Fuh@Decm Hydrogel Delays Intervertebral Disc Degeneration Through Macrophage Reprogramming and Antioxidant Properties

1.Abstract Key pathological factors contributing to intervertebral disc degeneration (IVDD) include excessive production of reactive oxygen species (ROS), depletion of the extracellular matrix (ECM), and an imbalance in the M1/M2 macrophage ratio. To address these challenges, we developed a novel bioactive hydrogel (FUH@dECM) by integrating high-concentration fucoidan (FU) with decellularized extracellular matrix (dECM). This hydrogel is designed for in situ injection, where it undergoes gelation at the site of administration, replenishing lost ECM in nucleus pulposus cells while gradually releasing FU. In vitro, experiments demonstrated that the controlled release of FU effectively scavenges ROS, promotes macrophage polarization towards the M2 phenotype, and restores ECM metabolic balance. RNA sequencing analysis revealed that the antioxidant effects of the FUH@dECM hydrogel are primarily mediated through activation of the FOXO signaling pathway, while inhibition of the NF-κB signaling pathway mitigates the inflammatory response. In an in vivo rat model of IVDD, this hydrogel system demonstrated a strong mechanistic alignment with the physiological processes of the intervertebral disc, significantly improving IVDD outcomes by maintaining disc height and preserving the structural integrity of the nucleus pulposus tissue. These results underscore the potential of FUH@dECM as a promising therapeutic strategy for the treatment of IVDD.