The role of loading-induced convection versus diffusion on the transport of small molecules into the intervertebral disc

Elias Salzer, Zahra Gorgin Karaji, Marina van Doeselaar, Marianna A. Tryfonidou, Keita Ito*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

Abstract

Purpose: Limited nutrient transport is hypothesized to be involved in intervertebral disc (IVD) degeneration. It is widely recognized that the dominant mode of transport of small molecules such as glucose is via diffusion, rather than convection. However, recent findings suggest a role for convection-induced by fast (motion-related) and slow (diurnal) dynamic loading in molecular transport of even such small solutes. The aim of this study was to investigate whether fluid exchange induced by simulated physiological loading (composed of both fast cyclic or slower diurnal loading) can influence the molecular transport of a small molecule through the cartilage endplate (CEP) into the nucleus pulposus (NP) of IVDs. Methods: The molecular transport of fluorescein through the CEP and into the NP was studied in a bovine CEP/NP explant model and loading was applied by an axial compression bioreactor. The loaded explants (convection and diffusion) were compared to unloaded explants (diffusion alone). Results: In the initial 24 h, there were no differences between loaded and unloaded explants, indicating that convection did not enhance molecular transport of small solutes over diffusion alone. Notably, after 48 h which corresponds to two complete diurnal cycles of tissue compression, fluid exudation/imbibing and redistribution, the fluorescein concentration was significantly increased in the top and bottom layer of the explant, when compared to the unloaded explant. Conclusions: Slower diurnal cyclic compression of the IVD might enhance the transport of small molecules into the IVD although it could not be discerned whether this was due to diffusion/convection or a combination.

Original languageEnglish
Pages (from-to)326–337
Number of pages12
JournalEuropean Spine Journal
Volume34
Issue number1
Early online date5 Dec 2024
DOIs
Publication statusPublished - 2025

Bibliographical note

Publisher Copyright:
© The Author(s) 2024.

Funding

We thank Jurgen Bulsink (Eindhoven University of Technology) for technical support with the culture chambers and the height measurement device. This project was partly funded by the European Union's Horizon 2020 project iPSpine (825925, (http://www.ipspine.eu) and AES Open Technology Program of the Dutch Research Council (NWO) under grant agreement BioAID (10025453).

FundersFunder number
Horizon 2020825925
European Union10025453
AES Open Technology Program of the Dutch Research Council (NWO)

    Keywords

    • Bioreactor
    • Diurnal loading
    • Dynamic loading
    • Ex vivo
    • Nucleus pulposus and cartilage endplate

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