Investigation into the interaction between quartz nanostructures and human cell lines for tissue engineering

Document Type : Article


Department of Mechanical Engineering, Sharif University of Technology, Tehran, Iran


Control of interaction between nanostructures and living cells is important for tissue engineering.The topography and hydrophilicity of nanotextured surfaces can provide information on the in vitro interactions between cells and the surrounding environment, which is of great importance in bio-applications. This study proposes a reactive ion etching (RIE) to texture the quartz surfaces with 5 and 10 nm surface roughnesses. The interaction of human cell lines (human breast cancer cells, MCF-7, and human dermal microvascular endothelial cells, HDMVEC) with the nanostructured surfaces exhibited different levels of morphogenesis when the cells adhered on the bare and nanotextured quartz surfaces. The chemical composition of the surfaces were characterized by X-ray photoelectron spectroscopy (XPS) and results showed that cells preferred to grow on hydrophilic surfaces with hydroxyl groups.Moreover, the cellular processes, such as adhesion and spreading, were affected by the combination of physical and chemical properties of the surface, namely, surface topology and hydrophilicity. These results demonstrated the potential applications of quartz nanostructure surfaces with high microscopic image quality in tissue engineering for controlling cell growth via appropriate surface modifications.


[1]    Shamloo, A., Mohammadaliha, N., and Mohseni, M. "Integrative utilization of microenvironments, biomaterials and computational techniques for advanced tissue engineering," Journal of biotechnology, vol. 212, pp. 71-89 (2015).
[2]    Chen, W., Villa-Diaz, L. G., Sun, Y. et al., "Nanotopography Influences Adhesion, Spreading, and Self-Renewal of Human Embryonic Stem Cells," ACS Nano, vol. 6, pp. 4094-4103 (2012).
[3]    Smith, I. O., Liu, X. H., Smith, L. A. et al., "Nanostructured polymer scaffolds for tissue engineering and regenerative medicine," Wiley Interdisciplinary Reviews: Nanomedicine and Nanobiotechnology, vol. 1, pp. 226-236 (2009).
[4]    Limongi, T., Tirinato, L., Pagliari, F. et al., "Fabrication and Applications of Micro/Nanostructured Devices for Tissue Engineering," Nano-Micro Letters, vol. 9, p. 1 (2016).
[5]    Yang, S.-P., Wen, H.-S.,  Lee, T.-M. et al., "Cell response on the biomimetic scaffold of silicon nano- and micro-topography," Journal of Materials Chemistry B, vol. 4, pp. 1891-1897 (2016).
[6]    Liu, Z.-M., Tingry, S., Innocent, C. et al., "Modification of microfiltration polypropylene membranes by allylamine plasma treatment: Influence of the attachment route on peroxidase immobilization and enzyme efficiency," Enzyme and microbial technology, vol. 39, pp. 868-876 (2006).
[7]    Xu, X., Kwok, R. W. M., and Lau, W. M., "Surface modification of polystyrene by low energy hydrogen ion beam," Thin Solid Films, vol. 514, pp. 182-187 (2006).
[8]    Guo, L., Kawazoe, N., Fan, Y. et al., "Chondrogenic differentiation of human mesenchymal stem cells on photoreactive polymer-modified surfaces," Biomaterials, vol. 29, pp. 23-32 (2008).
[9]    Kondyurin, A., Gan, B. K., Bilek, M. M. M. et al., "Etching and structural changes of polystyrene films during plasma immersion ion implantation from argon plasma," Nuclear Instruments and Methods in Physics Research Section B: Beam Interactions with Materials and Atoms, vol. 251, pp. 413-418 (2006).
[10]    Hu, Y., Winn, S. R., Krajbich, I. et al., "Porous polymer scaffolds surface-modified with arginine-glycine-aspartic acid enhance bone cell attachment and differentiation in vitro," Journal of Biomedical Materials Research Part A, vol. 64A, pp. 583-590 (2003).
[11]    Hamerli, P., Weigel, T., Groth, T. et al., "Surface properties of and cell adhesion onto allylamine-plasma-coated polyethylenterephtalat membranes," Biomaterials, vol. 24, pp. 3989-3999 (2003).
