Photothermal Hydrogel with Mn3O4 Nanoparticles Alleviates Intervertebral Disc Degeneration by Scavenging ROS and Regulating Extracellular Matrix Metabolism

Abstract Annulus fibrosus (AF) injury plays a critical role in intervertebral disc degeneration (IVDD), with oxidative stress and extracellular matrix (ECM) imbalance being major pathogenic factors. However, effective repair methods are limited. In this study, an injectable photothermal hydrogel, Mn 3 O 4 @ChS‐HA, composed of dopamine‐grafted oxidized chondroitin sulfate (dop‐OChS), adipic dihydrazide‐modified hyaluronic acid (ADH‐HA), and Mn 3 O 4 nanoparticles is constructed to repair AF damage. The Mn 3 O 4 @ChS‐HA mimics the native intervertebral disc environment, offering excellent mechanical properties and strong adhesion to the AF defect site, while enabling long‐term retention of Mn 3 O 4 nanoparticles. Mn 3 O 4 nanoparticles exhibit catalytic properties similar to those of superoxide dismutase, catalase, and glutathione peroxidase, efficiently scavenging reactive oxygen species and modulating ECM metabolism. In vitro and in vivo studies demonstrate that Mn 3 O 4 @ChS‐HA significantly inhibits apoptosis, delays cell senescence, reduces inflammation, and promotes autophagy, facilitating AF repair. The hydrogel also restores disc height and maintained ECM integrity in a rat model of AF injury. Mild photothermal therapy (MPTT) further enhances these effects, supporting tissue regeneration and delaying the progression of IVDD. The MPTT‐nanozyme‐hydrogel system, Mn 3 O 4 @ChS‐HA, exhibits various biological functions by regulating redox homeostasis and promoting tissue repair, highlighting the potential of this approach as a promising strategy for IVDD treatment.