Intervertebral disc (IVD) degeneration is a major cause of low back pain (LBP) in the lumbar spine. This phenomenon is caused by several processes, including matrix degradation in IVD tissues, which is mediated by matrix metalloproteinases (MMPs) and inflammatory responses, which can be mediated by interactions among immune cells, such as macrophages and IVD cells. In particular, interleukin (IL)-1 beta (β), which is a master regulator secreted by macrophages, mediates the inflammatory response in nucleus pulposus cells (NP) and plays a significant role in the development or progression of diseases. In this study, we developed a custom electrical stimulation (ES) platform that can apply low-constant-current stimulation (LCCS) signals to microfluidic chips. Using this platform, we examined the effects of LCCS on IL-1β-mediated inflammatory NP cells, administered at various currents (5, 10, 20, 50, and 100 μA at 200 Hz). Our results showed that the inflammatory response, induced by IL-1β in human NP cells, was successfully established. Furthermore, 5, 10, 20, and 100 μA LCCS positively modulated inflamed human NP cells’ morphological phenotype and kinetic properties. LCCS could affect the treatment of degenerative diseases, revealing the applicability of the LCCS platform for basic research of electroceuticals.

The degeneration of an intervertebral disc (IVD) is a major cause of lower back pain. IVD degeneration is characterized by the abnormal expression of inflammatory cytokines and matrix degradation enzymes secreted by IVD cells. In addition, macrophage-mediated inflammation is strongly associated with IVD degeneration. However, the precise pathomechanisms of macrophage-mediated inflammation in IVD are still unknown. In this study, we developed a microfluidic platform integrated with an electrical stimulation (ES) array to investigate macrophage-mediated inflammation in human nucleus pulposus (NP). This platform provides multiple cocultures of different cell types with ES. We observed macrophage-mediated inflammation and considerable migration properties via upregulated expression of interleukin (IL)-6 (p < 0.001), IL-8 (p < 0.05), matrix metalloproteinase (MMP)-1 (p < 0.05), and MMP-3 (p < 0.05) in human NP cells cocultured with macrophages. We also confirmed the inhibitory effects of ES at 10 μA due to the production of IL-6 (p < 0.05) and IL-8 (p < 0.01) under these conditions. Our findings indicate that ES positively affects degenerative inflammation in diverse diseases. Accordingly, the microfluidic electroceutical platform can serve as a degenerative IVD inflammation in vitro model and provide a therapeutic strategy for electroceuticals.