Lower back pain continues to be a global epidemic, limiting quality of life and ability to work, due in large part to symptomatic disc degeneration. Development of more effective and less invasive biological strategies are needed to treat disc degeneration. In vitro models such as macro- or micro-bioreactors or mechanically active organ-chips hold great promise in reducing the need for animal studies that may have limited clinical translatability, due to harsher and more complex mechanical loading environments in human discs than in most animal models. This review highlights the complex loading conditions of the disc in situ, evaluates state-of-the-art designs for applying such complex loads across multiple length scales, from macro-bioreactors that load whole discs to organ-chips that aim to replicate cellular or engineered tissue loading. Emphasis was placed on the rapidly evolving more customizable organ-chips, given their greater potential for studying the progression and treatment of symptomatic disc degeneration. Lastly, this review identifies new trends and challenges for using organ-chips to assess therapeutic strategies.

The leading cause of disability of all ages worldwide is severe lower back pain. To address this untreated epidemic, further investigation is needed into the leading cause of back pain, intervertebral disc degeneration. In particular, microphysiological systems modeling critical tissues in a degenerative disc, like the annulus fibrosus (AF), are needed to investigate the effects of complex multiaxial strains on AF cells. By replicating these mechanobiological effects unique to the AF that are not yet understood, we can advance therapies for early-stage degeneration at the cellular level. To this end, we designed, fabricated, and collected proof-of-concept data for a novel microphysiological device called the flexing annulus-on-a-chip (AoC). We used computational models and experimental measurements to characterize the device's ability to mimic complex physiologically relevant strains. As a result, these strains proved to be controllable, multi-directional, and uniformly distributed with magnitudes ranging from -10 % to 12% in the axial, radial, and circumferential directions, which differ greatly from applied strains possible in uniaxial devices. Furthermore, after withstanding accelerated life testing (66 K cycles of 10% strain) and maintaining 2000 bovine AF cells without loading for more than three weeks the AoC proved capable of long-term cell culture. Additionally, after strain (3.5% strain for 75 cycles at 0.5 Hz) was applied to a monolayer of AF cells in the AoC, a population remained adhered to the channel with spread morphology. The AoC can also be tailored for other annular structures in the body such as cardiovascular vessels, lymphatic vessels, and the cervix.