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

Yishu Liu,1– 3 Jingsong Liu,1– 3 Yangyang Wang,1– 3 Yubo Zhang,1– 3 Zhibin Peng,1– 3 Pengfei Li,1– 3 Mi Li,1– 3 Bing Xue,4 Yansong Wang1– 3,5 1Department of Orthopedics, The First Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang, People’s Republic of China; 2The Key Laboratory of Myocardial Ischemia, Ministry of Education, Harbin Medical University, Harbin, Heilongjiang, People’s Republic of China; 3State Key Laboratory of Frigid Zone Cardiovascular Diseases, Harbin Medical University, Harbin, Heilongjiang, People’s Republic of China; 4Department of Orthopedics, The Second Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang, People’s Republic of China; 5NHC Key Laboratory of Cell Transplantation, Harbin Medical University, Harbin, Heilongjiang, People’s Republic of ChinaCorrespondence: Yansong Wang, Email [email protected]: 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. Keywords: spinal cord injury, nerve regeneration, graphene, polylactic acid, anti-tumor necrosis factor α, neuroimmunomodulation