ROS-responsive magnesium-containing microspheres for antioxidative treatment of intervertebral disc degeneration

Intervertebral disc degeneration (IVDD) is a degenerative disease characterized by lower-back pain, causing disability globally. Antioxidant therapy is currently considered one of the most promising strategies for IVDD treatment, given the crucial role of reactive oxygen species (ROS) in IVDD pathogenesis. Herein, a ROS-responsive magnesium-containing microsphere ([email protected] MS) was constructed for the antioxidative treatment of IVDD. The [email protected] MS has a core-shell structure comprising poly(lactic-co-glycolic acid) (PLGA) and ROS-responsive polymer poly(PBT-co-EGDM) as the shell and a magnesium microparticle as the core. The poly(PBT-co-EGDM) can be destroyed by H2O2 through the H2O2-triggered hydrophobic-to-hydrophilic transition, subsequently promoting an Mg-water reaction to produce H2. Thus, [email protected] MS provides a valuable platform for H2O2 elimination and controlled H2 release. The generated H2 scavenge for ROS by reacting with noxious •OH. Notably, the [email protected] MS exerted significant antioxidative and anti-inflammatory effects in a disc degeneration rat model and alleviated extracellular matrix degradation and disc cells apoptosis, thereby underlining its efficacy in IVDD treatment. The [email protected] MS also exhibited robust biocompatibility and negligible toxicity, presenting the promise for the antioxidative treatment of IVDD in vivo. Antioxidant therapy is currently considered one of the most promising strategies for intervertebral disc degeneration (IVDD) treatment, given the crucial role of reactive oxygen species (ROS) in IVDD pathogenesis. Here, ROS-responsive magnesium-containing microspheres ([email protected] MSs) were constructed to alleviate IVDD through controlled release of hydrogen gas. The [email protected] MSs can effectively scavenge overproduced ROS by simultaneously reacting with H2O2 and •OH, thus creating a suitable microenvironment for inhibition of ECM degradation. As a result, [email protected] MSs treated IVDD rats exhibit minimal nucleus pulposus decrease, less extracellular matrix degradation, minimal radial fissure of fibrous rings, and higher disc height index. Therefore, the as-prepared [email protected] MSs may shed a new light on clinical treatment of IVDD.