Curcumin nanoparticles and mesenchymal stem cell exosomes embedded in gelatin hydrogel enhance healing of severe...

Severe burn injuries present a significant clinical challenge due to prolonged inflammation, delayed re-epithelialization, and high risk of infection. Recent advances in regenerative medicine have highlighted the potential of combining bioactive compounds with cell-derived products to enhance tissue repair. In this study, we developed a novel therapeutic hydrogel composed of gelatin, mesenchymal stem cell (MSC)-derived exosomes, and nanocurcumin (nCur) for promoting burn wound healing. The nanocurcumin was synthesized using a precipitation method and characterized for size, morphology, and loading efficiency. Exosomes were isolated from MSC culture supernatants using differential ultracentrifugation and confirmed via nanoparticle tracking analysis and CD63 expression. The gelatin hydrogel was loaded with both bioactive agents to form a composite wound dressing. In vitro assays demonstrated that the dual-loaded hydrogel enhanced fibroblast proliferation, migration, and angiogenesis compared to hydrogels containing only exosomes or nCur. In vivo studies using a rat deep second-degree burn model revealed that wounds treated with the exosome-nCur hydrogel exhibited significantly faster closure, enhanced granulation tissue formation, increased collagen deposition, and reduced inflammation compared to controls. Histological and immunohistochemical analyses confirmed enhanced re-epithelialization and neovascularization in the treated groups. Our results suggest that the complementary action of exosomes and nanocurcumin, delivered via a biocompatible gelatin matrix, can effectively accelerate burn wound healing by modulating inflammation, promoting angiogenesis, and supporting tissue regeneration. This multifunctional hydrogel dressing represents a promising and clinically translatable approach for advanced wound care.