# 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
#### 2.1.1 Photolithography and Soft Lithography  
Photolithography and soft lithography are two common methods for constructing vascular models on microfluidic chips using microfluidic techniques [53]. Photolithography starts with a uniform coating of photoresist on a silicon wafer, then, a patterned photolithographic mask is placed on top of the photoresist. The photoresist is then exposed or unexposed to UV light and removed with developer after UV cross-linking to produce a master with a clear microstructure on the substrate. The photolithography process requires a high degree of cleanliness of the environment to prevent contamination of the silicon wafer with particles [53]. Microfluidic chips are generally fabricated using lithography and replication molding technology following these steps (Figure 1): (i) fabrication of a silicon wafer mold by photolithography; (ii) mixing polydimethylsiloxane (PDMS) prepolymer and the curing agent in the silicon wafer mold for subsequent curing; (iii) removal of PDMS from the mold and irreversibly bonding it to a rigid or flexible substrate (e.g., glass, silicon, or polymer) to form a closed microfluidic chip [54; 55]. This sealing method is known as bonding technology and relies on the formation of irreversible chemical bonds between the activated PDMS and the substrate surface. Silicon-based materials (e.g., glass or silicon) \begin{table}
\begin{tabular}{c c c} \hline
**In Vitro Vascular Model Construction Methods** & **Advantages** & **Disadvantages** \\ \hline \multirow{8}{*}{Template} & \multirow{4}{*}{Low cost and easy to operate, the channels produced have a similar cross-section to physiological structures.} & High requirements for the mechanical properties of biomaterials; prone to deformation; only used to construct simple vascular structures. \\ \cline{3-3}  & & Inexpensive and convenient, suitable for most high-viscosity bioinks; widely used (extrusion bioprinting). & Low resolution and cell viability (extrusion viability \\ Non- & & High cell viability, fast printing & Nozzle clogging is prone to occur, requiring bioinks \\ microfluidics-based & \multirow{2}{*}{3D bioprinting} & \multirow{2}{*}{compatibility with various bioinks (nikef bioprinting). Ability to print high-viscosity bioinks, high cell viability, high cell viability, high resolution, and fast printing speed (light-assisted bioprinting).} & Nozzle clogging is prone to occur, requiring bioinks with low viscosity and low cell density \\  & & High resolution, easy to operate, and not limited by complex 3D shapes; guarantees & (nikef bioprinting). \\  & & a sterile & \\  & environment; low impact on cell viability. & biomaterials. \\ \hline \end{tabular}
\end{table} 
Table 2: _Cont._are more widely used in the field of microchannel sealing because they can be bonded to PDMS by a simple surface activation treatment [56]. Although conventional photolithography is well-established and has been extensively used for the fabrication of microfluidic chips, it is limited in the construction of in vitro vascular models due to its high cost, time, and labor-intensive nature, limited control over surface chemical properties, and limitations of photosensitive materials such as photosensors [37; 38]. With the advancement of microfabrication technology, we can now utilize soft lithography to construct intricate vascular models in vitro. Soft lithography, a non-photolithographic method first proposed by [PERSON] at Harvard University in the late 1990s, employs elastic materials such as PDMS as molds to replace the hard molds used in traditional photolithography technology. This technology is ideal for microstructure replication molding and offers a low-cost, convenient, effective, and time-efficient method for forming and fabricating micro- and nano-vascular structure models, overcoming the limitations of photolithography [39]. Early photolithography was the conventional method for fabricating microfluidic chips, using materials such as silicon wafers and glass.