Metal complexes with linear and crosslinked polysaccharides as mediators of angiogenesis

Bioactive macromolecules resulting from chemical modification of hyaluronic acid (Hyal) have been designed to improve the compatibility bf biomaterial s used for cardiovascular prostheses. Hyal has been sulphated to obtain der ivatives (HyalS) with a number of sulphate groups ranging from 1 to 4 per d isaccharide unit. Hydrogels of Hyal have been obtained by cross-linking the free polysaccharide. An appropriate Hyal/cross-linking agent ratio has pro duced a hydrogel with a degree of crosslinking of 50%. In the present study, the ability to stimulate endothelial cell adhesion an d migration teas evaluated for free Hyal, HyalS(3.5) and their complexes wi th Cu(II) and Zn(II) ions. The results revealed that Hyal and [Cu(OH)(2)Hya lS(3.5)]((4.5))- induced cell adhesion, while [ZnHyalS(3.5)]((2.5))- and [Z n(OH)(2)HyalS(3.5)]((4.5))- inhibited the process. The chemotactic activity of increasing concentrations of the above complexes was also evaluated; de monstrating that [Cu(OH)(2)HyalS(3.5)]((4.5)-) complex at 1 muM concentrati on was the most active in inducing cell migration. These results were also confirmed by analysing cell migration in agarose. The 50% hydrogel bound Cu (II) and Zn(II) and the in vivo biocompatibility of the complexes was found to be good. Copyright (C) 2001 John Wiley & Sons, Ltd.