Table 4.

Summarize the features, advantages, application, challenges, and future directions of models discussed in the review.

Model	Features	Advantages	Applications	Challenges	Directions
Single-cell Systems (2D)	Seeding only one cell type in a tissue culture plate (TCP)	- High availability - Easy to make - Cost-effective - High reproducibility - High throughput	- Evaluation of drug and drug delivery system - Mechanistic studies	- Fail to mimic the native plaque composition and vascular structure	- Creating a co-culture system
Direct Co-culture (2D)	Direct cell-to-cell seeding of multicell types in a TCP		- Study of cell-cell interaction and adhesion	- Difficulty mimicking native physiological structures and proper development of cellular interactions with ECM	- Using ECM - mimicking scaffold
In-direct Transwell Co-culture (2D)	Cells seeded in a TCP and trans-well inserts		- Study of cellular responses via secretory pathways and cytokine production		- Improving cell attachment - Using ECM mimicking scaffold
Cell Sheet (2D)	Layered structure seeded on the 2D scaffolds or no scaffolds	- Better mimicking the vascular wall structure than other 2D systems - Relatively easy to fabricate	- Potential for therapeutic evaluation - Potential for studying cell-cell interaction	- Prone to spontaneous shrinkage or contraction - Lacking adequate mechanical properties - More expensive than TCP based systems	- Increasing mechanical property through other types of scaffolds - Exploration of applications of such systems
Microfluidic Chip (2D)	Endothelium seeded on a chip with a flow	- Micro-analysis - Providing continuous monitoring and medium supply - Enhanced sensitivity - Dynamic culture - Relatively easy to make	- Mechanistic studies - Nanomedicine evaluation - Allowing real-time imaging	- Require additional types of equipment, such as pumps, tubing, and connectors - Not adequately model 3D native environments - Costly	- Using ECM mimicking scaffold - Using multiple vascular cells observed in the plaque
Spheroid (3D)	Cellular aggregates to provide 3D structures	- Providing spherical structures - Advanced plaque	- Mechanistic studies	- Limited capability or function in comparison to native tissue - Failing to provide the layered vascular structure - Low quantity of spheroids	- Large production of this model
Cell-laden Hydrogel Construct (3D)	Cells embedded within hydrogel scaffolds	- Ability to provide an ECM mimicking environment provided by the scaffold - relatively easy to make	- Mechanistic studies	- Difficult to reproduce - Poor mechanical properties	- Increase mechanical properties and reproducibility - Controlling the properties of hydrogels - Using these systems for various applications
Tissue-engineered Blood Vessel (3D)	Models reproducing native vessel structure and size with or without disease features	- Allowing controlled stimuli - Providing partially vessel-like structure - Dynamic culture - Providing similar size to that of native vessels	- Drug evaluation - Mechanistic studies - Potential for medical device evaluation - Allowing real-time imaging	- Majority are not developed using arterial cells - Lacking the fibroblast layer - Challenging to have a monolayer of endothelium - Failing to induce advanced atherosclerotic plaques - Expensive and difficult to reproduce - Time-consuming	- Producing three-layered vessel - Using arterial cells or stem cells - Incorporating T and B cells in the system - Large scale production for pharmaceutical use - Improving reproducibility - Providing advanced plaque
Vessel-on-a-chip (3D)	Models reproducing vessel structures with or without disease feature on a micro-sized chip	- Allowing controlled stimuli and real-time imaging - Providing partially vessel-like structure - Dynamic culture	- Applicable for drug screening - Mechanistic studies - Allowing real-time imaging	- Expensive and difficult to reproduce - Additional equipment to create a dynamic microenvironment - Lacking three-layered structures - Time-consuming - Inability to provide actual size vessel for medical device evaluation - Limited to drug screening