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  • Articles  (278)
  • Chemistry  (278)
  • 2020-2023
  • 1995-1999  (278)
  • 1996  (278)
  • Technology  (278)
  • Medicine  (277)
  • 1
    Electronic Resource
    Electronic Resource
    Perceptions of chemistry: Why is the common perception of chemistry, the most visual of sciences, so distorted? (1996)
    Springer
    Journal of science education and technology 5 (1996), S. 193-201 
    Details
    ISSN: 1573-1839
    Keywords: Chemistry ; chemistry education ; multiple intelligences ; imagery ; visual-spatial thinking
    Source: Springer Online Journal Archives 1860-2000
    Topics: Natural Sciences in General , Technology
    Notes: Abstract Chemistry has evolved from a science dominated by mathematics into a science highly dependent on spatial-visual intelligence. Yet the chemical content of introductory courses remains taught essentially the same as 40–50 years ago. Chemistry, today, is recognized by chemists as the molecular science. Yet, school chemistry is alienated from that perception. Thanks to the computer, young people are more comfortable with visual imaging than their instructors were at the same age. Thus the time is rife to reinvigorate chemistry education by means of the visual-spatial approach, an approach wholly in conformance with the way modern chemistry is thought about and practiced.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01575303
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  • 2
    Electronic Resource
    Electronic Resource
    Masthead (1996)
    Hoboken, NJ : Wiley-Blackwell
    Journal of Biomedical Materials Research 31 (1996) 
    Details
    ISSN: 0021-9304
    Keywords: Chemistry ; Polymer and Materials Science
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Medicine , Technology
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1002/jbm.1996.820310101
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  • 3
    Electronic Resource
    Electronic Resource
    Technical note: Activation of the plasma coagulation system induced by some biomaterials (1996)
    Hoboken, NJ : Wiley-Blackwell
    Journal of Biomedical Materials Research 31 (1996), S. 145-148 
    Details
    ISSN: 0021-9304
    Keywords: Chemistry ; Polymer and Materials Science
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Medicine , Technology
    Notes: The ability of some biomaterials to activate plasma coagulation system was examined in vitro. After contact of platelet-rich plasma with biomaterials, some markers of the thrombin formation process, i.e., fragment 1 + 2 and fibrinopeptide A, and some inhibitors of the blood coagulation mechanism were tested. Fragment 1 + 2 and fibrinopeptide A were found to be increased by all of the materials, though to a different extent. In particular, fragment 1 + 2 and fibrinopeptide A were significantly increased upon contact with polybutylene terephthalate and with collagen coated polyethylene terephthalate, respectively. Also, antithrombin III was shown to decrease following exposure to biomaterials, but statistical significance was found only for polyethylene terephthalate and polyvinylacetate. As a result of this wide range of variability in the parameters, it is advisable to explore the plasma coagulation system with a multiparametric approach in which thrombin formation and coagulation inhibitors are thoroughly investigated. © 1996 John Wiley & Sons, Inc.
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  • 4
    Electronic Resource
    Electronic Resource
    Effect of biomaterial surface charge on the inflammatory reponse: Evaluation of cellular infiltration and TNFα production (1996)
    Hoboken, NJ : Wiley-Blackwell
    Journal of Biomedical Materials Research 31 (1996), S. 139-144 
    Details
    ISSN: 0021-9304
    Keywords: Chemistry ; Polymer and Materials Science
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Medicine , Technology
    Notes: A rat model was used to investigate the effect of net surface charge on polymer biocompatibility and its potential to modify and stimulate the inflammatory response. Poly(ether)urethane was taken as the base material and the net charge altered by introducing sulphonate ionic groups to the polymer backbone. Three differently charged poly(ether)urethanes were made with 10, 20, and 30% sulphonate substitution, giving a range of negative charge, with unmodified poly(ether)urethane used as a control. The polymers were implanted intramuscularly into rats for 2 days, and for 1, 2, and 12 weeks. After explantation, the cellular infiltration in the tissue surrounding the implants was evaluated using immunohistochemistry to stain for specific cell types: macrophages, neutrophils, lymphocytes, and the cytokine TNFα. In situ hybridization was used to detect expression of mRNA encoding TNFα. Stained sections were analyzed and the cellular response quantified using image analysis. Initially macrophages and neutrophils were observed around all the materials, but neutrophils were absent in all samples at 12 weeks. The 2-day time point had significantly more macrophages than the later time points. By 2 weeks the 20%-charged polymer elicited significantly less neutrophil infiltration than the other three polymers. In all samples where macrophages were observed, cells staining positive for TNFα protein and message also were observed. No T or B lymphocytes were observed in the infiltrates around the materials at any time point. The results indicate that surface charge can influence the early phase acute inflammatory response to an implanted material. © 1996 John Wiley and Sons, Inc.
