A sprayable exosome-loaded hydrogel with controlled release and multifunctional synergistic effects for diabetic wound healing
Bo Liu, L. Chen, Chaoyang Huang, Huihui Zhang, Hai Zhou, Ying-Cheng Chen, Xiaoyang Liu, Zhenyong Xiao, Kangyan Liang, Xiangtao Xie, Yuan Gao, Kun Liu, Xiangdong Qi
Abstract
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.