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

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

Advanced Science, 2022 · DOI: 10.1002/advs.202105586 · Published: March 6, 2022

Spinal Cord InjuryGeneticsBiomedical

Simple Explanation

Electroconductive hydrogels are promising for spinal cord injury (SCI) repair due to their similarity to neural tissue. However, they can worsen inflammation. Bone marrow stem cell-derived exosomes (BMSC-exosomes) offer immunomodulatory and regenerative effects. The study develops neural tissue-like electroconductive hydrogels loaded with BMSC-exosomes for SCI treatment. These hydrogels modulate microglial polarization, enhance neural stem cell differentiation into neurons and oligodendrocytes, and increase axon outgrowth. In a mouse SCI model, the combined hydrogels significantly reduced inflammation, enhanced stem cell recruitment, and promoted nerve regeneration, leading to functional recovery. This suggests a promising therapeutic strategy for SCI repair.

Study Duration
Not specified
Participants
Adult male C57BL/6J mice (6–8 weeks old, n = 75)
Evidence Level
Not specified

Key Findings

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    Exosomes-loaded electroconductive hydrogels modulated microglial M2 polarization via the NF-𝜿B pathway.
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    The hydrogels synergistically enhanced neuronal and oligodendrocyte differentiation of neural stem cells (NSCs) while inhibiting astrocyte differentiation.
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    The hydrogels increased axon outgrowth via the PTEN/PI3K/AKT/mTOR pathway.

Research Summary

This study developed an exosome-loaded electroconductive hydrogel (GMPE) composed of gelatin methacrylate and polypyrrole. The GMPE hydrogel was shown to reduce early inflammation, enhance neural stem cell recruitment and promote myelin-associated axonal regrowth to synergistically promote locomotor recovery after spinal cord hemisection. The GMPE hydrogel significantly decreased the number of CD68-positive microglia, enhanced local NSCs recruitment, and promoted neuronal and axonal regeneration, resulting in significant functional recovery at the early stage in an SCI mouse model. The study's findings demonstrate that the combination of electroconductive hydrogels and BMSC-exosomes is a promising therapeutic strategy for SCI repair.

Practical Implications

Therapeutic Strategy

The combination of electroconductive hydrogels and BMSC-exosomes represents a promising therapeutic approach for spinal cord injury (SCI) treatment.

Immunomodulation

The GMPE hydrogel can modulate M1/M2 polarization from an M1- to M2-dominant phenotype via the NF-kB pathway, reducing adverse immune effects after SCI.

Enhanced Regeneration

The GMPE hydrogel enhances oligodendrocyte differentiation and myelin-associated axonal regeneration, promoting locomotor recovery after SCI.

Study Limitations

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