Journal Article

Exosomes‐Loaded Electroconductive Hydrogel Synergistically Promotes Tissue Repair after Spinal Cord Injury via Immunoregulation and Enhancement of Myelinated Axon Growth

Yu, Peng, Luo, Yian, Ning, Chengyun, Wen, Huiquan, Chen, Dafu, Chen, Xiuxing, Zheng, Lei, Liu, Can, Zou, Yan, Fan, Lei, Sun, Yongjian, Zhou, Lei, Lu, Fang, Guan, Pengfei, Deng, Chunlin, Tan, Guoxin

2022

Overview

Electroconductive hydrogels are very attractive candidates for accelerated spinal cord injury (SCI) repair because they match the electrical and mechanical properties of neural tissue. However, electroconductive hydrogel implantation can potentially aggravate inflammation, and hinder its repair efficacy. Bone marrow stem cell‐derived exosomes (BMSC‐exosomes) have shown immunomodulatory and tissue regeneration effects, therefore, neural tissue‐like electroconductive hydrogels loaded with BMSC‐exosomes are developed for the synergistic treatment of SCI. These exosomes‐loaded electroconductive hydrogels modulate microglial M2 polarization via the NF‐κB pathway, and synergistically enhance neuronal and oligodendrocyte differentiation of neural stem cells (NSCs) while inhibiting astrocyte differentiation, and also increase axon outgrowth via the PTEN/PI3K/AKT/mTOR pathway. Furthermore, exosomes combined electroconductive hydrogels significantly decrease the number of CD68‐positive microglia, enhance local NSCs recruitment, and promote neuronal and 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 electroconductive hydrogels and BMSC‐exosomes is a promising therapeutic strategy for SCI repair. Neural tissue‐like electroconductive hydrogels loaded with bone marrow stem cell‐derived exosomes are developed. The mechanism of the exosomes‐loaded electroconductive hydrogel synergistically regulating neural stem cell differentiation is explored. The exosomes‐combined electroconductive hydrogels significantly decrease inflammation reaction, enhance local neurogenesis, and promote axonal regeneration, resulting in significant functional recovery at the early stage in a spinal cord injury mouse model.

• Publisher: John Wiley & Sons, Inc,John Wiley and Sons Inc,Wiley
• Subject: Animals / anti‐inflammation / axonal regeneration / Axons - metabolism / Biocompatibility / BMSC‐derived exosomes / electroconductive hydrogels / Exosomes - metabolism / Hydrogels / Mice / Morphology / Nanoparticles / Phosphatidylinositol 3-Kinases - metabolism / Polymerization / Spinal cord injuries / Spinal Cord Injuries - metabolism / Spinal Cord Injuries - therapy / spinal cord injury / Stem cells