Reactive oxygen species-scavenging hydrogels loaded with tempol exert anti-oxidative effects in spinal cord injury rat models

Abstract

Traumatic spinal cord injury (SCI) is characterized by excessive reactive oxygen species (ROS) accumulation coupled with a sustained acidic lesion microenvironment, both of which severely hinder endogenous neural tissue repair. This study reports the fabrication and comprehensive in vitro and in vivo validation of a thermosensitive injectable hydrogel embedded with ROS-eliminating nanoparticles (DHA-PLL-TPL nanoparticles hydrogel, DT NP–Hydrogel) for localized SCI treatment. In hydrogen peroxide-challenged primary spinal cord neuron cultures and weight-drop contusion rat SCI models, locally injected DT NP–Hydrogel significantly reduced oxidative stress marker 4-hydroxynonenal (4HNE), pro-apoptotic Caspase-3 (Casp3) expression, and gap junction protein connexin 43 (Cx43) levels, while simultaneously upregulating the neuron-specific marker class III β-tubulin (Tuj1). Collectively, our in vitro and in vivo data demonstrate that DT NP–Hydrogel mitigates secondary spinal cord damage and delivers potent neuroprotective activity, establishing it as a promising therapeutic strategy for SCI.