3D hydrogel microfibers promote the differentiation of encapsulated neural stem cells and facilitate neuron protection and axon regrowth after complete transactional spinal cord injury

Spinal cord injury (SCI) can cause permanent impairment to motor or sensory functions. Pre-cultured neural stem cell (NSC) hydrogel scaffolds have emerged as a promising approach to treat SCI by promoting anti-inflammatory effects, axon regrowth, and motor function restoration. Here, in this study, we performed a coaxial extrusion process to fabricate a core-shell hydrogel microfiber with high NSC density in the core portion. Oxidized hyaluronic acid, carboxymethyl chitosan, and matrigel blend were used as a matrix for NSC growth and to facilitate the fabrication process. During the in vitro differentiation culture, it was found that NSC microfibers could differentiate into neurons and astrocytes with higher efficiency compared to NSC cultured in petri dishes. Furthermore, during in vivo transplantation, NSC microfibers were coated with polylactic acid nanosheets by electrospinning for reinforcement. The coated NSC nanofibers exhibited higher anti-inflammatory effect and lesion cavity filling rate compared with the control group. Meanwhile, more neuron- and oligodendrocyte-like cells were visualized at the lesion epicenter. Finally, axon regrowth across the whole lesion site was observed, demonstrating that the microfiber could guide renascent axon regrowth. Experiment results indicate that the NSC microfiber is a promising bioactive treatment for complete SCI treatment with superior outcomes.