Seeds-and-soil inspired hydrogel microspheres: A dual-action antioxidant and cellular therapy for reversing intervertebral disc degeneration

Intervertebral disc degeneration (IVDD) is a globally prevalent disease, yet achieving dual repair of tissue and function presents significant challenges. Considering reactive oxygen species (ROS) is a primary cause of IVDD, and given the decrease of nucleus pulposus cells (NPCs) and extensive degradation of extracellular matrix (ECM) during IVDD development, the present study, inspired by the “seeds-and-soil” strategy, has developed NPCs-loaded TBA@Gel&Chs hydrogel microspheres. These microspheres serve as exogenous supplements of NPCs and ECM analogs, replenishing “seeds” and “soil” for nucleus pulposus repair, and incorporating polyphenol antioxidant components to interrupt the oxidative stress-IVDD cycle, thereby constructing a microsphere system where NPCs and ECM support each other. Experiments proved that TBA@Gel&Chs exhibited significant extracellular ROS-scavenging antioxidant capabilities while effectively upregulating intracellular antioxidant proteins expression (Sirt3 and Sod2). This dual-action antioxidant capability effectively protects the vitality and physiological functions of NPCs. The therapeutic effects of microspheres on IVDD were also confirmed in rat models, which was found significantly restore histological structure and mechanical properties of degenerated discs. Additionally, RNA-seq results have provided evidences of antioxidant mechanism by which TBA@Gel&Chs protected NPCs from oxidative stress. Therefore, the NPCs-loaded TBA@Gel&Chs microspheres developed in this study have achieved excellent therapeutic effects, offering a paradigm using antioxidant biomaterials combined with cellular therapy for IVDD treatment.