Sulphated polysaccharides derived from dextran: biomaterials for vascular therapy

CMDBS are synthetic dextran derivatives randomly substituted with carboxyme thyl (CM), benzylamide (B), sulphonate and sulphate groups (S). Depending o n their overall composition, these compounds are endowed with heparin-like properties such as anticoagulant activity. Indeed, some CMDBS with high CIM and S contents delay blood coagulation, whilst some derivatized dextrans w ithout significant anticoagulant capacity are potent antiproliferative agen ts for rat smooth muscle cells (SMCs) in vitro as well as heparin. The grow th inhibition is dose dependent, reversible and nontoxic. This result is of prime interest for medical use because proliferation of vascular SMCs is p ostulated to be a key step in the pathogenesis of atherosclerosis or resten osis after vascular surgery such as angioplasty. By varying the overall com position in the different substituents, we have also prepared CMDBS exhibit ing 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 o nto the dextran backbone without considering that any can be responsible al one 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 ac tivity and antiproliferative capacity on SMC growth. Moreover, some CMDBS a re also endowed with a stimulatory effect on EC growth. These properties co nfer great interest to these synthetic polysaccharides for vascular therapy . (C) 1999 Society of Chemical Industry.