# Research Progress in the Construction and Application of In Vitro Vascular Models
## 4 Summary and Prospects  
The vasculature plays a crucial role in the body, and its dysfunction is closely linked to major diseases. Researchers have utilized various animal models and two-dimensional static in vitro platforms to study vascular diseases and develop related drugs. However, these models often fail to accurately replicate the vascular pathology and physiological environment in vitro. Furthermore, although tissue engineering has made significant advancements in recent decades, creating functional vascular constructs remains a major challenge. The vasculature is responsible for supplying nutrients to tissue engineering constructs, facilitating the removal of metabolic waste, and regulating signaling molecules involved in tissue growth. Traditional microfabrication techniques primarily focus on the overall structure while neglecting the intricate internal vascular network. This limitation makes it difficult to fabricate complex vascular networks. Therefore, this review examines the construction methods and applications of three-dimensional in vitro vascular models, aiming to address these challenges and improve our understanding of vascular biology and pathology. This article began by discussing the limitations of traditional models, the functional structure of blood vessels, and the process of blood vessel formation. Currently, most perfusion extracorporeal vascular models are developed using microfluidic technology. To complement these methods, this review categorized the construction of extracorporeal vascular models into microfluidics-based and non-microfluidics-based methods based on different fabrication techniques. Specifically, we explored the principles, advantages, and disadvantages of various vascular fabrication methods, including lithography and soft lithography, self-assembly, template, 3D bioprinting, and laser degradation/cavitation. These methods aim to create in vitro vascular models that accurately simulate the complexity of blood vessels. While the complexity and physiological context of these models may differ, they offer valuable approaches for studying the physiological/pathological environment of blood vessels and the vascularization of tissue engineering constructs. The use of microfluidics technology, self-assembly, and 3D bioprinting to construct in vitro vascular and disease models remains a prominent research focus. These methods can be combined to create more physiologically relevant models. However, it is important to note that these three methods can only generate vascular networks with large diameters and simple geometries. Although laser degradation technology provides higher resolution and complexity, it may compromise cell viability and hydrogel integrity. With the advancement of laser cavitation molding technology, it is now possible to produce smaller and more intricate tubes without compromising cell viability. It is anticipated that laser cavitation molding technology will find widespread use in studying complex tissues in the near future. During the process of in vitro vascular construction, the diameter and curvature of microchannels are influenced by the preparation methods, which significantly affect the formation of endothelial monolayers, barrier function, and cell viability [16; 128]. A smaller diameter promotes tighter cell-cell interactions and closer connections between endothelial cells, facilitating the formation of a denser and more intact endothelial monolayer, crucial for maintaining continuous integrity [2]. Curvature also plays a pivotal role. Microchannels with smaller curvature typically support more uniform cell alignment and monolayer formation compared to those with larger curvature, which may disrupt cell alignment and monolayer integrity. In terms of barrier function, the diameter of the microchannels affects the permeability of endothelial monolayers. Smaller diameters enhance permeability, indicating that dense packing of endothelial cells contributes to better barrier function.