[12]    Liu, Z.-M., Xu, Z.-K., Wan, L.-S. et al., "Surface modification of polypropylene microfiltration membranes by the immobilization of poly(N-vinyl-2-pyrrolidone): a facile plasma approach," Journal of Membrane Science, vol. 249, pp. 21-31 (2005).
[13]    Hamerli, P., Weigel, T., Groth, T. et al., "Enhanced tissue-compatibility of polyethylenterephtalat membranes by plasma aminofunctionalisation," Surface and Coatings Technology, vol. 174–175, pp. 574-578 (2003).
[14]    Di Mundo, R., Nardulli, M., Milella, A. et al., "Cell adhesion on nanotextured slippery superhydrophobic substrates," Langmuir, vol. 27, pp. 4914-4921 (2011).
[15]    Islam, M., Motasim Bellah, M., Sajid, A. et al., "Effects of Nanotexture on Electrical Profiling of Single Tumor Cell and Detection of Cancer from Blood in Microfluidic Channels," Scientific Reports, vol. 5, p. 13031 (2015).
[16]    Tsougeni, K., Tserepi, A., Boulousis, G. et al., "Control of Nanotexture and Wetting Properties of Polydimethylsiloxane from Very Hydrophobic to Super-Hydrophobic by Plasma Processing," Plasma Processes and Polymers, vol. 4, pp. 398-405 (2007).
[17]    Lopacinska, J. M., Gradinaru, C., Wierzbicki, R. et al., "Cell motility, morphology, viability and proliferation in response to nanotopography on silicon black," Nanoscale, vol. 4, pp. 3739-3745 (2012).
[18]    Tsougeni, K., Tserepi, A., Constantoudis, V. et al., "Plasma Nanotextured PMMA Surfaces for Protein Arrays: Increased Protein Binding and Enhanced Detection Sensitivity," Langmuir, vol. 26, pp. 13883-13891 (2010).
[19]    Bettinger, C. J., Langer, R., and Borenstein, J. T., "Engineering substrate topography at the micro‐and nanoscale to control cell function," Angewandte Chemie International Edition, vol. 48, pp. 5406-5415 (2009).
[20]    Hasirci, V. and Pepe-Mooney, B. J., "Understanding the cell behavior on nano-/micro-patterned surfaces," Nanomedicine, vol. 7, pp. 1375-1389 (2012).
[21]    Badique, F., Stamov, D. R., Davidson, P. M. et al., "Directing nuclear deformation on micropillared surfaces by substrate geometry and cytoskeleton organization," Biomaterials, vol. 34, pp. 2991-3001 (2013).
[22]    Lee, K. Y., Alsberg, E., Hsiong, S. et al., "Nanoscale adhesion ligand organization regulates osteoblast proliferation and differentiation," Nano letters, vol. 4, pp. 1501-1506, (2004).
[23]    Yang, S. Y., Kim, E.-S., Jeon, G. et al., "Enhanced adhesion of osteoblastic cells on polystyrene films by independent control of surface topography and wettability," Materials Science and Engineering: C, vol. 33, pp. 1689-1695 (2013).
[24]    Kontziampasis, D., Bourkoula, A., Petrou, P. et al., "Cell array fabrication by plasma nanotexturing," in Bio-MEMS and Medical Microdevices (2013), p. 87650B.
[25]    Reznickova, A., Novotna, Z., Kolska, Z. et al., "Enhanced adherence of mouse fibroblast and vascular cells to plasma modified polyethylene," Materials Science and Engineering: C, vol. 52, pp. 259-266 (2015).
[26]    Islam, M., Atmaramani, R., Mukherjee, S., et al., "Enhanced proliferation of PC12 neural cells on untreated, nanotextured glass coverslips," Nanotechnology, vol. 27, p. 415501 (2016).
[27]    Marcatti Amarú Maximiano, W., Marino Mazucato, V., Tambasco de Oliveira, P. et al., "Nanotextured titanium surfaces stimulate spreading, migration, and growth of rat mast cells," Journal of Biomedical Materials Research Part A, vol. 105, pp. 2150-2161 (2017).
