Aim: Intervertebral disc (IVD) degeneration is associated with chronic low back pain, a leading cause of disability worldwide. IVD regeneration strategies have shown promise in preclinical studies; however, despite such potential, no such therapies have been broadly adopted clinically. One drawback here is lack of a physiologically relevant IVD in vitro model. The IVD models available at present are standard in vitro cultures in 2D and 3D, ex vivo systems employing human or animal IVDs and bioreactors. Unfortunately, none of the current models can truly represent the IVD structure and function or resemble the microenvironment of the degenerated IVD.
Method: We have pioneered and developed a unique technique (simultaneous sonication and alkali digestion) to selectively eliminate IVD extracellular matrix components and reveal the organization of collagen and elastic fibres in IVD. Building on these, we successfully employed two-photon polymerization and 3D printing to develop the first reproducible and adaptable 3D IVD-on-a-chip organ model that recapitulates the relevant IVD function and its structural complexity. The model that we developed mimics the structural organization of collagen and elastic fibres that are often observed in different regions of IVD (lamellae [in-plane and cross-section], interlamellar matrix, partition boundaries, transition zone and nucleus).
Results and conclusions: Our organ model allows real-time monitoring in a controlled microenvironment, precise tuning of material, mechanical and biological properties, and IVD research that targets precise questions. We have so far successfully employed our organ model to evaluate cell viability and to understand the impact of IVD microstructure on cell behaviour. In addition, we found that increasing the stiffness of the microstructure in our organ model (two-fold) did not affect the biocompatibility (L929 mice fibroblast); however, significantly altered the cell response to the structure. Cells in the stiffer platform were more elongated in the annulus region, while more round cells were observed in the nucleus region of the organ model.