Immunomodulatory Effects Mediated by Nano Amorphous Calcium Phosphate/Chitosan Oligosaccharide Lactate Coatings Decorated with Selenium on Titanium Implants

The aim of this work is in situ anodization/anaphoretic deposition of a nano amorphous calcium phosphate (ACP)/chitosan oligosaccharide lactate (ChOL) multifunctional hybrid coating decorated with selenium (Se) on a titanium substrate and in vivo investigation of its immunomodulatory and anti-inflammatory effect. Investigating phenomena at the implant-tissue interface of interest for controlled inflammation and immunomodulation was also the aim of the research. In our earlier research, we designed coatings based on ACP and ChOL on titanium with anticorrosive, antibacterial and biocompatible properties, while in the presented results we show that selenium addition makes this coating an immunomodulator. The immunomodulatory effect of the novel hybrid coating is characterized by the examination of the functional aspects in the tissue around the implant (in vivo): proinflammatory cytokines' gene expression, M1 (iNOS) and M2 (Arg1) macrophages, fibrous capsule formation (TGF-β) and vascularization (VEGF). The EDS, FTIR and XRD analyses prove the formation of a ACP/ChOL/Se multifunctional hybrid coating on Ti and the presence of Se. A higher M2/M1 macrophage ratio in the ACP/ChOL/Se-coated implants compared to pure titanium implants (a higher level of Arg1 expression) is noted at all time points examined (after 7, 14 and 28 days). Lower inflammation measured by gene expression of proinflammatory cytokines IL-1β and TNF, lower expression of TGF-β in the surrounding tissue and higher IL-6 expression (solely at day 7 post-implantation) is noted in presence of the ACP/ChOL/Se-coated implants.