Page 312 - IJB-8-4

Vessel-on-a-Chip for Antiangiogenic Drug Screening
pause perfusion culture, one needs to: (i) Turn off the stent, a perfusion system was then set up for antiangiogenic
peristaltic pump; (ii) fasten the Robert clamps of inlet drug screening. Guided by rheological tests, the printability
and outlet separately; (iii) pull out the needles from the of coaxial bioprinting is discussed. The significance of the
injection stoppers at both ends, and vice versa. A quickly- inserted stent was also demonstrated by the mechanical,
separable perfusion chip is then obtained without the risk swelling, and perfusion tests. Afterward, diffusion analysis
of bacterial contamination. Side needles are applied at the proved the barrier function of the endothelialized vessel.
very start of perfusion to fill the cavity with medium and As a proof of concept, HUVECs encapsulated in hydrogel
exhaust gas. In addition, compared to microfluidic chips, constructs showed an excellent proliferation rate, good
our chip more closely mimics the vascular environment cell morphology, and expression of certain functional
in the human body with a larger-scale and higher flow markers. Finally, images and videoclips of HUVEC
rates, which greatly expands its possible applications. sprouting and bevacizumab-screening test revealed the
Nevertheless, the present study still has room for reliability of this perfusion system. We believe that this
improvement. Even though this system provided a long- proposed biofabrication process and its application may
term perfusion capability, the hydrogel bulk containing open up a new approach for the construction of vessel-on-
VEGF limited the subsequent culture duration. Since a-chip and offer an accessible tool for vascularization and
VEGF would certainly permeate into the culture medium pharmaceutical research.
gradually, the stimulus to HUVECs sprouting toward the
bulk would dissipate after several days. Introducing tumor Acknowledgments
cells, which can secrete VEGF persistently, might be a good The authors would like to thank Dr. Dengke Zhao, Dr. Xixia
solution. Instead of VEGF-containing, applying tumor- Liu and Mr Haina Ji in School of Mechanical Engineering,
cell-laden GelMA to cast into a hydrogel bulk enveloping Zhejiang University, for the assistance of mechanical,
endothelialized vessels would realize a tumor-cell-HUVEC rheological properties tests and real-time sprouting
coculture system, which would transform this antiangiogenic monitoring, and Hangzhou Putai Technology Co., Ltd. for
drug screening model into a more specific tumor model. In the assistance of coaxial nozzle ceramic printing.
addition, the improvement of coaxial bioprinting process
can bring deeper significance to biological applications. Funding
For example, three-layer coaxial bioprinting of endothelial
cells layer and smooth muscle cells layer would make these This work was sponsored by the National Key Research
vessels more biologically representative. and Development Program of China (2018YFA0703000),
Furthermore, the drug screening model we established National Natural Science Foundation of China (No.
in this study has great potential for the future studies. U1909218, T2121004), Adjunct Talent Fund of Zhejiang
Based on the vessel-on-a-chip approach, our perfusion Provincial People’s Hospital, China Postdoctoral Science
system cannot only be regarded as an antiangiogenic drug Foundation (No. 2021M702818).
screening model, but also serve as an effective tool to model Conflict of interest
interactions between various cells/organoids by changing
the perfusion liquid, encapsulated cells in the tube, or bulk The authors declare no conflicts of interest.
containing substances/biological reagents. For example,
to explore the effects of anti-inflammatory compounds on Author contributions
coagulation and thrombosis could be another application Conceptualization: Yong He, Chaoqi Xie
scenario of this model. In addition, based on the advantage Investigation: Zeming Gu, Mingjun Xie, Shang Lv
of coaxial bioprinting process, biofabrication of hydrogel Methodology: Zeming Gu, Mingjun Xie
tubes with variable-diameter or complex shapes would Formal analysis: Zeming Gu, Nian Liu
simulate a particular vascular microenvironment or a Visualization: Zeming Gu, Jing He, Yuanrong Li, Yuanbo
disease model. Adopting more than one vessel in one Zhu
chip with different perfusion liquids would also meet Writing – original draft: Zeming Gu
the requirements of some in vitro models. Moreover, Writing – review & editing: Yong He, Jianzhong Fu, Hui
connecting several perfusion chips in series with one-way Lin
flow would further provide a platform for investigating the
effects of upstream secretions on downstream components. References

5. Conclusion 1. Cherrington JM, Strawn LM, Shawver LK, 2000, New
In summary, we coaxially bioprinted HUVEC-laden Paradigms for the Treatment of Cancer: The Role of Anti-
GelMA tubes and cultured them to form endothelialized Angiogenesis Agents. Adv Cancer Res, 79:1–38.
biomimetic blood vessels. With the assistance of a PCL https://doi.org/10.1016/s0065-230x(00)79001-4

304 International Journal of Bioprinting (2022)–Volume 8, Issue 4