Biocompatibility implantation testing

Various standards and procedures exist for the evaluation of the biological and immunotoxicity response of an implant [81] from the point of view of biocompatibility. Acute toxicity screening and in vivo implantation tests are fundamental in this respect. Cytotoxicity testing to detect the biological activity of the material on a mammalian cell monolayer is often the first step in assessing biocompatibility of a device. An international standard on the biological evaluation... 

The problem arises when we start employing biocompatibility for describing material properties in contexts other than the regulatory. Statements like the material is known to be biocompatible, biocompatibility was assessed by ceU culture, or biocompatibility was tested by subcutaneous implantation might sound familiar, but what value do they have to predict clinical outcome ... 

Conventionally, animal biocompatibility test is done by the bio-implantation testing [5], which can be defined as test methods for assessment of local effects of implant material on living tissue, at macroscopic and microscopic level. The experiment involves animals such as dogs or rabbits, each of which received certain number of implanted fragments. 

Other sites for implantation include the subcutaneous space, bone, brain, and ocular, dental, or mucosal sites. If one of these locations is more appropriate for the finished test article, then that would be the better choice. Otherwise a muscle implantation test is generally used for biocompatibility evaluations. 

Implants in the rabbit corneas exhibited no observable inflammatory characteristics over a period of 6 weeks. Compared to other previously tested polymers, the inertness of these polyanhydrides rivals that of the biocompatible poly(hydroxyethyl methacrylate) and ethylene-vinyl acetate copolymer. Histological examination of the removed corneas also revealed the absence of inflammatory cells (21)... 

Although the initially reported tissue compatibility tests for subcutaneous implants of poly(BPA-iminocarbonate) were encouraging (41,42), it is doubtful whether this polymer will pass more stringent biocompatibility tests. In correspondence with the properties of most synthetic phenols, BPA is a known irritant and most recent results indicate that BPA is cytotoxic toward chick embryo fibroblasts in vitro (43). Thus, initial results indicate that poly(BPA-iminocarbonate) is a polymer with highly promising material properties, whose ultimate applicability as a biomaterial is questionable due to the possible toxicity of its monomeric building blocks. 

After 7 days, the acute inflammatory response at the implantation site was evaluated. Bisphenol A resulted in a moderate level of irritation at the implantation site and was clearly the least biocompatible test substance. Tyrosine derivatives containing the benzyloxycar-bonyl group caused a slight inflammatory response, while all other tyrosine derivatives produced no abnormal tissue response at all. These observations indicate that tyrosine dipeptide derivatives, even if fully protected, are more biocompatible than BPA, a synthetic diphenol. ... 

In order to test the tissue compatibility of tyrosine-derived poly-(iminocarbonates), solvent cast films of poIy(CTTH) were subcutaneously implanted into the back of outbread mice. In this study, conventional poly(L-tyrosine) served as a control (42). With only small variations, the experimental protocol described for the biocompatibility testing of poly(N-palmitoylhydroxyproline ester) (Sec. III. 

Initial tests in the rat revealed a high degree of tissue compatibility of Dat-Tyr-Hex derived polymers. More detailed tests are now in progress. In addition, tyrosine derived polymers are currently being evaluated in the formulation of an intracranial controlled release device for the release of dopamine, in the design of an intraarterial stent (to prevent the restenosis of coronary arteries after balloon angioplasty), and in the development of orthopedic implants. The use of tyrosine derived polymers in these applications will provide additional data on the biocompatibility of these polymers. 

Most of the bio-nanocomposites tested as implants for bone regeneration are based on the assembly of HAP nanoparticles with collagen, trying to reproduce the composition, biocompatibility and suitable mechanical properties of natural bone. 

Step 3 Biocompatibility. The biocompatibility of selected polymers, identified in Steps 1 and 2, were evaluated by implanting flat membranes into a C57/B16 mouse (Jackson Labs, Bar Harbor, ME). The membranes and capsules were implanted at various internal sites or in the back tissue under the skin. The results of these tests are not reported herein and will be discussed in a subsequent publication. They do, however, have important implications as to the ultimate selection of a polymeric system. 

The term biocompatibility needs some explanation and has to be defined for each application separately. The historical definition was based on unimpaired cell growth in the presence of the test article [12]. More recent definitions of the biocompatibility of implantable devices ask for the ability of the device to perform its intended function, without eliciting any undesirable local or systemic effects in the host. 

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