Bioengineered three-dimensional diseased intervertebral disc model revealed inflammatory crosstalk.

Abstract

Without an appropriate disease model, the understanding of the pathophysiology of intervertebral disc degeneration and inflammation is limited. The lack of understanding limits the potential discovery of therapeutic targets as viable treatment options. Here, we report a versatile method to develop a three-dimensional intervertebral disc (IVD) model to study the response of nucleus pulposus (NP) and annulus fibrosus (AF) cells to inflammatory (IL-1β-induced) stimulation. The cell shape regulated IVD model was engineered by modulating the crosslinking of a self-assembled collagen hydrogel. The developed model has provided us with an understanding of the molecular changes that occur at genetic level which modulate the production of extracellular matrix components and key inflammatory pathways in the inflamed IVD. We have identified the role of the suppressor of cytokine proteins (SOCS) family in combating detrimental effects of pro-inflammatory cytokines in degenerated human NP tissue as predicted by the developed diseased model. The model could also provide an understanding of the expression of glycans implicated in the diseased IVD.