Microfluidic chip with low constant-current stimulation (LCCS) platform: Human nucleus pulposus degeneration in vitro model for symptomatic intervertebral disc

Abstract

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. Further-more, 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, reveal-ing the applicability of the LCCS platform for basic research of electroceuticals.