A ROS-responsive loaded desferoxamine (DFO) hydrogel system for traumatic brain injury therapy

Abstract Traumatic brain injury (TBI) produces excess iron, and increased iron accumulation in the brain leads to lipid peroxidation and reactive oxygen species (ROSs), which can exacerbate secondary damage and lead to disability and death. Therefore, inhibition of iron overload and oxidative stress has a significant role in the treatment of TBI. Functionalized hydrogels with iron overload inhibiting ability and of oxidative stress inhibiting ability will greatly contribute to the repair of TBI. Herein, an injectable, post-traumatic microenvironment-responsive, ROS-responsive hydrogel encapsulated with deferrioxamine mesylate (DFO) was developed. The hydrogel is rapidly formed via dynamic covalent bonding between phenylboronic acid grafted hyaluronic acid (HA-PBA) and polyvinyl alcohol (PVA), and phenylboronate bonds are used to respond to and reduce ROS levels in damaged brain tissue to promote neuronal recovery. The release of DFO from HA-PBA/PVA hydrogels in response to ROS further promotes neuronal regeneration and recovery by relieving iron overload and thus eradicating ROS. In the Feeney model of Sprague Dawley rats, HA-PBA/PVA/DFO hydrogel treatment significantly improved the behavior of TBI rats and reduced the area of brain contusion in rats. In addition, HA-PBA/PVA/DFO hydrogel significantly reduced iron overload to reduce ROS and could effectively promote post-traumatic neuronal recovery. Its effects were also explored, and notably, HA-PBA/PVA/DFO hydrogel can reduce iron overload as well as ROS, thus protecting neurons from death. Thus, this injectable, biocompatible and ROS-responsive drug-loaded hydrogel has great potential for the treatment of TBI. This work suggests a novel method for the treatment of secondary brain injury by inhibiting iron overload and the oxidative stress response after TBI.