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  • 5
    Electronic Resource
    Electronic Resource
    Effects of growth-factor-enhanced culture on a chondrocyte-collagen implant for cartilage repair (1996)
    Hoboken, NJ : Wiley-Blackwell
    Journal of Biomedical Materials Research 31 (1996), S. 273-280 
    Details
    ISSN: 0021-9304
    Keywords: Chemistry ; Polymer and Materials Science
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Medicine , Technology
    Notes: The effects of incubation and addition of growth factors to a chondrocyte-seeded collagen implant for cartilage repair were studied. Type I collagen matrices seeded with lapine articular chondrocytes and unseeded controls cultured in the presence and absence of fibroblast growth factor and insulin for 2, 6, and 9 weeks were subjected to biomechanical, biochemical, and histological analysis. Aggregate modulus of elasticity of seeded implants decreased by half at 6 weeks, then rose by a factor of 10 above initial values. Permeability of seeded implants and their controls decreased steadily. Glycosaminoglycan content peaked at 6 weeks, coinciding with the greatest number of chondrocytes and mitotic activity in seeded implants. Chondrocytes remained phenotypically stable and metabolically active; they incorporated glycosaminoglycan into the extracellular matrix, and formed an organized pericellular environment despite the predicted resorption of the collagen matrix. Adding fibroblast growth factor and insulin tripled the rate of cell turnover and doubled the glycosaminoglycan content of seeded implants, but had no effect on their material properties. In vitro incubation for 6 weeks in the presence of fibroblast growth factor and insulin creates a metabolically and mitotically active chondrocyte-collagen composite for implantation into articular cartilage defects. © 1996 John Wiley & Sons, Inc.
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  • 6
    Electronic Resource
    Electronic Resource
    Studies on the mechanisms of tumorigenesis induced by polyetherurethanes in rats: Leachable and biodegradable oligomers involving the diphenyl carbamate structure acted as an initiator on the transformation of Balb 3T3 cells (1996)
    Hoboken, NJ : Wiley-Blackwell
    Journal of Biomedical Materials Research 31 (1996), S. 299-303 
    Details
    ISSN: 0021-9304
    Keywords: Chemistry ; Polymer and Materials Science
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Medicine , Technology
    Notes: The tumor-initiating activities of the methanol extracts of polyetherurethanes (PEUs) were first detected in the presence of 12-0-tetradecanyl-phorbol-13-acetate (TPA) using Balb 3T3 transformation assay. A model hard segment of PEUs, 4,4′-di(ethoxycarboamide) diphenylmethane (MDU), showed initiating activity, while chemical moieties other than the hard segment were shown to be negative in the test. The transformation assay was carried out using glass dishes half coated with two different PEUs, PU4 and PU8. In the presence of TPA, the transforming activities correlated with the tumorigenic potential in the rat implantation study on the coated surface of PEUs, but not on the uncoated glass area. From these results it was concluded that initiation was caused by the hard-segment moiety such as MDU structure derived not only from the leachable extracts but also from the biodegradable substances by the direct interaction of cells with the coated materials. © 1996 John Wiley & Sons, Inc.
