Implantation test Implant biocompatibility

Many semiconductor materials in various forms have been tested for biocompatibility and also compared with traditionally implanted materials such as titanium. We have reviewed this work previously [14]. 

Biocompatibility is expected for any implant material. However, a certain level of recipient site reactions can be expected. This is typically observed as a local inflammatory response that resolves over a reasonable period of time coincident with either implant degradation or local wound healing. Early implant biocompatibility assessments relied on a judgement regarding the extent of inflammation relative to the benefits provided by the implant. Considerations included the clinical need, duration of the implant and level of inflammation. Currently, a series of standardized tests are employed (ISO 10993) wherein the biocompatibility of a new device can be compared to positive and negative controls such that an acceptable level of biocompatibility can be appreciated. 

Toxicity. Toxicity is foimd to be a minor problem and many vesicle systems have passed standard toxicity tests. The hydrophilic PEO block effectively screens the influence of the hydrophobic cores on timescales of the measured circulation half-life ri/2. With respect to long-time applications, PEE is structurally similar to low-density polyethylene, which is commonly used in implants and is generally considered bioinert (214). PB is also understood to be bioinert as it is commonly chosen for the hydrophobic block in triblock copoljuners (215,216). In a more prolonged model test of biocompatibility, nondiflferentiated C2C12 cells were incubated with poljunersomes. The cells remained well spread with no evidence of cytotoxicity. As shown by the Trypan blue exclusion assay, polymersomes had no significant effect on cell survival. 

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. 

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 performance and response of the host toward an implanted material is indicated in terms of biocompatibility. Major initial evaluation tests used to assess the biocompatibility of an implant are listed in Table 4.1. These tests include ... 

Table 4.1 Examples of major initial tests for assessing the biocompatibility of an implant...

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