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Record 3781 to 3800

Structure of water incorporated in sulfobetaine polymer films as studied by ATR-FTIR
Kitano, H., T. Mori, et al. (2005), Macromol Biosci 5(4): 314-21.
Abstract: The structure and hydrogen bonding of water in the vicinity of a thin film of a sulfobetaine copolymer (poly[(N,N-dimethyl-N-(3-sulfopropyl)-3'-methacrylamidopropanaminium inner salt)-ran-(butyl methacrylate)], poly(SPB-r-BMA)), were analyzed with band shapes of O-H stretching of attenuated total reflection infrared (ATR-IR) spectra. The copolymer could be cast as a thin film, of approximate thickness 10 microm, on a ZnSe crystal for the ATR-IR spectroscopy. At an early stage of sorption of water into the polymer film, the O-H stretching band of the IR spectra for the water incorporated in the film was similar to that for free water. This is consistent with the tendency for another zwitterionic polymeric material, poly[(2-methacryloyloxyethylphosphorylcholine)-ran-(butyl methacrylate)] (poly(MPC-r-BMA). It is, however, contradictory to the drastic change in the O-H stretching band for water incorporated into films of polymers such as poly(2-hydroxyethyl methacrylate), poly(methyl methacrylate) and poly(butyl methacrylate). These results suggest that polymers with a zwitterionic structure do not significantly disturb the hydrogen bonding between water molecules incorporated in the thin films. The investigation into the blood-compatibility of both the poly(SPB-r-BMA) and the poly(MPC-r-BMA) films indicate a definite correlation between the blood-compatibility of the polymers and the lack of effect of the polymeric materials on the structure of the incorporated water.

Structure, microstructure, and magnetism in ferrimagnetic bioceramics
Leventouri, T., A. C. Kis, et al. (2005), Biomaterials 26(24): 4924-31.
Abstract: The structural and magnetic properties of ferrimagnetic bioglass ceramics in the system [0.45(CaO,P2O5)(0.52 - x)SiO2 xFe2O3 0.03Na2O], x = 0.05, 0.10, 0.15, 0.20 and heat-treated at the temperature range 600-1100 degrees C are assessed. The structure and microstructure of the samples are characterized with X-ray diffraction, scanning electron microscopy, and energy dispersive X-ray spectroscopy. Calcium phosphate and magnetite develop as the two major crystalline phases. For x = 0.10 and 0.20, calcium phosphate undergoes a gradual transition from the monoclinic to the rhombohedral crystal system (SG P21/a-->R3c) as the heat-treatment temperature increases from 800 to 1100 degrees C. Dendrites of iron oxide with crystallites of various sizes are observed to form within a glassy matrix enriched in calcium, phosphorous, and silicon. Saturation magnetization, remanence, and coercivity are found from dc magnetic measurements. They vary with the specific processing parameters of the composites, and these are correlated with the observed structure and microstructure of the materials.

Structure-activity relationship of alginate oligosaccharides in the induction of cytokine production from RAW264.7 cells
Iwamoto, M., M. Kurachi, et al. (2005), FEBS Lett 579(20): 4423-9.
Abstract: Guluronate and mannuronate oligomers with various degree of polymerization were prepared from polyguluronate (PG) and polymannuronate (PM) with an alginate lyase from a Pseudoalteromonas sp., and their activities to induce cytokine secretion from mouse macrophage cell line RAW264.7 cells were examined. Enzymatically depolymerized unsaturated alginate oligomers induced tumor necrosis factor (TNF)-alpha secretion from RAW264.7 cells in a structure-depending manner, while the activities of saturated alginate oligomers prepared by acid hydrolysis were fairly low or only trace levels. These results suggest that unsaturated end-structure of alginate oligomers was important for the TNF-alpha-inducing activity. Among the unsaturated guluronate (G3-G9) and mannuronate (M3-M9) oligomers, G8 and M7 showed the most potent activity, respectively. Bio-Plex assay revealed that interleukin (IL)-1alpha, IL-1beta, and IL-6 secretion from RAW264.7 cells were also induced by unsaturated alginate oligomers with similar structure-activity relationship profiles as seen in TNF-alpha, and the most potent activities were observed with G8 and M7. These results suggest that G8 and M7 may have the most suitable molecular size or entire structural conformation as stimulant for cytokine secretion. Since antibodies to Toll-like receptor (TLR)2 and TLR4 effectively inhibited the G8- and M7-induced production of TNF-alpha, these alginate oligomers may stimulate innate immunity through the pattern recognition receptors on macrophages similar to microbial products.

