Tannic Acid-Based Injectable Hydrogel Promotes the Recovery of Traumatic Brain Injury by Anti-Ferroptosis

Traumatic brain injury (TBI) can trigger a series of complex physiological responses, with iron overload and neuronal ferroptosis playing particularly pivotal roles. These processes exacerbate secondary brain injury and significantly deteriorate neurological function. To address this challenge, this study developed an innovative local drug delivery strategy: an injectable, post-traumatic microenvironment-responsive hydrogel. The hydrogel, composed of tannic acid (TA) and quaternized chitosan (QCS), is designed to alleviate neurological deficits secondary brain injury following TBI through its anti-ferroptosis mechanism. In vitro, a ferroptosis model was established using HT22 cells treated with the ferroptosis inducer RSL-3, demonstrating the hydrogel's antioxidant capacity in the TBI-like conditions. The results showed that the hydrogel significantly restored cell viability, reversed iron accumulation, alleviated lipid peroxidation, and restored mitochondrial function. Further in vivo experiments in the TBI model showed that the TA/QCS hydrogel not only effectively inhibited neuronal degeneration, reduced iron accumulation, and lipid peroxidation but also restored mitochondrial function in neurons. Additionally, the hydrogel significantly attenuated neuroinflammation by inhibiting the activation of microglia and astrocytes, thereby facilitating neurological recovery after TBI. This study offers novel insights into TBI management strategies aimed at preventing the progression of a secondary injury.