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Copper(II) and silver(I) hyaluronane-based hydrogel complexes were synthesised. The amount of metal ion uptaken by hydrogel was determined by atomic absorption and the hydrogel–metal ion complexes were characterised by water-uptake measurements, SEM-EDAX and FT-IR analysis. The coordination sites were identified for both metal ions and the stability at various pH levels was determined. The cytotoxicity of hydrogel metal ions was evaluated by using fibroblast (3T3) cells. The copper(II) complex was in vivo tested and showed proangiogenic activity, stimulating the growth of new vessels without inducing an inflammatory reaction.The antibacterial activity of a silver complex was determined, showing that the presence of silver ions drastically reduced the adhesion and proliferation of Staphylococcus epidermidis.

Blood tubings commonly represent an integral component of hemodialysis circuits. Different factors may influence their biocompatibility, such as the type of material, the sterilization mode and the geometry. In vivo the final biocompatibility may be further complicated by the individual host response, the flow parameters, and the impact of mechanical trauma on blood's cellular components (i.e. erythrocytes). In this in vitro study we evaluated some commercially available blood tubings sterilized by different methods as to their interaction with normal leukocyte population and tested the response of these cells in terms of cytokines (IL-1beta, IL-1Ra, TNF-alpha). As a positive control, leukocytes were incubated with 0.5 ng/mL of bacterial lipopolysaccharide (LPS) or with Cuprophan of comparable surface. The results showed that cytokine production was markedly reduced, particularly in the case of gamma-ray-sterilized tubings. Of interest, it was not always related to the adherence. However in some cases, particularly of gamma-ray sterilization, adherence was none, despite the cytokine production.

With the aim of improving the compatibility of biomaterials to be used for the construction of cardiovascular prosthesis, we have designed bioactive macromolecules resulting from chemical modifications of hyaluronic acid (Hyal). The stability constants of Cu(II) and Zn(II) complexes with the sulphated derivative of hyaluronic acid (HyalS3.5) were evaluated. Two different complexes have been found for each metal ion, CuL, Cu(OH)2L and ZnL, Zn(OH)2L (L means the disaccharide unit of the ligands) in aqueous solution at 37 degrees C. The dihydroxo Cu(II) complex was present in high percentage at pH=7.4. On the contrary, the Zn(II) ion was present with a relatively low percentage of both complexes. The ability to stimulate endothelial cell adhesion and migration was evaluated for Hyal, HyalS3.5 and their complexes with Cu(II) and Zn(II) ions. The results revealed that Hyal and [Cu(OH)2HyalS3.5](4.5)- induced cell adhesion, while [ZnHyalS3.5](2.5)- and [Zn(OH)2HyalS3.5](4.5)- inhibited the process. The chemotactic activity of increasing concentrations of the above complexes was also evaluated, demonstrating that [Cu(OH)2HyalS3.5](4.5)- complex at 1 microM concentration was the most active in inducing cell migration. These results have been also strengthened by analysing adherent cell migration in agarose. In conclusion, sulphated hyaluronic acid coordinated to Cu(II) seems to be a promising matrix molecule for the construction of cardiovascular prosthesis.