title: Cu(II) and Zn(II) complexes with hyaluronic acid and its sulphated derivative. Effect on the motility of vascular endothelial cells.
abstract: 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.
authors.affiliation: Department of Chemical and Biosystem Sciences and Technologies, University of Siena, Italy. barbucci@unisi.it
authors.forename: R
authors.initials: R
authors.lastname: Barbucci
authors.forename: A
authors.initials: A
authors.lastname: Magnani
authors.forename: S
authors.initials: S
authors.lastname: Lamponi
authors.forename: S
authors.initials: S
authors.lastname: Mitola
authors.forename: M
authors.initials: M
authors.lastname: Ziche
authors.forename: L
authors.initials: L
authors.lastname: Morbidelli
authors.forename: F
authors.initials: F
authors.lastname: Bussolino
mesh_terms: D000818:Animals; D001672:Biocompatible Materials / Q000494:pharmacology*; D002448:Cell Adhesion / Q000187:drug effects; D002465:Cell Movement / Q000187:drug effects; D002478:Cells, Cultured; D002633:Chemotaxis / Q000187:drug effects; D003300:Copper / Q000737:chemistry / Q000494:pharmacology*; D004355:Drug Stability; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects*; D006820:Hyaluronic Acid / Q000737:chemistry / Q000494:pharmacology*; D006863:Hydrogen-Ion Concentration; D008422:Materials Testing; D051379:Mice; D008815:Mice, Inbred Strains; D013431:Sulfates / Q000737:chemistry / Q000494:pharmacology; D015032:Zinc / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D001672:Biocompatible Materials; D013431:Sulfates; D003300:Copper; D006820:Hyaluronic Acid; D015032:Zinc