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International Journal of Bioprinting Increased ECM stiffness enhances chemoresistance

and noncellular components that drive tumor growth, Resources: Yilei Mao
invasion, metastasis, and response to therapy in a concerted Supervision: Huayu Yang
manner. Instead of using the typical set of ingredients Writing–original draft: Ying Shan, Mingchang Pang, Chang
31
including fibroblasts, endothelial cells, immune cells, etc., Zhou, Yixin Mao
we only utilized tumor cells, which constitute only part of Writing–review & editing: Huayu Yang
the actual tumor environment in the human body, in this All authors participated in the research and approved the
study. Secondly, the application of cell lines in preclinical final version of the article.
studies suffer from several shortcomings, including reduced
heterogeneity, potential of gene modification, and faster Ethics approval and consent to participate
growth rates, as compared to primary tumors. Therefore, Not applicable.
60
tumor specimens obtained from surgical resection should
be used to extract primary tumor cells, which are then Consent for publication
printed into 3D tumor models for the investigations of
mechanisms underlying tumor development and the Not applicable.
individualized drug screening. Tumor models fabricated
from actual human tissues allow for more realistic analysis Availability of data
of the correlation between primary tumor stiffness and Data used in this work are available from the corresponding
drug sensitivity. authors upon reasonable request.

5. Conclusion References
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tumor models have significant advantages in providing 1. Alkmin, S., Patankar, M. S. & Campagnola, P. J., 2022,
accurate preclinical drug testing results. Having biophysical Assessing the roles of collagen fiber morphology and matrix
characteristics, such as stiffness, equivalent to those of the stiffness on ovarian cancer cell migration dynamics using
natural TME, 3D in vitro tumor model holds promise as multiphoton fabricated orthogonal image-based models.
Acta Biomater, 153:342-354.
a more efficient and powerful platform for drug research.
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Funding 3. Vescarelli, E., Gerini, G., Megiorni, F. et al., 2020, MiR-
This work was supported by the National Natural 200c sensitizes Olaparib-resistant ovarian cancer cells by
Science Foundation of China (Grant No. 32271470), targeting Neuropilin 1. J Exp Clin Cancer Res, 39(1):3.
National High Level Hospital Clinical Research Funding doi: 10.1186/s13046-019-1490-7
(2022-PUMCH-C-045), Beijing Natural Science 4. Wang, M., Zhou, J., Zhang, L. et al., 2019, Surgical treatment
Foundation (7212077), and CAMS Innovation Fund for of ovarian cancer liver metastasis. Hepatobiliary Surg Nutr,
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Conflict of interest 5. Herrera, F. G., Irving, M., Kandalaft, L. E. et al., 2019,

The authors declare that the research was carried out Rational combinations of immunotherapy with radiotherapy
in ovarian cancer. Lancet Oncol, 20(8):e417-e433.
without any commercial or financial relationships that doi: 10.1016/s1470-2045(19)30401-2
could be perceived as a potential conflict of interest.
6. Raghavan, S., Mehta, P., Ward, M. R. et al., 2017,
Author contributions Personalized Medicine-Based Approach to Model Patterns
of Chemoresistance and Tumor Recurrence Using Ovarian
Conceptualization: Ying Shan, Yilei Mao, Ying Jin, Huayu Cancer Stem Cell Spheroids. Clin Cancer Res, 23(22):
Yang 6934-6945.
Formal analysis: Liqian Wang, Ruiyi Yan doi: 10.1158/1078-0432.CCR-17-0133
Funding acquisition: Yilei Mao, Huayu Yang 7. Lee, A., Hudson, A. R., Shiwarski, D. J. et al., 2019, 3D
Investigation: Ying Shan, Mingchang Pang bioprinting of collagen to rebuild components of the human
Methodology: Ying Shan, Mingchang Pang, Liqian Wang, heart. SCIENCE, 365(6452):482-487.
Yixin Mao, Chang Zhou, Jingyuan Ji doi: 10.1126/science.aav9051

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