Sulphated polysaccharides derived from dextran: biomaterials for vascular therapy

Abstract

CMDBS are synthetic dextran derivatives randomly substituted with carboxymethyl (CM), benzylamide (B), sulphonate and sulphate groups (S). Depending on their overall composition, these compounds are endowed with heparin-like properties such as anticoagulant activity. Indeed, some CMDBS with high CM and S contents delay blood coagulation, whilst some derivatized dextrans without significant anticoagulant capacity are potent antiproliferative agents for rat smooth muscle cells (SMCs) in vitro as well as heparin. The growth inhibition is dose dependent, reversible and nontoxic. This result is of prime interest for medical use because proliferation of vascular SMCs is postulated to be a key step in the pathogenesis of atherosclerosis or restenosis after vascular surgery such as angioplasty. By varying the overall composition in the different substituents, we have also prepared CMDBS exhibiting a stimulatory effect on the in vitro growth of human endothelial cells (EC). Heparin, under similar experimental conditions, slightly inhibited EC growth. The data indicate a synergistic role of all substituents grafted onto the dextran backbone without considering that any can be responsible alone for this effect. We conclude that a suitable distribution of CM, B and S groups on dextran can mimic heparin activity in terms of anticoagulant activity and antiproliferative capacity on SMC growth. Moreover, some CMDBS are also endowed with a stimulatory effect on EC growth. These properties confer great interest to these synthetic polysaccharides for vascular therapy.