[28]    Yiannakou, C., Simitzi, C., Manousaki, A. et al., "Cell patterning via laser micro/nano structured silicon surfaces," Biofabrication, vol. 9, p. 025024 (2017).
[29]    Wang, L.. Asghar, W., Demirci, U., et al., "Nanostructured substrates for isolation of circulating tumor cells," Nano today, vol. 8, pp. 374-387 (2013).
[30]    Wang, S., Wang, H., Jiao, J. et al, "Three‐dimensional nanostructured substrates toward efficient capture of circulating tumor cells," Angewandte Chemie, vol. 121, pp. 9132-9135 (2009).
[31]    Islam, M., Sajid, A., Mahmood, M. A. I. et al, "Nanotextured polymer substrates show enhanced cancer cell isolation and cell culture," Nanotechnology, vol. 26, p. 225101 (2015).
[32]    Hosseini, S. A., Abdolahad, M., Zanganeh, S. et al., "Nanoelectromechanical chip (NELMEC) combination of nanoelectronics and microfluidics to diagnose epithelial and mesenchymal circulating tumor cells from leukocytes," small, vol. 12, pp. 883-891 (2016).
[33]    Dou, X., Li, P., Jiang, S. et al., "Bioinspired hierarchically structured surfaces for efficient capture and release of circulating tumor cells," ACS applied materials & interfaces, vol. 9, pp. 8508-8518 (2017).
[34]    Tserepi, A.,  Gogolides, E., Bourkoula, A. et al., "Plasma nanotextured polymeric surfaces for controlling cell attachment and proliferation: a short review," Plasma Chemistry and Plasma Processing, vol. 36, pp. 107-120 (2016).
[35]    Ellinas, K., Tserepi, A., and Gogolides, E., "Durable superhydrophobic and superamphiphobic polymeric surfaces and their applications: A review," Advances in colloid and interface science (2017).
[36]    Variola, F., Vetrone, F., Richert, L. et al., "Improving biocompatibility of implantable metals by nanoscale modification of surfaces: an overview of strategies, fabrication methods, and challenges," small, vol. 5, pp. 996-1006, (2009).
[37]    Zhukova, Y. and Skorb, E. V., "Cell Guidance on Nanostructured Metal Based Surfaces," Advanced healthcare materials, vol. 6, p. 1600914 (2017).
[38]    Rajnicek, A., Britland, S., and McCaig, C. "Contact guidance of CNS neurites on grooved quartz: influence of groove dimensions, neuronal age and cell type," Journal of cell science, vol. 110, pp. 2905-2913 (1997).
[39]    Mahmood, M. A. I., Wan, Y., Islam, M. et al., "Micro+ nanotexturing of substrates to enhance ligand-assisted cancer cell isolation," Nanotechnology, vol. 25, p. 475102 (2014).
[40]    Thibaud, C., Koubassov, V., De Koninck, P. et al., "Destruction of polymer growth substrates for cell cultures in two-photon microscopy," Journal of Microscopy, vol. 220, pp. 120-127 (2005).
[41]    Lee, J. N., Jiang, X., Ryan, D. et al., "Compatibility of Mammalian Cells on Surfaces of Poly(dimethylsiloxane)," Langmuir, vol. 20, pp. 11684-11691 (2004).
[42]    Vandrovcova, M., Hanus, J., Drabik, M. et al., "Effect of different surface nanoroughness of titanium dioxide films on the growth of human osteoblast-like MG63 cells," Journal of Biomedical Materials Research Part A, vol. 100A, pp. 1016-1032 (2012).
[43]    HO, J., "Cell adhesion to biomaterials. The role of several extracellular matrix components in the attachment of non-transformed fibroblasts and parenchymal cells.," ASAIO Trans., vol. 33, pp. 66-74 (1987).
[44]    Wang, L., Sun, B., Ziemer, K. S. et al., "Chemical and physical modifications to poly(dimethylsiloxane) surfaces affect adhesion of Caco-2 cells," Journal of Biomedical Materials Research Part A, vol. 93A, pp. 1260-1271 (2010).
