Page 363 - IJB-10-3

International Journal of Bioprinting hNVU chip for brain modeling and drug screening

nondestructive drug detection within the brain region of the using the spinning disk confocal microscopy (Dragonfly,
chip. One of the two perfusion systems (channels A and B) Andor); Weihua Wang, Engineer Center of Pharmaceutical
provides a special medium for the endothelial cells of Technology, Tsinghua University, for assistance in using
the BBB, while the other sets (channels C and D) supply HPLC (Agilent, America); and Yongzhen Tao, Shanghai
a mixed medium to the co-culture environment of brain Institutes for Biological Sciences, Chinese Academy of
cells. The previously reported method mainly targets the Sciences, for assistance in using GCMS-QP2010 Ultra
drug penetration and efflux of BBB and the response to the (SHIMADZU).
drug, and has not been applied to study the mechanism
of action of chemotherapeutic drugs, and the model only Funding
has BBB, lacking the 3D NVU environment in vivo. The The work was financially supported by the National
22
hNVU device we developed in this study can be used to Key Research and Development Program of
study the behavior and mechanism of action of cells during China (2018YFA0703004).
drug administration. One of the characteristics of the NVU
chip model based on PDMS is that vascular endothelial Conflict of interest
cells grow on the surface of the hydrogel, resulting in
their TEER being unmeasurable. 23,24 The structure of the The authors declare no conflicts of interest.
hNVU chip requires the mechanical properties of the brain
region to support the structure while maintaining a high Author contributions
proportion of cell survival. This results in less stretching Conceptualization: Yuanyuan Xu, Wei Sun, Zhuo Xiong,
of cells in hydrocoagulation, with some cells present in the Ting Zhang
ECM as multicellular spheroids, unlike the intricate cell- Formal analysis: Yuanyuan Xu
to-cell contact in the body. The elastic modulus of ECM Investigation: Yuanyuan Xu
was reduced to about 3 kPa on the seventh day, which Methodology: Yuanyuan Xu, Zhuo Xiong, Ting Zhang
is close to the mechanical properties of brain tissue in Writing – original draft: Yuanyuan Xu
vivo. In view of the material system used in this study, Writing – review & editing: Wei Sun, Zhuo Xiong, Ting
33
it is currently impossible to simultaneously achieve the Zhang, Dongsheng Kong
desired structural integrity and 3D cell growth. In terms
of construction, it is unfortunate that the endothelial Ethics approval and consent to participate
cell monolayer formed by hCMEC/D3 cells with a more
complete phenotype has a lower electrical impedance Not applicable.
and leakage, which cannot be solved at present. The cell
density and proportion relationship in this study are not Consent for publication
consistent with the actual proportion relationship in vivo Not applicable.
(there were no in vivo data from the previous fundamental
studies), but the use of cell printing technology enables Availability of data
the fabrication of models based on cell types and cell
density gradient distributions in the future. Nevertheless, All data that support the findings of this study are included
this study has broad application value. Using the hNVU within the article.
chip, we investigated the therapeutic effects and toxicity
of chemotherapeutic drugs such as vorinostat and 5-FU. References
Vorinostat not only exhibits excellent therapeutic efficacy 1. Louis DN, Ohgaki H, Wiestler OD, et al. The 2007 WHO
but also has lower neurocognitive toxicity than 5-FU in the classification of tumors of the central nervous system. Acta
hNVU chip; this suggests that experimental results from Neuropathol. 2007;114:97-109.
3D models can be used to guide new treatment strategies. doi: 10.1007/s00401-007-0243-4
In summary, the hNVU chip provides a reliable platform
for comprehensive studies on the therapeutic effects of 2. Biserova K, Jakovlevs A, Uljanovs R, Strumfa I. Cancer stem
cells: significance in origin, pathogenesis and treatment of
chemotherapeutic drugs for brain tumors at multiple levels.
glioblastoma. Cells. 2021;10(3):621.
doi: 10.3390/cells10030621
Acknowledgments
3. Manoranjan B, Garg N, Bakhshinyan D, Singh SK. The role of
The authors would like to acknowledge the assistance of stem cells in pediatric central nervous system malignancies.
Yanli Zhang, Imaging Core Facility, Technology Center Adv Exp Med Biol. 2015;853:49-68.
for Protein Sciences, Tsinghua University, for assistance in doi: 10.1007/978-3-319-16537-0_4

Volume 10 Issue 3 (2024) 355 doi: 10.36922/ijb.1684