Royal College of Surgeons in Ireland
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Development and characterization of antacid microcapsules to buffer the acidic intervertebral disc microenvironment

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posted on 2024-10-24, 11:13 authored by Jennifer Gansau, Emily E McDonnell, Conor BuckleyConor Buckley

During intervertebral disc (IVD) degeneration, microenvironmental challenges such as decreasing levels of glucose, oxygen, and pH play crucial roles in cell survival and matrix turnover. Antacids, such as Mg(OH)2 and CaCO3, entrapped in microcapsules are capable of neutralizing acidic microenvironments in a controlled fashion and therefore may offer the potential to improve the acidic niche of the degenerated IVD and enhance cell-based regeneration strategies. The objectives of this work were, first, to develop and characterize antacid microcapsules and assess their neutralization capacity in an acidic microenvironment and, second, to combine antacid microcapsules with cellular microcapsules in a hybrid gel system to investigate their neutralization effect as a potential therapeutic in a disc explant model. To achieve this, we screened five different pH- neutralizing agents (Al(OH)3, Mg(OH)2, CaCO3, and HEPES) in terms of their pH neutralization capacities, with Mg(OH)2 or CaCO3 being carried forward for further investigation. Antacid-alginate microcapsules were formed at different concentrations using the electrohydrodynamic spraying process and assessed in terms of size, buffering kinetics, cell compatibility, and cytotoxicity. Finally, the combination of cellular microcapsules and antacid capsules was examined in a bovine disc explant model under physiological degenerative conditions. Overall, CaCO3 was found to be superior in terms of neutralization capacities, release kinetics, and cellular response. Specifically, CaCO3 elevated the acidic pH to neutral levels and is estimated to be maintained for several weeks based on Ca2+ release. Using a disc explant model, it was demonstrated that CaCO3 microcapsules were capable of increasing the local pH within the core of a hybrid cellular gel system. This work highlights the potential of antacid microcapsules to positively alter the challenging acidic microenvironment conditions typically observed in degenerative disc disease, which may be used in conjunction with cell therapies to augment regeneration. 

Funding

Intraoperative Single Stage Procedure for Intervertebral Disc Regeneration (INSPIRE)

Science Foundation Ireland

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History

Data Availability Statement

The data that support the findings of this study are available from the corresponding author upon reasonable request

Comments

The original article is available at https://onlinelibrary.wiley.com/

Published Citation

Gansau J, McDonnell EE, Buckley CT. Development and characterization of antacid microcapsules to buffer the acidic intervertebral disc microenvironment. J Biomed Mater Res A. 2024.

Publication Date

30 May 2024

PubMed ID

38817021

Department/Unit

  • Amber (Advanced Material & Bioengineering Research) Centre
  • Anatomy and Regenerative Medicine
  • Tissue Engineering Research Group (TERG)

Publisher

John Wiley & Sons.

Version

  • Published Version (Version of Record)