Blood-compatible materials

C. P. Sharma and M. Szycher, Blood Compatible Materials and Devices, Technomic Publishing Co., Inc., Lancaster, Pa., 1991. 

Chitosan is the main structural component of crab and shrimp shells. Chitosan contains both reactive amino and hydroxyl groups, which can be used to chemically alter its properties under mild reaction conditions. Al-acyl chitosans were already reported as blood-compatible materials. UV irradiation grafting technique was utilized to introduce obutyrylchitosan (OBCS) onto the grafted SR film in the presence of the photosensitive heterobifunctional cross-linking agent. The platelet adhesion test revealed that films grafted on OBCS show excellent antiplatelet adhesion. 

Mirzadeh H, Khorasani MT, and Sammez P. Laser surface modification of polymers A novel technique for the preparation of blood compatible materials-II In vitro assay. Iranian Polym, 1998, 7, 5. 

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. 

Chitin and chitosan derivatives have also been studied as blood compatible materials both in vivo and in vitro [520], Anticoagulant activity was greatest with O sulfated N acetyl chitosan, followed by N,0 sulfated chitosan, heparin, and finally sulfated N acetyl chitosan. The lipolytic activity was greatest for N,0 sulfated chitosan followed by heparin. The generally poor performance of chitosan was attributed to polyelectrolyte complexes with free amino groups present on the membrane surface. The O sulfate or acidic group at the 6 position in the hexosamine moiety was identified as the main active site for anticoagulant activity. 

The long quest for blood-compatible materials to some extent overshadows the vast number of other applications of polymers in medicine. Development and testing of biocompatible materials have in fact been pursued by a significant number of chemical engineers in collaboration with physicians, with incremental but no revolutionary results to date. Progress is certainly evident, however the Jarvik-7 artificial heart is largely built from polymers [34]. Much attention has been focused on new classes of materials, such... 

In addition to microelectronic and optical applications, polymers deposited using thermal and plasma assisted CVD are increasingly being used in several biomedical applications as well. For instance, drug particles microencapsulated with parylenes provide effective control release activity. Plasma polymerized tetrafiuoroethylene, parylenes and ethylene/nitrogen mixtures can be used as blood compatible materials. An excellent review of plasma polymers used in biomedical applications can be found in reference 131. 

X Biomaterials has reiterated the need for the development of blood-compatible materials since progress in this field is a condition for advances in the application of cardiocirculatory-assist devices and other procedures which require continuous or intermittent handling of blood (I). For example, the task force has specifically identified the development of small-diameter blood vessel prostheses and chronic blood access catheters as priority applications of blood-compatible materials. Both of these devices are used in low-flow situations where red thrombus formation (i.e., intrinsic clotting system activation) predominates (2). 

Cuypers, P.A., Hemker, H.C., Hermens, W.Th. In Blood compatible materials and their testing Davids, S., Bantjes, A. Ed. Publishers Martinus Nijhoff, Dordrecht, 1986, 45-55. 

Blood compatible materials are essential for artificial organs which are used in contact with blood. The immunological aspects of blood compatibility are stressed. Complement activation induced by material-blood interaction is most likely related to transient leukopenia during extracorporeal circulation such as hemodialysis. Although transient, it may be harmful, especially if it occurs frequently. Some complications associated with hemodialysis may be caused due to the repeated complement activation and leukostasis in the lung. Cellulosic membranes induce the phenomenon more severely than synthetic membranes. Reused cellulosic membranes sterilized with aldehyde after the first use show less complement activation and leukopenia. Aldehyde treated biological substances may play a important role in enhancing blood compatibility. 

Dellsperger, K.C. and Chandran, K.B. 1991. Prosthetic heart valves. In Blood Compatible Materials and Devices. Perspectives towards the 21st Century. Sharma, C.P. and Szycher, M., Eds., Technomic Publishing Company Inc., Lancaster, PA, pp. 153-165. 

Urokinase has been widely used for the clinical treatment of thrombogenetic disease and hemorrhoidal disease. Artificial organ materials, on which urokinase was immobilized for its fibrinolytic activity, have been developed for blood-compatible materials. For example, Liu et al. immobilized urokinase by encapsulation in poly(2-hydroxyethyl methacrylate) and Kbnig et al. introduced urokinase on the surface of the polytetrafluoroethylene using plasma modification technique by covalent bond. Another example of immobilized urokinase application was reported by Kato and coworkers, who had used mokinase immobilized in a Teflon catheter for treatment of thrombosis. 

Blood compatible materials are essential to circulatory support devices. Numerous materials have been considered for use in prosthetic devices. 

PEG surface modification was used to increase biocompatibility (Saw-hney et al, 1993) or to obtain blood-compatible materials (Han et al, 1993). PEG grafting on various substrates was shown to reduce the adsorption of various proteins (Prime and Whitesides, 1993 Llanos and Sefton, 1993) and fibrinogen (Han et al, 1993) to the surface and to reduce complement activation (Kishida et a/., 1992). 

Courtney JM, Lamba NMK, Sundaram S, Forbes CD (1994) Biomaterials 15 737 Salzman EW (1986) Blood material interaction In Interaction of tbe blood with natural and artificial surfaces, Dekker Inc, New York, p 39 Meyer JG (1986) Blutgerinnung und Fibrinolyse, Deutsche Arzte Verlag, Koln Baszkin A (1986) The effect of polymer surface composition and structure on adsorption of plasma proteins. In Dawids S, Bantjes A (eds) Blood compatible materials and their testing. Martinus Nijhoff Publishers, Dortrecht, p 39... 

Sharma CP, Szycher M (1991) Blood compatible materials and devices. Tecbnomic, Lancaster... 

Sharma CP. Blood-compatible materials a perspective. J Biomater Appl 2001 15(4) 359-81. 

Initially, it was postulated that hydrophilic polymers or polymer surfaces would be suitable blood-compatible materials, i.e., they should not induce the coagulation process. A variant of this thinking was the use of a gradient modulus material, tough but flexible on the outside, but becoming soft and highly swollen on the inside. Other people examined the electrical properties of the surface of polymers, such as polarizability, net surface electrical charge, or overall surface potential. 

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