Biomaterials blood-compatible

Keywords Biomaterials Blood compatibility Surface modification Polyurethane Hydrogen bond Endothelialization Protein adsorption... 

Xie X, Wang R, Li J, Luo L, Wen D, Zhong Y, et al. Fluorocarbon chain end-capped poly(carbonate urethane)s as biomaterials blood compatibility and chemical stability assessments. J Biomed Mater Res Part B Appl Biomater 2009 89B(1) 223-41. 

After almost half a century of use in the health field, PU remains one of the most popular biomaterials for medical applications. Their segmented block copolymeric character endows them with a wide range of versatility in tailoring their physical properties, biodegradation character, and blood compatibility. The physical properties of urethanes can be varied from soft thermoplastic elastomers to hard, brittle, and highly cross-linked thermoset material. 

As a preeminent biomaterial, silicones have been the most thoroughly studied polymer over the last half century. From lubrication for syringes to replacements for soft tissue, silicones have set the standard for excellent blood compatibility, low toxicity durability, and bioinertness. Many medical applications would not have been possible without this unique polymer. 

Williams RL, Wilson DJ, and Rhodes, NP. Stability of plasma-treated silicone rubber and its influence on the interfacial aspects of blood compatibility. Biomaterials, 2004, 25, 4659 673. 

We have recently turned our attention to cellulose-heparin, blood-compatible, nanoporous composite membranes for use in kidney dialysis (Murugesan et al., 2006a, b). Advanced kidney dialysis system contains heparin covalently bound to the surface of biomaterials to reduce clotting effects. Our new approach relies instead on composite materials. Unfortunately, no technology has been available to... 

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. 

Biocompatibility (See Table 1), which is a phenomenological concept, is the essential property of biomaterials. For instance, the inner surface of an implanted vascular graft or blood pump (artificial heart) must be blood-compatible, while its outer surface must be tissue-compatible. In other words, the material surfaces must not exert any adverse elfects upon blood or tissue, or upon other biological elements at the interfaces. 

Since the 1970s, a number of reports on biomaterials other than SPU have also been presented, providing us with evidence which shows the important role played by microdomain structures in realizing excellent biomedical properties. For instance, an A-B-A type block copolymer (HEMA-St—HEMA) (See Sect. 4.2) was shown to form microdomain structure and to exhibit excellent blood compatibility in both in vitro and in vivo tests. 

A variety of researches on bio-conjugate (or bio-mimicking) materials have been carried out during the last few years. As seen in Table 1, the aims and scope of many of the researchers are directly connected with clinical applications. For instance, endothelial-cell seeding (or sodding) on the luminal surface of vascular grafts is a widely-known technique [165-169] for improving the blood compatibility of polymetric materials. On the other hand, not a few of researchers are oriented to the exploitation of future possibilities of biomaterials. 

Implantation materials, which are in direct contact with blood, have to meet a particularly large range of requirements bio- and blood compatibility, mechanical strength against blood pressure, impermeability to the blood and its constituents, and sterilizability. In addition, the healing process that takes place on the inner and the outer surface of the artificial vessel is very different. The inner surface of the biomaterial should not stimulate adhesion of cellular blood components but should be covered with endothelial cells, whereas the outer surface of the prosthesis should be wrapped with connective tissue. 

It is of prime importance to establish the assessment method relevant to the expected clinical application of biomaterials when they are to be studied for improvement of the surface blood compatibility. A large hurdle preventing... 

Another promising area for polymer development, as alluded to by Tirrell [5], is microelectronics. Plasma polymerization can be used to produce a polymeric coating directly on a substrate changing the composition of the gas feed allows a wide variation in the chemical composition of the surface produced [32], The same technique can also be used to modify surfaces for other applications, such as to improve the blood compatibility of biomaterials. The essential processes occurring in a plasma—mass transfer and reaction kinetics—have long been the domain of chemical engineers. 

New experimental results on specific polymer material problems are presented in the last nine chapters. Several cases involve the study of polymers from commercial sources. The topics include (1) surface chemistry as induced by (a) outdoor weathering, (b) chemical reactions, and (c) plasma exposure (2) chemical bond formation at the polymer -metal interface and (3)biomaterials characterization and relationship to blood compatibility. 

Bernacca GM, Gnlbranson MJ, Wilkinson R, Wheatly DJ. In vitro blood compatibility of snrface-modified pol)mrethanes. Biomaterials 1998 19 1151-1165. 

