journal article·2026-07-09Open access

Hydrophobic pp-HMDSO Coating for Three-Dimensional Cell Culture

Marina Rakhmanova, Anastasia Leonteva, Maxim Chagin, Evgeniya Ermakova, David Sergeevichev, Vladimir Richter, Marina Kosinova, Anna Nushtaeva

Abstract

The interaction of biomaterial surface with cells is a pivotal factor in tissue engineering and three-dimensional (3D) modeling. This paper presents an approach to modifying polystyrene surface by plasma-enhanced chemical vapor deposition of thin plasma-polymerized hexamethyldisiloxane (pp-HMDSO) films to enhance biocompatibility and stimulate the formation of 3D cellular structures. The coatings were characterized by SEM, EDS, XPS, FTIR, AFM, contact angle measurements, and surface free energy (SFE) analysis. A hydrophobic surface initiates 3D structure formation by ensuring uniform cell repulsion and stimulating intercellular interactions. Biological evaluation was performed on U-87 MG (glioblastoma) and HMC3 (microglia) cell lines. For U-87 MG, the pp-HMDSO layer proved critical: cell death and atypical adhesion occurred on untreated plastic, whereas stable spheroids formed on the modified surface. HMC3 cells formed small spheroids even on unmodified surfaces, but on pp-HMDSO coatings, the process was more intense and the structures more uniform due to surface hydrophobicity. These results demonstrate the potential of plasma-polymerized HMDSO films as a scalable platform for creating biomaterials with controlled properties for 3D culturing.
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Research context

OpenAlex topics: Surface Modification and Superhydrophobicity · Polymer Surface Interaction Studies · Bone Tissue Engineering Materials

SciVX discovery tags are terminology-based. OpenAlex topics are source-provided classifications.

Affiliations

Institute of Chemical Biology and Fundamental Medicine Siberian Branch of the Russian Academy of Sciences, 8 Acad. Lavrentiev Ave., Novosibirsk 630090, Russia

Scientific Center of Genetics and Life Sciences, Sirius University of Science and Technology, 1 Olimpiysky Ave., Sirius Federal Territory, Sirius 354340, Russia

Nikolaev Institute of Inorganic Chemistry Siberian Branch of the Russian Academy of Sciences, 3 Acad. Lavrentiev Ave., Novosibirsk 630090, Russia

Funding

STATE PROGRAM OF THE “SIRIUS” FEDERAL TERRITORY, “Scientific and technological development of the “Sirius” Federal Territory”

References (49)

