Modeling Foam Cell Formation in A Hydrogel‐Based 3D‐Intimal Model: A Study of The Role of Multi‐Diseases During Early Atherosclerosis

Abstract

Monocyte recruitment and transmigration are crucial in atherosclerotic plaque development. The multi‐disease complexities aggravate the situation and continue to be a constant concern for understanding atherosclerosis plaque development. Herein, a 3D hydrogel‐based model that integrates disease‐induced microenvironments is sought to be designed, allowing us to explore the early stages of atherosclerosis, specifically examining monocyte fate in multi‐disease complexities. As a proof‐of‐concept study, murine cells are employed to develop the model. The model is constructed with collagen embedded with murine aortic smooth muscle cells and a murine endothelial monolayer lining. The model achieves in vitro disease complexities using external stimuli such as glucose and lipopolysaccharide (LPS). Hyperglycemia exhibits a significant increase in monocyte adhesion but no enhancement in monocyte transmigration and foam cell conversion compared to euglycemia. Chronic infection achieved by LPS stimulation results in a remarkable augment in initial monocyte attachment and a significant increment in monocyte transmigration and foam cells in all concentrations. Moreover, the model exhibits synergistic sensitivity under multi‐disease conditions such as hyperglycemia and infection, enhancing initial monocyte attachment, cell transmigration, and foam cell formation. Additionally, western blot data prove the enhanced levels of inflammatory biomarkers, indicating the model's capability to mimic disease‐induced complexities during early atherosclerosis progression.

Evaluating thrombosis risk and patient-specific treatment strategy using an atherothrombosis-on-chip model

“…Vulnerable atherosclerosis plaque is responsible for atherothrombosis development, whereas upregulation of the prethrombotic factors, changes in blood flow and other blood factors regulate the thrombus growth. 8–16 Certain diseases, such as diabetes, chronic inflammatory conditions, and hypercholesterolaemia, induce hyperactivation of platelets and accelerate aggregation to exacerbate the situation.…”