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  • 7
    Electronic Resource
    Electronic Resource
    Radiation-induced graft copolymer SBS-g-VP for biomaterial usage (1996)
    Hoboken, NJ : Wiley-Blackwell
    Journal of Biomedical Materials Research 31 (1996), S. 281-286 
    Details
    ISSN: 0021-9304
    Keywords: Chemistry ; Polymer and Materials Science
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Medicine , Technology
    Notes: The grafting of 4-vinyl pyridine (VP) to styrene-butadiene-styrene triblock copolymer (SBS) by radiation-induced graft copolymerization was studied. The cohesive properties such as cohesive energy (Ecoh), molar volume (V), solubility parameter (δ), molar molecular weight (WM), specific volume (Vg), and density (1/Vg) of SBS-g-VP graft copolymer were calculated according to the group contribution of Fedors. The morphology of SBS-g-VP was studied by optical polarizing microscopy. We also measured the glass transition temperature and the mechanical properties of SBS-g-VP graft copolymer. Contact angle and blood-clotting time experiments were also performed to evaluate the biocompatibility of SBS-g-VP. A second domain was found in the SBS-g-VP graft copolymer, which resulted in different properties between SBS-g-VP and SBS. The blood compatibility of SBS-g-VP as measured by the Lee-White clotting test was better than that of SBS and polystyrene. © 1996 John Wiley & Sons, Inc.
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  • 8
    Electronic Resource
    Electronic Resource
    Heparin-like polymers derived from dextran enhance colonic anastomosis resistance to leakage (1996)
    Hoboken, NJ : Wiley-Blackwell
    Journal of Biomedical Materials Research 31 (1996), S. 293-297 
    Details
    ISSN: 0021-9304
    Keywords: Chemistry ; Polymer and Materials Science
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Medicine , Technology
    Notes: A new tissue repair agent, RGTA11, is described for its ability to enhance colonic anastomosis repair and resistance to leakage. RGTA11 is a dextran derivative containing 110% carboxymethyl groups, 2.6% carboxymethyl benzylamide groups, and 36.6% carboxymethyl benzylamide sulfonate groups. RGTA11 was deemed efficient to protect the heparin-binding growth factors FGF2 against trypsin digestion. By this property RGTA11 mimicked heparin or heparan sulfate. We have also found that RGTA11 protected TGFβ1 against trypsin digestion while heparin did not. RGTA11 was then tested in an in vivo wound-healing model of colonic anastomosis. Our results indicate that after 48 h, RGTA11- or RGTA11/FGF-2-treated animals presented a resistance of the anastomosis to leakage which was increased twofold (p 〈 0.05) over untreated controls. After 96 h and until day 7 there was no more difference with control animals. Our results suggest that RGTA11 presents potential clinical interest by preventing earlier leakage of colonic anastomosis. © 1996 John Wiley & Sons, Inc.
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  • 9
    Electronic Resource
    Electronic Resource
    Comparative study of the corrosion behavior of MA-956 and conventional metallic biomaterials (1996)
    Hoboken, NJ : Wiley-Blackwell
    Journal of Biomedical Materials Research 31 (1996), S. 313-317 
    Details
    ISSN: 0021-9304
    Keywords: Chemistry ; Polymer and Materials Science
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Medicine , Technology
    Notes: In this work the corrosion behavior of a new biomaterial, the MA-956 superalloy, immersed in Hank's solution is evaluated. A comparison with conventional metallic alloys used as articular implants is established. To determine the corrosion behavior we employed electrochemical methods: evaluation of corrosion potential Ecorr, electrochemical impedance spectroscopy (EIS), and anodic polarization curves. The corrosion resistance of the MA-956 superalloy preoxidized at 1100°C during 100 h is at least two orders of magnitude higher than for the other alloys. This satisfactory behavior is stationary with time. Also the probability of the appearance of the pitting corrosion process is very low. When cracking is generated in the α-alumina layer the repassivation process is assured because of the high Cr content in the superalloy. This study is the first step in proposing this new alloy as a biomaterial. The low toxicity of these metallic alloys in the physiological environment suggests that in vivo their biocompatibility could be satisfactory. © 1996 John Wiley & Sons, Inc.
