在椎间盘(IVD)退变期间,微环境挑战,如降低葡萄糖水平,氧气,pH在细胞存活和基质周转中起着至关重要的作用。抗酸剂,包埋在微胶囊中的例如Mg(OH)2和CaCO3能够以受控的方式中和酸性微环境,因此可以提供改善退化IVD的酸性生态位和增强基于细胞的再生策略的潜力。这项工作的目标是,首先,开发和表征抗酸剂微胶囊,并评估它们在酸性微环境中的中和能力,第二,在混合凝胶系统中将抗酸剂微胶囊与细胞微胶囊结合,以研究它们在椎间盘外植体模型中作为潜在治疗剂的中和作用。为了实现这一点,我们筛选了五种不同的pH中和剂(Al(OH)3,Mg(OH)2,CaCO3和HEPES),其中Mg(OH)2或CaCO3进行进一步研究。使用电流体动力喷雾工艺形成不同浓度的抗酸-藻酸盐微胶囊,并根据尺寸进行评估,缓冲动力学,细胞相容性,和细胞毒性。最后,在生理变性条件下,在牛椎间盘外植体模型中检查了细胞微胶囊和抗酸胶囊的组合。总的来说,发现CaCO3在中和能力方面是优越的,释放动力学,和细胞反应。具体来说,CaCO3将酸性pH升高至中性水平,并且基于Ca2+释放估计维持数周。使用圆盘外植体模型,已证明CaCO3微胶囊能够增加混合细胞凝胶系统核心内的局部pH。这项工作强调了抗酸剂微胶囊积极改变退行性椎间盘疾病中通常观察到的具有挑战性的酸性微环境条件的潜力。它可以与细胞疗法结合使用以增强再生。
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.