Hydrogel-based delivery of MSCs and derivatives for improved diabetic retinopathy therapy

Abstract Diabetic retinopathy (DR), the most prevalent ocular complication of diabetes, progresses from non-proliferative (NPDR) to sight-threatening proliferative (PDR) stages. Current interventions—including retinal photocoagulation, intravitreal anti-VEGF agents, and surgery—address advanced disease, often require repeated administration, and carry risks like retinal injury. Safer, more effective, and longer-lasting treatments are needed, especially for early-stage DR. Mesenchymal stem cells (MSCs) and their derivatives offer a promising alternative, with advantages including low immunogenicity, paracrine signaling, and the ability to mitigate inflammation and vascular permeability. However, challenges in delivery efficiency and targeting specificity remain. Hydrogel-based scaffold materials are increasingly important due to their superior biocompatibility and ability to overcome ocular barriers. Recent advances include novel injectable hydrogels that can be combined with drugs or stem cells, enabling targeted delivery to retinal layers, prolonging therapeutic retention, and significantly improving bioavailability for sustained treatment of DR. Graphical Abstract