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  • 10
    Electronic Resource
    Electronic Resource
    Effect of polymeric nanoparticle administration on the clearance activity of the mononuclear phagocyte system in mice (1996)
    Hoboken, NJ : Wiley-Blackwell
    Journal of Biomedical Materials Research 31 (1996), S. 401-408 
    Details
    ISSN: 0021-9304
    Keywords: Chemistry ; Polymer and Materials Science
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Medicine , Technology
    Notes: We investigated the consequences of acute and subacute administration of mice with polyisobutylcyanoacrylate (PIBCA), polyisohexylcyanoacrylate (PIHCA), poly(d,l-lactic) acid (PLA), and polystyrene (PS) nanoparticles on the mononuclear phagocyte system phagocytic function. This was done by measuring the clearance rate of colloidal carbon. Single administration of PIBCA and PIHCA (but not PLA and PS) nanoparticles reduced carbon clearance in both a time- and dose-dependent fashion. Since clearance of preopsonized carbon was normal, it was assumed that PIBCA and PIHCA nanoparticles deplete opsonins specific for carbon recognition. A decrease in plasma fibronectin levels resulting from nanoparticle administration suggested its implication in their removal from blood. However, fibronectin does not seem to be responsible for PIBCA and PIHCA blockade. Phagocytic function was preserved after repeated treatment with nanoparticles, probably as a result of increased Kupffer cell phagocytic activity and the contribution of spleen macrophages. Neither toxicity nor effects due to nanoparticle hepatic accumulation were observed. © 1996 John Wiley & Sons, Inc.
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  • 11
    Electronic Resource
    Electronic Resource
    The effects of electrolytes on the rates of hydroxyapatite formation at 25 and 38°C (1996)
    Hoboken, NJ : Wiley-Blackwell
    Journal of Biomedical Materials Research 31 (1996), S. 395-400 
    Details
    ISSN: 0021-9304
    Keywords: Chemistry ; Polymer and Materials Science
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Medicine , Technology
    Notes: The effects of electrolytes on the rates of hydroxyapatite (HAp) formation at 25 and 38°C were investigated. Solutions were selected to contain ions in common with HAp lattice ions or to contain ions capable of substituting into HAp. The effects of phosphate, calcium, chloride, and fluoride were studied in particular. The reactants from which HAp was formed were a mixture of the particulate solids CaHPO4 and Ca4(PO4)2O. These reactants were proportioned to form the calcium deficient composition Ca9HPO4(PO4)5OH at complete reaction. The rates of HAp formation were examined by determining rates of heat liberation at 25 and 38°C using isothermal calorimetry and by analyzing the variations in solution chemistry. HAp formation initially occurs by a mechanism which is interfacially controlled. However, because the reactants dissolve incongruently, HAp overgrows these particles and eventually the conversion becomes diffusionally controlled. The presence of electrolytes influences HAp formation but in differing ways. Solutions containing phosphate salts initially accelerate the rate of HAp formation by reducing the incongruency of the CaHPO4 dissolution. Sodium fluoride accelerates reaction by improving the crystallinity of the apatite overgrowths as a result of fluoride incorporation into the HAp, thereby making them less effective as diffusion barriers. Calcium chloride solutions tend to reduce the proportion of HAp formed prior to the onset of the diffusionally controlled reactions. Although the reactants used were proportioned to produce calcium-deficient HAp at complete reaction, no evidence was obtained to indicate the uptake of calcium and chloride from CaCl2 solutions to form a chloroapatite having a Ca/P ratio 〉 1.5. © 1996 John Wiley & Sons, Inc.
