Electrostimulation via a 3D-printed, biomimetic, neurotrophic, electroconductive scaffold for the promotion of axonal regrowth after spinal cord injury

Abstract

Spinal cord injury (SCI) is a devastating neurotrauma, affecting 250,000 to 500,000 people annually, and typically results in paralysis. Electrostimulation can promote neuronal growth, but the formation of a lesion cavity post-SCI inhibits regrowth, limiting its efficacy. Bridging the lesion with a structured, electroactive substrate to direct electrostimulation to growing neurites could support and drive neuronal regrowth through the lesion to enable functional recovery but to date, no such platform exists. This study describes the development of an electroconductive (15 ± 5 S/m), 3D-printed scaffold, comprising a polypyrrole/polycaprolactone framework filled with biomimetic & neurotrophic extracellular matrix. 3D printing allowed inclusion of channels in the scaffold designed to mimic the size of human corticospinal tracts to direct electrostimulation to growing neurons. Scaffolds exhibited excellent biocompatibility with both neurons and human primary astrocytes and maintained electrical and biofunctionality when scaled to match the size of human corticospinal tracts. When neurons were cultured for 7 days on the scaffolds under continuous electrostimulation (200 mV/mm, 12 Hz), significantly longer neurites were observed on electrically stimulated electroconductive scaffolds. These results demonstrate that electrostimulation applied via an anatomically-mimetic, 3D-printed electroconductive scaffold drives neurite outgrowth and represents a promising approach for treatment of spinal cord injury.