Bioactive microneedles enabled by Ca-MOF-regulated collagenase for synergistic hypertrophic scar remodeling

Hypertrophic scars resulting from pathological fibrosis and excessive collagen deposition cause significant functional and aesthetic impairment. Conventional therapies often fail to address the underlying molecular mechanisms of collagen overproduction. To overcome these limitations, we developed a novel layered dissolving microneedle system (MOF-CCH-MN) capable of delivering a synergistic therapeutic payload. This system incorporates Clostridium histolyticum collagenase (CCH) loaded within a calcium-based metal-organic framework (Ca-MOF), embedded in a γ-polyglutamic acid (γ-PGA) matrix. Characterization studies demonstrate that the microneedles possess a uniform pyramidal structure, penetrate the stratum corneum effectively, and dissolve within 25 min. Mechanistically, the Ca-MOF acts as a smart reservoir, protecting enzymatic activity while releasing Ca²⁺ and gallic acid to scavenge reactive oxygen species(ROS) and inhibit fibroblast - to - myofibroblast transition. In vitro assays confirmed that the system significantly downregulates pro-inflammatory cytokines (TNF-α, IL-1β) and suppresses fibrogenic gene expression (α-SMA, COL1A1, TGF-β). In vivo evaluation in a rabbit ear hypertrophic scar model demonstrated that a 20-day treatment regimen with MOF-CCH-MN significantly reduced scar thickness and promoted the reorganization of collagen fibers. These findings establish MOF-CCH-MN as a safe, effective, and minimally invasive platform for clinical scar management.