Heparin and non-heparin-like dextrans differentially modulate endothelial cell proliferation: in vitro evaluation with soluble and crosslinked polysaccharide matrices

Abstract

Proliferation of endothelial cells (ECs) is a cellular step of particular importance for implanted cardiovascular biomaterials. Heparin and some synthetic water-soluble non-anticoagulant polysaccharides derived from dextran and bearing anionic carboxymethyl and hydrophobic benzylamine groups were first investigated for their effects on EC proliferation in vitro. The results assessed by cell counting, 3H-thymidine uptake, and flow cytometry analysis, showed that the derivatized dextran-bearing hydrophobic groups stimulated the EC growth in the presence of serum, whereas native dextran or dextran-bearing anionic carboxymethyl groups were inactive and heparin was slightly inhibitory. Then, we showed that the derivatized dextran enhanced EC proliferation by potentiation of the mitogenic activities of vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (FGF-2), two potent EC growth factors. In the presence of 2 nM of derivatized dextran, a 3-fold and 13-fold increase of 3H-thymidine uptake was obtained with VEGF and FGF-2, respectively. Finally, proliferation of ECs was investigated on crosslinked gels made of polysaccharides. It is of interest that EC proliferation was higher on gels containing the derivatized dextran than on plain hydrogels, and heparinized gels inhibited cell proliferation. From the obtained results, we propose that the synthetic non-heparin-like dextran may be of interest as a coating for the endothelialization of cardiovascular biomaterials.