# Research Progress in the Construction and Application of In Vitro Vascular Models
## 2 Construction of In Vitro Vascular Models
### Construction of In Vitro Vascular Model Based on Microfluidic Technology
#### 2.1.2 Self-Assembly  
Self-assembly is a technique where endothelial cells naturally form blood vessels in a hydrogel after fulfilling the conditions of vasculogenesis or angiogenesis in vitro, which are also the two primary ways blood vessels form in vivo. The main advantage of self-assembly is that the process of vessel formation is similar to that of the vasculature in vivo. As a result, the vessel model created using this technique closely resembles an in vivo blood vessel in terms of function and morphology [40].  
Microfluidic chips are a common platform for studying self-assembly, and they can be inoculated with different hydrogels containing endothelial cells. This method differs from other vascular construction methods because endothelial cells are mixed directly with the hydrogel and placed in a microfluidic device. The cells then spontaneously reconstruct the three-dimensional vasculature in a few days, using the mechanisms of vasculogenesis and angiogenesis, resulting in vessels with more physiological properties than those constructed by other methods [12]. [PERSON] et al. [83] developed a microfluidic three-dimensional in vitro vascular model by co-culturing human umbilical vein endothelial cells and fibroblasts to study the effects of interstitial flow and angiogenic factors on vascular growth. Interstitial flow was found to promote the sprouting and growth of blood vessels under the synergistic effect of angiogenic factors. [PERSON] et al. [84] established an in vitro model of VEGF-induced sprouting angiogenesis in a microfluidic chip, which can be used to screen the anti-angiogenic properties of candidate compounds and study the mechanism of angiogenesis in vitro and the endothelial barrier's function. The self-assembly method is preferred for studying vasculogenesis or angiogenesis and can also be used to study the effects of mechanical stress and chemical factors on vessel formation, as well as the morphological characteristics of blood vessels in abnormal locations such as near tumors.  
However, this method has some limitations. Although it can adjust the morphological characteristics of vessels (e.g., average vessel diameter, average branch length, number of branches, proportion of vascularized area, etc.) by controlling key parameters--such as mechanical properties of the hydrogel, cell seeding density, and paracrine signaling factors--it cannot control microchannels well and ensure easy perfusion. Additionally, constructing a vascular network using this method requires considerable time and effort, which limits its widespread application and research.  
There are two methods of constructing in vitro vascular models based on microfluidics: photolithography--including soft lithography--and self-assembly. Microfluidic chips constructed by photolithography and soft lithography have several advantages, including reduced reagent waste, precise fluid control, and high operability, which allow for the construction of vascular models with complex geometries. However, the most commonly used material in microfluidics, PDMS, has some limitations due to its hydrophobicity, which can limit its application. Therefore, several surface modification strategies have been developed to increase the hydrophilicity of the PDMS surface and promote the wider application of microfluidic technology in the construction of vascular models. In addition, the self-assembly method using microfluidics constructs in vitro vascular models that are closer to the human physiological environment. Although this method can control changes in vascular morphology by adjusting parameters, it cannot easily control the formation of the vascular network. Overall, these advantages over traditional in vitro models make microfluidic chips an ideal platform for the construction of in vitro vascular models.