Abstract
The microvasculature plays a critical role in human physiology and is closely associated to various human diseases. By combining advanced microfluidic-based techniques, the engineered 3D microvascular network model provides a precise and reproducible platform to study the microvasculature in vitro, which is an essential and primary component to engineer organ-on-chips and achieve greater biological relevance. In this review, we discuss current strategies to engineer microvessels in vitro, which can be broadly classified into endothelial cell lining-based methods, vasculogenesis and angiogenesis-based methods, and hybrid methods. By closely simulating relevant factors found in vivo such as biomechanical, biochemical, and biological microenvironment, it is possible to create more accurate organ-specific models, including both healthy and pathological vascularized microtissue with their respective vascular barrier properties. We further discuss the integration of tumor cells/spheroids into the engineered microvascular to model the vascularized microtumor tissue, and their potential application in the study of cancer metastasis and anti-cancer drug screening. Finally, we conclude with our commentaries on current progress and future perspective of on-chip vascularization techniques for fundamental and clinical/translational research.
Highlights
The circulatory system plays a vital role to maintain homeostasis in the human body
Several in vitro studies have been performed to study tumor angiogenesis by co-culturing cancer cells and endothelial cells (ECs) in microfluidic devices. It is normally performed by establishing a vertical 2D endothelial monolayers on the side walls, which can facilitate the better imaging of angiogenic sprouting into the 3D extracellular matrix (ECM) on the axial plane
We have provided an overview of different vascularization strategies based on microfluidic technology
Summary
The circulatory system plays a vital role to maintain homeostasis in the human body. It comprises a closed network of arteries, veins, and capillaries that allow blood to circulate throughout the body, for waste product removal, and for gas exchange and nutrient transportation, all of which are essential for organ viability. Microfluidic technologies have emerged as useful tools for the development of organ-on-a-chip, which can offer precise control over various aspects of the cellular microenvironment such as a different profile of fluid flow, gradient of various growth factors, and mechanical properties of versatile biomaterials. All these advantages can facilitate the formation of biomimicking in vitro vascularized microtissue models. We review the current, state-of-the-art in vitro vascularized tumor-on-a-chip models in various disease stages, and their potential applications for anti-cancer drug screening. This review will provide a better understanding of the vascularization process for organ-on-a-chip systems and its applications in cancer biology
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