Biomimetic "Trojan Horse" Fibers Modulate Innate Immunity Cascades for Nerve Regeneration

Area of Science:

• Biomaterials Science
• Immunology
• Neuroscience

Background:

• Neutrophil membrane vesicles (NMVs) show potential in managing spinal cord injury (SCI) inflammation.
• Mechanisms of NMV-mediated macrophage reprogramming and outcomes remain underexplored.

Purpose of the Study:

• To elucidate how NMVs influence macrophage phenotype and function post-SCI.
• To develop and evaluate a novel composite scaffold for SCI treatment.

Main Methods:

• Investigated NMV-macrophage interaction, focusing on efferocytosis-like effects.
• Analyzed metabolic pathways (glutamine metabolism, TCA cycle) and signaling (NF-κB).
• Constructed a composite fiber scaffold with NMVs and brain-derived neurotrophic factor (BDNF).

Main Results:

• NMVs promote macrophage efferocytosis, enhance oxidative phosphorylation via α-KG, and inhibit NF-κB signaling.
• The NMV-BDNF scaffold modulated the inflammatory microenvironment by 39.23%.
• Sustained nerve regeneration was promoted by 85.67% in vivo.

Conclusions:

• NMVs reprogram macrophages to a pro-regenerative phenotype by modulating metabolism and signaling pathways.
• The developed composite scaffold effectively coordinates inflammatory response and nerve regeneration in SCI.
• This study offers a novel strategy for SCI treatment by targeting immune cell reprogramming.