The in vitro study of the hemocompatibility of biomaterials requires the consideration of many parameters, static or dynamic contact, flow rate, wall shear rate, form of biomaterial to be tested, pathway to consider (platelet adhesion, platelet activation, complement activation, contact phase activation etc..) and duration of contact(39). It has previously been demonstrated t t hemodynamic circumstances play a significant role in determining localization, growth and fiagmentation of thrombi and platelet adhesion in vivo, and that flow rate controls platelet transport to a surface and their adhesion (40). This evidence is siqtpoited by observed differences in platelet activity predominance in venous and arterial flow (41). Qearly, defining the blood compatibility of a material is a conqrromise between a number of these factors. 

Rhodes. N.P, Kumary. T.V and Williams. D.F, Influence of wall shear rate on parameters of blood compatibility ofintravascular catheters. Biomaterials, 17,1995-2002(1996). 

Zhang H, Annich GM, Miskulin J, Oster-holzer K, Merz SI, et al. 2002. Nitric oxide releasing silicone rubbers with improved blood compatibility preparation, characterization, and in vivo evaluation. Biomaterials 23 1485-94... 

Early attempts to functionalize biomaterial surfaces with biological molecules were focused on improving blood compatibility of cardiovascular devices, such as the artificial heart and synthetic blood vessels, by immobilizing heparin or albumin on polyurethane or Dacron . To enhance cell adhesion to biomaterial surfaces, entire extracellular matrix (ECM) proteins, such as fibronectin and laminin, have been used directly as coatings. However, because of the nonspecific manner of whole protein adsorption, most of the cell binding capability is often lost. Using a molecular templating technique, it may be possible to select which protein(s) to absorb on biomaterial surfaces. ... 

Lee KY, Ha WS, Park WH (1995) Blood compatibility and biodegradability of partially N-acylated chitosan derivatives. Biomaterials 16(16) 1211—1216... 

The formation of thrombus is one of the most frequent complications of introducing an artificial organ into a living body. Although many approaches to improving the blood compatibility to biomaterial have been tried, the results, so far, are not completely satisfactory. 

In recent years the surface characterization of biomaterials has been forcefully emphasized (1—3). Unfortunately, a clear understanding of how surface characterization can be of value to biomaterials research, development, and production has, in many cases, not been realized. This chapter addresses the subject of surface characterization of biomaterials by considering three aspects of the problem first how surfaces differ from the bulk of materials second, how the important parameters of surfaces can be measured and what new techniques might be developed and finally, how surface characterization can help in understanding and predicting the biocompatibility (and in particular, the blood compatibility) of synthetic materials. 

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). 

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. 

Biological and physiological criteria are related to the specific applications of biomaterials in the body. Fundamentals of blood compatibility are analyzed expertly in the overview by Hoffman (16) included in this volume. Blood-compatible biomaterials should not cause cancer or teratological effects, and they should not be toxic. Toxicity may be related to functional groups of the polymer surface structure, or to migration of residual monomers under quiescent or flow conditions. 

Surface characterization is very important in the development of blood-compatible biomaterials, since the surface characteristics of the polymer have been linked to polymer-tissue and polymer-blood interactions. Further information on surface characterization of biomaterials can be found elsewhere (20, 21). 

L. Montanaro, C. R. Arciola, E. Cenni, Cytotoxicity, blood compatibility and antimicrobial activity of two cyanoacrylate glues for surgical use, Biomaterials., 22 [1] 59-66 (2001). 

Hirano, S., Zhang, M., Nakagawa, M. And Miyata, T., Wet spun chitosan-collagen fibers, their chemical N-modifications, and blood compatibility. Biomaterials, 21, 997, 2000. 

The synthesis of some polymeric biomaterials with potential blood compatibility. 

Singhal, J.P. and Raya, A.R. 2002. Synthesis of blood compatible polyamide blocks copolymers. Biomaterials. 23 1139-1145. 

Hydrophilic coatings have also been popular because of their low interfacial tension in biological environments [Hoffman, 1981]. Hydrogels as well as various combinations of hydrophilic and hydrophobic monomers have been studied on the premise that there will be an optimum polar-dispersion force ratio which could be matched on the surfaces of the most passivating proteins. The passive surface may induce less clot formation. Polyethylene oxide coated surfaces have been found to resist protein adsorption and cell adhesion and have therefore been proposed as potential blood compatible coatings [Lee et al., 1990a]. General physical and chemical methods to modify the surfaces of polymeric biomaterials are listed in Table 40.7 [Ratner et al., 1996]. 

Kambic,H.E. andNose,Y. 1991. Biomaterials for blood pumps. 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. 141-151. 

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