Hyaluronic Acid Modified with Bisphosphonic Groups and Peptides as Organic Coating for Titanium Implants

The work presents the results on the development of organic coatings based on conjugates of hyaluronic acid with bisphosphonates of amino acids and oligopeptides – KRGD or the osteogenic growth peptide (OGP) – for modifying the metal surface with a porous inorganic sublayer obtained through plasma-electrolytic oxidation (PEO). Derivatives of hyaluronic acid (HYA) were synthesized via a Michael reaction involving maleimides of γ-aminobutyric acid bisphosphonate and oligopeptides, as well as SH-functionalized HYA. The conjugates were introduced into the pores of PEO coating on coarse-grained Ti (Grade 2) by immersing the metal samples in the solutions. The presence of organic molecules in the PEO sublayer was confirmed by X-ray photoelectron spectroscopy (XPS). The immobilization of organic molecules on the metal surface led to an increase in its hydrophilicity. Further, studies were carried out on human dermal fibroblasts (hDF) and human adipose-derived mesenchymal stem cells (hASC) to assess the cytotoxicity of the materials, as well as to evaluate the adhesion and proliferation of cells on the modified surface. Research has demonstrated a reduction in cell adhesion and proliferation on the samples modified with conjugates of HYA with peptides and bisphosphonates, which may be attributed to the high hydrophilicity of the surface. OGP applied to the Ti-PEO sublayer exhibited a significant positive effect on hASC adhesion and proliferation.