Biomimetic Microparticles with Myocardial and Endocardial Integration for Drug Toxicity Studies

Abstract

Hydrogel microparticles are versatile tools for organ modeling due to their simplicity, uniformity, and customizability, yet their limited physiological relevance constrains practical applications. In this study, a heart microparticle model that incorporates endocardial and myocardial structures and functions was developed. Hydrogel microparticles with rough surfaces, embedded with cardiomyocytes, were created using a custom-designed microfluidic device. Surface modification with matrigel enhanced the adhesion and connectivity of endothelial cells, enabling the formation of a densely packed endothelial layer. Real-time analysis, combining microparticle culture with a microfluidic chip-mass spectrometry system, demonstrated the utility of these particles in detecting the cardiotoxicity of heart-related drugs. For example, the analysis revealed that the cardiotoxicity of aconitine and Tie-bang-chui (TBC) was associated with elevated lactate and succinate levels, while processed TBC mitigated this toxicity of TBC by reducing these metabolites. These biomimetic microparticle models provide a novel platform for real-time metabolite analysis and cardiotoxicity research.