A bioinspired biotin-avidin hydrogel with prolonged SHED Exo delivery enhances diabetic wound healing by modulating the Treg/Th17 balance

Stem cell-derived exosomes from human exfoliated deciduous Teeth (SHED-Exos) show promising treatment effects through immune modulation and angiogenic properties. However, when applied to diabetic wound healing, their inactivation and rapid clearance limit their clinical application. In this study, we aimed to develop a chitosan/dextran-based hydrogel using a biotin-avidin system that showed excellent injectability, adhesiveness, and antibacterial effects and enabled the slow and steady release of SHED-Exos to enhance diabetic wound healing. SHED-Exos were immobilized within a hydrogel through the biotin-avidin interaction and electrostatic forces of chitosan, allowing for slow release over >7 days. Additionally, the hydrogel exhibited excellent cell compatibility and supported cell spheroid growth in a 3D network. In vivo , the hydrogel significantly enhanced wound healing in diabetic rats by reducing inflammation and decreasing the ratio of Th17/Treg cells around wounds. This innovative noncellular hydrogel shows promise in facilitating the healing of diabetic wounds and may serve as a potential clinical therapy using natural bioactive materials delivery of exosomes.