[45]    Draux, F., Jeannesson, P., Beljebbar, A. et al., "Raman spectral imaging of single living cancer cells: a preliminary study," Analyst, vol. 134, pp. 542-548 (2009).
[46]    Bhatt, S., Pulpytel, J., Mirshahi, M. et al., "Catalyst-Free Plasma-Assisted Copolymerization of Poly(ε-caprolactone)-poly(ethylene glycol) for Biomedical Applications," ACS Macro Letters, vol. 1, pp. 764-767 (2012).
[47]    Bhatt, S., Pulpytel, J., Mirshahi, M. et al., "Nano thick poly(ε-caprolactone)-poly(ethylene glycol) coatings developed by catalyst-free plasma assisted copolymerization process for biomedical applications," RSC Advances, vol. 2, pp. 9114-9123 (2012).
[48]    (2016), Department of Cell Bank, Pasteur Institute of Iran. Available:
[49]    Maioli, E., Torricelli, C., Fortino, V. et al., "Critical Appraisal of the MTT Assay in the Presence of Rottlerin and Uncouplers," vol. 11, pp. 227-240 (2009).
[50]    Carriere, B., Deville, J. P., Brion, D. et al., "X-ray photoelectron study of some silicon-oxygen compounds," Journal of Electron Spectroscopy and Related Phenomena, vol. 10, pp. 85-91 (1977).
[51]    Sharma, V., Dhayal, M., Govind, et al., "Surface characterization of plasma-treated and PEG-grafted PDMS for micro fluidic applications," Vacuum, vol. 81, pp. 1094-1100 (2007).
[52]    Oehr, C., "Plasma surface modification of polymers for biomedical use," Nuclear Instruments and Methods in Physics Research Section B: Beam Interactions with Materials and Atoms, vol. 208, pp. 40-47 (2003).
[53]    Wang, N., Tytell, J. D., and Ingber, D. E., "Mechanotransduction at a distance: mechanically coupling the extracellular matrix with the nucleus," Nature reviews Molecular cell biology, vol. 10, p. 75 (2009).
[54]    Shamloo, A., Manchandia, M., Ferreira, M. et al., "Complex chemoattractive and chemorepellent Kit signals revealed by direct imaging of murine mast cells in microfluidic gradient chambers," Integrative Biology, vol. 5, pp. 1076-1085 (2013).
[55]    Shamloo, A., Heibatollahi, M., and Mofrad, M. R., "Directional migration and differentiation of neural stem cells within three-dimensional microenvironments," Integrative Biology, vol. 7, pp. 335-344 (2015).
[56]    Dalby, M. J., "Topographically induced direct cell mechanotransduction," Medical engineering & physics, vol. 27, pp. 730-742 (2005).
[57]    Shamloo, A., Mohammadaliha, N., Heilshorn, S. C. et al., "A comparative study of collagen matrix density effect on endothelial sprout formation using experimental and computational approaches," Annals of biomedical engineering, vol. 44, pp. 929-941 (2016).
[58]    Le Clainche, C., and Carlier, M.-F.,  "Regulation of actin assembly associated with protrusion and adhesion in cell migration," Physiological reviews, vol. 88, pp. 489-513 (2008).
[59]    Davidson, P. M., Özçelik, H., Hasirci, V., et al., "Microstructured surfaces cause severe but non‐detrimental deformation of the cell nucleus," Advanced Materials, vol. 21, pp. 3586-3590 (2009).
[60]    Davidson, P. M., Fromigué, O., Marie, P. J. et al., "Topographically induced self-deformation of the nuclei of cells: dependence on cell type and proposed mechanisms," Journal of Materials Science: Materials in Medicine, vol. 21, pp. 939-946 (2010).
[61]    Ermis, M., Akkaynak, D., Chen, P. et al., "A high throughput approach for analysis of cell nuclear deformability at single cell level," Scientific reports, vol. 6, p. 36917 (2016).
[62]    Richert, L., Vetrone, F., Yi, J. H. et al., "Surface nanopatterning to control cell growth," Advanced Materials, vol. 20, pp. 1488-1492 (2008).