Royal Jelly Extracellular Vesicles Enhance Diabetic Wound Healing via Inflammation Modulation, Fibroblast Migration,...

Diabetic wounds present a significant clinical challenge because of impaired healing and persistent inflammation. This study explored the therapeutic potential of extracellular vesicles derived from Apis mellifera royal jelly (RJEVs) to enhance diabetic wound repair.

RJEVs were characterized using nanoparticle tracking analysis, transmission electron microscopy, and Western blotting. The results showed that RJEVs had a nanoscale size of approximately 118 nm and were characterized by a double-layered lipid membrane and extracellular vesicle markers CD63 and syntenin. In vitro, RJEVs significantly improved migration by 31.4 ± 4.4% and reduced senescence by 24.7 ± 5.8% in high-glucose-stimulated human dermal fibroblasts. Furthermore, RJEVs restored collagen type I protein expression by 41.9 ± 7.6% under hyperglycemic conditions. RJEVs also mitigated inflammation in lipopolysaccharide-stimulated macrophages and THP-1 cells by downregulating pro-inflammatory cytokines IL-1β, IL-6, IL-8, and TNF-α. Additionally, RJEVs restored endothelial cell migration by 35.7 ± 5.6% and tube formation by 36.1 ± 2.4% under hyperglycemic conditions, accompanied by increased expression of VEGF and CD31. In vivo, RJEVs treatment significantly accelerated wound closure in streptozotocin-induced diabetic porcine models by 32.5 ± 7.2% compared to the control group.

These findings indicate that RJEVs facilitate diabetic wound healing through the coordinated regulation of fibroblast function, immune modulation, and angiogenesis. This study introduces a nature-derived, non-mammalian extracellular vesicle platform with translational potential for chronic wound management in diabetes, offering a biocompatible and multifaceted therapeutic alternative to conventional approaches.