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  • 12
    Electronic Resource
    Electronic Resource
    Deformation behavior of low-carbon Co-Cr-Mo alloys for low-friction implant applications (1996)
    Hoboken, NJ : Wiley-Blackwell
    Journal of Biomedical Materials Research 31 (1996), S. 409-419 
    Details
    ISSN: 0021-9304
    Keywords: Chemistry ; Polymer and Materials Science
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Medicine , Technology
    Notes: The plastic flow behavior of wrought Co-27Cr-5Mo-0.05C alloy was investigated at 298 K as a function of grain size using uniaxial tension testing. The microstructures produced by deformation were characterized using X-ray diffraction, reflected light, and scanning electron microscopy. This study revealed that material with initially coarse face-centered cubic (fcc) grains exhibits larger uniform ductility than material with fine grain size. Typically, increasing the grain size from 7 to 70 μm reduces the yield strength by about 50% and increases the elongation to fracture from 12 to 30% with a small effect on the tensile strength. The material is capable of deforming uniformly to large strains without developing plastic instabilities until the point of fracture. This effect was found to be associated with the occurrence of transformation-induced plasticity (TRIP) in the coarse-grained material. TRIP enhances the material's ability to deform uniformly by maintaining a high rate of strain hardening during deformation. Smaller fcc initial grain size inhibits the transformation kinetics of the fcc-hexagonal close-packed phase transition according to the Olson-Cohen model. © 1996 John Wiley & Sons, Inc.
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  • 13
    Electronic Resource
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    Promotion and control of selective adhesion and proliferation of endothelial cells on polymer surface by carbon deposition (1996)
    Hoboken, NJ : Wiley-Blackwell
    Journal of Biomedical Materials Research 31 (1996), S. 429-435 
    Details
    ISSN: 0021-9304
    Keywords: Chemistry ; Polymer and Materials Science
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Medicine , Technology
    Notes: The adhesion and proliferation of endothelial cells can be drastically improved when cultivated on a carbon-deposited polymer surface. When the surface of segmented polyurethane, in which endothelial cells are not capable of proliferating, is modified by carbon deposition, cell adhesion and proliferation occurred selectively on the carbon-deposited region. Carbon deposition to a tissue culture-treated polystyrene surface on which cells are capable of proliferating further promoted cell spreading and proliferation. Cell patterning on carbon-deposited segmented polyurethane was also attempted by controlling the direction or region of cell proliferation. Carbon deposition onto the polymer surface brought about a decrease in the water contact angle of the surface. Precoating fibronectin or laminin on the carbon-deposited polymer surface brought about cell adhesion and proliferation in the carbon-deposited region, but not in the noncarbon-deposited region. Our data suggest that promotion of cell proliferation on a carbon-deposited surface is probably due to selective adhesion of adhesive proteins to the surface. © 1996 John Wiley & Sons, Inc.
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  • 14
    Electronic Resource
    Electronic Resource
    Stress analysis of a bulk-filled class-V chemical-cured dental composite restoration (1996)
    Hoboken, NJ : Wiley-Blackwell
    Journal of Biomedical Materials Research 31 (1996), S. 445-449 
    Details
    ISSN: 0021-9304
    Keywords: Chemistry ; Polymer and Materials Science
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Medicine , Technology
    Notes: Clinical problems associated with the polymerization shrinkage of dental composite restorations include tooth sensitivity, crown fracture, discoloration, recurrent decay, and loss of restoration. Our goal was to determine whether these complications could be attributed to the transient stresses developed during contraction. Thus, a finite element model was used to calculate the transitory deformations and composite-tooth interface stresses produced during the shrinkage of a chemical-cured ideal Class-V composite restoration. It was found that the interface stress peaks moved with the polymerization front, and that in some instances, their intermediate magnitudes were higher than the final, fully cured, values. Therefore, the results indicate that clinical failure may be related to these transitory changes during the polymerization process. © 1996 John Wiley & Sons, Inc.
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  • 15
    Electronic Resource
    Electronic Resource
    Importance of microanalysis in understanding mechanism of transformation in active glassy biomaterials (1996)
    Hoboken, NJ : Wiley-Blackwell
    Journal of Biomedical Materials Research 31 (1996), S. 475-480 
    Details
    ISSN: 0021-9304
    Keywords: Chemistry ; Polymer and Materials Science
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Medicine , Technology
    Notes: This work deals with a method to study bioactive glassy materials used for repair of bone defects in order to understand the mechanism of the bioactivity and thus have its in vivo behavior optimized. The study of these materials takes into account their changes in morphology, by means of electron microscopy, after implantation in different animal models and evaluates the mechanism of the bioactivity through semi- and quantitative microanalytical evaluations in order to quantify the phenomenon of glass corrosion and the formation of a chemical bond with bone. Special preparations of glass granules before implantation were prepared to microanalytically study surfaces with different permeabilities. © 1996 John Wiley & Sons, Inc.
