Engineering antioxidant poly (citrate-gallic acid)-Exosome hybrid hydrogel with microglia immunoregulation for Traumatic Brain Injury-post neuro-restoration

Traumatic brain injury (TBI) leads to high rates of morbidity and mortality worldwide with few effective treatments. Excessive oxidative stress and local inflammation at the injury site are considered as the critical factors that determine the therapeutic outcome. In our previous study, stem cells from human exfoliated deciduous teeth-derived exosomes (SHED-Exo) promoted functional recovery of TBI by amelioration of neuro-inflammation. However, the effect was restricted due to unsustainable exosome release and existed oxidative stress that aggravate secondary insult of TBI. To obtain a long-time anti-inflammatory effect of SHED-Exo and attenuate oxidative stress simultaneously, we designed a bioactive antioxidant poly (citrate-gallic acid)-based hybrid hydrogel (FPGEGa) that encapsulate SHED-Exo for treating TBI. The thermosensitive, injectable, self-healing and antioxidant FPGEGa presented ultralong sustained release of SHED-Exo (above 21 days) and significantly decreased the intracellular ROS production of microglia in the central nervous system. FPGEGa carrying SHED-Exo ([email protected]) exhibited better anti-inflammatory potential on microglia, by promoting M2 (anti-inflammatory) polarization and inhibiting M1 (pro-inflammatory) polarization. [email protected] could improve the neuro-regeneration of TBI rats by rescuing damaged motor functions in rats as well as regenerating impaired cortical tissues. The present work suggested that SHED-Exo engineered bioactive antioxidative hydrogel may be promising in achieving satisfactory functional recovery in TBI and other related neurological disorders.