Structure-property correlations in a combinatorial library of degradable biomaterials
Brocchini, S., K. James, et al. (1998), J Biomed Mater Res 42(1): 66-75.
Abstract: A combinatorial library of degradable polyarylates was prepared. These polymers are A-B-type copolymers consisting of an alternating sequence of a diphenol and a diacid. The library was prepared by copolymerizing, in all possible combinations, 14 different tyrosine-derived diphenols and eight different aliphatic diacids, resulting in 8 x 14 = 112 distinct polymers. This approach (a) increases the number of available polymeric candidate materials for medical applications, and (b) facilitates the identification of correlations between polymer structure and glass transition temperature, air-water contact angle, mechanical properties, and fibroblast proliferation. The pendent chain and backbone structures were systematically varied by (a) simple homologative variations in the number of methylene groups, (b) substitution of oxygen for methylene groups, and (c) introduction of branched and aromatic structures. The polymers contained within the library exhibited incremental variations in Tg (from 2 degrees C to 91 degrees C) and air-water contact angle (from 64 degrees to 101 degrees). Fibroblast proliferation (in vitro, serum-containing media) ranged from approximating that measured on tissue culture polystyrene to complete absence of proliferation. Generally, decreased proliferation correlated linearly with increased surface hydrophobicity, except in those polymers derived from oxygen-containing diacids in their backbone which were uniformly good growth substrates even if their surfaces were very hydrophobic. In a selected subgroup of polymers, tensile strength of thin solvent cast films ranged from about 6 to 45 MPa, while Young's modulus (stiffness) ranged from about 0.3 to 1.7 GPa. Combinatorial biomaterial libraries such as these tyrosine-derived polyarylates permit the systematic study of material-dependent biological responses and provide the medical device designer with the option to choose a suitable material from a library of related polymers that encompasses a broad range of properties.

Structure-release rate correlation in collagen gels containing fluorescent drug analog
De Paoli Lacerda, S. H., B. Ingber, et al. (2005), Biomaterials 26(34): 7164-72.
Abstract: The paper examines the release properties of collagen gels that contain covalently bound fluorescent drug analogs. Collagen gels were prepared by fibrilogenesis. The gels were stabilized by cross linking with EDAC/NHS. SEM studies showed that increasing the cross-linking time with EDAC/NHS resulted in decreasing pore size and increasing gel density. Fluorescence spectroscopy measurements showed a clear correlation between decreasing pore size and increasing gel density, and lower release rate from the gels. Additives like chondrotitin-6-sulfate (CS) and amino acids altered the release properties of the cross-linked collagen gels. CS increased the stability of collagen gels to enzymatic degradation and non-enzymatic degradation. This was attributed to increasing gel rigidity due to carbohydrate-protein interactions. The amino acid lysine increased the stability of collagen gels which was attributed to increasing cross-linking level between the collagen fibrils and the primary amine group on the lysine side chain. The amino acid histidine decreased the stability of the gels, particularly to non-enzymatic degradation. These results correlated with increasing pore size following treatment with histidine. Our study shows, for the first time, a clear correlation between structure and release properties of collagen gels. It describes in detail the effect of additives on the structural and release properties of collagen gels. The study focused on gels that were prepared through fibrillogenesis and were therefore similar in structure to native collagen.

