Regulation of Neuroimmune Microenvironment by PLA/GO/Anti-TNF-α Composite to Enhance Neurological Repair After Spinal Cord Injury

Abstract

Introduction: Spinal cord injury (SCI) is a severe neurological condition with limited treatment options. Polylactic acid (PLA)+graphene oxide (GO)+anti-TNF-α (Ab) composites have shown potential in regulating immune responses and promoting neural repair. Methods: Electrospinning PLA+GO+Ab materials were characterized using scanning electron microscopy (SEM), Fourier-transform infrared spectroscopy (FTIR), X-ray photoelectron spectroscopy (XPS), Raman spectroscopy, and X-ray diffraction (XRD). Their effects on neural stem cells (NSCs) and macrophage polarization were evaluated through in vitro assays, including proliferation, migration, differentiation, and flow cytometry. A rat SCI model was used to assess motor function recovery and histological changes. Results: PLA+GO+Ab promoted NSC proliferation, migration, and differentiation while inducing macrophage polarization toward the M2 phenotype, reducing inflammation. In the SCI model, PLA+GO+Ab treatment enhanced motor function recovery, reduced spinal cord damage, and promoted axonal regeneration and oligodendrocyte maturation. RNA sequencing identified activation of the Rap1 signaling pathway, contributing to these effects. Discussion: PLA+GO+Ab composites effectively modulate the neuroimmune microenvironment, supporting SCI recovery by promoting neural repair and immune regulation. These findings suggest its potential as a therapeutic biomaterial for SCI treatment.