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However, side effects, particularly pain, pose a significant challenge to injection therapy. A fractional ultrasound (FRUS) platform is developed to treat keloids and deliver drugs with minimal invasiveness and ease of operation. Keloid\u2010bearing nude mice models are developed to investigate the in vivo effectiveness of FRUS. A pilot clinical trial is further undertaken to uncover its significancein clinical practice. This platform activated Piezo1 channels through low\u2010frequency ultrasound, inhibiting fibroblast proliferation, and utilized the cavitation effect to remold fibrous tissues, improving drug diffusion, and finally alleviating side effects associated with injection therapy. In vivo mice experiments demonstrated that FRUS platform increased the expression of Piezo1 channels and inhibited keloids growth without causing systematic adverse events. Eight participants with keloids are enrolled in the clinical trial and treated with this approach combined with anti\u2010keloid drugs. The findings indicated that FRUS significantly alleviated injection\u2010associated pain by 51.9% and reduced the keloid volume. These results reveal the potential therapeutic mechanism and provide a foundation for the clinical application of this approach in enhancing keloids treatment.<\/jats:p>","DOI":"10.1002\/adhm.202503332","type":"journal-article","created":{"date-parts":[[2025,10,3]],"date-time":"2025-10-03T05:38:47Z","timestamp":1759469927000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Synergistic Intervention of Piezo1 Activation and Fibrous Tissue Remodeling to Ease Side Effects of Intralesional Therapy for Keloids"],"prefix":"10.1002","volume":"15","author":[{"given":"Zixi","family":"Jiang","sequence":"first","affiliation":[{"name":"Department of Dermatology Xiangya Hospital Central South University  Changsha 410008 China"},{"name":"Furong Laboratory (Precision Medicine)  Changsha 410008 China"},{"name":"National Engineering Research Center of Personalized Diagnostic and Therapeutic Technology Xiangya Hospital Central South 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