Biocompatibility

Biocompatibility as defined in Section 2.5 is a main prerequisite for the proper and safe use of medical devices consisting of a single material or material composition. In Section 4.5.1, it was demonstrated that the biophysical characterization of material surfaces only draws attention to some aspects of their response to biological systems. In order to assess biocompatibility for a device or a material, it is necessary to do a battery of tests depending on its intended use, with body contact ranging from transient skin contact to contact with blood to permanent implantation. Biocompatibihty is usually examined with three types of biological tests in vitro tests, animal experiments (in vivo tests), and clinical tests. 

In the following, we will focus on in vitro tests for cell compatibility and blood compatibility. In this context, we will also discuss ISO 10993-5 (tests for in vitro cytotoxicity) and ISO 10993-4 (selection of tests for interactions with blood). Finally, the risk of pyrogens in the biomaterial context, especially of bacterial toxins (endotoxins), will be briefly highhghted and selected methods for determining pyrogens/endotoxins (cf. also ISO 10993-11) will be presented. 

1 Evaluation and testing within a risk management process 

4 Selection of tests for medical devices that interact with blood 

8 Selection and qualification of reference materials for biological tests 

4 Biocompatibility. The analysis of polymer implants has been employed using FTIR spectroscopy to elucidate the long-term biocompatibility and quality control of biomedical materials. This method of surface analysis allows the determination of the specific molecular composition and structures most appropriate for long-term compatibility in humans. 

The biocompatibility of the glass polyalkenoate cement is good (Wilson McLean, 1988 Nicholson, Braybrook Wasson, 1991) and its capacity to release fluoride in a sustained fashion makes it cariostatic (Hicks, Flaitz Silverstone, 1986 Kidd, 1978). Its ability to provide an excellent seal (Section 5.9.9) is an important attribute because in recent years it has 

No problems arise when the glass-ionomer cement is used to restore abrasion/erosion lesions in primary teeth and as a lining material in shallow cavity preparations (Tobias et al., 1978, 1987). In deeper 

Post-operative sensitivity has occasionally been reported when the glass-ionomer cement has been used as a luting agent. This observation is more than anecdotal, but the reason for it is unknown. It is not connected with pulpal irritation but may be related to hydraulic pressures (Pameijer Stanley, 1988). The indication is that sensitivity is related to clinical technique and is exacerbated if certain slow-setting glass-ionomer cements are used, especially if they are mixed too thinly. 

The glass-ionomer cement was found to be non-toxic. There were no signs of inflammation or irritation with any of the glass polyalkenoate cement implants even after several months. By contrast a proportion of PMMA cement implants caused swelling and bone reactions. There were also signs of possible hyperaemia (blood congestion) and infarcts (areas deprived of blood supply) and dead tissue. 

the glass polyalkenoate cement has distinct biological advantages stemming from its dynamic surface chemistry, which is favourable to bone 

The safety and biocompatibility of the dmg delivery system and its components have been extensively tested according to Tripartite Biocompatibility Testing Guidelines (Center for Devices and Radiological Health, 1993). Specifically, these studies have shown that PLA is nontoxic and the hazard potential of NMP is insignificant. Additional preclinical tests to evaluate tissue irritation potential, implantation effects, and biodegradation have been completed for formulations prepared with PLA, PLG, and PLC polymers dissolved in NMP or DMSO. The pharmacokinetics of these formulations have also been tested for specific dmg delivery applications. 

The in vivo release kinetics were determined for [ IJ-PDGF-BB, [ IJ-IGF-I (Institute of Molecular Biology), and [ IJ-EGF (Dupont NEN) delivered from different formulations in albino rats. Two 50-mg implants were injected subcutaneously per animal in each of the six groups. Formulations were composed of 75 25 PLG with DMSO or NMP as the solvent containing 0.25 uCi of [ IJ-PDGF, 0.25//Ci of [ IJ-IGF-I, or 

This trial demonstrated that sustained in vivo delivery of protein can be achieved from formulations over a 7-day to 2-week period Also, the choice 

The most appropriate interpretation of biocompatibility for PE biomaterial applications is that the biocompatibility be defined in terms of the success of a device in fulfilling its intended function. For example, for a hip joint prosthesis, one must take into consideration the fatigue resistance of the device, its corrosion resistance, the distribution of the stresses transferred to the bone by the device, the solid angle of mobility provided, and the overall success of the device in restoring a patient to an ambulatory state. The performance of a hip joint prosthesis might also be assessed in terms of the tissue reaction to acetabular cup. The performance of individual materials is sometimes referred to as biocompatibility and sometimes as bioreaction . Hardness, shape, porosity, and specific implant site are very important [58]. 

