Blood compatibility: medical devices

Yui et al. [41] reported a series of polyrotaxanes, in which sulfopropyl-modified CDs are threaded onto PEG-PPG-PEG triblock copolymers and capped with bulky end group. These polyrotaxanes are suggested to be a promising candidate when fabricating blood-compatible medical devices by blending with or coating on clinically used polymers. 

One method of producing a biocompatible surface is to prevent adsorption of proteins. If proteins adsorb or otherwise become attached to a polymer surface, the attachment can interfere with the normal cell functions. The interaction of a polymer surface and blood is equally problematic. A component in blood known as the Hageman factor detects hydrophobic surfaces. The signaling involves attachment of the factor to the surface and by the process of attachment, the factor becomes activated. This is the first step in the inflammation response that can lead to rejection. Thus, the development of a hydrophilic surface with minimal protein adsorption may become a strategy for the development of compatible medical devices. 

DNA has been used to modify the PSf membrane by blending and immobilizing DNA onto its surface [123,124]. PSf is one of the most important polymeric materials and is widely used in artificial and medical devices. However, when used as a hemodialysis hollow fiber, the blood compatibility of the PSf membrane is not adequate. The hydrophilicity of the DNA-modified surface increased, but the amount of adsorbed protein did not decrease significantly, which indicates that the DNA-modified membrane might have a better blood compatibility. 

In ASTM F78-98 Standard Practice for Selecting Generic Biological Tests Methods for Materials and Devices , the selection test methods to evaluate medical devices is described. Regarding hemocompatibility tests for blood compatibility, hemolysis, and complement activation are described. Under blood compatibility, hemolysis and thrombosis are described as the most obvious examples of incompatibility with blood. It is suggested that thrombogenicity (formation of thromboemboli or platelet activation) be tested under dynamic conditions that simulate in the use procedures for the device. Complement activation is of concern in some cases and should be tested in vitro by assessing the status of various complement components. However, complement activation will probably not represent the only portion of the inflammatory response stimulated by medical devices. 

Extracorporeal medical machines (e.g., artificial kidney, pump-oxygenator) perfused with blood have been an effective part of the therapeutic armamentarium for many years. These devices all rely on systemic heparinization to provide blood compatibility. Despite continuous efforts to improve anticoagulation techniques, many patients still develop coagulation abnormalities with the use of these devices (1-3). Even longer perfusion times may occur with machines such as the membrane oxygenator. In such cases, the drawbacks of systemic heparinization are multiplied (4). A number of ap-... 

Adhesives used in medical devices that are implanted or in contact with the body must be tested and shown to be non-toxic, biologically inert, and compatible with blood and body fluids. Compatibility with blood and other body fluids is especially critical. Surfaces in contact with blood must not serve as sites for coagulation and clotting of blood. Generally, qualification testing is performed to ISO-10993 or to U.S. Pharmacopoeia (USP) Class VI. The two standards specify slightly different tests. The USP Class VI standard specifies acute systemic (over the tissue), intracutaneous (under the skin), and muscle implantation tests. The lSO-10993 standard is a set of 12 documents that is more universal and more extensive than the USP standard. It specifies ... 

Blood-compatible metals and alloys are essential for certain types of medical devices. The experiments, described in the previous section, demon-... 

Here, we will shortly highlight a commercially available heparin-based biofunctional surface coating that is used to enhance blood compatibility of medical devices. The second example will illustrate that biomolecular function can be translated into fully synthetic systems and altered beyond the naturally... 

Several issues are important in the selection of tests for hemocompatibility of medical devices or biomaterials. In vivo testing in animals may be convenient however, species differences in blood reactivity must be considered and these may limit the predictability of any given test in the human clinical situation. While species differences may complicate hemocompatibility evaluation, the utilization of animals in short- and long-term testing is considered to be appropriate for evaluating thrombosis and tissue interaction. European community law prohibits the use of nonhuman primates for blood compatibility and medical device testing, even though blood values and reactivity between humans and nonhuman primates are very similar. Hemocompatibility evaluation in animals is... 

P. N. Sawyer and S. Srinivasan, New Approaches in the Selection of Materials Compatible with Blood, Annual Reports on Contract PH-68-75 for 1968-1970 (submitted to Medical Devices and Application Program), National Heart Institute, National Institute of Health. 

Silicone elastomers have a long history of use in the medical field. They have been applied to cannulas, catheters, drainage tubes, balloon catheters, finger and toe joints, pacemaker lead wire insulation, components of artificial heart valves, breast implants, intraocular lenses, contraceptive devices, burn dressings and a variety of associated medical devices. A silicone reference material has been made available by the National Institutes of Health to equate the blood compatibility of different surfaces for vascular applications. This material is available as a silica-free sheet. Contact the Artificial Heart Program, NHBLI, NIH, Bethesda, Md. for further information. 

The data presented in this lecture permit to conclude that the chemistry of chitin and chitosan offers the opportunity to exploit an abundant natural resource for the preparation of such sophisticated medical aids as heparin-like substances and blood-compatible devices. 

Special efforts are being carried out to improve the blood compatibility of biomaterials which are already in use for medical devices. In order to hydrophilize the surface of the commonly used cycloaliphatic poly(ether urethane), Tecoflex and argon (Ar) and sulfur dioxide (SO2) plasma treatment has been appHed. The surfaces of treated Tecoflex foils were characterized as a function of plasma treatment time (10,60 and 300 s). XPS shows SO groups in the Tecoflex smface after SO2 plasma treatment. The results of the dynamic contact angle determination of Ar or SO2 plasma treated Tecoflex surfaces are presented in Fig. 13. 

Grafting of a poly(MPC) chain on a PU surface by a surface-initiated living radical polymerization technique was reported and the surface platelet adhesion resistance postgrafting was confirmed [97]. Because the procedure for obtaining a blood-compatible PU surface is very complicated, it is not applicable for preparing bloodcontacting medical devices. 

Important application of TPEEs is in medical devices owing to their compatibility with hurrian blood and tissue, as well as inherent resistance to radiation used for sterilization. For example, biodegradable TPEEs based on PBT and PEO under trade name Poly Active could be used in tissue engineering scaffold, bone replacement, wound dressing, artificial skin and as drug release carrier, due to mechanical properties similar to native cartilage [102]. 

When artificial materials contact living organisms, serious responses such as thrombus formation, unfavorable immunoresponse, capsulation, etc., are observed. This is a very important response for living but induces many problems in the treatment of patients using the artificial medical devices. Therefore, biocompatibility, particularly blood compatibility, is the most important property required for biomedical materials. 

MPC can be dissolved in alcohol and easily polymerized with other vinyl monomers by conventional radical copolymerization using a radical initiator. Moreover, the MPC copolymers obtained are soluble in alcohol but insoluble in water, depending on the MPC composition. This is one of the good characteristics required for biomedical polymers for surface modification of medical devices. Among these copolymers, poly(MPC-c0-n-butyl methacrylate (BMA))s exhibit excellent blood compatibility as shown by reduction of platelet adhesion and aggregation and suppression of protein adsorption (7-10). 

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