Injectable, antioxidant, biomechanically supported nanocomposite hydrogels for the treatment of intervertebral disc degeneration

Intervertebral disc degeneration (IVDD) is one of the leading causes of lower back pain, typically accompanied by oxidative stress, inflammatory responses, and imbalances in the mechanical microenvironment. In this study, we developed a multifunctional nanocomposite hydrogel for minimally invasive treatment of IVDD. This hydrogel (TP-Arg@MTG) incorporates tea polyphenol and L-arginine self-assembled nanoparticles (TP-Arg) into a gelatin–mucin matrix, followed by enzymatic crosslinking via transglutaminase to enhance structural stability. The nanoparticles of TP-Arg not only exhibit an exceptional ability to scavenge reactive oxygen species (ROS) but also effectively promote the synthesis of the extracellular matrix (ECM) through nitric oxide (NO)-mediated signaling pathways. Their integration significantly improves the mechanical strength of the hydrogel while enabling sustained release functionality. Gelatin offers cell adhesion and ECM-like architecture, whereas mucin enhances lubrication and moisture retention, better mimicking the native microenvironment of the nucleus pulposus. In vitro and in vivo experiments demonstrate that the hydrogel possesses favorable biocompatibility, effectively attenuates inflammatory responses in nucleus pulposus cells (NPCs), and maintains cellular viability and ECM stability. Collectively, TP-Arg@MTG holds great promise as a novel therapeutic strategy for IVDD by synergistically addressing oxidative damage and mechanical instability through antioxidation, tissue repair promotion, and mechanical reinforcement.