Tissue compatibility

In the beginning of the twentieth century, surgical techniques were developed for the fixation of bone fractures with a plate and screw combination. Sherman-type bone plates were fabricated from the best available alloy at the time, vanadium steel. By the 1920s the use of vanadium steel became questionable because of poor tissue compatibility. At that time however, no other alloy was available with high strength and good corrosion resistant properties. 

Fluoroplastic FPs have superior heat and chemical resistance, excellent electrical properties, but only moderate strength. Variations include PTFE, FEP, PFA, CTFE, ECTFE, ETFE, and PVDF. Used for bearings, valves, pumps handling concentrated corrosive chemicals, skillet linings, and as a film over textile webs for inflatables such as pneumatic sheds. Excellent human-tissue compatibility allows its use for medical implants. 

Materials used in body implants must meet several essential requirements such as tissue compatibility, enzymatic and hydrolytic stability. They must also be chemically resistant and have good mechanical properties. They must not be toxic, or the surrounding tissue will die. They must be resistant to the body fluids which usually have a high percentage of chloride ions. They must be biologically active if an interfacial bond is to be achieved. In some cases, they must be able to withstand continued high mechanical stresses for many years. 

Aryloxyphosphazene polymers, such as compound 1 or its mixed-substituent analogs, are also hydrophobic (contact angles in the region of 100°). These too show promise as inert biomaterials on the basis of preliminary in vivo tissue compatibility tests (13). 

The connection between hydrophobicity and tissue compatibility has been noted for classical organic polymers (19). A key feature of the polyphosphazene substitutive synthesis method is the ease with which the surface hydrophobicity or hydrophilicity can be fine-tuned by variations in the ratios of two or more different side groups. It can also be varied by chemical reactions carried out on the organo-phosphazene polymer molecules themselves or on the surfaces of the solid materials. 

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. 

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. 

Furthermore, our results on the characterization of the physico-mechanical properties of tyrosine-derived poly(iminocarbonates) provide preliminary evidence for the soundness of the underlying experimental rationale The incorporation of tyrosine into the backbone of poly(iminocarbonates) did indeed result in the formation of mechanically strong yet apparently tissue-compatible polymers. 

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. 

To provide a complete assessment of all these variables, the final evaluation of safety must be made in the in vivo model using the preparation under the proposed conditions for use, following tissue compatibility with many of the techniques already discussed. Confocal microscopy is a relatively new noninvasive technique that allows a detailed examination of the endothelium in the live animal, and thus may prove useful in following changes in this delicate tissue over time. As in ex vivo models, the... 

The tissue-compatible microprobes represent an advance over the typical aluminum wire electrodes used in studies of the cortex and other brain structures. Researchers accumulate much data using traditional electrodes, but there is a question of how much damage they cause to the nervous system. Microprobes, which are about as thin as a human hair, cause minimal damage and disruption of neurons when inserted into the brain. 

Using the above multimicroprocessed surfaces, which are manufactured by semiautomatic manipulations, early events of tissue-material interactions possibly predicting the tissue compatibility of implant materials have been... 

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. 

Biosensor-tissue compatibility is a significant obstacle in the development of viable, enduring implantable biosensors.1,2 The clinical literature and product development files in industry are littered with biosensor failures in many different sites and... 

Historically, in vivo biocompatibility has been qualitatively assessed by histological evaluation of explanted devices.6 The presence or absence of specific inflammatory and fibrotic cell types and the degree and duration of the incidence of these cells at the implant site can be correlated to arelative degree of success or failure in terms of tissue compatibility. However, this common implant, sacrifice, explant, and evaluate single-time-point-per-animal approach is quite limited in assessment of time-depen-dent phenomena (e.g., direct assay of molecular and cellular mediators) associated with the progression of the inflammatory response and the development of the FBR. 

The results by Hetrick et al.32 support the use of NO-release coatings for developing more tissue-compatible sensors. However, the impact of NO on the biocompatibility at a NO-releasing implant is a multifaceted question that is still not fully understood. Further study into the mechanisms by which NO decreases tissue encapsulation and chronic immune response while increasing angiogenesis will aid in optimization of the NO release properties (e.g., flux, concentration, and duration) of an implant coating for sensor applications. 

Poly(amino acids) are insoluble in common solvents, are difficult to fabricate due to high melting point, and absorb a significant amount of water when their acid content reaches over 50 mol%. To solve these problems, polyesters derived from amino acids and lactic acids [e.g., poly (lactic acid-co-lysine) PLAL] are developed. The PLAL system is further modified by reaction with lysine A-carboxyanhydride derivatives. Another modification of poly(amino acids) includes poly(iminocarbon-ates), which are derived from the polymerization of desaminotyrosyl tyrosine alkyl esters. These polymers are easily processable and can be used as support materials for cell growth due to a high tissue compatibility. Mechanical properties of tyrosine-derived poly(carbonates) are in between those of poly(orthoesters) and poly(lactic acid) or poly(gly-colic acid). The rate of degradation of poly(iminocarbonates) is similar to that of poly (lactic acid). 

Miller DR, Tizard IR, Keeton JT, ProchaskaJF (2003) System for polymerizing collagen and collagen composites in situ for a tissue compatible wound sealant, delivery vehicle, binding agent and/or chemically modifiable matrix. US Patent 6509031... 

As a result of these unique delivery routes, there is an increased potential for toxicity to tissues at or near the injection site. Assessment of local tolerance and tissue compatibility of the clinical formulation is usually evaluated as part of the animal model of efficacy and/or general toxicity study, thus obviating the need for separate local tolerance studies. There may be additional concerns in cases where analogous products are used including potential differences in formulation, stability, and so forth. 

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