Affiliation:
1. Trinity Centre for Biomedical Engineering, Trinity Biomedical Sciences Institute, Trinity College Dublin The University of Dublin Dublin Ireland
2. Discipline of Mechanical, Manufacturing and Biomedical Engineering, School of Engineering, Trinity College Dublin The University of Dublin Dublin Ireland
3. Department of Orthopaedics Icahn School of Medicine at Mount Sinai New York USA
4. Advanced Materials and Bioengineering Research (AMBER) Centre, Royal College of Surgeons in Ireland & Trinity College Dublin The University of Dublin Dublin Ireland
5. Tissue Engineering Research Group, Department of Anatomy and Regenerative Medicine Royal College of Surgeons in Ireland Dublin Ireland
Abstract
AbstractDuring 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.