Blood Compatibility Investigations

The contact of biomaterial surfaces with the biological system blood provokes, with different intensity, activation of the intrinsic coagulation pathway at the blood/biomaterial interface. Clinically important and reproducible investigation methods are carried out to evaluate blood compatibility. The following coagulation parameters, obtained after the contact of the foreign surface with native, non-anticoagulant human whole blood in a modified Bowry blood chamber [93] and compared to the initial citrate plasma values, are evaluated  

Both aPTT and PTT measure the coagulation factors of the intrinsic system during a defined activation time until clotting occurs. The difference between both tests resides in the fact that in aPTT kaolin is added to provoke an additional contact activation of factor XII. 

The most important parameters to characterize blood compatibility are thrombocyte adhesion and thrombocyte number. In contact with a foreign body platelets tend to adhere similarly as in the case of an external injury. For this reason materials which show strong platelet adhesion as a consequence of their contact with a foreign body or provoke a decrease in the munber of blood platelets are considered as thrombogenic [94]. The decrease in the quantity of blood leucocytes after contact with a foreign body is a sign of a cellular immunore-sponse of the biological system toward the biomaterial. 

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Polyelectrolytes have been widely investigated as components of biocompatible materials. Biomaterials come into contact with blood when used as components in invasive instruments, implant devices, extracorporeal devices in contact with blood flow, implanted parts of hard structural elements, implanted parts of organs, implanted soft tissue substitutes and drug delivery devices. Approaches to the development of blood compatible materials include surface modification to give blood compatibility, polyelectrolyte-based systems which adsorb and/or release heparin as well as polyelectrolytes which mimic the biological activity of heparin. 

Significant research has been directed toward the use of polyelectrolyte complexes as blood compatible materials. Several investigators found that water-insoluble polyelectrolyte complexes can suppress blood coagulation [487-490]. Davison and coworkers reviewed and studied the biological properties of water-soluble polyelectrolyte complexes [491] between quatemized poly(vinyl imidazole) or polyvinyl pyridine) and excess sulfonated dextran or poly(methacrylic acid). By forming complexes with a stoichiometric excess of anionic charge, a more compact conformation with anionic character was obtained. 

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. 

Three types of plasticised PVC sheet were investigated for blood compatibility using fibrinogen adsorption. Plasticisers used were diethylhexyl phthalate, triethylhexyl trimellitate and butyltrihexyl citrate. FTIR was used to monitor surface chemistry. 14 refs. 

Besides the diversity in composition of metals and alloys employed with in vivo testing for blood compatibility, studies investigating the interaction between metals and proteins, either by immersion-induced effects or effects from polarization, mainly have been confined to platinum (7, 10,12—15) and... 

Biomedical materials include metals, ceramics, natural polymers (biopolymers), and synthetic polymers of simple or complex chemical and/or physical structure. This volume addresses, to a large measure, fundamental research on phenomena related to the use of synthetic polymers as blood-compatible biomaterials. Relevant research stems from major efforts to investigate clotting phenomena related to the response of blood in contact with polymeric surfaces, and to develop systems with nonthrombogenic behavior in short- and long-term applications. These systems can be used as implants or replacements, and they include artificial hearts, lung oxygenators, hemodialysis systems, artificial blood vessels, artificial pancreas, catheters, etc. 

Material characteristics can be tailored to suit a desired application. For example, blood compatibility of various Blon elastomers was Investigated In the atria of goats by Dr. Williams group (15) In Toronto. Initial results Indicated that elastomers containing high levels of carbon black showed greater thrombo resistance than those with lower amounts or no carbon black. 

In this study, PU surface was chemically grafted with hydrophilic PEO and then sulfonated to investigate the relationship between surface characteristics and blood compatibility, and in particular, to study a possible synergistic effect of PEO and sulfonate groups. 

Due to the important role of adhesion of plasma proteins in determining blood compatibility and the key role of fibrinogen in these processes, investigators developed an in vitro assay to test fibrinogen adsorption to polymer surfaces. Casting of 46 different polymers (44 polyarylates, poly(lactic... 

The primary approach widely adopted for investigating the blood compatibility of polymers is to vary the molecular properties of the polymer surface while keeping other parameters constant. This means that the surface structure of the polymer is regarded as a dominant factor of blood compatibility. 

One group of investigators considers the surface free energy as very important. Bair has concluded that the polymer surface will be blood-compatible if it has a critical surface tension ranging between 20 and 25 dyne cm , while Andrade formerly postulated that the smaller the interfacial free energy between blood and the polymer surface, the better the blood compatibility Recently, he and his ooworkers... 

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. 

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