Student Research Award in the Undergraduate Degree Candidate category, 30th Annual Meeting of the Society for Biomaterials, Memphis, Tennessee, April 27-30, 2005. Monocyte/lymphocyte interactions and the foreign body response: in vitro effects of biomaterial surface chemistry
MacEwan, M. R., W. G. Brodbeck, et al. (2005), J Biomed Mater Res A 74(3): 285-93.
Abstract: To determine the effect of biomaterial surface chemistry on leukocyte interaction and activity at the material/tissue interface, human peripheral blood monocytes and lymphocytes were cultured on a series of poly(ethylene terephthalate) (PET)-based biomaterials. Both monocytes and lymphocytes were isolated from whole human blood and separated by a nonadherent density centrifugation method before being plated on PET disks, surface modified by photograft copolymerization to yield hydrophobic, hydrophilic, anionic, and cationic surface properties. Monocytes and lymphocytes were cultured separately, to elicit baseline levels of activity, in direct coculture, to promote direct cell surface interactions, or in an indirect coculture system with both cell types separated by a -0.02-microm Transwell apparatus, to promote indirect paracrine interactions. Monocyte adhesion, macrophage fusion, and lymphocyte proliferation were measured on days 3, 7, 10, and 14 of culture. Results demonstrated that the presence of monocytes increased the activity of cocultured lymphocytes at the biomaterial/tissue interface, while the corresponding presence of lymphocytes increased the activation and fusion of indirectly cocultured monocytes. Biomaterial surface chemistry was also found to have a significant effect on monocyte adhesion and activation, and lymphocyte activity. Hydrophilic surfaces significantly inhibited both initial and longterm monocyte adhesion, and inhibited lymphocyte proliferation at longer time points. Anionic and cationic surfaces both exhibited mild inhibition of monocyte adhesion at prolonged time points and increased levels of macrophage fusion, while cationic surfaces decreased levels of lymphocyte proliferation and inhibited monocyte activity. These results elucidate the complex role of juxtacrine and paracrine interactions between monocytes and lymphocytes in the foreign body response, as well as promote the consideration of hydrophilic surfaces in future designs of implantable biomedical devices and prostheses.

Studies of host response to orthopedic implants and biomaterials
Santavirta, S., M. Takagi, et al. (1999), J Long Term Eff Med Implants 9(1-2): 67-76.
Abstract: The use of implanted biomaterials in orthopedic surgery has increased rapidly during the past two decades. Total joint replacement of the hip or knee joint has become common treatment; at the same time, an increasing number of fractures are treated with osteosynthesis. The original Charnley low-friction arthroplasty of the hip is still widely used and gives in large series excellent results. Aseptic loosening of this arthroplasty has been thought to be due to wear debris of the methylmethacrylate used for fixation of the implants, or to debris generated from wear of the polyethylene socket. To date, many different materials have been tried in order to reduce wear and generation of macrophage irritating submicron sized particles, or to provide more biocompatible components. However, trials to improve the methylmethacrylate cement or to invent better polyethylenes have often failed. Diamond coating of the metallic components seems promising: there is less wear and diamond is very biocompatible in bulk and small particulate form. Biodegradable implants have also been found useful in treating fractures. Bioactive bioabsorbable materials may also make possible a tissue engineering approach and can be used as carriers for selected drugs and cytokines. Because many promising materials and designs have failed in clinical use, extensive theoretical and experimental testing is mandatory before introducing new materials and implants in a clinical setting.

Studies on a new radiopaque polymeric biomaterial
Benzina, A., M. A. Kruft, et al. (1994), Biomaterials 15(14): 1122-8.
Abstract: A new radiopaque polymeric biomaterial has been synthesized. The material, which actually represents an entire family of analogous radiopaque materials, is composed of 2-(p-iodobenzoyl)-ethyl methacrylate (compound 1, 21 mol%), methyl methacrylate (MMA, 60 mol%), and 2-hydroxyethyl methacrylate (HEMA, 19 mol%). The terpolymer was synthesized in a radical polymerization reaction at elevated temperature in N,N-dimethylformamide (DMF). The product was subjected to a set of physicochemical characterization techniques (gel permeation chromatography, 500 MHz 1H NMR in deuterated dimethylsulphoxide (d6-DMSO) solution, differential scanning calorimetry, dynamic water contact angle measurements), as well as to an in vitro thrombogenicity assay. Furthermore, scanning electron microscopy was used to study interactions of the material with blood platelets. The most important findings are: (a) the material is a genuine polymer with excellent X-ray visibility, even in the form of thin (0.4 mm) drawn fibres. This was established under realistic conditions. (b) The material exhibits low in vitro thrombogenicity, i.e. comparable to polyvinyl chloride, which is known as a passive material. These observations lead us to the suggestion that this type of radiopaque polymer holds promise with respect to application as a construction material for a new type of endovascular stent. This could be relevant in particular to stents to be used in conjunction with percutaneous transluminal coronary angioplasty (PTCA), also known as Dottering. Currently there is a clear trend away from metallic stents towards all-polymeric stents, since the latter have superior biocompatibility.(ABSTRACT TRUNCATED AT 250 WORDS)

