The role of regioselectively sulfated and acetylated polysaccharide coatings of biomaterials for reducing platelet and plasma protein adhesion.

Abstract

A brief survey is given about the role of natural polysaccharides such as heparin (HE), heparan sulfate (HS), chondroitin sulfate (CS), and dermatan sulfate (DS) in reducing blood coagulation and their potential use as athrombogenic coatings in the development of tailor-made athrombogenic biomaterials. Furthermore, known literature and new results about platelet adhesion on regioselectively modified polysaccharides such as HE, chitosan with HE-like functional groups, and sulfated cellulose are presented in two different perfusion systems at different shear rates. Regioselectively modified polysaccharides were tested as coatings of two polymers. The strongest influence on platelet adhesion was observed when the three regioselectively modified polysaccharides contained 6-O-sulfo- groups. No or little influence was seen with 3-O-sulfo- groups. A variable effect on platelet adhesion was found in position 2. N-sulfo- groups in HE induced a medium platelet adhesion, and O-sulfo- groups of iduronic acid moiety in HE induced none. Cellulose containing 2-O-sulfo- groups induced little platelet adhesion, and 2-N- sulfo- groups in chitosan induced a variable platelet adhesion response, depending on the N-SO(3)/NAc ratio. Preliminary plasma protein adhesion measurements on immobilized HE derivatives with four different fluorescence-labeled plasma proteins showed a regioselective influence with serum albumin and fibrinogen. 6-O-desulfated HE gave the strongest reduction in protein adsorption followed by N-desulfation and 2-O-desulfation; the lowest reduction was observed with 3-O-desulfation. Tailor-made athrombogenic coatings of HE should not carry high amounts of 6-O-sulfo- groups or of N-sulfo- groups. Regioselectively modified cellulose and chitosan may become suitable for tailor-made athrombogenic biomaterials when regioselective reactions are further optimized.