A reactive oxygen species-responsive hydrogel loaded with Apelin-13 promotes the repair of spinal cord injury by regulating macrophage M1/M2 polarization and neuroinflammation

Journal of Nanobiotechnology, 2025 · DOI: https://doi.org/10.1186/s12951-024-02978-4 · Published: January 1, 2025

Simple Explanation

Spinal cord injury (SCI) is a chronic condition where ongoing macrophage activation interferes with healing. M1 macrophages, prominent during acute trauma, release high levels of reactive oxygen species (ROS), increasing cell death. This study explores how a ROS-responsive hydrogel with Apelin-13 affects macrophage behavior and inflammation, influencing SCI repair. Apelin-13 was found to be reduced in SCI rats. Administering Apelin-13 improved recovery, reduced inflammation, and adjusted macrophage polarization. The Apelin-13@ROS-hydrogel showed superior ROS scavenging, decreased pro-inflammatory factors, and increased anti-inflammatory mediators in microglia BV2 cells. The hydrogel enhanced healing and neurological function by day 28, decreasing inflammation and M1 markers while increasing M2 markers in rats. Apelin-13 boosts SCI repair by regulating macrophages and reducing neuroinflammation, and the ROS-responsive hydrogel enhances these effects.

Study Duration

28 days

Participants

Sprague-Dawley rats and Microglia BV2 cells

Evidence Level

Not specified

Key Findings

1
Apelin-13 is significantly downregulated in the injured sites of the SCI model rats since day 14 after modeling.
2
Apelin-13 treatment significantly increased BBB scores compared with the SCI plus vehicle group, whereas APJ silencing by APJ siRNA transduction also significantly lowered BBB scores compared with the Apelin-13 or Apelin-13 plus scramble siRNA group.
3
Apelin-13@ROS-hydrogel can promote recovery in SCI rats by facilitating neuroinflammation, promoting M2 polarization, and suppressing M1 polarization of macrophages, as well as scavenging ROS through the continuous and stable release of Apelin-13.

Research Summary

This study investigates the effects of Apelin-13, delivered via a ROS-responsive hydrogel, on macrophage polarization and neuroinflammation in a rat model of spinal cord injury (SCI). The hydrogel was designed to scavenge reactive oxygen species (ROS) and provide sustained release of Apelin-13. The results showed that Apelin-13 was downregulated in SCI rats, and treatment with Apelin-13, especially when delivered via the ROS-responsive hydrogel, improved functional recovery, reduced inflammation, and promoted M2 macrophage polarization. The study concludes that Apelin-13 enhances SCI repair through macrophage regulation and neuroinflammation reduction, and the ROS-responsive hydrogel amplifies these effects, suggesting a promising therapeutic strategy for SCI.

Practical Implications

Therapeutic Potential

Apelin-13@ROS-hydrogel shows promise as a therapeutic strategy for spinal cord injury by promoting functional recovery and reducing inflammation.

Targeted Drug Delivery

The ROS-responsive hydrogel provides a means for targeted and sustained drug delivery to the injury site, improving treatment efficacy.

Macrophage Polarization

Modulating macrophage polarization from M1 to M2 phenotype can improve the micro-inflammatory environment, accelerating tissue repair post-injury.

Study Limitations

1
Lack of long-term follow-up to fully assess the chronic effects of the treatment.
2
The study is limited by the lack of long-term follow-up to fully assess the chronic effects of the treatment. Future research should focus on optimizing the hydrogel formulation for clinical use
3
Future research should focus on optimizing the hydrogel formulation for clinical use and investigating the long-term safety and efficacy of Apelin-13@ROS-hydrogel in larger animal models.

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