# 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
However, the process was time-consuming and expensive, making mass production of microfluidic chips even more uneconomical [57]. Nowadays, microfluidic chip fabrication primarily involves photolithography of organic polymers like photoresists that are cheaper and easier to fabricate into microfluidic chips than silicon wafers and glass; moreover, these polymers possess better mechanical properties than silicon wafers and glass [58]. PDMS is the most commonly used material for soft lithography, followed by thermoplastics like polymethyl methacrylate, polyvinyl chloride, polycarbonate, thermoplastic elastomer, and polyurethane [57; 59; 60]. Although thermoplastics can be reused and are transparent, they have poor permeability, high cost, high stiffness, and are not easy to bend. Hence, most researchers prefer PDMS as a photolithography and soft lithography material. PDMS is an elastomer that possesses excellent optical, mechanical, and electrical properties, which make it the primary material for fabricating micro- and nanovascular structures using photolithography and soft lithography techniques. It is particularly suitable for simulating blood vessels [38]. PDMS is a macromolecular polymer consisting of repeated silicon-oxygen bonds, offering several advantages: PDMS material has lower cost, is easy to manufacture microfluidic chips, and exhibits good biocompatibility and mechanical performance. The transmittance of PDMS in the range of 390-780 nm wavelength can reach 90%, making it suitable for various optical detections such as UV/visible absorption and fluorescence [61]. Its excellent resistance to bio-degradation, non-toxicity,  
Figure 1: Schematic diagram of microfluidic chip preparation. and good permeability to oxygen and carbon dioxide make PDMS channels suitable for cell studies. The material can also be used as insulation for pacemakers and as a coating for biomedical implant materials, with only minimal foreign body reactions [62; 63]. The Young's modulus of PDMS is approximately 1-3 MPa, which is four orders of magnitude lower than glass (approximately 50 GPa), making it highly flexible. Therefore, it can recover its original shape after external forces are removed. It is suitable for curved surfaces and can be demolded from molds with intricate structures without damaging itself [64]. It has the ability to replicate microscale features, making it ideal for accurately constructing channel structures on microfluidic chips. Another key advantage of PDMS is that it can irreversibly bond with glass or itself without the need for adhesive [65]. Therefore, PDMS material has become the main material for constructing vascular models due to these advantages. Although PDMS has numerous advantages, it may also have some limitations in certain applications. For instance, it tends to swell in many common solvents such as toluene [57]. Additionally, shrinkage during the curing of the PDMS prepolymer can affect the fabrication and processing of microfluidic chips. Among these limitations, hydrophobicity is the most significant drawback of PDMS. The intrinsic hydrophobicity of PDMS restricts its application in specific fields, as most experiments in microchannels require the use of water-soluble fluids (e.g., blood, buffers) or cells [66]. For example, the unmodified highly hydrophobic PDMS surface is not conducive to long-term cell culture, which can lead to cell detachment from the wall, agglomeration, and death [38]. Additionally, the high hydrophobicity of PDMS makes it easy to adsorb other hydrophobic biological small molecules and biological solvents, which can result in reagent loss, local concentration changes, bubble formation, and even inaccurate quantitative analysis [67]. To overcome this drawback, several surface modification strategies to improve the hydrophilicity of PDMS surfaces are described below, which can be classified into surface activation modification, physical adsorption, and chemical modification methods according to different principles (Table 3) [68].