T.V. Chembarova1, S.Yu. Filippova2, I.V. Mezhevova3, N.V. Gnennaya4, I.A. Novikova5, S.V. Chapek6

1–5 Federal State Budgetary Institution «National Medical Research Center of Oncology» (Rostov-on-Don, Russia)

6 The Smart Materials Research Institute, Southern Federal University (Rostov-on-Don, Russia)

1 tanyshamova@mail.ru, 2 filsv@yandex.ru, 3 mezhevova88@gmail.com, 4 ngnennaya@inbox.ru, 5 novikovainna@yahoo.com, 6 chapek@sfedu.ru

Two-dimensional models, which are a monolayer of commercial tumor cell lines, are used in the pharmaceutical industry to test anticancer drugs. However, because they may not accurately reflect response to test substances, there is a growing demand for 3D models that more fully mimic tumor organization and behavior in vivo. Provided that tissue samples obtained from patients are used in such models, we can talk about personalized screening for the effectiveness of drugs. Modeling of tumors in microfluidic chips makes it possible to completely control the composition of the medium and the physical parameters of cultivation, as well as to simulate the tumor microenvironment in vivo. In addition, the chips can be freely integrated with various cell imaging and research methods.

Microfluidic systems such as lab-on-chip, cancer-on-chip, organ-on-chip already exist, and models are being developed that represent the connection of different organs-on-chips into an interacting system. Also, microfluidic chips have the potential to simulate the process of tumor metastasis.

One way to create microfluidic chips is photopolymer 3D printing. The material from which chips are made for modeling tumors must be non-toxic to cells, and also promote their adhesion and proliferation. Most of the materials used in photopolymer printing are not intended for cell culture and therefore are not tested for biocompatibility.

The aim of this work was to test the biocompatibility of human cell culture constructs made from photopolymer resins by 3D printing.

The experiment was carried out using an adherent cell line of non-small cell lung cancer H1299 and a suspension line of chronic myelogenous leukemia K562. Constructs for culturing cells 37x78x10 mm in size were made on an Anycubic Photon D2 DLP printer (China) from Nano clear resins (Fun to do, the Netherlands) and Dental Clear PRO resins (HARZ Labs, Russia). Cell viability was counted and determined on days 3 and 7 of cultivation.

As a result, it was found that the structures obtained from the tested resins do not support cell adhesion and have a pronounced cytotoxic activity. It is possible that repeated washing and surface treatment may improve the compatibility of such constructs with cell cultures. However, the resin derived from Dental Clear PRO resin proved unsuitable for biochip prototyping due to its high hygroscopicity and deformability. Further research will focus on a deeper understanding of the properties of the Nano clear resin.

Chembarova T.V., Filippova S.Yu., Mezhevova I.V., Gnennaya N.V., Novikova I.A., Chapek S.V. Evaluation of the biocompatibility of constructs made from photopolymer resins by 3D printing. Technologies of Living Systems. 2023. V. 20. № 4. Р. 45-52. DOI: https://doi.org/10.18127/j20700997-202304-04 (In Russian).

1. Sung H., Ferlay J., Siegel R. L., Laversanne M., Soerjomataram I., Jemal A., Bray F. Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries. CA Cancer J. Clin. 2021. V. 71(3). P. 209–249. Doi: 10.3322/caac.21660
2. Kitayeva K.V., Rizvanov A.A., Solovyeva V.V. Sovremennyye metody doklinicheskogo skrininga protivoopukholevykh preparatov s primeneniyem test-sistem na osnove kultur kletok. Uchen. zap. Kazan. un-ta. Ser. Estestv. nauki. 2021. № 2. S. 155–176. Doi: 10.26907/2542-064X.2021.2.155-176 (in Russian).
3. Timofeyeva S.V., Shamova T.V., Sitkovskaya A.O. 3D-bioprinting mikrookruzheniya opukholi: posledniye dostizheniya. Zhurnal obshchey biologii. 2021. T. 82. № 5. S. 389–400. Doi: 10.31857/S0044459621050067 (in Russian).
4. Sun W., Luo Z., Lee J., Kim H.J., Lee K., Tebon P., Feng Y., Dokmeci M. R., Sengupta S., Khademhosseini A. Organ-on-a-Chip for Cancer and Immune Organs Modeling. Adv. Healthc. Mater. 2019. V. 8(4). P. e1801363. Doi: 10.1002/adhm.201801363
5. Niculescu A.G., Chircov C., Bîrcă A.C., Grumezescu A.M. Fabrication and Applications of Microfluidic Devices: A Review. Int. J. Mol. Sci. 2021. V. 22(4). P. 2011. Doi: 10.3390/ijms22042011
6. Cui Р., Wang S. Application of microfluidic chip technology in pharmaceutical analysis: A review. Journal of Pharmaceutical Analysis. 2019. V. 9(4). P. 238–247. Doi: 10.1016/j.jpha.2018.12.001
7. Azizipour N., Avazpour R., Rosenzweig D.H., Sawan M., Ajji A. Evolution of Biochip Technology: A Review from Lab-on-a-Chip to Organ-on-a-Chip. Micromachines (Basel). 2020. V. 11(6). P. 599. Doi: 10.3390/mi11060599
8. Del Piccolo N., Shirure V.S., Bi Y., Goedegebuure S.P., Gholami S., Hughes C.C.W., Fields R.C., George S.C. Tumor-on-chip modeling of organ-specific cancer and metastasis. Advanced Drug Delivery Reviews. 2021. V. 175. P. 113798. Doi: 10.1016/j.addr.2021.05.008
9. Monteiro M.V., Zhang Y.S., Gaspar V.M., Mano J.F. 3D-bioprinted cancer-on-a-chip: level-up organotypic in vitro models. Trends Biotechnol. 2022. V. 40(4). P. 432–447. Doi: 10.1016/j.tibtech.2021.08.007
10. Zhang J., Hu Q., Wang S., Tao J., Gou M. Digital Light Processing Based Three-dimensional Printing for Medical Applications. Int. J. Bioprint. 2019. V. 6(1). P. 242. Doi: 10.18063/ijb.v6i1.242
11. Tsolakis I.A., Papaioannou W., Papadopoulou E., Dalampira M., Tsolakis A.I. Comparison in Terms of Accuracy between DLP and LCD Printing Technology for Dental Model Printing. Dent. J. (Basel). 2022. V. 10(10). P. 181. Doi: 10.3390/dj10100181