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  • 16
    Electronic Resource
    Electronic Resource
    Three-dimensional defects in hydroxyapatite of biological interest (1996)
    Hoboken, NJ : Wiley-Blackwell
    Journal of Biomedical Materials Research 31 (1996), S. 495-501 
    Details
    ISSN: 0021-9304
    Keywords: Chemistry ; Polymer and Materials Science
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Medicine , Technology
    Notes: Hydroxyapatite (HA) ceramics are widely used as bone substitutes in the repair of bony defects. These ceramics sometimes differ in their sintering temperatures. High resolution transmission electron microscopy was used to characterize HA ceramics sintered at different temperatures. A new type of defect was observed for the first time for ceramics prepared at 900°C but not on those prepared at 1250°C. This may cause a difference in their in vitro dissolution and in vivo performance. © 1996 John Wiley & Sons, Inc.
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  • 17
    Electronic Resource
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    Crosslinking characteristics of an epoxy-fixed porcine tendon: Effects of pH, temperature, and fixative concentration (1996)
    Hoboken, NJ : Wiley-Blackwell
    Journal of Biomedical Materials Research 31 (1996), S. 511-518 
    Details
    ISSN: 0021-9304
    Keywords: Chemistry ; Polymer and Materials Science
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Medicine , Technology
    Notes: Injury to the anterior cruciate ligament (ACL) often results in functional instability within the knee joint and may induce a severe articular deterioration. Clinically, these patients may require an ACL reconstruction. In an attempt to develop an improved ligament prosthesis, a prototype xenograft - an epoxy-fixed porcine Achilles tendon - was developed. The study was intended to investigate the crosslinking characteristics of the epoxy-fixed porcine tendons fixed at different pHs (4.0, 7.4, 9.0, and 10.5), temperatures (4, 25, and 37°C), and fixative concentrations (1, 2, or 4%). Samples of each group were taken out at various elapsed fixation periods. The crosslinking characteristics - fixation index, denaturation temperature, and moisture content - of each sample were determined. Additionally, the stiffness of the epoxy-fixed tendons under various fixation conditions was qualitatively compared. In the study it was noted that the color of porcine Achilles tendons remained natural after epoxy fixation. With increasing pH, temperature, or fixative concentration, the fixation indices and denaturation temperatures of the epoxy-fixed tendons increased. However, the fixed porcine tendons tended to be stiffer at a higher pH, temperature, or fixative concentration. The moisture contents of the epoxy-fixed tendons were relatively lower than the fresh ones, while they were approximately the same at different pHs, temperatures, and fixative concentrations. The implications of these findings for the epoxy-fixed porcine tendons in ACL reconstruction require further investigation. © 1996 John Wiley & Sons, Inc.
