Biomimicking 3D soft scaffold combined with electrical stimulation to manipulate neural stem cell differentiation for guidance spinal cord injury repair

Spinal cord injury repair has remained a challenging issue in the medical field, and in recent years neural stem cell-based therapies have shown great potential. However, the survival and controlled differentiation of neural stem cells (NSCs) remain a problem, since the majority of materials can’t provide a suitable microenvironment for NSCs. In this work, we design and develop a conductive hydrogel mimicking spinal cord tissue as a biomimetic 3D biomaterial soft scaffold to improve the survival microenvironment and regulate the differentiation direction of NSCs. Significantly, the designed hydrogel matches the spinal cord tissue in aspects of mechanical properties, electrical conductivity, and pore structure. Moreover, the hydrogel possesses injectability, self-healing and haemostatic properties. Combining hydrogel with electrical stimulation (ES) induces loaded NSCs to be more inclined toward neuronal differentiation, axonal growth, and myelin regeneration, while reducing astrocyte development. This treatment strategy will ultimately achieve spinal cord injury repair and motor function restoration while avoiding glial scar deposition. This mimicking spinal cord 3D soft scaffolds combined with ES provide a promising therapeutic strategy for spinal cord injury repair.