Xudong Li

This study aims to develop an ex vivo organ‐on‐a‐chip model, intervertebral Disc‐on‐a‐Chip MF , to investigate integrated effects of mechanical loading and nutrition on disc health. The system consists of a detachable multilayer microfluidic chip, a Computer‐Arduino‐based control system, and a mechanical loading unit, which are optimized for accurate axial force measurement and the maintenance of a 21‐day ex vivo disc culture. To ensure accuracy of axial force, the axial mechanical loading regimen is optimized, using the Computer‐Arduino‐based system and low‐profile force sensors (LPFS) to control the mechanical loading unit, and the force distribution on the disc surface is modeled by computational simulation. A 21‐day ex vivo disc culture is demonstrated using the Disc‐on‐a‐Chip MF system, with optimized mechanical loading (0.02 MPa at 1Hz, 1.5 hr day −1 ) and flow rate (1 µL min −1 ). The structural integrity, collagen breakdown, catabolic enzyme activities, and disc cell and collagen alignment reveal that the on‐chip cultured discs exhibit a preferred disc health similar to that of native discs for up to 21 days, while discs in a static culture show degenerative changes. The mouse Disc‐on‐a‐Chip MF system mimics in vivo disc microenvironment and provides a valuable platform for studying the effects of various factors on disc health and degeneration and testing new therapies.