Concepts for preparation of novel regioselective modified cellulose derivatives sulfated, aminated, carboxylated and acetylated for hemocompatible ultrathin coatings on biomaterials

Abstract

Some regioselective cellulose derivatives were synthesized on the basis of the just started longterm concept by variation of O-SO 3 , N-SO 3 , N-Ac, and N-carboxymethyl groups solely or in combination for the development of athrombogenic and antithrombogenic nanocoatings on cellulose membranes. Similar regioselectively arranged functional groups are known partially in type 1 glycosaminoglycane (dermatan sulfate DS, and chondroitin sulfate CS) and all the groups are present in type 2 GAC (heparin HE and heparansulfat HS). The goal of this concept was to use instead of the backbone structure β 1 ->4, β 1->3 (DS, CS) or β 1->4, α &6>4 (HE, HS or regioselective desulfated HE, the β 1->4 backbone structure of cellulose or chitosan, with the same functional groups as in HE. Furthermore different regioselective sulfated cellulose derivatives, such as cellulose636sulfate, cellulose-2,6-disulfate, and cellulose-2,3-sulfates with varied sulfation degrees have been synthesized and immobilized ionically on cellulose membranes. They were tested concerning their reduction of platelet adhesion from citrated whole blood in a perfusion system as well for AT III affinity. The lowest latelet adhesion and AT III affinity was observed using cellulose-2,3-sulfates and cellulose-3-sulfate derivatives, whereas cellulose-6-O-sulfate derivatives show high AT III affinity and high platelet adhesion. This means that a high 6-O-sulfate content seems to promote anticoagulant properties of the derivatives with high (AT III) affinity, whereas low concentrations of 2-O- and 3-O-sulfate groups show the lowest platelet adhesion. The latter seems to be important for developing athrombogenic coatings for biomaterials. The starting material chitosan with molecular weight of 150 KD was used to synthesize additionally some of 2-deoxyaminocellulose derivatives containing N-Ac or N-SO 3 or N-CH 2 -COOH and O-SO 3 group. These derivatives are structurally closer to HE and HS and should enable us to work out the influence of each heparin like functional group in cellulose derivative on the athrombogenic and antithrombogenic properties. We synthesized only some of the latter mentioned derivatives with a distribution of the functional groups according to a Bernoulli statistics. Totally sulfated 2-deoxyaminocellulose-3,6-disulfate derivatives will be regioselectively desulfated by reactions known from heparin chemistry.