Bimetallic nanozyme-functionalized injectable hydrogel for enhanced therapy for intervertebral disc degeneration

Intervertebral disc degeneration (IVDD) is a major reason for low back pain. Inflammation and oxidative stress are key drivers for initiating and progressing IVDD, triggering extracellular matrix (ECM) degradation and inducing the apoptosis of nucleus pulposus cells. However, effective treatment modalities targeting the harsh and degenerative nature of the intervertebral disc are lacking. Herein, we prepared an advanced multifunctional injectable bimetallic metal–organic framework (MOF)-loaded OHA@PA@Fe@QCS (OPQ) hydrogel (OPQ@MOFs) to alleviate IVDD. The bimetallic MOF nanozymes exhibited potent antioxidant enzyme-like activity, counteracting oxidative stress and normalizing the redox equilibrium. The hydrogel OPQ exhibited injectability, biodegradability, favorable biocompatibility, and antibacterial and hemostatic capabilities, working collectively to synergistically enhance the therapeutic efficacy of MOFs. In vitro studies revealed that OPQ@MOFs can alleviate oxidative stress, decrease inflammatory responses, and prevent abnormal ECM degradation. RNA sequencing revealed that its underlying mechanism was associated with the PPARγ signaling pathway. In vivo experiments validated that OPQ@MOFs facilitated ECM regeneration, preserved the morphological and structural integrity of the nucleus pulposus, and alleviated IVDD. Collectively, these results suggest the substantial potential of the bimetallic MOFs-loaded hydrogel in treating IVDD. • The bimetallic nanozyme MIL-101(FeMn) exhibited excellent SOD-, POD-, and CAT-like activities. • OPQ@MOFs exhibited good biocompatibility and could effectively scavenge ROS, restoring intracellular redox balance. • OPQ@MOFs effectively alleviated the inflammation and restored the metabolic homeostasis of the ECM. • OPQ@MOFs can maintain disc height, promote ECM synthesis, preserve NP tissue structure, and effectively attenuate IVDD progression. • This study provided a feasible and applicable alternative to manage IVDD in clinical.