# Research Progress in the Construction and Application of In Vitro Vascular Models
## 3 Application
### Vascularized In Vitro Organs-on-Chips  
Organ-on-a-chip is an innovative technology that combines tissue engineering and microfluidics to recreate human tissues and organs on a small chip. This technology aims to accurately simulate the complex structure, microenvironment, and physiological functions of human tissues and organs [122]. One crucial aspect of this technology is the development of perfusable vascular structures to ensure a constant supply of nutrients and removal of metabolic waste for the engineered tissues and organs. In this context, the focus will be on the vascularized organ chip model, which involves the integration of functional blood vessel networks within the chip. [PERSON] et al. [123] developed an alveolar chip that can monitor the expansion and contraction of the lung organ in real-time by changing the color of the chip. The top and bottom layers of the chip simulate respiration or blood flow, respectively, while the sustained stretchability of the chip film mimics the physiological changes in the alveoli. This method extends the application of organ chips for real-time monitoring, which has potential applications in biological research, disease monitoring, and drug discovery. The study showed that the chip maintains high cell viability even under cyclic stretching and helps to maintain tight connections between cells. Apart from single organ chips like lung, heart, liver, kidney, and small intestine, multiple tissues and organs can be constructed simultaneously and connected through the chip pipeline to form multi-organ chips. For instance, [PERSON] et al. [124] (Figure 7) developed a four-organ microchip for toxicity testing that included liver, heart, skeletal muscle, and neurons. The results of all drug treatments during a 14-day incubation period with continuous media circulation in the device were generally consistent with toxicity results published in human and animal data. The model can study cardiotoxicity through the study of liver metabolites and serve as a new platform for preclinical studies. Figure 6: Schematic diagram of the blood–brain barrier (BBB) model. (**a**) Design of microfluidic devices simulating the BBB model. (**b**) Schematic diagram of the microfluidic device. Human-umbilical-vein endothelial cells (HUVECs) suspended in culture medium are injected and trapped within the microchannel array. Number 1 is the cell injection port, and Number 2 is the drug injection port. (**c**) Tight contact between HUVECs trapped on microchannels. (**d**) Staining of HUVECs using monoclonal antibodies showing tight junctions between endothelial cells. Reprinted/adapted with permission from Ref. [120]. 2012, [PERSON]. [PERSON] et al. [125] developed a heart and breast cancer microarray platform for disease modeling and monitoring of cancer-chemotherapy-induced cardiotoxicity. They encapsulated breast cancer cells in hydrogel beads to create a tissue model and controlled the average diameter of the beads to avoid necrosis in the core region of the cell beads. Additionally, researchers encapsulated heart spheroids in a water gel to form a cardiac tissue model, which has a similar Young's modulus to that of natural human heart tissue. The sensing platform has excellent accuracy and high sensitivity with very low detection limits, which can be used to detect and predict cardiotoxicity caused by early chemotherapy in patients. Applying biofabrication methods to organs-on-chips involves a series of challenges that affect their effectiveness and reliability in biomedical research and applications [13; 126; 127]. First, biofabrication methods need to achieve highly precise control at the microscale to simulate complex biological structures and functions. In particular, in the construction of organ chips, precise control over cell arrangement, tissue structure, and the simulation of microenvironments pose challenges to the complexity and accuracy of manufacturing techniques.