Neuroimmune modulating and energy supporting nanozyme-mimic scaffold synergistically promotes axon regeneration after spinal cord injury

Journal of Nanobiotechnology, 2024 · DOI: https://doi.org/10.1186/s12951-024-02594-2 · Published: May 28, 2024

Spinal Cord Injury Immunology Biomedical

Simple Explanation

Spinal cord injury (SCI) leads to inflammation, high levels of M1 macrophages, and energy deficits, worsening damage and preventing axon regeneration. This study explores SCI mechanisms related to neuroimmune regulation and mitochondrial function. A smart scaffold (NS@COP) was developed, incorporating enzyme mimicry nanoparticle-ceriumoxide into nanofibers, to target neuroimmune repair and remodel mitochondrial function. The integrated COPs restore macrophage responsiveness to CGRP signal, promoting an anti-inflammatory M2 phenotype and protecting neuronal mitochondrial function, suggesting it as a promising therapeutic candidate for SCI.

Study Duration

8 weeks

Participants

Sprague Dawley rats (200 ± 20 g)

Evidence Level

Not specified

Key Findings

1
NS@COP restores the responsiveness of pro-inflammatory macrophages to CGRP by upregulating RAMP1, promoting an anti-inflammatory M2 phenotype.
2
NS@COP protects neuronal mitochondrial function by maintaining mitochondrial membrane potential and structural integrity.
3
NS@COP promotes axon regeneration and functional recovery in a rat SCI model, reducing glial scar formation and improving hindlimb coordination.

Research Summary

This study introduces a nanoenzyme-based scaffold (NS@COP) designed to address key challenges in spinal cord injury (SCI) repair, including inflammation, mitochondrial dysfunction, and glial scar formation. The NS@COP scaffold restores neuroimmune communication by promoting macrophage polarization towards an anti-inflammatory M2 phenotype and protecting neuronal mitochondrial function. In a rat SCI model, NS@COP implantation significantly improved locomotor function, reduced glial scarring, and enhanced axon regeneration, indicating its potential as a therapeutic candidate.

Practical Implications

Therapeutic Development

The NS@COP scaffold shows promise as a therapeutic intervention for spinal cord injury by modulating the immune response and supporting neuronal function.

Neuroimmune Crosstalk

The study highlights the importance of neuroimmune communication in SCI repair, particularly the role of the CGRP/RAMP1/AKT axis in macrophage polarization.

Mitochondrial Protection

Maintaining mitochondrial function with nanozymes like COPs can improve neuronal energy supply and axon regeneration after SCI.

Study Limitations

1
The study is limited to motor function settings and lacks information regarding other organ function settings.
2
Murine studies are limited to motor function settings
3
Further investigation is needed to optimize the material and explore its potential for other clinical indications.

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