LDH-doped gelatin-chitosan scaffold with aligned microchannels improves anti-inflammation and neuronal regeneration with guided axonal growth for effectively recovering spinal cord injury

Abstract

Spinal cord injury (SCI) causes immune cell infiltration, neuronal death and permanent motor dysfunction. Effective treatment for SCI requires simultaneous suppression of the inhibitory and inflammatory microenvironment and enhancement of the pro-regenerative potential at SCI sites. However, realizing neuronal regeneration with guided axon growth and anti-inflammation simultaneously is currently challenging. In this study, a layered double hydroxides (LDH)-doped gelatin-chitosan scaffold with aligned microchannels (GC-LDH/A scaffold) combined with chemical and structural repair effects was developed to regulate immune microenvironment and promote directional neurogenesis. The GC-LDH/A scaffold was prepared by anisotropic freezing of a mixture of Mg-Fe layered double hydroxides (Mg-Fe LDH), gelatin and chitosan. The LDH, gelatin and aligned microchannel structure work together to promote neuronal regeneration. Chitosan and the aligned microchannel structure have a function of anti-inflammation while the latter also guides axonal growth. The repair effect of this scaffold was assessed by restoring a completely transected spinal cord injury, and the results showed that the GC-LDH/A scaffold effectively activated the anti-inflammatory polarization of macrophages and microglia, promoted neurogenesis and guided axonal growth from the rostral to caudal of the lesion site. The key mediator of functional recovery in SCI is Myosin II, which negatively regulates axonal growth; however, the aligned microchannel structure inhibits its activity and reverses the repair effect. This study provides a promising strategy for addressing the repair challenges for effective SCI treatment.