Photobiomodulation Reduces Fibrous Scar Formation After Spinal Cord Injury by Downregulating CXCL3 Expression in Macrophages.

Although the inhibitory role of photobiomodulation (PBM) in glial scar formation after spinal cord injury (SCI) has been identified, its effects on fibrous scar formation and the underlying mechanisms remain unexplored. To assess fibrous scar deposition, Sirius Red, Masson's trichrome, and immunostaining of extracellular matrix molecules after SCI were performed. Fibroblast viability was evaluated using the CCK-8 assay, whereas migration capacity was measured using Transwell and scratch assays. RNA sequencing was performed on macrophages subjected to inflammation with and without PBM intervention. To validate the mechanism in vivo, CXCL3 and a CXCR2 inhibitor were administered to mice intraperitoneally. Findings demonstrated that PBM treatment suppressed fibrous scar formation post-SCI. Temporal profiling revealed distinct patterns of macrophage and fibroblast infiltration after injury, with fibroblast migration influenced by the macrophage-conditioned medium. RNA sequencing analysis identified CXCL3 as a key mediator of macrophage-fibroblast crosstalk under PBM modulation. More specifically, PBM downregulated CXCL3 expression in macrophages, thereby attenuating fibrous scar progression.