Along with PP, PTFE, and polyesters, PE is used for sutures, soft tissue augmentation, vascular prosthesis, implants, and so on. 

Oriented PE foils, 10 [am thick with a molecular weight of 1.8 x 10 and a density of 945 kg/m, were irradiated with 10 and 63 keV Ar ions at fluences from 10 to 3 x 10 7m. The ion beam current density was below 50 nA/cm and the pressure in the implanter chamber was 10 -10 Pa. The irradiated specimens were exposed to solutions of 2 wt% alanine [CH3CH(NH2)COOH] in water, at room temperature, for 12 hours [59]. The adhesion of 3T3 rat fibroblasts on the modified PE was studied in vitro. The radiation damages to the polymer chain, such as free radicals and 

In earlier definitions of material and organism biocompatibility was equated with inertia. The so-called no-definition contains demands from the biomaterials like, for example, no changes in the surrounding tissue and no thrombogen-ic, allergenic, carcinogenic and toxic reactions [9]. Yet a concept of inertia is questionable as there is no material that does not interact with the body in the case of inertia of a biomaterial there is only a tolerance of the organism [10]. 

As a result of this insight Williams defined biocompatibility as the ability of a material to perform with an appropriate host response in a specific application . In Ratner s latest definition biocompatibility even means the body s acceptance of the material, i.e. the ability of an implant surface to interact with cells and liquids of the biological system and to cause exactly the reactions which the analogous body tissue would bring about [2]. This definition requires knowledge of the processes between the biomaterial s surface and the biological system. 

Numerous overlapping processes determine biocompatibility. Not only do the mechanical and chemical/physical characteristics of the material influence the tolerance but also the special place of application, the individual reaction of the complement system and the cellular immune system as well as the physical condition of the patient. 

The chemical and physical characteristics of the biomaterial s surface which are responsible for the biological reactions at the interface and which, in accordance with Ikada, determine the tolerance of the interface are certainly of great 

The surface characteristics concerned can considerably differ from the polymer s bulk characteristics. Due to the minimization of the surface energy and the chain mobility the non-polar groups move to the phase boimdary with air [14,15]. Additionally, the migration of low molecular components leads to differences between surface and bulk [ 16,17]. At the phase boundary between the biomaterial and the aqueous surrounding of the tissue a different situation arises than at the phase boundary between the biomaterial and air. Thus, the surface characteristics can considerably change after the biomaterial is taken from an air mediiun into an aqueous system. 

Because the PHSS electrochemical components are separated from sample solution by the H2S-permeable polymer membrane which is essentially inert with respect to 

Electrochemical Sensors, Biosensors and Their Biomedical Applications 

Various membranes are in common use for the filtration of blood during dialysis. In this investigation cellulosic (Cuprophan) and synthetic (acryl nitrile, SPAN) capillary membranes were tested. The fluorine gas treatment was performed as described before. Three parameters are chosen for the assessment 

Acknowledgments We thank Mr. B. Moller, Fluortec GmbH for the technical support in these investigations and Mr. Bowry and Dr. Budgell for their contributions to this article. 

Weber and D. Schilo, Paper presented at International Man-Made Fibers Congress in Dornbim, Austria, 25-27 September 1996. 

Rijpkema and W. E. Weening, Paper presented at Adhesion 93 York (UK) 6-8 September 1993. 

A successful catheter design comprises a biocompatible, microsized, low cost device with a certain optimum structural rigidity, which can be actuated under safe operating conditions. 

Granulocyte degree of activation was found to be inversely correlated to the degree of previous stimulation in the resting state (see Table 27). 

