Spinal cord injury is among the most fatal diseases. The complicated inhibitory microenvironment requires comprehensive mitigation. Exosomes derived from mesenchymal stem cells (MSCs) are natural biocarriers of cell paracrine secretions that bear the functions of microenvironment regulation. However, the effective retention, release, and integration of exosomes into the injured spinal cord tissue are poorly defined. Herein, an innovative implantation strategy is established using human MSC-derived exosomes immobilized in a peptide-modified adhesive hydrogel (Exo-pGel). Unlike systemic admistration of exosomes, topical transplantation of the Exo-pGel provides an exosome-encapsulated extracellular matrix to the injured nerve tissue, thereby inducing effecient comprehensive mitigation of the SCI microenvironment. The implanted exosomes exhibit efficient retention and sustained release in the host nerve tissues. The Exo-pGel elicits significant nerve recovery and urinary tissue preservation by effectively mitigating inflammation and oxidation. The Exo-pGel therapy presents a promising strategy for effective treatment of central nervous system diseases based on exosome implantation.

Spinal cord injury (SCI) is one of the most debilitating injuries and transplantation of stem cells in a scaffold is a promising strategy for the treatment. However, the stem cell treatment of SCI has been severely impaired by the increased generation of reactive oxygen Video S8. Recording of rat hindlimb motor functions in MnO2 group at Day 14 (MP4) Video S9. Recording of rat hindlimb motor functions in MnO2 group at Day 21 (MP4) Video S10. Recording of rat hindlimb motor functions in MnO2 group at Day 28 (MP4)

A novel TEMPO-immobilized hyaluronic hydrogel is fabricated to promote nerve repair through mitigating the oxidant microenvironment of spinal cord injury.

Implantation of hypoxia-stimulated mesenchymal stem cell-derived exosome encapsulated in an adhesive hydrogel induced pro-angiogenic spinal cord repair through transporting HIF-1α and upregulating vascular endothelial growth factor expression in recipient endothelial cells.

Revascularization treatment is a critical measure for tissue engineering therapies like spinal cord repair. As multipotent stem cells, mesenchymal stem cells (MSCs) have proven to regulate the lesion microenvironment through feedback to the microenvironment signals. The angiogenic capacities of MSCs have been reported to be facilitated by vein endothelial cells in the niche. As emerging evidence demonstrated the roles of exosomes in cell−cell and cell−microenvironment communications, to cope with the ischemia complication for treatment of traumatic spinal cord injury, the study extracts the microenvironment factors to stimulate angiogenic MSCs through using exosomes (EX) derived from hypoxic preconditioned (HPC) human umbilical vein endothelial cells (HUVEC). The HPC treatment with a hypoxia time segment of only 15 min efficiently enhanced the function of EX in facilitating MSCs angiogenesis activity. MSCs stimulated by HPC-EX showed significant tube formation within 2 h, and the in vivo transplantation of the stimulated MSCs elicited effective nerve tissue repair after rat spinal cord transection, which could be attributed to the pro-angiogenic and antiinflammatory impacts of the MSCs. Through the simulation of MSCs using HPC-tailored HUVEC exosomes, the results proposed an efficient angiogenic nerve tissue repair strategy for spinal cord injury treatment and could provide inspiration for therapies based on stem cells and exosomes.