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  • 18
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    Solvent environment modulates effects of glutaraldehyde crosslinking on tissue-derived biomaterials (1996)
    Hoboken, NJ : Wiley-Blackwell
    Journal of Biomedical Materials Research 31 (1996), S. 533-543 
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    ISSN: 0021-9304
    Keywords: Chemistry ; Polymer and Materials Science
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Medicine , Technology
    Notes: Bioprosthetic materials utilized in the construction of heart valves and vascular grafts possess limited performance and viability in vivo. This is due (in part) to the failure of these materials to mimic the mechanical properties of the host tissue they replace. If bioprosthetic materials could be engineered to meet the mechanical performance required in vivo, the functional lifetime of implants would be increased. In this study, glutaraldehyde/solvent solutions of decreasing dielectric constant (polarity) were utilized to modify the properties of crosslinked collagen in whole bovine pericardial tissue. Solvents included phosphate buffer, methanol, 95% (w/w) ethanol, n-propanol, and n-butanol. Exogenous crosslinking was verified in collagen by thermal denaturation tests and amino acid analyses. Tensile mechanical behavior of collagenous pericardial samples was found to depend upon the dielectric constant (polarity) of the glutaraldehyde/solvent solutions employed; however, treatment in the solvents alone had little, if any, effect. As the dielectric constant of the solvents decreased, three mechanical properties were systematically altered: plastic strain fell from a mean of 8.9 ± 1.5% (buffer) to 1.6 ± 0.4% (n-butanol); strain at fracture increased from 32.2 ± 2.6% (buffer) to 55.6 ± 4.6% (n-butanol); and percent stress remaining after 1000-s stress relaxation from an 80-g initial load fell from 86.3 ± 1.1% (buffer) to 76.9 ± 1.0% (n-butanol). Crosslinking using a glutaraldehyde/n-butanol solution produced materials with tensile mechanical behavior that was very close to that of fresh tissue; however, the flexural properties of the treated tissue were different from those of fresh tissue. This decoupling of the flexural and tensile mechanical behaviors of crosslinked bioprosthetic materials is unique to this form of treatment. The observed phenomena may be the results of conformational changes in collagen facilitated by polar/non-polar interactions with the solvent that are “locked in” by the action of glutaraldehyde. This technique may aid in the “customized” design of mechanical properties in tissue-derived biomaterials. © 1996 John Wiley & Sons, Inc.
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  • 19
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    Announcement (1996)
    Hoboken, NJ : Wiley-Blackwell
    Journal of Biomedical Materials Research 31 (1996), S. 569-569 
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    ISSN: 0021-9304
    Keywords: Chemistry ; Polymer and Materials Science
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Medicine , Technology
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1002/jbm.1996.820310402
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  • 20
    Electronic Resource
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    Surface adsorption and fibrinogen interactions with hirudin-thrombin complex (1996)
    Hoboken, NJ : Wiley-Blackwell
    Journal of Biomedical Materials Research 32 (1996), S. 11-18 
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    ISSN: 0021-9304
    Keywords: Chemistry ; Polymer and Materials Science
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Medicine , Technology
    Notes: This study describes the protein interaction properties of hirudin-thrombin complex adsorbed onto a surface. Hirudin-thrombin complex, preadsorbed thrombin bound with hirudin, and thrombin were coated onto the surfaces of glass beads. The activity of the thrombin component adsorbed onto the surface, and hence the ability of hirudin to bind and inactivate thrombin, was determined by measuring the activity of thrombin to cleave fibrinogen to generate fibrin and to cleave a chromogenic substrate, S-2238. Pure thrombin adsorbed on the surface (without hirudin) retained its activity to cleave fibrinogen and cleave S-2238. Hirudin-thrombin complex adsorbed on the surface did not stimulate the activation of fibrinogen, nor did it cleave S-2238.Thrombin first adsorbed onto the surface was able to bind hirudin; this complex did not activate fibrinogen or the hydrolysis of S-2238. However, when hirudin was first adsorbed onto the surface followed by incubation with thrombin, the protein did not bind and neutralize thrombin, and therefore lost its biologic activity. Furthermore, all proteins and the hirudin-thrombin complex adsorbed onto the surface, as determined by protein binding assays. These results suggest that the hirudin-thrombin complex physically adsorbed onto the surface did not stimulate subsequent pathways in the coagulation system, mainly the activation of fibrinogen to fibrin. © 1996 John Wiley & Sons, Inc.
