Multichannel Bioactive Silk Nanofiber Conduits Direct and Enhance Axonal Regeneration after Spinal Cord Injury.

ABSTRACT

After a spinal cord injury, axonal regeneration over long distances is challenging due to the lack of physical guidance cues and bioactive signals. In this study, a multichannel bioactive silk fibroin nanofiber conduit was fabricated to improve spinal cord injury repair by enhancing axonal regeneration. The conduit was composed of longitudinally oriented silk fibroin nanofibers and then functionalized with laminin. In vitro, the bioactive conduits could promote neuron-like development and directional neurite extension of PC12 cells by providing a bioactive stimulus and physical guidance. In a spinal cord injury model in Sprague-Dawley rats, the biofunctionalized conduits displayed superior integration with the host tissue due to enhanced cell infiltration and tissue ingrowth. The glial scar was significantly reduced, allowing axonal ingrowth along with the channel direction. Compared to a single-channel conduit, the multichannel conduit improved spinal cord regeneration by boosting tissue ingrowth and axonal regeneration, indicating that the conduit architectures play critical roles in spinal cord regeneration. These silk fibroin conduits, along with the multichannel architecture, nanoscale cues, and the ability to bind bioactive compounds, represent promising candidates for spinal cord regeneration.