Advanced in vitro organ degeneration models for musculoskeletal research

Swiss National Funds
S Grad, M Alini, A Secerovic, A Ristaniemi

Background

Currently, the translation of research from the lab to the clinic is not reliable due to an oversimplification of the in vitro models and limitations of animal testing. Most in vitro models provide static or oversimplified dynamic (e.g., only compression) environments over short-term tissue culture periods. 

 

Goal

The overall objective is to develop a multi-axis dynamic in vitro system to mimic movement, with a focus on intervertebral discs (IVD), for long-term musculoskeletal tissue culture. This interdisciplinary project is a collaboration between CSEM (6-DOF bioreactor), ETH Zurich (biomechanics) and ARI (in vitro organ models).

 

Results

In a biological and mechanical study a new sample holder for bovine IVDs with adjacent bone was validated according to bioreactor requirements for multiaxial loading and long-term IVD culture. During three weeks of culture under axial compression loading, the new model maintained the cell viability comparable to the standard model. When differently directed motions were applied, the holder-IVD interface with side screws resisted compression and torsion above reference values, and the combination of side and top screws resisted tension and bending at high values

New holding system for whole bovine intervertebral disc with vertebral bone, allowing multiaxial loading.
  • Publication

    Šećerović A, Ristaniemi A, Cui S, Li Z, Soubrier A, Alini M, Ferguson SJ, Weder G, Heub S, Ledroit D, Grad S. Towards the next generation of spine bioreactors: validation of an ex vivo intervertebral disc organ model and customized specimen holder for multiaxial loading. ACS Biomater Sci Eng. 2022 Aug 17. doi: 10.1021/acsbiomaterials.2c00330. Online ahead of print. PMID: 35977717

    Ristaniemi A, Šećerović A, Dischl V, Crivelli F, Heub S, Ledroit D, Weder G, Grad S, Ferguson SJ. Physiological and degenerative loading of bovine intervertebral disc in a bioreactor: A finite element study of complex motions. J Mech Behav Biomed Mater. 2023;143:105900. https://doi.org/10.1016/j.jmbbm.2023.105900

    Mürner M. Flexion, shear, and dynamic compression-induced IVD degeneration models for the evaluation of injectable biomaterial efficacy. 2023 ETH Zürich (S.J. Ferguson, S. Grad, A. Šećerović – MSc)

     
    Ristaniemi A, Šećerović A, Grad S, Ferguson SJ. A novel fiber-reinforced poroviscoelastic bovine intervertebral disc finite element model for organ culture experiment simulations. J Biomech Eng. 2023;145(12). https://doi.org/10.1115/1.4063557 
     


  • Presentation

    Ristaniemi A, Secerovic A, Ferguson SJ, Grad S. Viscoelastic characterization of bovine annulus fibrosus lamellae. 2022 WCB (oral)

    Šećerović A, Ristaniemi A, Cui S, Li Z, Alini M, Crivelli F, Heub S, Weder G, Ferguson SJ, Ledroit D, Grad S. Development and validation of the new generation of bioreactors for long-term intervertebral disc organ culture under multiaxial loading. 2023 ORS (poster)

    Šećerović A, Mürner M, Crivelli F, Heub S, Weder G, Ferguson SJ, Ledroit D, Grad S. A biofidelic platform for preclinical assessment of hydrogel efficacy in multiaxially loaded intervertebral discs. 2023 ESB (Biomaterials) / (poster) 

    Šećerović A, Ristaniemi A, Crivelli F, Heub S, Weder G, Ferguson SJ, Ledroit D, Grad S. Advanced bioreactor studies of region-specific response in the intervertebral disc to compression, flexion/extension and torsion. 2023 EORS (oral)

     
     

     

     
  • Partner

    Ferguson SJ (Prof), ETH Zürich, Switzerland

    Weder G (Dr), CSEM Neuchâtel, Switzerland

    Heub S (Dr), CSEM Neuchâtel, Switzerland

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