ROS-responsive hydrogel-delivered miR-665 targets STAT3 to alleviate inflammation and promote hair follicle regeneration in alopecia areata

Evidence from laboratory and animal studies provides groundwork for understanding mechanisms and potential before human studies continue.

• Level A · Stronger Clinical Evidence
• Level B · Emerging clinical evidence with positive signals
• Level C · Early human research exploring benefits
• Level D · Scientific groundwork from lab and animal studies
• Emerging · Emerging topic under active research

Abstract (original English)

Background Alopecia areata (AA) is an autoimmune disorder characterized by γ-interferon (IFN-γ)-driven CD8 + T-cell infiltration and overactivation of the JAK-STAT pathway; however, safe and long-acting therapies are lacking. MicroRNA (miRNA)-based interventions hold promise as alternatives, but their clinical translation is hindered by poor stability and the absence of targeted delivery systems. Methods We identified miR-665 as a key regulator of STAT3 in embryonic mesenchymal stem cell-derived extracellular vesicles via RNA sequencing and functional screening. An injectable, reactive oxygen species (ROS)-responsive hydrogel (PVA-TSPBA) was developed to enable localized and sustained delivery of miR-665. The physicochemical properties, miRNA release kinetics, and biocompatibility of the hydrogels were systematically characterized. Therapeutic efficacy was evaluated in an imiquimod-induced AA mouse model through macroscopic, histological, and immunohistochemical analyses. Results The PVA-TSPBA hydrogel exhibited excellent injectability, ROS-dependent degradation, and sustained release of miR-665. In vitro, miR-665 overexpression counteracted the IFN-γ-induced suppression of proliferation and migration in keratinocytes and dermal papilla cells by inhibiting STAT3 phosphorylation. In vivo, injection of PVA-TSPBA@miR-665 hydrogel resulted in prolonged miRNA retention, and signific

Evidence level

Evidence from laboratory and animal studies provides groundwork for understanding mechanisms and potential before human studies continue.

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