Abstract

An imbalance in oxidative and inflammatory regulation is the main contributor to intervertebral disc degeneration (IDD). Hydrogen (H2) therapy is a promising antioxidation and anti-inflammatory approach. However, the key to the treatment is how to maintain the long-term effective H2 concentration in the intervertebral disc (IVD). Therefore, we developed a pH-responsive delivery of H2 through ammonia borane-loaded hollow polydopamine ([email protected]) for IDD therapy, which has sufficient capacity to control long-term H2 release in an acid-dependent manner in degenerative IVD. The characterization, toxicity, and pH-responsive H2 release of [email protected] was detected in vitro. The metabolization of [email protected] in the degenerated IVD was tested by in vivo imaging. The therapeutic effect of [email protected] on IDD was tested in vivo by X-ray, MRI, water content of the disc, and histological changes. Nuclear extracellular matrix (ECM) components, oxidative stress, and inflammation were also tested to explore potential therapeutic mechanisms. [email protected] has good biocompatibility at concentrations less than 500 μg/mL. The H2 release of [email protected] was pH responsive. Therefore, [email protected] can provide efficient hydrogen therapy with controlled H2 release in response to the acidic degenerated IVD microenvironment. The metabolization of [email protected] in IVD was slow and lasted up to 11 days. HPDA and [email protected] significantly inhibited IDD, as tested by X-ray, MRI, disc water content, and histology (). pH-responsive H2 delivery through [email protected] has the potential to efficiently treat IDD by inhibiting ECM degradation and rebalancing oxidative stress and inflammation in degenerative IVDs.