Oxidative Stress, inflammation and metallomatrix Proteinase-Regulated hydrogels for intervertebral disc regeneration

Intervertebral disc degeneration (IVDD) is still a challenge and the efficient treatment approaches are still lacking, due to the high oxidative stress and inflammation and matrix degradation. The utilization of bioactive hydrogels as carriers for therapeutic factors offers a powerful means to enhance IVDD treatment. However, the therapeutic efficacy of existing hydrogels heavily relies on the loaded therapeutic drugs, resulting in reduced treatment efficiency. Herein, we report a dual-component polymer network hydrogel (FPFG) based on gelatin methacrylate (GelMA) and poly (ferulic acid)-F127- poly (ferulic acid) (FPF). The FPFG hydrogel exhibited injectability, antioxidative properties, good biocompatibility, and biodegradability. FPFG hydrogel could efficiently suppress the intracellular reactive oxygen species (ROS) and metallomatrix proteinase in nucleus pulposus (NP) cells, inhibit the expression of inflammatory factors in macrophages and enhance the extracellular matrix formation. The rat puncture model revealed that the FPFG hydrogel effectively restored disc height, maintained disc hydration, and preserved tissue structure. By exerting anti-inflammatory and antioxidant activities, the FPFG hydrogel successfully ameliorated the hostile microenvironment commonly found in degenerated disc tissue. These findings highlight the potential application of FPFG hydrogel in enhancing IVDD treatment.