Engineering of M2 Macrophages‐Derived Exosomes via Click Chemistry for Spinal Cord Injury Repair

Abstract

Spinal cord injury (SCI) is one of the most common causes of death and disability. The effective modulation of complicated microenvironment, regeneration of injured spinal cord tissue, and the functional recovery after SCI are still clinical challenges. Recently, macrophages‐derived exosomes have shown great potential for various diseases due to their inflammation‐targeting property. However, further modifications are needed to endow exosomes with the neural regenerative potential for SCI recovery. In the current study, a novel nanoagent (MEXI) is designed for SCI treatment by conjugating bioactive IKVAV peptides to the surface of M2 macrophages‐derived exosomes via an easy and rapid click chemistry method. In vitro, MEXI inhibits the inflammation by reprograming macrophages and promotes neuronal differentiation of neural stem cells. In vivo, engineered exosomes target the injured site of the spinal cord after tail vein injection. Furthermore, histological analysis reveals that MEXI improves motor functional recovery of SCI mice by reducing infiltration of macrophages, downregulating pro‐inflammatory factors, and improving the regeneration of injured nervous tissues. Taken together, this study provides strong evidence for the significance of MEXI in SCI recovery.

Triple Cross‐linked Dynamic Responsive Hydrogel Loaded with Selenium Nanoparticles for Modulating the Inflammatory Microenvironment via PI3K/Akt/NF‐κB and MAPK Signaling Pathways

“…Clinical evidences disclose that many macrophages are significantly increased in IDs patients with the inflammatory tissue. [ 73 ] Macrophages have many phenotypes, and the balance of different phenotypes plays an essential role in the inflammatory cascade, mainly divided into M0 (resting state), M1, and M2 phenotypes. [ 74 ] The M1 phenotype secretes inflammatory cytokines, accelerating oxidative processes and inhibiting tissue repair.…”

Engineered Macrophage Membrane‐Coated Nanoparticles with Enhanced CCR2 Expression Promote Spinal Cord Injury Repair by Suppressing Neuroinflammation and Neuronal death

“…The immunostaining analysis of the 200 kDa subunit of neurofilament (NF200), a marker protein of axon, was employed to evaluate the axonal regeneration. [ 61 ] Moreover, barriers created by scar‐forming astroglia have been proposed to be the primary causes of axon regeneration failure after SCI. [ 71 ] Thus, glial fibrillary acidic protein (GFAP) expression was employed as a marker of astrogliosis.…”

“…Promoting the transition of microglia from M1 to M2 type is considered an important therapeutic target for improving the neurological outcome of SCI. [59][60][61] Several studies have demonstrated that the CCL2-CCR2 axis played an important role in microglia activation and polarization. [62,63] In light of this, we next explored the effect of CCR2-MM@PLGA/NPs on microglia activation and polarization in vitro.…”

Unlocking the potential of exosomes: a breakthrough in the theranosis of degenerative orthopaedic diseases

“…In vitro experiments demonstrated that MEXI effectively attenuated inflammation by modulating macrophage activity and facilitated the differentiation of neural stem cells into neurons. Furthermore, in vivo administration of engineered exosomes via tail vein injection resulted in targeted delivery to the site of spinal cord injury ( Zeng et al, 2023a ).…”