\u2010seeded SF\u2010SIS scaffolds have potential for the treatment of IUA.<\/jats:p>","DOI":"10.1155\/2022\/2818433","type":"journal-article","created":{"date-parts":[[2022,5,6]],"date-time":"2022-05-06T23:50:18Z","timestamp":1651881018000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":19,"title":["circPTP4A2\u2010miR\u2010330\u20105p\u2010PDK2 Signaling Facilitates In Vivo Survival of HuMSCs on SF\u2010SIS Scaffolds and Improves the Repair of Damaged 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