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In vivo chemical reprogramming that harnessing the patient's own cells in damaged tissue is of substantial interest to regenerate organs endogenously by pharmacological manipulation, which could compensate for tissue loss in devastating diseases and injuries, for example, burns. However, achieving in vivo chemical reprogramming is challenging due to the low reprogramming efficiency and an unfavorable tissue environment. Herein, this work has developed a functionalized proteinaceous nanoformulation delivery system containing prefabricated epidermal growth factor structure for on\u2010demand delivery of a cocktail of seven SwG reprogramming components to the dermal site. Such a chemical reprogramming system can efficiently induce the conversion of epidermal keratinocytes\u00a0into SwG myoepithelial cells, resulting in successful in situ regeneration of functional SwGs. Notably, in vivo chemical reprogramming of SwGs is achieved for the first time with an impressive efficiency of 30.6%, surpassing previously reported efficiencies. Overall, this proteinaceous nanoformulation provides a platform for coordinating the target delivery of multiple pharmacological agents and facilitating in vivo SwG reprogramming by chemicals. This advancement greatly improves the clinical accessibility of in vivo reprogramming and offers a non\u2010surgical, non\u2010viral, and cell\u2010free strategy for in situ SwG regeneration.<\/jats:p>","DOI":"10.1002\/adma.202311845","type":"journal-article","created":{"date-parts":[[2024,5,9]],"date-time":"2024-05-09T00:11:14Z","timestamp":1715213474000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Customized Proteinaceous Nanoformulation for In Vivo Chemical Reprogramming"],"prefix":"10.1002","volume":"36","author":[{"given":"Huating","family":"Chen","sequence":"first","affiliation":[{"name":"Research Center for Tissue Repair and Regeneration affiliated to the Medical Innovation Research Department PLA General Hospital and PLA Medical College State Key Laboratory of Trauma and Chemical Poisoning PLA Key Laboratory of Tissue Repair and Regenerative Medicine and Beijing Key Research Laboratory of Skin Injury Repair and Regeneration Research Unit of Trauma Care Tissue Repair and Regeneration Chinese Academy of Medical Sciences  2019RU051 Beijing 100048 P. 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