Injectable ROS-Scavenging Trimetallic Nanocomposite Hydrogel Modulates Oxidative Microenvironment for Treatment of Intervertebral Disc Degeneration

Abstract

As a central driver of intervertebral disc degeneration (IVDD), oxidative stress mediates pathological changes by promoting extracellular matrix (ECM) breakdown, thereby accelerating the degenerative process. To target this pathological cascade, trimetallic nanoparticles (TriNPs) are designed and developed to modulate the oxidative microenvironment of intervertebral discs and restore ECM homeostasis through reactive oxygen species (ROS) scavenging. In vitro studies demonstrate that TriNPs provide significant cytoprotection against H2O2-induced oxidative damage in nucleus pulposus (NP) cells through efficient ROS elimination. For translational applications, TriNPs are encapsulated within an injectable hydrogel (termed TOH) to evaluate their therapeutic potential in a rat IVDD model. In vivo studies encompassing both radiographic and histomorphometric analyses reveal that TOH administration significantly improves the Disc Height Index (DHI) and T2-weighted Magnetic Resonance Imaging (MRI) grading, while also reducing histological scores. Collectively, these results indicate that TOH may serve as an innovative therapeutic approach to modulate disc microenvironment and attenuate IVDD progression.