Curcumin-loaded polydopamine nanoparticles-based antioxidant scaffold promote spinal cord repair though dural-regulation of macrophage polarization.

Severe spinal cord injury (SCI) disrupts neuronal circulation and results in irreversible motor function loss. Treating SCI is a major challenge due to the limited regenerative capacity of axons and the inflammatory environment that hinders recovery. Macrophages play a dual role in SCI, with their polarization determining whether they exacerbate the injury or promote tissue repair. In this study, we developed a curcumin-loaded polydopamine nanoparticle antioxidant scaffold (cur-PDA@gel) as a novel therapeutic approach for SCI. This scaffold was designed to bidirectionally modulate macrophage polarization. The polydopamine-coated nanoparticles demonstrated strong antioxidant activity, effectively neutralizing reactive oxygen species (ROS) and reducing inflammation. Curcumin released from the scaffold promoted M2-type macrophage polarization while inhibiting M1-type polarization, thereby reshaping the inflammatory microenvironment at the injury site and facilitating axonal regeneration. Mechanistically, curcumin regulated macrophage polarization by suppressing the NF-κB signaling pathway and activating the JAK/STAT pathway, particularly in the context of cur-PDA@gel implantation. These findings underscore the potential of cur-PDA@gel as a promising therapeutic strategy for SCI repair by targeting macrophage polarization.