# Research Progress in the Construction and Application of In Vitro Vascular Models
###### Abstract  
The vascular system maintains cellular homeostasis by transporting oxygen, nutrients, and metabolic waste products. The vascular system is involved in a variety of fundamental physiological phenomena and is closely associated with human vascular diseases. Additionally, the stability of drugs in the vasculature affects their efficacy. Therefore, researchers have used vascular models to study vascular diseases, assess drug stability, and screen drugs. However, there are many shortcomings in the animal models and in vitro two-dimensional vascular models that have been extensively developed. In this paper, we specifically review the construction methods of in vitro vascular models and classify the specific methods into photolithography, soft lithography, self-assembly, template, 3D bioprinting, and laser degradation/cavitation. The first two are microfluidics-based methods and the last three are non-microfluidics-based methods. The vascular model construction methods reviewed in this paper overcome the shortcomings of traditional models--which cannot accurately reproduce the human vascular microenvironment--and can assist in the construction of in vitro 3D vascular models and tissue engineering vascularization. These models can be reused by perfusion devices, and the cells within the channels reside on biocompatible materials that are used to simulate the microenvironment and 3D cellular organization of the vasculature in vivo. In addition, these models are reproducible in shape and length, allowing experiments to be repeated, which is difficult to do with natural vessels. In vitro vascular models are widely used in research and drug screening for diseases associated with endothelial dysfunction, cancer, and other vascular abnormalities. angiogenesis; vasculogenesis; microfluidics; self-assembly; templating; 3D bioprinting Article  
Drug development spending has increased over the past 20 years but the number of drugs approved annually has decreased due to the limitations of current animal and in vitro models in predicting efficacy. While animal models have contributed significantly to drug development and safety, they fall short in simulating the human body's physiological or pathological environment [6]. Animal models tend to overestimate the effectiveness of drug treatments, resulting in only 10-15% of drugs approved for human use, even when effective in animal models [7]. This is likely due to differences in species' physiological environments, bias in animal model research, and differences in research methods between animal models and human clinical trials [8]. Additionally, some human tissues or systems are too complex or costly to model accurately using animal models, such as atherosclerosis and the human blood-brain barrier tissue [9]. The use of animal models is also time-consuming, laborious, and raises ethical concerns [10]. In vitro vascular models can be broadly classified into two-dimensional (2D) and three-dimensional (3D) models. Two-dimensional models are typically constructed using culture dishes, which offer the advantages of low cost, ease of operation, and compatibility with high-resolution microscopes [11]. However, despite being widely used as high-throughput tools for drug discovery and screening, the success rate of drugs from phase I clinical trials to market approval is only 9.6% using 2D models. Moreover, 2D models are typically static and do not accurately reproduce the microenvironment of fluid flow. Therefore, conventional 2D models are often inadequate for studying the mechanisms of human vascular disease and developing related drugs [12; 13]. Tissue engineering is an interdisciplinary technique that combines cell biology and materials science to develop new structures with specific morphological shapes and functions to replace damaged tissues and organs. However, the production of vascular structures remains a major challenge [14].