Studies on a new strategy for surface modification of polymeric biomaterials
Aldenhoff, Y. B. and L. H. Koole (1995), J Biomed Mater Res 29(8): 917-28.
Abstract: A new methodology to improve the hemocompatibility of polyurethane (medical grade Pellethane D-55) surfaces is reported. The approach is essentially based on a photochemical immobilization reaction. Two new conjugate molecules, compounds 2 and 3, were prepared. They consist of (i) dipyridamole, a well-known inhibitor of platelet activation, and a vasodilating drug with clinical application, for instance before and during pecutaneous transluminar coronary angioplasty (Dottering); and (ii) an aryl azide, a moiety that exhibits marked photoreactivity. In 2, the dipyridamole unit is directly linked to the aryl azide (via an ester bond), while a short spacer chain separates both units in 3. Upon irradiation of 2 or 3, adsorbed onto the polyurethane foil, the aryl azide is converted into a highly reactive species which reacts with a nucleophilic group on the polymer surface. In this way, the dipyridamole is covalently linked to the polymer. The underlying principle is also used in photoaffinity labeling, a well-known technique in biochemical studies on enzyme structure and function. From UV extinction experiments it could be deduced that the surface-density of immobilized 2 is 4.9 nmol/cm2. The surface density for 3 was 14.6 nmol/cm2. The surfaces were subjected to an in vitro thrombin generation assay. This assay gives a valuable impression about the hemocompatibility of artificial surfaces. These experiments revealed that the clotting times were substantially prolonged as a result of the photoimmobilization of dipyridamole. This was especially the case for immobilized 3. This effect cannot be readily explained. Possibly, the enhanced activity of immobilized 3 is due to the spacer chain. An alternative explanation is that the surface density is larger for 3 than for 2. In addition, the photomodified surfaces were incubated with platelet-rich blood plasma (37 degrees C, 30 min) and subsequently examined by scanning electron microscopy. The morphology of the blood platelets adhered to the surface also showed that hemocompatibility increased in the order untreated polyurethane < polyurethane with immobilized 2 < polyurethane with immobilized 3. Future work will concentrate on evaluation of the role of the spacer (length, hydrophilicity, etc.), as well as on the possible use of this approach with respect to the construction of biomaterials with improved in vivo biocompatibility, in particular hemocompatibility.

Studies on calcium deficient apatites structure by means of MAS-NMR spectroscopy
Rodriguez-Lorenzo, L. M. (2005), J Mater Sci Mater Med 16(5): 393-8.
Abstract: The development of synthetic apatites that replicate the features and properties of the contained in natural tissues will help to diminish the misfit between artificial implants and natural hostesses but the structure of these compounds is still under discussion. The variability in Ca/P ratio of calcium deficient apatites has been explained through different models: surface adsorption, lattice substitution and intercrystalline mixtures of hydroxyapatite and octacalcium phosphate. This work investigates which of the models mentioned suits better in a range of samples. Hydroxyapatites obtained by precipitation, by hydrolysis of dicalcium phosphate and calcined samples with Ca/P ratio between 1.50 and 1.77 and specific surface area between 7 and 108 m2/g have been analysed. OCP and surface adsorption models suit better for great SSA particles and low Ca/P ratio while for smaller SSA particles the lattice substitution model is more accurate. SSA also plays the main role when the capacity to absorb substances is studied though their chemistry can not be explained solely in terms of surface reactivity.

