A pH/ROS dual responsive smart microgel miRNA delivery system for repair of intervertebral disc degeneration

The progression of intervertebral disc degeneration (IDD) is due to the progressive exacerbation of apoptosis and impaired extracellular matrix (ECM) synthesis, both of which are induced by progressive inflammation. Therefore, addressing the inflammatory microenvironment and correcting excessive apoptosis of nucleus pulposus cells (NPCs) are key to achieving intervertebral disc (IVD) regeneration. In this study, we designed a microenvironment-responsive smart microgel gene delivery system that for the first time combines phenylboronic acid-functionalized microgels with strontium sulfite nanoparticles to load miR-155 to enhance their anti-apoptosis capacity and promote ECM regenerative effects. In addition, strontium sulfite nanoparticles were able to respond to pH changes and dissolve at endosomal pH to release genetic materials. This highly biocompatible microgel drug system (MS-TSNPs@miR-155) was capable of continuously releasing miR-155, effectively modulating inflammation and attenuating apoptosis in NPCs. These minimally invasive and smart delivery capabilities promote the restoration of metabolic homeostasis within the medullary ECM, effectively delaying IDD progression.