Heparinized polymers, blood-compatible

Ikada and coworkers also studied the blood compatibility and protein denaturation properties of heparin covalently and ionically bound onto polymer surfaces [513], Both types of bound heparin gave deactivation of the coagulation process. Clotting deactivation was attributed to a heparin/ antithrombin III complex by covalently bound heparin which gave adsorbed protein denaturation and platelet deformation as compared with lack of these features with ionically bound heparin. 

Problems of desorption and loss of activity encountered with natural heparin have led numerous workers to explore synthetic heparin-like polymers or heparinoids, as reviewed by Gebelein and Murphy [475, 514, 515]. The blood compatibility of 5% blended polyelectrolyte/polyfvinly alcohol) membranes was studied by Aleyamma and Sharma [516,517]. The membranes were modified with synthetic heparinoid polyelectrolytes, and surface properties (platelet adhesion, water contact angle, protein adsorption) and bulk properties such as permeability and mechanical characteristics were evaluated. The blended membrane had a lower tendency to adhere platelets than standard cellulose membranes and were useful as dialysis grade materials. 

Blood-compatible polymer materials are required to inhibit both platelet adhesion and coagulation just as the endothelial on the polymer surface. It is known that there are many investigations in the design and the synthesis of socalled antithrombogenic materials. The immobilization of biologically active substances such as heparin [74, 75], urokinase [76], and prostaglandins [77-81] is one of the practical approaches. 

Wilson, at Bishop College, and Eberhart and Elkowitz at University of Texas (27) have irradiated a silicone substrate in the presence of chloromethylstyrene monomer to produce a reactive graft polymer that can be quarternized with pyridine and reacted with sodium heparin to produce a thromboresistant heparinized product that has a higher blood compatibility than the untreated silicone. The same group has used essentially the same methods to create a heparin grafted polyethylene surface. 

Implanted polymeric materials can also adsorb and absorb from the body various chemicals that could also effect the properties of the polymer. Lipids (triglycerides, fatty acids, cholesterol, etc.) could act as plasticizers for some polymers and change their physical properties. Lipid absorption has been suggested to increase the degradation of silicone rubbers in heart valves (13). but this does not appear to be a factor in nonvascular Implants. Poly(dimethylsiloxane) shows very little tensile strength loss after 17 months of implantation (16). Adsorbed proteins, or other materials, can modify the interactions of the body with the polymer this effect has been observed with various plasma proteins and with heparin in connection with blood compatibility. 

These studies indicate that heparin directly affixed to a surface does not provide optimal, solution-like, anticoagulant behavior. The immobilization of heparin directly to the polymer surface resulted in alterations of the surface properties relative to control surfaces, which greatly influenced the plasma protein adsorption characteristics, a controlling factor in platelet adhesion and overall blood compatibility (12). 

This article describes polymer surfaces the blood compatibility of which is achieved neither by the use of heparin nor by the formation of neointima, but by the antithrombogenic surface by itself. Thus, a blood-compatible polymer here means an mti-thrombogenic biomaterial and not a water-soluble polymer which is completely soluble in blood and works as plasma expander or anticoagulant. 

HEPARIN-LIKE SUBSTANCES AND BLOOD-COMPATIBLE POLYMERS OBTAINED FROM CHITIN AND CHITOSAN... 

Chitosan-heparin coated polymers display excellent thrombo-resistance properties. The lifetime of the thromboresistance can be extended by covalently binding the heparin to chitosan with the aid of sodium cyanoborohydride. This surface treatment is useful for biomedical applications requiring blood compatibility for periods as long as four days. 

Recently, it has been realized that biomaterials that are surface-modified with zwitterionic compounds demonstrate excellent blood compatibility (Figure 11.6). Zwitterionic compounds have both cationic and anioific groups in the same molecules and form a betaine structure. There are three kinds of zwitterionic groups that have been investigated for use in obtaining a blood-compatible surface. Sulfobetaine compounds have a sulfonate anion and trimethyl ammonium cation in the same molecule, similar to heparin. The sulfobetaine group is introduced at the surface of PU and has been evaluated for blood compatibihty. Lin et al. reported that sulfobetaine polymers can effectively suppress platelet adhesion and protein adsorption [60-71]. Also, Lowe et al. 

The promising results in blood compatibility of heparinized-PUs demonstrated that these new polymers reduce thrombus formation compared to nonheparinized PUs. Furthermore, the residual bioactivity of heparin was found to be approximately 25%, slightly higher than those reported elsewhere [143]. 

Wettability, surface free energy, surface charge and compliance have been studied. Heparinized surfaces have exhibited considerable compatibility with blood. Typically, heparin is surface bound using cationic materials including tridodecyl methylammonium chloride, benzalkonium chloride, octadecylamine and quaternary ammonium polymers. Since polyelectrolyte complexes of heparin and chitosan have been prepared and exhibit either thrombogenic or non thrombogenic properties chitosan can be coated onto artificial polymeric supports and then reacted with heparin or with heparin-like substances... 

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