The role of non-coding RNAs in exosome-mediated wound healing: A systematic review and meta-analysis

Clinically, wound healing remains a significant challenge, particularly in the management of chronic wounds such as diabetic foot ulcers. The comparative effectiveness of various non-coding RNA (ncRNA) categories has not yet been thoroughly assessed, even though exosomal ncRNA has become a promising therapeutic molecule. To assess the effectiveness and safety of exosomal ncRNA in wound healing within preclinical trials, we carried out a comprehensive systematic assessment of the available data. Up until July 5, 2025, a comprehensive search of PubMed, Embase, and Ovid MEDLINE was conducted. Included were preclinical investigations that contrasted exosomal ncRNA with controls in animal wound models. Of the 44 included studies, 37 contributed to the quantitative synthesis. Exosomal ncRNA demonstrated a statistically significant improvement in wound closure rate (SMD = 2.89, 95% CI: 2.44 to 3.34, P < 0.00001). A pre-specified subgroup analysis revealed a statistically significant difference among ncRNA categories (P = 0.01), with long non-coding RNA (lncRNA) exhibiting the largest effect size (SMD = 3.72), followed by microRNA (miRNA) (SMD = 3.00) and circular RNA (circRNA) (SMD = 1.98). Significant improvements were also observed across all secondary outcomes, including angiogenesis (SMD = 5.46), collagen deposition (SMD = 3.65), re-epithelialization (SMD = 5.03), and scar width reduction (SMD = -5.05). Sensitivity analyses validated the robustness of the results. This study provides encouraging preclinical evidence that exosomal ncRNA is a promising strategy for wound healing. The discovery that lncRNAs, miRNAs, and circRNAs delivered by exosome might have diverse therapeutic effects provides preliminary insights, suggesting the potential value of exploring specific ncRNA classes for particular therapeutic targets.