Functional Hydrogel Co-Remolding Migration And Differentiation Microenvironment for Severe Spinal Cord Injury Repair.

Spinal cord injury (SCI) activates nestin + neural stem cells (NSCs), which can be regarded as potential seed cells for neuronal regeneration. However, the lesion microenvironment seriously hinders the migration of the nestin + cells to the lesion epicenter and their differentiation into neurons to rebuild the bridging neural circuits. In this study, we prepared a photosensitive hydrogel scaffold as drug delivery carrier. Genetically engineered SDF1α and NT3 were designed and binary modified the scaffold to reshape the lesion microenvironment. The binary modified scaffold could effectively induce the migration and neuronal differentiation of nestin + NSCs in vitro. When implanted into a rat complete spinal cord transection model, the lesion microenvironment was remolded and many of the SCI-activated nestin + cells migrated into the lesion site and gave rise to neurons in short-term. Meanwhile, long-term repair results also showed that implantation of the binary modified scaffold could effectively promote the maturation, functionalization and synaptic network reconstruction of neurons in the lesion site. In addition, animals treated with binary scaffold also showed better improvement in motor functions. The therapeutic strategy based on remolding the migration and neuronal differentiation lesion microenvironment provides a new insight into SCI repair by targeting activated nestin + cells, which exhibits excellent clinical transformation prospects. This article is protected by copyright. All rights reserved.