mRNA-based nanomedicine for diabetic wound repair: advances in LNP delivery, immune modulation, and regenerative pathways.

Diabetic wounds represent a major complication of diabetes mellitus, characterized by chronic inflammation, impaired angiogenesis, immune imbalance, oxidative stress, endothelial dysfunction, and defective extracellular matrix remodeling, which hinder tissue repair. Although current therapies have shown potential, their clinical efficacy remains limited due to poor stability, degradation, insufficient tissue retention, and inconsistent outcomes. Messenger RNA (mRNA)-based nanomedicine has emerged as an innovative regenerative approach, enabling transient, localized, and non-integrative expression of therapeutic proteins within wound microenvironments. Recent advances in delivery platforms, including ionizable lipid nanoparticles, polymeric nanoparticles, hydrogels, microneedles, have enhanced mRNA stability, cellular uptake, and therapeutic performance. Beyond protein replacement, mRNA nanomedicine can modulate regenerative pathways, including macrophage polarization, inflammatory resolution, angiogenesis, oxidative stress regulation, autophagy, ferroptosis inhibition, extracellular matrix remodeling, and regulatory RNA networks. This review summarizes recent progress in mRNA-based nanomedicine for diabetic wound healing, highlighting delivery strategies, immune modulation, and biomaterial-assisted RNA therapeutics. Literature searches were conducted using PubMed, Scopus, Web of Science, and Google Scholar databases for studies published between 2010 and 2026. Translational challenges involving biosafety, regulatory barriers, and preclinical limitations are discussed. Overall, mRNA nanomedicine represents a promising platform for next-generation diabetic wound therapies.