Studies on cell-biomaterial interaction: role of tyrosine phosphorylation during fibroblast spreading on surfaces varying in wettability
Groth, T. and G. Altankov (1996), Biomaterials 17(12): 1227-34.
Abstract: In a previous study we observed that protein tyrosine phosphorylation was significantly diminished in the focal adhesions of human fibroblasts attached on a hydrophobic surface in comparison with hydrophilic glass. This result raises the possibility that the tyrosine phosphorylation pathway may be involved in the regulation of cell-biomaterial interaction. To learn more about the interaction of anchorage-dependent cells with biomaterials, four different materials with wettability ranging from hydrophilic (water contact angle 25 degrees) to hydrophobic (water contact angle 111 degrees) were investigated, i.e. clean glass (glass), aminopropylsilane (APS), octadecylsilane (ODS) and silicone (SI). Immunofluorescence microscopy revealed increased stress formation and fibronectin (FN) receptor-rich focal adhesions for fibroblasts attached on more hydrophilic surfaces (glass and APS) in comparison to the relatively hydrophobic materials (ODS and SI). Phosphorylation of tyrosine residues, also studied by immunofluorescence microscopy, was considerably higher on glass and APS, lower for ODS, negligible for SI, and was found to colocalize with FN receptor-rich focal adhesions. Preadsorption of FN tended to restore cell adhesion and spreading on the hydrophobic ODS and SI. Quantitative data on cell proliferation and tyrosine phosphorylation showed moderate wettable material maximum values for APS, followed by glass. ODS and SI, demonstrating a non-linearity of these parameters with the wettability of materials. Interestingly, the preadsorption of FN increased both parameters, particularly for the hydrophobic materials ODS and SI. Phosphorylation of tyrosine on FN-coated substrata was corroborated by the accessibility of binding sites estimated by ELISA using polyclonal and monoclonal FN antibodies. Our results suggest that measurement of the phosphotyrosine activity of cells may be a sensitive parameter for the ability of biomaterials to support the attachment and proliferation of cells.

Studies on in vitro evaluation for the biocompatibility of various biomaterials: inhibitory activity of various kinds of polymer microspheres on metabolic cooperation
Nakaoka, R., T. Tsuchiya, et al. (2001), J Biomed Mater Res 57(2): 279-84.
Abstract: Gap junctional intercellular communication is a function that plays an important role in maintaining cell and tissue homeostasis and in regulating cell growth, development, and differentiation. Change in this function when contacting fibroblasts with various polymer microspheres was estimated using the metabolic cooperation assay system. When the cells were in contact with the microspheres after their adhesion onto a substrate, the function did not alter. However, when they were in contact with precoated microspheres on test dishes, the function was inhibited as the quantity of microspheres increased. Moreover, the inhibition level increased as the diameters of polyethylene and polystyrene microspheres decreased. However, no inhibition was observed if precoated microspheres were composed from poly(L-lactic acid). These findings suggest that the size and the material of microspheres, and how cells recognize the microspheres, are factors affecting cell function of gap junctional intercellular communication. Therefore, estimating this function may provide valuable information about the biocompatibility of many kinds of materials even in the form of particles.

Studies on new polymeric biomaterials with tunable hydrophilicity, and their possible utility in corneal repair surgery
Bruining, M. J., A. P. Pijpers, et al. (2002), Biomaterials 23(4): 1213-9.
Abstract: A well-known complication in corneal repair surgery is (recurrent) rejection of donor corneal tissue. particularly in patients suffering from an auto-immune disease such as rheumatoid arthritis. Down-regulation of their immune system, by means of drugs, is necessary in order to perform an allograft implantation afterwards. The patient may need a temporary prosthetic cornea while the immune system is inactivated. Recently, NeuroPatch, a mesh-type polyurethane, was used for this purpose. The material exhibits excellent biocompatibility and allows ingrowth of stromal fibroblasts which deposit matrix material into the pores. A serious drawback of NeuroPatch is its non-transparency, which impairs vision. In this work we attempted to develop an improved biomaterial that combines the advantages of NeuroPatch with optical transparency. Based on previous findings that copolymers of hexaethyleneglycolmethacrylate (HEGMA) and butylmethacrylate (BMA), are transparent and well accepted by human corneal epithelial cells, we studied these materials further in detail. (Bruining et al., Bio-Macromolecules 1 (2000) 418) Copolymerizations were studied by means of 1H NMR. The influence of the HEGMA content on hydrophilicity, flexibility and resistance to protein adsorption was studied. The results indicate that materials with a HEGMA content of approximately 20 mol% are potentially useful in corneal repair surgery. These biomaterials meet most of the stringent physical and biological requirements.

