Skin regenerative potential of hydrogel matrices incorporated with stem cell-derived extracellular vesicles enriched with MicroRNAs: a systematic review.

Stem cell-derived extracellular vesicles (SC-EVs) are one huge promise in skin regenerative medicine, similar in advantages to stem cells with low immunerejection and tumor formations. These microvesicles are laden with microRNAs, which assist in wound healing via angiogenesis and immune modulation. However, quick degradation and poor cellular uptake limit their regenerative capacity. Thanks to their adjustable characteristics, hydrogels can act as vehicles for transporting and sustainably releasing miRNA-SC-EVs at injury sites. Therefore, a systematic literature review was conducted on miRNA-enriched SC-EVs incorporated into hydrogels in animal skin regeneration models published from 2010 to 2024 (PROSPERO ID: CRD42024588072). Out of the 89 records, 12 met the criteria. Diabetic wounds are characterized by chronic inflammation, oxidative stress, and defective macrophage polarization, resulting in less satisfactory regeneration. The hydrogels tackled these issues by shifting macrophages from a pro-inflammatory M1 phenotype to a healing M2 phenotype, promoting collagen production, enhancing fibroblast movement, and boosting angiogenesis. Burn injuries frequently lead to slow recovery due to hypertrophic scarring, extended inflammation, and infection. Hyaluronic acid (HA)-derived hydrogels, infused with miR-21-5p and surface-treated with polydopamine and cationic antimicrobial peptides, promoted wound healing by lowering scarring and demonstrating anti-inflammatory, anti-apoptotic, and pro-angiogenic characteristics. The cell adhesion of these hydrogels can be enhanced by adding MOFs, chitosan, and extracellular matrix elements. The application of stimulus-responsive or stage-specific hydrogels is another mode of targeted healing. Further research and clinical trials will enhance the wound-healing efficiency of hybrid hydrogels.