Injectable Nanoreinforced Shape-Memory Hydrogel System for Regenerating Spinal Cord Tissue from Traumatic Injury

Traumatic injury in the central nervous system can lead to loss of functional neurons. Transplantation of neural progenitors is a promising therapeutic strategy. However, infusion of dissociated cells often suffers from low viability, uneven cell distribution, and poor in vivo engraftment that could be reinforced by a better cell delivery system. Here, we develop an injectable composite hydrogel system for use as a minimally invasive treatment of spinal cord injury (SCI) using motor neurons (MNs) derived from embryonic stem cells (ESCs). The composite hydrogel is based on a modified gelatin matrix integrated with shape-memory polymer fibers. The gelatin matrix creates a local microenvironment for cell assembly and also acts as a lubricant during injection through a fine catheter. Notably, shape-memory fiber scaffolds are able to recover to maintain the microstructures even after dramatic deformation from injection operation, providing the necessary support and guidance for motor neuron differentiation. We find that the composite hydrogel with an aligned fiber scaffold greatly improves the viability of ESCs and their differentiation toward MNs both in vitro and in vivo. When transplanted to SCI animals by injection, the ESC-loaded composite hydrogels are identified to significantly enhance tissue regeneration and motor function recovery in mice. With this proof-of-concept study, we believe that the injectable composite hydrogel system provides a promising solution for in vivo cell delivery with minimum invasiveness and can be readily extended to other stem-cell-based regenerative treatments.