Microfluidic Disc-on-a-Chip Device for Mouse Intervertebral Disc-Pitching a Next-Generation Research Platform To Study Disc Degeneration.

Low back pain is the most common cause of disability worldwide, and intervertebral disc degeneration is a major cause of low back pain. Unfortunately, discogenic low back pain is often treated with symptomatic relief interventions, as no disease-modifying medications are yet available. Both to-be-deciphered disc biology/pathology and inadequate in vitro research platform are major hurdles limiting drug discovery progress for disc degeneration. Here, we developed a microfluidic disc-on-a-chip device tailored for mouse disc organ as an in vitro research platform. We hypothesize that continuous nutrients empowered by a microfluidic device would improve biological performance of cultured mouse discs compared to those in static condition. This device permitted continuous media flow to mimic in vivo disc microenvironment. Intriguingly, mouse discs cultured on the microfluidic device exhibited much higher cell viability, better preserved structure integrity and anabolic-catabolic metabolism in both nucleus pulposus and annulus fibrosus, for up to 21 days compared to those in static culture. This first "disc-on-a-chip" device lays groundwork for future preclinical studies in a relative long-term organ culture given the chronic nature of intervertebral disc degeneration. In addition, this platform is readily transformable into a streamlined in vitro research platform to recapitulate physiological and pathophysiological microenvironment to accelerate disc research.