A DAMP-scavenging, IL-10-releasing hydrogel promotes neural regeneration and motor function recovery after spinal cord injury

Abstract

Spinal cord injury (SCI) creates an inflammatory microenvironment characterized by damage-associated molecular patterns (DAMPs) and immune cell activation that exacerbate secondary damage and impair neurological recovery. Here we develop an immunoregulatory hydrogel scaffold for treating SCI that scavenges DAMPs and slowly releases the anti-inflammatory cytokine interleukin-10 (IL-10). We created this dual-functional scaffold by modifying a photocrosslinked gelatin hydrogel with the cationic, DAMP-binding polymer poly (amidoamine) and with IL-10, and compared the therapeutic activity of this scaffold with that of gelatin-only, gelatin + poly (amidoamine), and gelatin + IL-10 scaffolds in vitro and in vivo. In vitro, the dual-functional scaffold scavenged anionic DAMPs and exhibited sustained release of IL-10, reduced the proinflammatory responses of macrophages and microglia, and enhanced the neurogenic differentiation of neural stem cells. In a complete transection SCI mouse model, the injected dual-functional scaffold suppressed proinflammatory cytokine production, promoted the M2 macrophage/microglia phenotype, and led to neural regeneration and axon growth without scar formation to a greater extent than the single-function or control scaffolds. This DAMP-scavenging, IL-10-releasing scaffold provides a new strategy for promoting neural regeneration and motor function recovery following severe SCI.

Keywords: Complete spinal cord injury; Dual-functional scaffold; Hydrogel; Inflammatory microenvironment; Neuroregeneration.