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Herein, a biomimetic corneal stroma with immunomodulatory properties is bioengineered for scarless corneal defect repair. First, a fully defined serum\u2010free system is established to derive stromal keratocytes (hAESC\u2010SKs) from a current Good Manufacturing Practice (cGMP)\u2010grade human amniotic epithelial stem cells (hAESCs), and RNA\u2010seq is used to validate the phenotypic transition. Moreover, hAESC\u2010SKs are shown to possess robust immunomodulatory properties in addition to the keratocyte phenotype. Inspired by the corneal stromal extracellular matrix (ECM), a photocurable gelatin\u2010based hydrogel is fabricated to serve as a scaffold for hAESC\u2010SKs for bioengineering of a biomimetic corneal stroma. The rabbit corneal defect model is used to confirm that this biomimetic corneal stroma rapidly restores the corneal structure, and effectively reshapes the tissue microenvironment via proteoglycan secretion to promote transparency and inhibition of the inflammatory cascade to alleviate fibrosis, which synergistically reduces scar formation by \u224875% in addition to promoting wound healing. Overall, the strategy proposed here provides a promising solution for scarless corneal defect repair.<\/jats:p>","DOI":"10.1002\/adhm.202302889","type":"journal-article","created":{"date-parts":[[2023,11,21]],"date-time":"2023-11-21T23:47:13Z","timestamp":1700610433000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":20,"title":["Biomimetic Corneal Stroma for Scarless Corneal Wound Healing via Structural Restoration and Microenvironment Modulation"],"prefix":"10.1002","volume":"13","author":[{"given":"Jianan","family":"Huang","sequence":"first","affiliation":[{"name":"Eye Center the Second Affiliated Hospital School of Medicine Zhejiang University Zhejiang Provincial Key Laboratory of Ophthalmology Zhejiang Provincial Clinical Research Center for Eye Diseases Zhejiang Provincial Engineering Institute on Eye Diseases  Hangzhou 310009 P. R. 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