Hyaluronic acid bisphosphonates as antifouling antimicrobial coatings for PEO-modified titanium implants

The work is aimed at the development of biocompatible coatings based on bisphosphonic acid derivatives of a natural polymer matrix – hyaluronic acid, for modification of the surface of nanostructured and coarse-grained Ti Grade 4 with a sublayer obtained by plasma electrolytic oxidation (PEO). The synthesis of hyaluronic acid (HA) derivatives was carried out by oxidation of HA with TEMPO+Cl−, as well as by the Michael addition of maleimides of γ-aminobutanoic and ε-aminocaproic acid bisphosphonates to SH-functionalized HA. Organic molecules were deposited to the PEO-modified titanium surface by physicochemical adsorption from solutions. The presence of the organic coating in the pores of the PEO-sublayer was confirmed by X-ray photoelectron spectroscopy (XPS). The contact angle measurements showed the increase in the hydrophilicity of the Ti-PEO surface modified with the hyaluronic acid bisphosphonates. The study of biological activity in vitro revealed that the HA bisphosphonates are non-toxic, and the coatings based on them decrease the viability of fibroblasts (by 20–40%), osteoblast-like cells MG-63 (by 30–60%), and mesenchymal stem cells (more than 60%) compared to Ti-PEO control surfaces. As a result of antibacterial property studies, a significant decrease in the adhesion of pathogens P. aeruginosa, S. aureus, and E. faecium on the surface of nanostructured titanium modified with PEO and HA derivatives was found. Therefore, the resulting hybrid PEO-organic coatings can contribute to further development of antifouling antimicrobial coatings for metal implants.