Magnesium Ion-Doped Mesoporous Bioactive Glasses Loaded with Gallic Acid Against Myocardial Ischemia/Reperfusion Injury by Affecting the Biological Functions of Multiple Cells

Abstract

Introduction

Excessive generation of reactive oxygen species (ROS) following myocardial ischemia-reperfusion (I/R) can result in additional death of myocardial cells. The rapid clearance of ROS after reperfusion injury and intervention during subsequent cardiac repair stages are crucial for the ultimate recovery of cardiac function.

Methods

Magnesium-doped mesoporous bioactive glasses were prepared and loaded with the antioxidant drug gallic acid into MgNPs by sol-gel method. The antioxidant effects of MgNPs/GA were tested for their pro-angiogenic and anti-inflammatory effects based on the release characteristics of GA and Mg²⁺ from MgNPs/GA. Later, we confirmed in our in vivo tests through immunofluorescence staining of tissue sections at various time points that MgNPs/GA exhibited initial antioxidant effects and had both pro-angiogenic and anti-inflammatory effects during the cardiac repair phase. Finally, we evaluated the cardiac function in mice treated with MgNPs/GA.

Results

We provide evidence that GA released by MgNPs/GA can effectively eliminate ROS in the early stage, decreasing myocardial cell apoptosis. During the subsequent cardiac repair phase, the gradual release of Mg²⁺ from MgNPs/GA stimulated angiogenesis and promoted M2 macrophage polarization, thereby reducing the release of inflammatory factors.

Conclusion

MgNPs/GA acting on multiple cell types is an integrated solution for comprehensive attenuation of myocardial ischaemia-reperfusion injury and cardiac function protection.

Keywords:

• myocardial ischemia/reperfusion injury
• mesoporous bioactive glass
• gallic acid
• magnesium ion
• macrophage polarization

Author Contributions

All authors have made significant contributions to the work reported, including conception, study design, execution, data acquisition, analysis and interpretation, as well as manuscript drafting, revision, and critical review. All authors have provided final approval of the submitted version for publication and have agreed to the journal to which the article has been submitted, with full accountability for all aspects of the work.

Disclosure

The authors report no conflicts of interest in this work.

Additional information

Funding

This work was funded by the National Natural Science Foundation of China (grant no. 82270382, 82170505, 82200534), the Natural Science Foundation of Jiangxi Province (grant no. 20204BCJ22028, 20212ACB206020, 20203BBGL73141 and 20192BAB205070), the Natural Science Foundation of Hubei Province (2023AFB817), Key Research and Development Project of Hubei Provincial Department of Science and Technology (2023BCB002), Wuhan Talent’s Industry-Leading Talent Project (WHYCCYLJ2021002), the talent Project of Zhongnan Hospital of Wuhan University (grant no. rcyj20210601, xkjs202002, CXPY2022046).