Hydrogel loaded with cerium‑manganese nanoparticles and nerve growth factor enhances spinal cord injury repair by modulating immune microenvironment and promoting neuronal regeneration

Journal of Nanobiotechnology, 2025 · DOI: https://doi.org/10.1186/s12951-025-03098-3 · Published: January 7, 2025

Spinal Cord Injury Immunology Biomedical

Simple Explanation

This study introduces a novel composite material, Lightgel/NGF/CeMn NP-PEG, designed to improve spinal cord injury (SCI) repair. It combines nanozymes and nerve growth factor (NGF) within a hydrogel to modulate the immune microenvironment. The composite's components work synergistically: CeMn NP-PEG nanozymes scavenge harmful reactive oxygen species (ROS) and reduce inflammation, while NGF promotes neuronal regeneration. The hydrogel provides a supportive matrix and enables sustained release of these therapeutic agents. In a rat SCI model, the composite significantly enhanced motor function recovery, reduced inflammation, and promoted a shift towards an anti-inflammatory immune response, suggesting its potential for clinical applications in SCI treatment.

Study Duration

Not specified

Participants

Fifty 6-week-old CD (SD) IGS female rats

Evidence Level

Not specified

Key Findings

1
The Lightgel/NGF/CeMn NP-PEG composite effectively eliminates ROS, promoting M2 macrophage polarization. It also reduces pro-inflammatory cytokines, and supports neuronal regeneration in SCI rats.
2
The composite's nanozyme component, CeMn NP-PEG, exhibits enhanced anti-inflammatory and ROS-scavenging biological activity, making it a potent therapeutic agent.
3
In vitro experiments demonstrated that the composite significantly enhances the expression of nerve growth-associated proteins, indicating its potential in facilitating nerve regeneration.

Research Summary

This study developed a Lightgel/NGF/CeMn NP-PEG composite material that promotes neuronal repair and regeneration, enhances the immune microenvironment post-SCI, and demonstrates remarkable therapeutic potential in both cell and animal models. The composite material can significantly attenuate the neuroinflammatory response in SCI rats, promote the shift of macrophages from the pro-inflammatory M1 to the anti-inflammatory M2 phenotype, eliminate ROS, facilitate neuronal repair, and ultimately improve neurological function. Lightgel/NGF/CeMn NP-PEG demonstrates significant therapeutic potential for SCI treatment due to its sustained and controlled release of active substances, coupled with its excellent biocompatibility.

Practical Implications

Clinical Translation

The Lightgel/NGF/CeMn NP-PEG composite shows promise for clinical translation as a novel therapeutic strategy for spinal cord injury, potentially improving patient outcomes and quality of life.

Targeted Therapy

The composite's ability to modulate the immune microenvironment and promote neuronal regeneration offers a targeted approach to SCI treatment, addressing key pathological mechanisms of the injury.

Biomaterial Design

The study provides insights into the design of biomaterials for SCI therapy, highlighting the importance of combining neurotrophic factors, ROS scavengers, and biocompatible carriers for effective treatment.

Study Limitations

1
The use of H2O2 may not fully replicate the complex conditions of actual SCI, which could limit the generalizability of our findings to human nerve cells
2
The study exclusively used female rats, and the impact of sex differences on SCI repair remains unexplored
3
The mechanism by which cGAS-STING-p-IRF3 activation mediates M2 polarization of macrophages was not further investigated

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