Modulation of the inflammatory microenvironment after SCI to achieve enhanced nerve regeneration using pteryxin-releasing methylacrylated hyaluronic acid

Spinal cord injury (SCI) still lacks effective treatment methods. The inflammatory storm after SCI is one of the critical obstacles to nerve repair. In this study, we aimed to address the critical challenge of the inflammatory storm after SCI-a key driver of exacerbated neural damage-by developing an innovative hydrogel scaffold functionalized with sustained-release pteryxin and encapsulated NSCs. This scaffold is designed to modulate the post-SCI inflammatory response, thereby mitigating inflammation-induced neural injury and enhancing neural repair. Briefly, we first synthesized and characterized a hyaluronic acid methacryloyl (HAMA) hydrogel. Subsequently, a 5% HAMA hydrogel and 10 μM pteryxin were used to prepare a pHAMA hydrogel (pteryxin-loaded HAMA). The pHAMA hydrogel possessed good biocompatibility and promoted the differentiation of NSCs towards neurons. Finally, the pHAMA hydrogel combined with NSCs could significantly enhance SCI repair and functional recovery by reducing the inflammatory responses, decreasing the infiltration of macrophages and microglia, and downregulating the expression of inflammation-related genes.