Toxicity, biocompatibility

Keywords carbon nanotubes, biomaterials, biocompatibility, toxicity, nanomaterials... 

As a basic in B LMs for the wastewater treatment the author presents two-phase partitioning bioreactors. He presents the main criteria which must be considered in the selection of the LM solvent biocompatibility (toxicity of the solvent to the microorganism), bioavailabihty (resistance of the solvent to biodegradation by the microorganism used), immiscibility in the aqueous phase, high solubility of pollutant in the solvent, favorable mass-transfer characteristics, etc. Biodegradation mechanisms and kinetics are discussed. Apphcations of bioreactors in wastewater treatment in laboratory, phot, and industrial scale are reviewed. Potential applications are considered also. 

Classical polymers have become increasingly used in medicine as components of biomedical devices, but with the development of new techniques for functionaUzalion, more sophisticated polymers have been developed, for instance as constituents of implants and drug delivery. In addition, chemical modification applied to polymers by y-irradiation to create new materials and applications is an effective alternative to reintegrate some polymers whose use has been limited due to problems associated with biocompatibility, toxicity, or bacterial colonization. All monomers and synthetic polymers presented in this chapter and their corresponding abbreviations are given in Table 10.1. 

Merritt, K. (1986) Biochemistry/hypersensitivity/clinical reactions, in Lang B, Morris, J. and Rassoog, J. (eds). Froc, International Workshop on Biocompatibility, Toxicity, and Hypersensitivity to Alloy Systems used in Dentistry. Ann Arbor, U. MI pp 195-223. Review article. Covers the literature through 1984. Good discussion of the problem in the discussion section of the symposium. 

In this brief review of the elastic and plastic protein-based polymers, the chemical and microbial syntheses of these pohmers are noted several of the more commonly used physical characterizations of these polymers are described the important biological characterizations of biocompatibility (toxicity), immunogenicity, and biodegradability are considered, and the applications of drug delivery and tissue reconstruction are discussed. 

International Workshop Biocompatibility, Toxicity and Hypersensitivity to Alloy Systems Used in Dentistry, B. R. Lang, H. F. Morris, and M. E. Razzoog, eds., 1986. Ann Arbor The University of Michigan School of Dentistry. 

Similarly, after a longer time of incubation, no significant changes in the cell proliferation rate was detected, as can be seen in the data for 72 h (Figure 13). In fact, this was expected due to the biocompatible nature of xylan. As a natural polyssacharide, this type of biomaterial is considered to be highly stable, non-toxic and hydrophilic (Liu et al., 2008). Accordingly, the alkaline extraction of xylan from corn has proved to be a safe approach for obtaining the polymer with no relevant toxicity (Unpublished data). 

Brem, H., Tamargo, R. J., Finn, M., and Chasin, M., Biocompatibility of a BCNU-loaded biodegradable polymer A toxicity study in primates, Abstracts of the 1988 Annual Meeting of the American Association of Neurological Surgeons, 1988,... 

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. 

A fundamental criticism of the resin-modified glass polyalkenoate cements is that, to some extent, they go against the philosophy of the glass polyalkenoate cement namely, that the freshly mixed material should contain no monomer. Monomers are toxic, and HEMA is no exception. This disadvantage of composite resins is avoided in the glass polyalkenoate cement as the polyacid is pre-polymerized during manufacture, but the same cannot be said of these new materials. For this reason they may lack the biocompatibility of conventional glass polyalkenoate cements. These materials also absorb excessive amounts of water because of the hydrophilic nature of polyHEMA (Nicholson, Anstice McLean, 1992). 

In a different way, metallic-core nanoparticles [346-349] (prepared cf. Section 3.10) equipped with biocompatible coats such as L-cysteine or dextrane may be exploited for highly efficient and cell-specific cancer cell targeting, i.e., for improving diagnosis and therapy of human cancer. In a recent proof-of-principle experiment an unexpectedly low toxicity of the L-cysteine-covered cobalt nanoparticles was demonstrated [433] For diagnostic purposes, it is expected to use the advantageous magnetic properties of the metallic-core nanoparticles to obtain a contrast medium for MRI with considerably increased sensitivity, capable to detect micro-metastases in the environment of healthy tissues [434 37]. 

In an attempt to identify new, biocompatible diphenols for the synthesis of polyiminocarbonates and polycarbonates, we considered derivatives of tyrosine dipeptide as potential monomers. Our experimental rationale was based on the assumption that a diphenol derived from natural amino acids may be less toxic than many of the industrial diphenols. After protection of the amino and carboxylic acid groups, we expected the dipeptide to be chemically equivalent to conventional diphenols. In preliminary studies (14) this hypothesis was confirmed by the successful preparation of poly(Z-Tyr-Tyr-Et iminocarbonate) from the protected tyrosine dipeptide Z-Tyr-Tyr-Et (Figure 3). Unfortunately, poly (Z-Tyr-Tyr-Et iminocarbonate) was an insoluble, nonprocessible material for which no practical applications could be identified. This result illustrated the difficulty of balancing the requirement for biocompatibility with the need to obtain a material with suitable "engineering" properties. 

As mentioned previously (and discussed in detail in Sec. IX), contact lens products have specific guidelines that focus on compatibility with the contact lens and biocompatibility with the cornea and conjunctiva [75], These solutions are viewed as new medical devices and require testing with the contact lenses with which they are to be used. Tests include a 21-day ocular study in rabbits and employ the appropriate types of contact lenses with which they are to be used and may include the other solutions that might be used with the lens. Additional tests to evaluate cytotoxicity potential, acute toxicity, sensitization potential (allergenicity), and risks specific to the preparation are also required [75-77], These tests are sufficient to meet requirements in the majority of countries, though testing requirements for Japan are currently much more extensive. 

Despite the evidence for the cytotoxicity of CNTs, there are an increasing number of published studies that support the potential development of CNT-based biomaterials for tissue regeneration (e.g., neuronal substrates [143] and orthopedic materials [154—156]), cancer treatment [157], and drug/vaccine delivery systems [158, 159]. Most of these applications will involve the implantation and/or administration of such materials into patients as for any therapeutic or diagnostic agent used, the toxic potential of the CNTs must be evaluated in relation to their potential benefits [160]. For this reason, detailed investigations of the interactions between CNTs/CNT-based implants and various cell types have been carried out [154, 155, 161]. A comprehensive description of such results, however, is beyond the scope of this chapter. Extensive reviews on the biocompatibility of implantable CNT composite materials [21, 143, 162] and of CNT drug-delivery systems [162] are available. 

Mutlu, G.M. et al. (2010) Biocompatible nanoscale dispersion of single-walled carbon nanotubes minimizes in vivo pulmonary toxicity. Nano Letters, 10 (5), 1664-1670. 

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