162. Iron-Based Metal-Organic Framework MIL-100(Fe) Modulates Keloid Scarring

PURPOSE: Pathological scarring such as keloids poses significant therapeutic challenges due to their complex pathophysiology, often resulting in substantial functional impairments and aesthetic concerns. Metal-Organic Frameworks (MOFs), specifically MIL-100(Fe), have emerged as a promising treatment modality for keloid scars. This study aims to synthesize and characterize MIL-100(Fe) while investigating its effects on keloid fibroblasts. METHODS: MIL-100(Fe) was synthesized via microwave-assisted methods, and its morphology was analyzed using high-resolution Transmission Electron Microscopy (TEM) and Scanning Electron Microscopy (SEM). Crystallinity was confirmed through X-ray Diffraction (XRD), while functional groups were identified by Fourier-transform infrared spectroscopy (FTIR). Specific surface area was determined using Brunauer-Emmett-Teller (BET) analysis, and particle size and stability were assessed by Dynamic Light Scattering (DLS) and Zeta Potential analysis. Thermogravimetric analysis (TGA) was used to study thermal stability. Human keloid fibroblasts, isolated from biopsies, were treated with MIL-100(Fe) at concentrations of 0, 10, 50, and 100 μg/ml. Cell viability was measured using the AlamarBlue assay, cellular uptake was observed via calcein-AM staining, migration was assessed using a cell migration assay, and Western blot analysis quantified the expression of key wound healing proteins. RESULTS: MIL-100(Fe) was successfully synthesized, with XRD confirming retention of its crystal structure. FTIR confirmed the presence of key functional groups, validating successful synthesis. TGA indicated high thermal stability, with 80% weight retention up to 400°C. MIL-100(Fe) exhibited a high specific surface area of 1575.67 ± 35.31 m²/g, demonstrating substantial porosity. DLS revealed an optimal particle size of 202.30 nm and a zeta potential of -24.9 mV, indicating good dispersion and biocompatibility. Viability and cellular uptake assays demonstrated that fibroblast cell viability exceeded 90% with significant uptake of MIL-100(Fe) across all treatment concentrations. Treatment with 100 μg/ml MIL-100(Fe) treatment demonstrated a significant reduction in fibroblast mobility. Western blot analysis revealed substantial downregulation of collagen I (0.25 ± 0.06 vs. 0.83 ± 0.10, p < 0.0001), collagen III (0.27 ± 0.04 vs. 0.91 ± 0.05, p < 0.0001), TGF-β1 (0.49 ± 0.11 vs. 0.83 ± 0.06, p = 0.001), SMAD3 (0.33 ± 0.13 vs. 0.76 ± 0.06, p = 0.0005), and P4HA1 (0.74 ± 0.05 vs. 0.85 ± 0.07, p = 0.02). CONCLUSION: This study successfully synthesized and characterized MIL-100(Fe), demonstrating its high porosity and biocompatibility, making it a promising carrier for therapeutic agents. Treatment with MIL-100(Fe) not only reduced fibroblast mobility but also significantly downregulated key fibrosis-related proteins, including P4HA1, TGF-β1, and SMAD3. This suggests that MIL-100(Fe) may effectively inhibit TGF-β/SMAD and P4HA1 pathways, which are central to collagen synthesis and keloid scarring. Mechanistically, MIL-100(Fe) may disrupt fibrotic pathways by modulating intracellular iron ion homeostasis.