A reactive oxygen species- and acidic pH-responsive hydrogel loaded with Tempol and poly-lysine enhances spinal cord injury repair in rat models

Abstract Spinal cord injury (SCI) is characterized by excessive reactive oxygen species (ROS) and an acidic pH, which hinder repair. This study aimed to develop and evaluate a local therapeutic strategy using a temperature-sensitive hydrogel loaded with antioxidant and acid-neutralizing nanoparticles to form a DT NP–Hydrogel designed to clear ROS, neutralize acidity, and promote neurological recovery after SCI. Both in vitro and in vivo, DT NP and the local administration of DT NP–Hydrogel significantly reduced ROS levels (4-hydroxynonenal), cell apoptosis (caspase-3), and connexin 43 expressions in primary spinal cord neuron models induced by hydrogen peroxide, and in SCI rat models caused by fall injury, while increasing class III β-tubulin expression. Moreover, our findings also revealed that the locally administered DT NP–Hydrogel exhibited no side effects, making it a promising therapeutic alternative for SCI.