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Chelidonic acid (ChA) is small molecule capable of inducing the differentiation of mesenchymal stem cells (MSCs) into osteoblasts and the formation of mineralized bone matrix (MBM) both in vitro and in vivo. However, the molecular mechanisms underlying these effects are unknown. Therefore, in silico modelling of potential molecular targets of ChA was performed. ChA was isolated from Saussurea controversa. The ability of ChA to induce in vitro differentiation MSCs into osteoblasts synthesizing MBM was detected using alizarin red staining. ChA osteogenic activity was studied in mice by in situ test of ectopic osteogenesis, using the subcutaneous implantation of syngeneic bone marrow on the calcium phosphate coated titanium plates. DIGEP-Pred web service was used to simulate in silico the effect of ChA on gene expression, and overrepresentation analysis to search for common ontologies and pathways. ChA linearly increased the number of single (R 2  = 0.92, p = 0.039) and the total areas of MBM sites (R 2  = 0.96, p = 0.019) in a 21-day MSC culture. Oral administration of ChA led to two to three times improved bone and bone marrow formation in situ. In silico modelling identified 306 genes (including 7 calcium import genes) and 9 signalling pathways potentially involved in ChA osteogenic effect and calcium metabolism in MSCs. In silico analysis revealed a list of key signalling pathways and genes for calcium influx into MSCs and their differentiation into osteoblasts as the first target candidates for studying real gene expression and molecular mechanisms of the ChA osteogenic effects., Competing Interests: Declarations. Conflict of interest: The authors declare no conflicts of interest. Ethical approval and consent to participate: Informed consent from the volunteers was obtained for the procedure, and the study was approved by the Local Ethics Committee of the Innovation Park of the Immanuel Kant Baltic Federal University (Permission Number 1 on February 28, 2019). The Local Ethics Committee of the Siberian State Medical University (approval number 6901 on 29 October 2018) approved the experimental study on animals. Consent for publication: Not applicable., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

This paper focuses mainly on the in vitro study of a five-week biodegradation of a-C:H:SiO x films of different thickness, obtained by plasma-assisted chemical vapor deposition onto Ti-6Al-4V alloy substrate using its pulsed bipolar biasing. In vitro immersion of a-C:H:SiO x films in a solution of 0.9% NaCl was used. It is shown how the a-C:H:SiO x film thickness (0.5-3 µm) affects the surface morphology, adhesive strength, and Na + and Cl - precipitation on the film surface from the NaCl solution. With increasing film thickness, the roughness indices are reducing a little. The adhesive strength of the a-C:H:SiO x films to metal substrate corresponds to quality HF1 (0.5 µm in thickness) and HF2-HF3 (1.5-3 µm in thickness) of the Rockwell hardness test (VDI 3198) that defines strong interfacial adhesion and is usually applied in practice. The morphometric analysis of the film surface shows that on a-C:H:SiO x -coated Ti-6Al-4V alloy surface, the area occupied by the grains of sodium chloride is lower than on the uncoated surface. The reduction in the ion precipitation from 0.9% NaCl onto the film surface depended on the elemental composition of the surface layer conditioned by the thickness growth of the a-C:H:SiO x film. Based on the results of energy dispersive X-ray spectroscopy, the multiple regression equations are suggested to explain the effect of the elemental composition of the a-C:H:SiO x film on the decreased Na + and Cl - precipitation. As a result, the a-C:H:SiO x films successfully combine good adhesion strength and rare ion precipitation and thus are rather promising for medical applications on cardiovascular stents and/or friction parts of heart pumps.