Iron‐Based Metal‐Organic Framework MIL‐100(Fe) Regulates Keloid Scarring in a Humanized Keloid Model

Keloids are characterized by excessive collagen deposition and persistent inflammation, causing high morbidity and recurrence with limited effective treatments. In this study, MIL-100(Fe)- a metal-organic framework composed of ferrous/ferric ion nodes and 1,3,5-benzenetricarboxylate ligands- is synthesized via a microwave-assisted hydrothermal method and demonstrated nanoscale particle size (141.7 nm). In vitro, human keloid fibroblasts maintained >90% viability after 48 h with MIL-100(Fe) treatment and showed robust cellular uptake within 2 h, compared to PBS-treated controls. MIL-100(Fe) significantly reduced fibroblast migration and downregulated fibrosis-associated proteins after 48 h, including collagen I, collagen III, transforming growth factor beta 1 (TGF-β1), SMAD3, and prolyl 4-hydroxylase subunit alpha 1 (P4HA1). Western blot analysis confirmed that TGF-β1 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-100(Fe) injection reduced fibrous tissue volume by 27% by week two post-treatment compared with controls. Histological analysis showed decreased fibroblast density, decreased collagen fiber area, polarized macrophage infiltration, and vacuolization in the MIL-100(Fe) treated group. These findings suggest that MIL-100(Fe) selectively targets the TGF-β/SMAD pathway, thereby reducing collagen deposition and fibrosis, and highlight its potential as a therapeutic nanoplatform for keloid treatment.