pH and enzyme dual-responsive release of hydrogen sulfide for disc degeneration therapy

Intervertebral disc degeneration (IDD) usually causes lower back and neck pain with a high incidence, which significantly reduces the life quality of patients. However, there is no effective treatment available currently. Our previous study has found that hydrogen sulfide (H₂S) shows potential therapeutic effect toward IDD. However, the burst release and fast vanishing of H₂S in the lesion severely limit its further application. Therefore, in this study, we develop a pH and enzyme dual-responsive H₂S releasing hydrogel system to treat IDD. This hydrogel named Col-JK1 is quite stable under neutral conditions but rapidly releases H₂S by responding to acidic pH and high matrix metalloproteinases (MMPs) levels in the pathological IDD environment. In vivo study firstly uncovered that Col-JK1 can effectively impede disc degeneration in a puncture-induced IDD rat model. Further in vitro studies reveal that Col-JK1 protects the disc from degeneration by inhibiting the apoptosis of nucleus pulposus (NP) cells and attenuating the degradation of the disc extracellular matrix (ECM). And the protective effect of Col-JK1 is attributed to its anti-inflammatory effects through the regulation of the NF-κB signaling pathway. Thus, our study provides a novel therapeutic option for IDD therapy by controlling the release of H₂S.