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In this study, MIL\u2010100(Fe)\u2013 a metal\u2010organic framework composed of ferrous\/ferric ion nodes and 1,3,5\u2010benzenetricarboxylate ligands\u2013 is synthesized via a microwave\u2010assisted hydrothermal method and demonstrated nanoscale particle size (141.7\u00a0nm). In vitro, human keloid fibroblasts maintained &gt;90% viability after 48\u00a0h with MIL\u2010100(Fe) treatment and showed robust cellular uptake within 2\u00a0h, compared to PBS\u2010treated controls. MIL\u2010100(Fe) significantly reduced fibroblast migration and downregulated fibrosis\u2010associated proteins after 48\u00a0h, including collagen I, collagen III, transforming growth factor beta 1 (TGF\u2010\u03b21), SMAD3, and prolyl 4\u2010hydroxylase subunit alpha 1 (P4HA1). Western blot analysis confirmed that TGF\u2010\u03b21 expression is more strongly suppressed in human keloid fibroblasts than in human monocytes. In an in vivo humanized keloid mouse model, four weeks of intralesional MIL\u2010100(Fe) injection reduced fibrous tissue volume by 27% by week two post\u2010treatment compared with controls. Histological analysis showed decreased fibroblast density, decreased collagen fiber area, polarized macrophage infiltration, and vacuolization in the MIL\u2010100(Fe) treated group. These findings suggest that MIL\u2010100(Fe) selectively targets the TGF\u2010\u03b2\/SMAD pathway, thereby reducing collagen deposition and fibrosis, and highlight its potential as a therapeutic nanoplatform for keloid treatment.<\/jats:p>","DOI":"10.1002\/smll.202511971","type":"journal-article","created":{"date-parts":[[2026,4,10]],"date-time":"2026-04-10T07:21:34Z","timestamp":1775805694000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Iron\u2010Based Metal\u2010Organic Framework MIL\u2010100(Fe) Regulates Keloid Scarring in a Humanized Keloid Model"],"prefix":"10.1002","volume":"22","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7064-4093","authenticated-orcid":false,"given":"Po\u2010Hsiu","family":"Cheng","sequence":"first","affiliation":[{"name":"International Graduate Program of Molecular Science and Technology Taiwan International Graduate Program Academia Sinica  Taipei 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