Integral Algorithms to Evaluate TiO2 and N-TiO2 Thin Films’ Cytocompatibility

Abstract

Titanium oxide (TiO2) and oxynitride (N-TiO2) coatings can increase nitinol stents’ cytocompatibility with endothelial cells. Methods of TiO2 and N-TiO2 sputtering and cytocompatibility assessments vary significantly among different research groups, making it difficult to compare results. The aim of this work was to develop an integral cytocompatibility index (ICI) and a decision tree algorithm (DTA) using the “EA.hy926 cell/TiO2 or N-TiO2 coating” model and to determine the optimal cytocompatible coating. Magnetron sputtering was performed in a reaction gas medium with various N2:O2 ratios and bias voltages. The samples’ morphology was studied by scanning electron microscopy (SEM) and Raman spectroscopy. The cytocompatibility of the coatings was evaluated in terms of their cytotoxicity, adhesion, viability, and NO production. The ICI and DTA were developed to assess the cytocompatibility of the samples. Both algorithms demonstrated the best cytocompatibility for the sample sputtered at Ubias = 0 V and a gas ratio of N2:O2 = 2:1, in which the rutile phase dominated. The DTA provided more detailed information about the cytocompatibility, which depended on the sputtering mode, surface morphology, and crystalline phase. The proposed mathematical models relate the cytocompatibility and the studied physical characteristics.

Effect of the Nanorough Surface of TiO2 Thin Films on the Compatibility with Endothelial Cells

“…It is well known that anatase is significantly higher cytotoxic than rutile [ 17 , 18 ]. We also found this in the direct cytotoxicity test [ 16 ]. Therefore, we considered it reasonable that the surfaces formed at −100 V belong to the group of “unacceptable” (samples 1 and 9) or “uncertain” (Nos.…”

“…Only one polished sample No. 11 turned out to be in the “acceptable” group, which was somewhat unexpected, since it was sputtered at N 2 :O 2 = 1:1 and U b = −100 V. Previously, we showed that the crystal structure of thin films sputtered at −100 V are mainly represented by anatase [ 15 , 16 ]. It is well known that anatase is significantly higher cytotoxic than rutile [ 17 , 18 ].…”

“…A decision tree with a hierarchical sequential assessment of the significance of each biological test was used to select TiO 2 and TiO x N y coatings with optimal cytocompatibility ( Figure 5 ). For integral assessing the biocompatibility of the TiO 2 and TiO x N y coatings, the decision tree-like graph visualization, developed earlier [ 16 ], was chosen. We used the boundary values of the tests as the branch node ( Table 9 ), and the overall level of thin film cytocompatibility as the predicted outcome.…”

“…Therefore, the initial surface for deposition should be selected in such a way that the structure and composition of the prepared thin film provide a final surface with optimal cytocompatibility. We have previously shown that varying the sputtering modes makes it possible to obtain surfaces of various structures and compositions, both elemental and crystalline (rutile or anatase) [ 15 , 16 ]. Regardless of these varieties, all coatings improved the adhesion and proliferation of endothelial cells compared to control bare nitinol.…”