Table 3.

Summarization of the models, cell types, and biological processes studied using in vitro 2D culture systems and in vitro 3D systems covered in the current review.

Model	Cell types	Model function (biological process)	References
Direct cell-to-cell Interaction (2D)	VSMCs, monocytes, ECs	To study the effect of diseased conditions (M-CSF, diabetic, or vascular injury) on atherosclerotic development, including macrophage activation/adhesion to VSMC, or SMC phenotype switch	(96–98)
	Monocytes, HUVECs, bacterium	To study the impact of bacterial infection on atherosclerosis development (inflammation and EC apoptosis)	(99–105)
	ECs, THP-1s	To evaluate potential atherosclerosis treatment	(106–108)
In-direct Transwell Co-culture (2D)	SMCs, THP-1s	To study the significance of physical contact between SMC and monocyte for atherosclerosis development	(109)
	SMCs, ECs, THP-1s	To study the interactions between different cell types and their effects on atherogenesis.	(16, 110–112)
Cell Sheet (2D) (Decellularized ECM)	ECs and SMCs differentiated from BMCs; fibroblast, SMCs, ECs, chondrocytes	To mimic the native ECM component to improve vascular cell spreading and proliferation.	(117–121)
Cell Sheet (Polymer Scaffold)	SMCs	To partially mimic arterial structure	(122–124)
Microfluidic Chip (2D)	ECs (endothelium-on-a-chip), THP-1s	To observe endothelial response, inflammation, and interaction with monocytes during atherosclerosis.	(127–130, 132, 133)
		To evaluate the effect of nanomedicine on dysfunctional endothelium	(128, 134)
	Multi-layer including SMCs, ECs, and foam cells	To study the mechanism of atorvastatin under the atherosclerotic condition	(131)
Spheroid (3D)	Foam cells	To evaluate therapeutic effects on atherosclerosis	(150, 151)
	SMCs	To study SMC remodeling during atherosclerosis	(152, 153)
	Myeloid cells, THP-1s, macrophage, dendritic, myofibroblasts	To emulate late-stage fibroatheroma	(15)
Cell-laden Hydrogel Construct (3D)	ECs, SMCs, monocytes neutrophil in collagen gel	To mimic early atherosclerosis and study the effect of SMC on monocyte adhesion	(157, 158)
	THP-1s in collagen gel	To study ECM effect on macrophage behavior under early and late atherosclerosis	(159)
	ECs, SMCs, monocytes	To study early atherosclerosis development	(160, 161)
Tissue-engineered Blood Vessel (3D)	ECs, fibroblasts, or SMCs (2-layered vessels)	To study the mechanism of atherogenesis or drug screening	(165–167)
	ECs, monocytes (branched geometry)	To study the endothelial behavior in the athero-prone region	(169, 170)
	ECs, SMCs, monocytes, fibroblasts	To mimic key early atherosclerotic plaque features for mechanism study or drug screening	(18, 21, 171)
Vessel-on-a-chip (3D)	ECs, SMCs	To mimic the natural vascular features on a chip with controlled geometry	(178–180)
	ECs, SMCs, and macrophages	To emulate atherosclerotic plaque on a chip	(181–183)