ArticleJournal of nanobiotechnology2026
ROS-responsive hydrogel-delivered miR-665 targets STAT3 to alleviate inflammation and promote hair follicle regeneration in alopecia areata.
Article in Journal of nanobiotechnology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
backgroundAlopecia 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.
methodsWe 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.
resultsThe 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 significantly promoted hair regeneration, restored follicular structure, and reduced T-cell infiltration compared with the control groups.
conclusionsWe developed a biocompatible, ROS-responsive hydrogel platform for the local delivery of miR-665, which effectively attenuated inflammatory signaling and stimulated hair follicle regeneration in AA. This study provides a novel miRNA-biomaterial combination strategy that holds promise for targeted, durable, and safe treatment of AA.
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