Nanozyme-integrated hydrogel orchestrates mitochondrial quality control to counter inflammatory and oxidative milieu during disc degeneration.
TL;DR
In vitro and in vivo evidence confirms that this dual-functional hydrogel attenuates NP cell inflammation and significantly retards the progression of IDD, offering a synergistic strategy that couples nanozyme-mediated antioxidant therapy with targeted FPR1 blockade, holding substantial promise for intervertebral disc repair.
Abstract
Intervertebral disc degeneration (IDD) is a major cause of low back pain, driven by nucleus pulposus (NP) cell dysfunction, excessive reactive oxygen species (ROS), and chronic inflammation. Current biomaterial-based strategies often fail to simultaneously address oxidative stress and inflammatory signaling in a sustained and synergistic manner. Here, we develop a thermosensitive Pluronic F127-based composite hydrogel co-delivering a tannic acid‑cerium nanozyme and the FPR1 antagonist HCH6-1. The hydrogel undergoes sol-gel transition at body temperature, enabling minimally invasive injection and sustained local release in the intervertebral disc. The cerium nanozyme exerts potent ROS-scavenging activity, effectively reducing intracellular ROS levels and upregulating the antioxidant protein TXNRD1. Meanwhile, HCH6-1 specifically antagonizes FPR1, thereby suppressing cGAS-STING pathway activation and suppressing downstream inflammatory cascades. Beyond direct anti-inflammatory effects, this system significantly enhances mitophagy activity in NP cells, facilitating the clearance of dysfunctional mitochondria and restoring autophagic flux. Collectively, in vitro and in vivo evidence confirms that this dual-functional hydrogel attenuates NP cell inflammation and significantly retards the progression of IDD. Thus, this injectable and biocompatible platform offers a synergistic strategy that couples nanozyme-mediated antioxidant therapy with targeted FPR1 blockade, holding substantial promise for intervertebral disc repair.