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Gu, et al.
screening adopted the use of animal model such as construct a vascular model for the assessment of vascular
zebrafish [4,5] , which has relatively low relevance to human physiological functions and pathological observation
microenvironment. Some researchers have attempted to of airway inflammatory in 2018 . In 2019, Cui et al.
[40]
establish antiangiogenic drug screening platform using implanted 3D bioprinted vasculature, consisting of smooth
microfluidics [6,7] , which require high threshold and high muscle and endothelium, in immunodeficient mice to
cost; however, it is difficult to simulate the structure observe its development . Pennings et al. developed a
[41]
or texture of blood vessel with polydimethylsiloxane bioreactor system to culture bi-layered vascular grafts
(PDMS) or polycarbonate, which are the most commonly under shear stress, with a compartmentalized exposure of
used substrates. In contrast, hydrogels have been the graft’s luminal and outer layer to cell-specific media .
[42]
increasingly proposed for the construction of microfluidic However, almost no studies concerning antiangiogenetic
chips . drug screening models fabricated using 3D bioprinting
[8]
Organ-on-a-chip, which was first reported by have been reported.
Donald Ingber for the development of a microfluidic In this study, utilizing 3D bioprinting, an innovative
chip to observe human lung organ-level functions in perfusion system for antiangiogenic drug screening,
2010 , refers to a microfabricated biomimetic system was established. In this work, process optimization and
[9]
combining the technologies of tissue engineering, printability of coaxial bioprinting are discussed. Since
microfluidics, and cytology, to simulate significant the GelMA tube with excellent cell activity is too soft
features of targeted tissue microenvironments and to maintain its shape, a polycaprolactone (PCL) stent is
constructions [10] . Among its numerous applications, introduced to hold up the tubular lumen from the inside,
3D cell culture [11-14] , drug screening [15-18] , disease which is inspired by coronary artery stents used to keep
modeling [19-22] , and tissue regeneration [23-25] have received arteries open. Then, a comparison between hydrogel
much attention. The bionic fabrication of blood vessels structures with/without a stent was conducted. Afterward,
has also been rapidly developed in recent decades. In diffusion analysis verified the barrier function. Next,
general speaking, there are four typical approaches bioactivity characterization of cell-laden constructs was
to build a vessel-on-a-chip: microfluidics, sacrificial measured throughout the perfusion system. A perfusion
templating, 3D bioprinting, and self-organization [26] . 3D chip was also elaborately designed with three main
bioprinting, which has attracted substantial attention in advantages: (i) Long-term perfusion with no leaking;
recent decades, is increasingly being applied for the (ii) cells surrounded by nutrients; and (iii) convenient
creation of tissue models [27-29] . 3D bioprinting, which is observation.
an inexpensive, fast, and controllable printing process The U.S. Food and Drug Administration has
and can utilize a wide range of bioink/biologics, approved 14 kinds of angiogenesis inhibitors to treat
can overcome many limitations of the other three cancer in humans thus far [43] . As the first approved agent
techniques [30,31] . Its ability to fabricate 3D freeform to target tumor angiogenesis in 2004, bevacizumab,
bioactive architectures brings new ideas for vessel-on- which is the most common antiangiogenic drug, is a
a-chip. Since our group developed a coaxial bioprinting recombinant, humanized monoclonal antibody that
approach to print alginate hollow filaments in 2015 [32] , binds to vascular endothelial growth factor (VEGF)
coaxial bioprinting has become a popular research and prevents it from binding to its receptors, VEGF
methodology with diverse applications [33-37] . In simple receptor (VEGFR)-1 and VEGFR-2 on the surface of
terms, coaxial bioprinting utilizes different materials vascular endothelial cells, thereby inhibiting tumor
(or same material with different loads) that are extruded angiogenesis [44] (Figure 1). Based on the ingenious
through a coaxial nozzle to form a fiber with core-shell perfusion system, the application of antiangiogenic
structure. If the core material is sacrificial (e.g., gelatin, drug screening model was finally assessed by different
Pluronic F-127, etc.), the filament presents tubular sprouting levels corresponding to bevacizumab at a
structure. Based on our previous work [38] , gelatin gradient of concentrations. From the results, the sprouting
methacryloyl (GelMA)/gelatin is the ideal bioinks of HUVECs was observed, which demonstrated
for bioprinting human umbilical vein endothelial cell the effectiveness of this perfusion system, and the
(HUVEC)-laden hydrogel tubes. differences in the bevacizumab gradient-screening
In recent years, a few scholars have committed to the test provided evidence that this antiangiogenic drug
research in biomimetic vessel fabrication and perfusion screening system is reliable. This study contributes
culture. Using gelatin as sacrificial bioink, Lee et al. to advancing basic scientific research and clinical
developed a functional in vitro vascular channel with applications related to not only antiangiogenic drug
perfused open lumen fully covered with endothelial cells evaluation, but also vascular disease drug assessment
in 2014, in which active angiogenic invasion of cells was in the areas of tissue engineering, drug screening,
observed . Gao et al. used coaxial bioprinting as a tool to pharmacokinetics, and regenerative medicine.
[39]
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