A cryo‑shocked M2 macrophages based treatment strategy promoting repair of spinal cord injury via immunomodulation and axonal regeneration effects

Journal of Nanobiotechnology, 2025 · DOI: https://doi.org/10.1186/s12951-024-03018-x · Published: January 1, 2025

Spinal Cord Injury Pharmacology Biomedical

Simple Explanation

This study introduces a novel treatment for spinal cord injury (SCI) using cryo-shocked M2 macrophages loaded with paclitaxel nanoparticles (LNT M2/PTX-NPs) embedded in a GelMA scaffold. The LNT M2 macrophages retain inflammatory factor receptors, helping to neutralize inflammation at the injury site. The slow release of paclitaxel promotes axonal regeneration and reduces scar formation, contributing to improved neurological recovery in SCI rats.

Study Duration

6 Weeks

Participants

Sprague Dawley (SD) rats (female, average weight 200–220 g)

Evidence Level

Not specified

Key Findings

1
LNT M2/PTX-NPs@Gel treatment significantly improved motor function recovery in SCI rats, as evidenced by increased BBB scores and MEP amplitudes.
2
The treatment effectively modulated the inflammatory microenvironment by inhibiting immune cell infiltration and promoting M2 macrophage polarization.
3
LNT M2/PTX-NPs@Gel promoted axonal regeneration and reduced glial and fibrotic scar formation at the injury site.

Research Summary

The study presents LNT M2/PTX-NPs@Gel as an effective treatment for SCI, demonstrating significant improvements in neurological function recovery. The treatment modulates the inflammatory microenvironment, inhibits scar formation, and promotes axonal regeneration, creating a favorable environment for neural repair. Transcriptomic analysis supports the observed neuroprotective effects and motor function recovery, revealing downregulation of inflammation-related genes and upregulation of genes associated with axonal regeneration and synaptic signaling.

Practical Implications

Clinical Translation

The straightforward preparation, ease of standardization, and convenient storage of LNT M2/PTX-NPs@Gel make it a promising candidate for clinical applications in acute SCI intervention.

Multifaceted Therapeutic Approach

The combination of axonal regeneration, scarring inhibition, and immunomodulatory capabilities within a single scaffold offers a multifaceted approach to addressing the complex pathology of SCI.

Potential for Other Neurological Diseases

Due to the inflammatory tropism of macrophages, this strategy could potentially be extended to treat other neurological diseases, such as stroke.

Study Limitations

1
Further validation is needed to compare the neutralization efficiency of cryo-shocked M2 macrophages with membrane-coated nanodrugs.
2
The study focuses on a rat model of SCI, and further research is required to assess the efficacy and safety of LNT M2/PTX-NPs@Gel in larger animal models and human clinical trials.
3
Long-term effects and potential side effects of the LNT M2/PTX-NPs@Gel treatment were not fully explored in this study and warrant further investigation.

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