Granulocyte heat production rate in the presence of different polymers. Values are expressed as pW/cell, mean SD. The percentage increase after zymosan stimulation is given in parentheses. Source reference 115. 

it appears that the interaction between granulocytes and erythrocytes during granulocyte activation occurs at haeme group of the erythrocytes, leading to metabolic stimulation of the erythrocytes with heat production. 

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Much of tire science of biocompatibility can be reduced to tire principles of how to detennine tire interfacial energies between biopolymer and surface. The biopolymer is considered to be large enough to behave as bulk material witli a surface since (for example) a water cluster containing only 15 molecules and witli a diameter of 0.5 nm already behaves as a bulk liquid [132] it appears tliat most biological macromolecules can be considered to... 

Refreshingly original approach to a topic of central importance in biology and biocompatibility. 

Applications. Polymers with small alkyl substituents, particularly (13), are ideal candidates for elastomer formulation because of quite low temperature flexibiUty, hydrolytic and chemical stabiUty, and high temperature stabiUty. The abiUty to readily incorporate other substituents (ia addition to methyl), particularly vinyl groups, should provide for conventional cure sites. In light of the biocompatibiUty of polysdoxanes and P—O- and P—N-substituted polyphosphazenes, poly(alkyl/arylphosphazenes) are also likely to be biocompatible polymers. Therefore, biomedical appHcations can also be envisaged for (3). A third potential appHcation is ia the area of soHd-state batteries. The first steps toward ionic conductivity have been observed with polymers (13) and (15) using lithium and silver salts (78). 

To be biocompatible is to interact with all tissues and organs of the body in a nontoxic manner, not destroying the cellular constituents of the body fluids with which the material interfaces. In some appHcations, interaction of an implant with the body is both desirable and necessary, as, for example, when a fibrous capsule forms and prevents implant movement (2). 

Vitahium FHS ahoy is a cobalt—chromium—molybdenum ahoy having a high modulus of elasticity. This ahoy is also a preferred material. When combiaed with a properly designed stem, the properties of this ahoy provide protection for the cement mantle by decreasing proximal cement stress. This ahoy also exhibits high yields and tensile strength, is corrosion resistant, and biocompatible. Composites used ia orthopedics include carbon—carbon, carbon—epoxy, hydroxyapatite, ceramics, etc. 

M. Szycher, Biocompatible Polymers, Metals and Composites, Technomic Publishing Co., Inc., Lancaster, Pa., 1983. 

Requirements. Requirements for dental implant materials are the same as those for orthopedic uses. The first requirement is that the material used ia the implant must be biocompatible and not cause any adverse reaction ia the body. The material must be able to withstand the environment of the body, and not degrade and be unable to perform the iatended function. 

Hydroxyapaite, the mineral constituent of bone, is appHed to the surfaces of many dental implants for the purpose of increasing initial bone growth. Some iavestigators beHeve that an added benefit is that the hydroxyapatite shields the bone from the metal. However, titanium and its aHoy, Ti-6A1-4V, are biocompatible and have anchored successfuHy as dental implants without the hydroxyapatite coating. 

The realization of sensitive bioanalytical methods for measuring dmg and metaboUte concentrations in plasma and other biological fluids (see Automatic INSTRUMENTATION BlosENSORs) and the development of biocompatible polymers that can be tailor made with a wide range of predictable physical properties (see Prosthetic and biomedical devices) have revolutionized the development of pharmaceuticals (qv). Such bioanalytical techniques permit the characterization of pharmacokinetics, ie, the fate of a dmg in the plasma and body as a function of time. The pharmacokinetics of a dmg encompass absorption from the physiological site, distribution to the various compartments of the body, metaboHsm (if any), and excretion from the body (ADME). Clearance is the rate of removal of a dmg from the body and is the sum of all rates of clearance including metaboHsm, elimination, and excretion. 

J. Hermansson, A. Grahn and I. Hermansson, Direct injection of large volumes of plasma/semm of a new biocompatible exti action column for the determination of atenolol, propanolol and ibuprofen . Mechanisms for the improvement of clrromato-grapliic performance , J. Chromatogr. A 797 251-263 (1998). 

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