# Research Progress in the Construction and Application of In Vitro Vascular Models
###### Abstract
Vascularizing tissues and organs in vitro is crucial for tissue-engineered constructs to mimic the in vivo environment, since cells within these constructs may die after crossing the oxygen diffusion limit distance due to insufficient oxygen and nutrient uptake. Therefore, researchers are increasingly interested in constructing 3D vascular models in vitro, given the rapid development of tissue engineering, biomaterials science, cell biology, 3D bioprinting technology, and microfabrication technology. An in vitro 3D vascular model can reproduce the microenvironment of the vascular system in vitro by manipulating gas, nutrient diffusion, and shear stress [11]. Due to its unique advantages, 3D vascular models have the potential to replace animal models and 2D vascular models as research platforms for studying vascular diseases and related drugs. The human body has a network of blood vessels that control the flow of blood into and out of tissues. The vascular system can be divided into veins, arteries, and capillaries based on their internal diameter. Veins and arteries have diameters of 1-20 mm, while capillaries can be as small as 10 \(\upmu\)m [15]. The walls of arteries and veins consist of three layers--the tunica intima, tunica media, and tunica adventitia--from the inside to the outside. The tunica intima comprises a layer of endothelial cells that are in direct contact with the blood flow in the lumen. Endothelial cells are arranged along the direction of blood flow and act as a selective permeability barrier between the vessel wall and \begin{table}
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**Traditional In Vitro** & **Advantages** & **Disadvantages** \\ \hline Animal models & Significant contribution to drug development and safety. & Differences in physiological environments between different species; one-sidedness of animal model research reports; not feasible to accurately model complex vascular structures; time-consuming, cumbersome, and raises ethical concerns. \\ \hline In vitro two-dimensional models & Low price, easy operation, and good compatibility with high-resolution microscopes. & Usually static and difficult to reproduce the microenvironment of fluid flow in vivo. \\ \hline \end{tabular}
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Table 1: Comparison of traditional in vitro models [6; 7; 8; 9; 10; 11; 12; 13]. circulating blood [11; 16]. They maintain vascular function, integrity, and the internal environment balance. Endothelial dysfunction is a sign of the onset of atherosclerosis [8]. Between the endothelial cells and media lies the basement membrane protein, mainly composed of laminin and type IV collagen, while elastin forms the outer layer. The media is mainly composed of smooth muscle cells that regulate blood flow and pressure by causing vasoconstriction and vasodilation. Therefore, most mechanical properties of arteries are regulated by this layer [17]. Finally, fibroblasts and loose connective tissue form the outermost layer of blood vessels, the tunica adventitia, which repairs vascular damage and anchors blood vessels [18]. In contrast to arterial and venous walls, capillary walls are thinner and consist of a single layer of endothelial cells supported on the outside by pericytes. This thin monolayer facilitates efficient transport of oxygen and nutrients, and the timely removal of metabolic waste [19]. These characteristics make capillaries crucial for drug extravasation and regulating substance exchange. The endothelial cells of arteries and veins are continuous monolayers, while capillaries can be classified into three types based on the different tissue functions of their endothelial cells: continuous, fenestrated, and sinusoidal capillaries [20]. To construct vascular models in vitro, it is crucial to understand the main processes of vessel formation in vivo: vasculogenesis and angiogenesis. Vasculogenesis is the initial formation of blood vessels, which primarily occurs during embryogenesis [21].