Dynamic dual-network hydrogel microspheres for enhanced nucleus pulposus regeneration via extracellular matrix mimicry

The degeneration of intervertebral discs (IVD) remains a significant challenge in regenerative medicine. This study introduces novel hydrogel microspheres (GelMA-FCD-GA) designed to mimic the native extracellular matrix (ECM) of nucleus pulposus cells (NPCs). These microspheres integrate Gelatin Methacrylate (GelMA) with Fucoidan (FCD) and are further modified with aldehyde groups (GA) to establish a dynamic viscoelastic scaffold capable of transducing mechanical signals and promoting cellular functions. In vitro, GelMA-FCD-GA microspheres enhanced mitochondrial function and antioxidant capacity of NPCs, with increased expression of respiratory chain factors and reduced reactive oxygen species. In vivo, the transplantation of NPC-laden GelMA-FCD-GA microspheres into Rat caudal IVDs demonstrated significant regenerative effects, as evidenced by improved MRI signals, restored disc height, and favorable histological outcomes compared to controls. This innovative approach presents a significant advancement in IVDD treatment, combining the mechanical benefits of bioactive materials with the bioactive properties of fucoidan. The dual-network design supports cell adhesion and growth and dynamically adapts to the physiological environment, offering a robust platform for regenerative medicine applications.