Chip's got your back

There's good news for people suffering from low back pain (LBP). A team from the Indian Institute of Technology (IIT) Madras has developed a disc-on-a-chip that will help researchers understand the mechanisms of LBP and aid in testing drugs and potential therapies for this medical condition, which currently affects 10% of the world population (bit.ly/WHO-back-pain). Organ-on-chip platforms offer better drug-testing results than animal trials.

Chronic LBP usually occurs due to the wearing off of a disc — the cushion between spinal bones. While a healthy disc lacks blood vessels or nerves, these begin to form when bones degenerate due to ageing or disease. The nerves and blood vessels are the primary cause of pain. As the disc cannot repair itself, doctors treat LBP by replacing the disc or spinal fusion through surgery, managing the pain through steroids and painkillers or injecting extracellular matrix components, such as glycosaminoglycan (GAG) and hyaluronic acid.

"While many in vitro and in vivo models have been developed to study disc degeneration, the exact biochemical and biophysical processes that drive disease progression are still not fully understood," says Greeshma Thrivikraman, Assistant Professor at the institute's Department of Biotechnology.

To study this condition in depth, Thrivikraman's team developed a chip that mimicked the complex environment of the human disc on a tiny microfluidic device. The central chamber of the chip contained two types of disc cells — nucleus pulposus and annulus fibrosus — separated by a hydrogel. The peripheral zone of the chip had cells that form nerves and blood vessels. A micro grating separated these central and peripheral zones in such a way that when the researchers triggered an inflammation using an inflammatory protein in the central disc, the disc cells sent distress signals, due to which cells that made nerves and blood vessels migrated towards the central chamber of the chip; that is, they invaded the disc. The chip was made using a 5-axis computer numerical control (CNC) micro-milling machine.

They validated the chip by assessing the effects of two treatment options — an anti-inflammatory drug (celecoxib) and GAG supplementation — in an inflamed disc environment. "Therapeutic interventions using glycosaminoglycan supplementation and celecoxib treatment resulted in a fourfold reduction in macrophage infiltration and over a twentyfold decrease in neural invasion compared to the inflamed control group," they said in a paper (bit.ly/disc-on-chip) published in Acta Biomaterialia.