Studies on radio-opaque polymeric biomaterials with potential applications to endovascular prostheses
Kruft, M. A., A. Benzina, et al. (1996), Biomaterials 17(18): 1803-12.
Abstract: A new polymeric biomaterial, which uniquely combines radio-opacity (X-ray visibility) and low thrombogenicity, is described. First, preparation, purification, and identification of the essential monomeric building block, 2-[2'-iodobenzoyl]-ethyl methacrylate (3), are outlined. Second, [Figure: See text] the synthesis of the biomaterial, a terpolymer with composition MMA: HEMA: 3 = 65:15:20 (mole/mole/mole) is described. Third, the physico-chemical characteristics of the polymer (e.g. NMR spectroscopy, thermal behaviour) are given. Fourth, the in vitro thrombogenicity of the material was characterized by means of recent test assay. The combined results reveal that the terpolymer is very suitable for prosthetic applications in the cardiovascular system. A new prototype of an endovascular stent, made from the terpolymer, is presented. Stents find clinical use in interventional cardiology, in conjunction with percutaneous transluminal coronary angioplasty (PTCA). It is put forward that the stent prototype presented herein has, at least in principle, some advantages over existing (metallic) stents; these advantages are primarily owing to the unique combination of X-ray visibility and haemocompatibility which is presently achieved.

Studies on the application of immobilization technique for the production of cyclosporin A by a local strain of Aspergillus terreus
Sallam, L. A., A. M. El-Refai, et al. (2005), J Gen Appl Microbiol 51(3): 143-9.
Abstract: The formation of cyclosporin A (Cy A) by immobilized spores and mycelia of Aspergillus terreus was investigated. Different carriers were tested as immobilizing carriers, whereby Ca-alginate was selected for further experimentation. The role of alginate concentration, biomass weight, pH value of the cultivation medium, repeated utilization of the immobilized fungus as well as the supplementation of different amino acid precursors were studied. Best Cy A outputs were attained with Ca-alginate 3% (w/v), mycelial weight 15% (w/v), pH 4.5 and four repeated cycles. Similarly, the Cy A productivity was markedly accelerated in the presence of L-valine and L-valine and L-leucine mixture.

Studies on the standardization of cytotoxicity tests and new standard reference materials useful for evaluating the safety of biomaterials
Tsuchiya, T. (1994), J Biomater Appl 9(2): 138-57.
Abstract: Standard reference materials (SRM) made of polyurethane films containing various amounts of cytotoxic compounds such as zinc diethyldithiocarbamate (ZDEC) and zinc dibutyldithiocarbamate (ZDBC) are proposed. The cytotoxicity indices of five dithiocarbamates and the SRM films obtained by colony assay were compared with those by published standards, i.e., neutral red assay (NF S 90-702), agar diffusion assay (USP XXII), and millipore filter diffusion assay (DIN-V 13 930). Among them, colony assay using 3 cell lines of Balb 3T3, L929 and V79 was found to be most sensitive. The extraction method and direct contact method were proposed as two test methods of colony assay. In the former, culture media after incubation with test materials were used as test solution, and in the latter, cells were directly cultured on test materials. The extraction method gave a linear relationship between the cytotoxic potentials of the SRM and its concentration of ZDEC or ZDBC. The cytotoxic potentials of the SRM correlated well with the thickness of inflammatory layer in rabbit muscle implantation tests of the SRM. The direct contact method was found to be useful to detect weak cytotoxicity because of its high sensitivity. Based on these data, we propose the colony assay and the two kinds of new SRMs as Japanese standard test method for evaluating the cytotoxicity of biomaterials.

Studies on the tumor-promoting activities of additives in biomaterials: inhibition of metabolic cooperation by additives such as pigments and phenolic antioxidants
Tsuchiya, T., Y. Ikarashi, et al. (1995), J Long Term Eff Med Implants 5(4): 243-52.
Abstract: The inhibitory activities on the intercellular gap-junctional communication were investigated using the V79 metabolic cooperation (MC) assay for the detection of tumor-promoting activities of additives such as pigments and phenolic antioxidants. Among six pigments, four chemicals showed inhibitory activities. The inhibitory potencies were ranked in the following order: sudan I > purple 201 > blue 204 > green 202. Sudan I and purple 201 showed stronger inhibitory activities than lithocholic acid, which is known to be a tumor promotor. However, quinizarine and red 225 did not inhibit at any concentration. Relating to eight phenolic antioxidants, four chemicals also showed inhibitory activities. Combining the present findings with previous ones, there are many factors that have tumor-promoting activities via inhibitory action on gap-junctional intercellular communication in biomaterials.

