Noncoding RNAs in chronic wound healing: Mechanisms, exosome therapeutics, and translational frontiers.

Chronic wounds have become major clinical problems due to dysregulated inflammation, impaired angiogenesis, and abnormal extracellular matrix (ECM) remodeling. Noncoding RNA (ncRNA), including microRNA (miRNA), long noncoding RNA (lncRNA), and circular RNA (circRNA), serve as key molecules to regulate these pathological processes. These ncRNA also constructs a competitive endogenous RNA (ceRNA) network to precisely adjust miRNA activity and target gene expression. Through gene editing or chemical modification, exosomes achieve ncRNA delivery with high efficiency and targeting and show exciting promise in preclinical models. Combining with biomaterials such as hydrogels can prolong the exosome half-life and achieve the continuous release of ncRNA. In addition, researchers explore how machine learning (ML) and artificial intelligence (AI) could advance future therapeutic applications. Drug delivery system can be improved both by predicting personalized ceRNA networks for individual patients, and designing smart wound dressings that combine exosomes with hydrogel materials tailored to specific wound types. By integrating these recent advances, this review helps bridge basic research and the future creation of targeted chronic wound treatments.