Microsphere-loaded Thermosensitive Hydrogel with Leptin and VEGF for Combined Radiation and Wound Injury Treatment

Abstract

Combined radiation and wound injury (CRWI), caused by the interaction between radiation and trauma, presents major challenges to wound healing and is a key focus in trauma and radiation medicine. This study developed a microsphere-encapsulated composite hydrogel loaded with leptin (LP) and vascular endothelial growth factor (VEGF) to enhance CRWI wound healing. Drug-loaded sodium alginate (SA) microspheres were fabricated using the emulsion cross-linking method and integrated into thermosensitive Pluronic hydrogel to form the VEGF/LP-SA@P nanodelivery system. The microspheres’ physicochemical properties were characterized using scanning electron microscopy (SEM), rheometry, and enzyme-linked immunosorbent assay (ELISA) kits. The results showed that the microspheres had an intact structure with uniform size distribution, LP and VEGF encapsulation efficiencies of 48.01% and 49.58%, respectively, and enabled sustained drug release over 14 d. The hydrogel exhibited a phase transition temperature of 21.2 °C and a rapid phase transition time of 8 s. In vitro, VEGF/LP-SA@P reversed radiation-induced reductions in cell migration, oxidative stress elevation, and apoptosis. In vivo, the hydrogel accelerated CRWI wound healing and reduced scar tissue formation, likely through promoting angiogenesis, modulating collagen fiber ratios, and inhibiting apoptosis. In conclusion, VEGF/LP-SA@P shows significant potential for CRWI treatment.

Keywords

Combined radiation and wound injury / Leptin / Vascular endothelial growth factor (VEGF)

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