Studies on the tumor-promoting activity of additives in biomaterials: inhibition of metabolic cooperation by phenolic antioxidants involved in rubber materials
Tsuchiya, T., K. Fukuhara, et al. (1995), J Biomed Mater Res 29(1): 121-6.
Abstract: For the detection of tumor-promoting activities of phenolic antioxidants, the inhibitory activities on the intercellular gap-junctional communication were investigated using the V79 metabolic cooperation (MC) assay. Among eight antioxidants, 4,4'-butylidene-bis(3-methyl-6-tert-butyl-phenol), 2,2'-methylene-bis(4-methyl-6-tert-butylphenol) (MBMBP), and styrenated phenol (SP) showed stronger inhibitory activities than lithocholic acid, which is known to be a tumor promotor. However, 4,4'-thio-bis(3-methyl-6-tert-butylphenol), Irganox 1010, and 1330 did not inhibit at any concentrations. When the single-electron oxidation potentials were compared among antioxidants, the electrochemical ease estimated with the first oxidation potential was correlated with the cytotoxic potentials (r = 0.88), but not with the inhibitory activities in an MC assay. The tumor-promoting activity of MBMBP was also investigated using an in vitro, two-stage Balb/c 3T3 transformation assay. MBMBP did not show initiating activity, but significant promoting activity at concentrations of both 1 and 2.5 micrograms/ml were noted. These concentrations were close to the lowest effective inhibitory concentration (1.3 micrograms/ml) of MBMBP in an MC assay. In conclusion, there is a possibility that the phenolic antioxidants that show inhibitory activities in an MC assay contribute to the enhancement of tumor incidence induced by biomaterials.

Studies on the tumor-promoting activity of biomaterials: inhibition of metabolic cooperation by polyetherurethane and silicone
Tsuchiya, T., H. Hata, et al. (1995), J Biomed Mater Res 29(1): 113-9.
Abstract: When V79 metabolic cooperation (MC) assay was performed to detect tumor-promoting activities, inhibitory activities on the gap-junctional intercellular communication were first detected in both extracts prepared from polyetherurethane (PEU) and silicone. The former inhibited more strongly than the latter. Furthermore, the lowest effective concentrations in MC assay correlated well with the values of the total active incidences obtained by histologic evaluation of the 2-year implantation test in rats. Poly(tetramethylene oxide) (PTMO) showed the highest inhibitory activities among the constituents of PU. Thus, the shorter the chain length of PTMO, the stronger the inhibitory activities of PTMO in MC assay. PTMO moiety may play an important role in the tumor-promotion stage during tumorigenesis induced by PU.

Studies on two new radiopaque polymeric biomaterials
Kruft, M. A., A. Benzina, et al. (1994), J Biomed Mater Res 28(11): 1259-66.
Abstract: Two new polymeric materials (polymers A and B) containing covalently bound iodine were prepared. These polymers were evaluated with respect to their possible use as radiopaque implant biomaterials--that is, materials that are visible in a noninvasive manner using routine X-ray absorption imaging techniques. Polymer A is a copolymer of methyl methacrylate (MMA) and 1 (80 and 20 mol%, respectively). Polymer B was prepared from MMA, 1, and 2-hydroxyethyl methacrylate (HEMA) (mol ratio 65:20:15, respectively). Compound 1 was synthesized from 4-iodophenol and methacryloyl chloride. The resulting polymers were characterized with GPC, DSC, NMR, and by measuring both the advancing and receding contact angles. Thrombogenicity of the polymers was determined by an in vitro thrombin generation test procedure. The maximum concentration of free thrombin was 76 +/- 1 nM for polymer A, and 64 +/- 3 nM for polymer B. The lag times (i.e., time onset of thrombin generation) were 392 seconds for polymer A and 553 seconds for polymer B. For PVC-T, which is known as a passive material, a lag time of 583 seconds was found. This indicates that polymer B is comparable to PVC-T, and more passive than polymer A. Polymer A exhibited minor activation of platelets. Polymer B did not induce platelet activation at all. The polymers exhibited, even as fibers with a diameter of ca. 0.3 mm, good radiopacity with routine imaging X-ray techniques in the clinic.(ABSTRACT TRUNCATED AT 250 WORDS)

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