Oral Presentation ANZBMS-MEPSA-ANZORS 2022

Intervertebral disc-on-a-chip: a precision-engineered platform for low back pain studies (#27)

Saie Sunil Bangar 1 , David Wen 1 , Louise Cole 2 , Amy Bottomley 2 , Joanne Tipper 1 , Javad Tavakoli 1
  1. Centre for Health Technologies, School of Biomedical Engineering, Faculty of Engineering and Information Technology, , University of Technology Sydney, Sydney, NSW, Australia
  2. Microbial Imaging Facility, Australian Institute for Microbiology and Infection, Faculty of Science, University of Technology Sydney, Sydney, New South Wales, Australia

 Intervertebral disc (IVD) degeneration is associated with chronic low back pain, a leading cause of disability worldwide. Current back pain treatment options are unable to fully address symptoms and have limited long-term efficacy. In addition, IVD regeneration strategies have shown promise in preclinical studies; however, despite such potential, no such therapies have been broadly adopted clinically. Understanding the mechanisms of IVD degeneration to stop or reverse this process is a challenge at the intersection of biomaterials, biomechanics, and cell biology which would benefit from having a reproducible and adaptable 3D model able to recapitulate the relevant complexity of the IVD. 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 (Fig 1). Unfortunately, none of the current models can truly represent the IVD structure and function or resemble the microenvironment of the degenerated IVD.

We have pioneered and developed a unique technique (simultaneous sonication and alkali digestion) to selectively eliminate extracellular matrix and cells to reveal the collagen and elastic fibers of the IVD (Fig 1), which has identified its novel structural features not reported previously [1-8]. These new insights have significantly enhanced knowledge about the IVD structure-function relationship over multiple scales. Building on these, we successfully employed additive manufacturing techniques to develop the first reproducible and adaptable 3D IVD-on-a-chip organ model that recapitulates the relevant IVD function and its structural complexity (Fig 1). 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 behavior.

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  1. [1]Tavakoli, J. et al., Acta Biomater 148, 2022; [2]Tavakoli, J. et al., Acta Biomater 123, 2021; [3]Tavakoli, J. et al., Acta Biomater 114, 2020; [4]Tavakoli, J. et al., Acta Biomater 113, 2020; [5]Tavakoli, J. et al., Acta Biomater 77, 2018; [6]Tavakoli, J. et al., Acta Biomater 71, 2018; [7] Tavakoli, J. et al., Acta Biomater 68, 2018; [8] Tavakoli, J. et al., Acta Biomater 58, 2017