Show source-provided references
1. The evolution of endometriosis research models: A paradigm shift from immortalized cell lines to organoids10.1093/biolre/ioag011 ↗
2. A hitchhiker’s guide to cancer models10.1016/j.tibtech.2022.04.003 ↗
3. Cultures cellulaires en trois dimensions: Applications à la biologie des cancers [Three-dimensional cell cultures: Applications to cancer biology]10.1016/j.bulcan.2025.09.004 ↗
4. Marconi, G.D., Mazzone, A., Della Rocca, Y., Trubiani, O., Pizzicannella, J., and Diomede, F. (2025). Three-Dimensional Culture System: A New Frontier in Cancer Research, Drug Discovery, and Stem Cell-Based Therapy. Biology, 14.10.3390/biology14070875 ↗
5. Zhang, L., Liao, W., Chen, S., Chen, Y., Cheng, P., Lu, X., and Ma, Y. (2023). Towards a New 3Rs Era in the construction of 3D cell culture models simulating tumor microenvironment. Front. Oncol., 13.10.3389/fonc.2023.1146477 ↗
6. Calvillo, L. (2022). Editorial: 3Rs approach (replace, reduce and refine animal models) to improve preclinical research. Front. Physiol., 13.10.3389/fphys.2022.1040575 ↗
7. 3D cell culture models: How to obtain and characterize the main models10.18699/vjgb-25-21 ↗
8. The choice of ultra-low attachment plates impacts primary human and primary canine hepatocyte spheroid formation, phenotypes, and function10.1002/biot.202300587 ↗
9. Vitacolonna, M., Bruch, R., Agaçi, A., Nürnberg, E., Cesetti, T., Keller, F., Padovani, F., Sauer, S., Schmoller, K.M., and Reischl, M. (2024). A multiparametric analysis including single-cell and subcellular feature assessment reveals differential behavior of spheroid cultures on distinct ultra-low attachment plate types. Front. Bioeng. Biotechnol., 12.10.3389/fbioe.2024.1422235 ↗
10. Ferrari, M., Cirisano, F., and Morán, M.C. (2022). Super Liquid-repellent Surfaces and 3D Spheroids Growth. Front. Biosci., 27.10.31083/j.fbl2705144 ↗
11. Cirisano, F., Ferrari, M., and Morán, M.C. (2025). Superhydrophobicity Effects on Spheroid Formation, Structure, and Viability on Co-Culture Conditions. Pharmaceuticals, 18.10.3390/ph18070953 ↗
12. Ferrari, M., Cirisano, F., and Morán, M.C. (2022). Mammalian Cell Spheroids on Mixed Organic–Inorganic Superhydrophobic Coating. Molecules, 27.10.3390/molecules27041247 ↗
13. Cell Spheroid Formation on the Surface of Multi-Block Copolymers Composed of Poly(2-methoxyethyl acrylate) and Polyethylene Glycol10.1002/mabi.202200486 ↗
14. Surface Modification of Biopolymers by Argon Plasma and Thermal Treatment
15. Surface characterization of plasma treated polymers for applications as biocompatible carriers10.3144/expresspolymlett.2013.50 ↗
16. Characterization of Plasma Polymerized Hexamethyldisiloxane Films Prepared by Arc Discharge10.1007/s11090-013-9516-y ↗
17. PECVD of biocompatible coatings on 316L stainless steel10.1016/j.surfcoat.2005.02.009 ↗
18. Martinez-Pacheco, S., and O’Driscoll, L. (2021). Pre-Clinical In Vitro Models Used in Cancer Research: Results of a Worldwide Survey. Cancers, 13.10.3390/cancers13236033 ↗
19. Vinci, M., Gowan, S., Boxall, F., Patterson, L., Zimmermann, M., Court, W., Lomas, C., Mendiola, M., Hardisson, D., and Eccles, S.A. (2012). Advances in establishment and analysis of three-dimensional tumor spheroid-based functional assays for target validation and drug evaluation. BMC Biol., 10.10.1186/1741-7007-10-29 ↗
20. Hartree–Slater Subshell Photoionization Cross-Sections at 1254 and 1487 eV10.1016/0368-2048(76)80015-1 ↗
21. Fairley, N. (2026, March 28). CasaXPS: Processing Software for XPS Spectra. Available online: www.casaxps.com.
22. Isolation of spheroid-forming single cells from gastric cancer cell lines: Enrichment of cancer stem-like cells10.2144/btn-2018-0046 ↗
23. A simple and robust serum-free media for the proliferation of muscle cells10.1016/j.foodres.2023.113194 ↗
