A sprayable exosome-loaded hydrogel with controlled release and multifunctional synergistic effects for diabetic wound healing

Diabetic wound healing is hindered by bacterial infections, oxidative stress, impaired vascularization, and chronic inflammation. Conventional dressings, limited by static drug release and single-functionality, fail to dynamically match the varying demands of different healing stages and dressing replacement frequencies. This study developed a multifunctional sprayable hydrogel dressing (Exo@AMCN) by photocrosslinking methacrylated decellularized dermal matrix co-loaded with human umbilical cord mesenchymal stem cell-derived exosomes (hUCMSC-Exo) and β-cyclodextrin-borneol inclusion complexes (CN). The hydrogel can be sprayed onto irregularly shaped wounds, with its crosslinking density and degradation kinetics precisely modulated by adjusting the photocuring duration. This tunability enables controlled release of exosomes and borneol over 2 – 7 days. Experimental findings demonstrate that Exo@AMCN displays excellent biocompatibility, broad-spectrum antibacterial activity (> 85% efficacy), and robust reactive oxygen species scavenging capacity. The dressing significantly boosts cell migration, fosters angiogenesis, and prompts macrophage polarization toward anti-inflammatory phenotypes. In a diabetic wound model, Exo@AMCN reduced residual wound area to 1.07 ± 1.27% within 14 days by modulating tissue inflammation, enhancing collagen deposition, and stimulating neovascularization. This innovative approach, combining controlled drug release with multifunctional synergy, offers a promising individualized solution for managing diabetic wounds. This study introduces a novel approach for the targeted delivery of therapeutic agents by developing a photocrosslinkable ADM hydrogel. As illustrated in graph, methacrylation-modified ADM was functionalized with photosensitive double bonds and combined with lithium phenyl-2,4,6-trimethylbenzoylphosphinate (LAP) as a photoinitiator, forming a sprayable photocrosslinkable hydrogel. By regulating exposure to 405 nm blue light for different durations (10–300 seconds), the crosslinking density and degradation rate of the hydrogel were controlled to meet the specific requirements for dressing changes in diabetic wound healing. This system enables the simultaneous delivery of hUCMSC-Exo and β-cyclodextrin-nature borneol complexes (CN), offering antimicrobial and ROS scavenging capabilities while promoting keratinocyte migration, endothelial angiogenesis, and macrophage polarization to modulate the wound microenvironment. Evaluation through in vivo experiments on full-thickness skin wounds in type I diabetic mice confirmed the hydrogel’s therapeutic efficacy. The synergistic effects of its dynamic adaptability and multifunctional coordination reduced the residual wound area to 1.07 ± 1.27% within 14 days, showing significant improvements in collagen deposition and neovascularization. These findings highligh the promising potential of this smart hydrogel system for diabetic wound management.