Current progress of in vitro vascular models on microfluidic chips

Abstract The vascular tissue, as an integral component of the human circulatory system, plays a crucial role in retaining normal physiological functions within the body. Pathologies associated with the vasculature, whether direct or indirect, also constitute significant public health concerns that afflict humanity, leading to the wide studies on vascular physiology and pathophysiology. Given the precious nature of human derived vascular tissue, substantial efforts have been dedicated to the construction of vascular models. Due to the high cost associated with animal experimentation and the inability to directly translate results to human, there is an increasing emphasis on the use of primary human cells for the development of in vitro vascular models. For instance, obtaining an ApoE -/- mouse model for atherosclerosis research typically requires feeding a high-fat diet for over 10 weeks, whereas in vitro vascular models can usually be formed within 2 weeks. With advancements in microfluidic technology, in vitro vascular models capable of precisely emulating the hemodynamic environment within human vessels are becoming increasingly sophisticated. Microfluidic vascular models are primarily constructed through two approaches: (1) directly constructing the vascular models based on the three-layer structure of the vascular wall; (2) co-culture of endothelial cells and supporting cells within hydrogels. The former is effective to replicate vascular tissue structure mimicking vascular wall, while the latter has the capacity to establish microvascular networks. This review predominantly presents and discusses recent advancements in template design, construction methods, and potential applications of microfluidic vascular models based on polydimethylsiloxane (PDMS) soft lithography. Additionally, some refined methodologies addressing the limitations of conventional PDMS-based soft lithography techniques are also elaborated, which might hold profound importance in the field of vascular tissue engineering on microfluidic chips.