Exosome-loaded conductive hydrogel with immune-modulating and neurogenesis-enhancing properties for synergistic spinal cord injury repair

Abstract Conductive hydrogels are very attractive candidates for accelerated spinal cord injury (SCI) repair because they match the electrical and mechanical properties of neural tissue. However, conductive hydrogel implantation can potentially aggravate inflammation, and hinder its repair efficacy. Bone marrow stem cell-derived exosomes (BMSC-exos) have shown immunomodulatory and tissue regeneration effects, therefore, we developed neural tissue-like conductive hydrogels loaded with BMSC-exos for the synergistic treatment of SCI. These exos-loaded conductive hydrogels modulated microglial M2 polarization via the NF-κB pathway, and synergistically enhanced neuronal and oligodendrocyte differentiation of neural stem cells (NSCs) while inhibiting astrocyte differentiation, and also increased axon outgrowth via the PTEN/PI3K/AKT/mTOR pathway. Furthermore, exos combined conductive hydrogels significantly decreased the number of CD68-positive microglia, enhanced local neurogenesis, and promoted axonal regeneration, resulting in significant functional recovery at the early stage in an SCI mouse model. Hence, the findings of this study demonstrate that the combination of conductive hydrogels and BMSC-exos is a promising therapeutic strategy for SCI repair.