Harnessing Mesenchymal Stem Cell-Derived EVs-Loaded Hydrogels: Therapeutic Mechanisms and Applications in Retinal Injury Repair.

Retinal damage remains a leading cause of irreversible vision loss, with conventional surgical and pharmacological approaches limited by suboptimal efficacy and safety concerns. Mesenchymal stem cell-derived extracellular vesicles (MSC-EVs) demonstrate promise for retinal repair through their low immunogenicity, anti-inflammatory, antioxidant, and neuroprotective properties. These nanovesicles deliver functional proteins and miRNAs that enhance neuronal survival, suppress pathological angiogenesis, and attenuate inflammatory cascades, demonstrating efficacy in models of retinal injury. However, rapid systemic clearance and frequent dosing requirements hinder clinical translation. Hydrogel-based delivery systems address these challenges by improving intraocular retention and bioavailability via biocompatibility, controlled release, and barrier protection. This review critically analyzes current retinal treatments, discusses the mechanisms and translational challenges of MSC-EVs, and evaluates the design principles of hydrogel biomaterials. It also synthesizes progress in hydrogel-EV combination strategies for ocular diseases, highlighting their synergistic therapeutic effects while addressing scalability and biosafety issues. The innovative integration of biomaterial and EV therapeutics advances targeted approaches for retinal regeneration.