24. Optimized survival of hippocampal neurons in B27-supplemented Neurobasal™, a new serum-free medium combination10.1002/jnr.490350513 ↗
25. High-throughput image analysis of tumor spheroids: A user-friendly software application to measure the size of spheroids automatically and accurately
26. Štampar, M., Breznik, B., Filipič, M., and Žegura, B. (2020). Characterization of In Vitro 3D Cell Model Developed from Human Hepatocellular Carcinoma (HepG2) Cell Line. Cells, 9.10.3390/cells9122557 ↗
27. Launer, P., and Arkles, B. (2013). Infrared Analysis of Organosilicon Compounds: Spectra-structure correlations. Silicon Compounds: Silanes & Silicones, Gelest, Inc.
28. Bellamy, L.J. (1980). The Infrared Spectra of Complex Molecules, Springer.10.1007/978-94-011-6520-4 ↗
29. Tolstoy, V.P., Chernyshova, I.V., and Skryshevsky, V.A. (2003). Handbook of Infrared Spectroscopy of Ultrathin Films, John Wiley & Sons.10.1002/047123432X ↗
30. Growth and surface chemistry of oxynitride gate dielectric using nitric oxide10.1063/1.113461 ↗
31. Influence of process conditions on the surface oxidation of silicon nitride green compacts10.1023/A:1018543703475 ↗
32. Surface Modification of Si3N4 Powders by Coprecipitation of Sintering Aids10.1111/j.1151-2916.1999.tb02137.x ↗
33. Composition Analysis of SiO2/SiC Interfaces by Electron Spectroscopic Measurements Using Slope-Shaped Oxide Films10.1016/S0169-4332(01)00491-3 ↗
34. Surface modification of silicon oxycarbide films produced by remote hydrogen microwave plasma chemical vapour deposition from tetramethyldisiloxane precursor10.1016/j.surfcoat.2018.07.050 ↗
35. Surface modification of poly(dimethylsiloxane) through oxygen and nitrogen plasma treatment to improve its characteristics towards biomedical applications10.1088/2051-672X/3/3/035005 ↗
36. The characterization of plasma-modified polydimethylsiloxane interfaces with media of different surface energy10.1016/0267-6605(90)90014-M ↗
37. Plasma polymerized organosilicon thin films from hexamethyldisiloxane and oxygen: Chemical structure, wettability and surface energy10.1002/ppap.202200052 ↗
38. Poornima, K., Francis, A.P., Hoda, M., Eladl, M.A., Subramanian, S., Veeraraghavan, V.P., El-Sherbiny, M., Asseri, S.M., Hussamuldin, A.B.A., and Surapaneni, K.M. (2022). Implications of Three-Dimensional Cell Culture in Cancer Therapeutic Research. Front. Oncol., 12.10.3389/fonc.2022.891673 ↗
39. Engineering Tissues without the Use of a Synthetic Scaffold: A Twenty-Year History of the Self-Assembly Method10.1155/2018/5684679 ↗
40. Spheroids in cancer research: Recent advances and opportunities10.1016/j.jddst.2024.106033 ↗
41. Morphological and Functional Analysis of Hepatocyte Spheroids Generated on Poly-HEMA-Treated Surfaces under the Influence of Fetal Calf Serum and Nonparenchymal Cells10.3390/biom3010242 ↗
42. Protein exclusion is preserved by temperature sensitive PEG brushes10.1016/j.polymer.2017.10.063 ↗
43. E-cadherin, actin, microtubules and FAK dominate different spheroid formation phases and important elements of tissue integrity
44. A self-assembled monolayer-based micropatterned array for controlling cell adhesion and protein adsorption10.1002/bit.23029 ↗
45. Hypoxia activates cadherin-22 synthesis via eIF4E2 to drive cancer cell migration, invasion and adhesion10.1038/onc.2017.372 ↗
46. Are 3D Tumor Cell Spheroids a Utile System for the In Vitro Evaluation of Diagnostic Radiotracers?10.1021/acsomega.4c08214 ↗
47. The human microglial HMC3 cell line: Where do we stand? A systematic literature review10.1186/s12974-018-1288-0 ↗
48. Ahuja, S., and Lazar, I.M. (2021). Systems-Level Proteomics Evaluation of Microglia Response to Tumor-Supportive Anti-Inflammatory Cytokines. Front. Immunol., 12.10.3389/fimmu.2021.646043 ↗
49. 3D heterotypic models of glioblastoma reveal the impact of microglia on cellular organization and the production of a distinct secretome10.1038/s41598-026-37395-0 ↗