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  • 21
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    Carcinogenicity of CoCrMo (F-75) implants in the rat (1996)
    Hoboken, NJ : Wiley-Blackwell
    Journal of Biomedical Materials Research 32 (1996), S. 37-44 
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    ISSN: 0021-9304
    Keywords: Chemistry ; Polymer and Materials Science
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Medicine , Technology
    Notes: A long-term study was conducted in rats to assess the contribution of the surface area of CoCrMo devices to carcinogenesis. Groups consisting of 104 rats each (52 male, 52 female) were either implanted with metal cylinders fixed on the left, lateral femur (groups 1-3) or injected with a suspension of metal microspheres in the dorsal subcutis (group 4). Group 1 (control) received solid Ti6Al4V cylinders [surface area to body weight (SA/BW) ratio measuring 1.35 times that of human total hip prosthesis (HTHP)]. Group 2 was implanted with solid CoCrMo (SA/BW ratio: identical to implants of group 1). Group 3 received sintered-porous CoCrMo devices (SA/BW ratio: 30 × HTHP). Group 4 was injected with a suspension of CoCrMO microspheres (SA/BW ratio: 135 × HTHP). Implant-associated tumors (IATs) were observed in 23, 14, 3, and 15 rats of groups 1, 2, 3, and 4, respectively. Within groups 1 and 2, 34 IATs were associated with loose implants, three with undetermined implant fixation status, and none with fixed implants. A significantly increased accumulation of chronic inflammatory tissues around loose rather than fixed implants suggested a foreign-body reaction as the primary mechanism of carcinogenesis. A secondary role in carcinogenesis was ascribed to the increased CoCrMo implant SA/BW ratios as indicated by a 14.6% IAT incidence in group 4 versus 3% in group 3. These results support the notion that early intervention in the removal of loose metal devices is warranted to mitigate against foreign body-induced carcinogenesis, at least in this animal model. © 1996 John Wiley & Sons, Inc.
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    Surface roughness modulates the local production of growth factors and cytokines by osteoblast-like MG-63 cells (1996)
    Hoboken, NJ : Wiley-Blackwell
    Journal of Biomedical Materials Research 32 (1996), S. 55-63 
    Details
    ISSN: 0021-9304
    Keywords: Chemistry ; Polymer and Materials Science
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Medicine , Technology
    Notes: Titanium (Ti) surface roughness affects proliferation, differentiation, and matrix production of MG-63 osteoblast-like cells. Cytokines and growth factors produced in the milieu surrounding an implant may also be influenced by its surface, thereby modulating the healing process. This study examined the effect of surface roughness on the production of two factors known to have potent effects on bone, prostaglandin E2 (PGE2) and transforming growth factor β1 (TGF-β1). MG-63 cells were cultured on Ti disks of varying roughness. The surfaces were ranked from smoothest to roughest: electropolished (EP), pretreated with hydrofluoric acid-nitric acid (PT), fine sand-blasted, etched with HCl and H2SO4, and washed (EA), coarse sand-blasted, etched with HCl and H2SO4, and washed (CA), and Ti plasma-sprayed (TPS). Cells were cultured in 24-well polystyrene (plastic) dishes as controls and to determine when confluence was achieved. Media were collected and cell number determined 24 h postconfluence. PGE2 and TGF-β1 levels in the conditioned media were determined using commercial radioimmunoassay and enzyme-linked immunosorbent assay kits, respectively. There was an inverse relationship between cell number and Ti surface roughness. Total PGE2 content in the media of cultures grown on the three roughest surfaces (FA, CA, and TPS) was significantly increased 1.5-4.0 times over that found in media of cultures grown on plastic or smooth surfaces. When PGE2 production was expressed per cell number, CA and TPS cultures exhibited six- to eightfold increases compared to cultures on plastic and smooth surfaces. There was a direct relationship between TGF-β1 production and surface roughness, both in terms of total TGF-β1 per culture and when normalized for cell number. TGF-β1 production on rough surfaces (CA and TPS) was three to five times higher than on plastic. These studies indicate that substrate surface roughness affects cytokine and growth factor production by MG-63 cells, suggesting that surface roughness may modulate the activity of cells interacting with an implant, and thereby affect tissue healing and implant success. © 1996 John Wiley & Sons, Inc.
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    In vitro properties of a chitosan-bonded bone-filling paste: Studies on solubility of calcium phosphate compounds (1996)
    Hoboken, NJ : Wiley-Blackwell
    Journal of Biomedical Materials Research 32 (1996), S. 95-98 
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    ISSN: 0021-9304
    Keywords: Chemistry ; Polymer and Materials Science
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Medicine , Technology
    Notes: The present study investigated properties of various mixtures of organic acids (malic and malonic) and calcium phosphate compounds (β-tricalcium phosphate, ashed bovine bone, and synthetic hydroxyapatite) with the objective of determining the optimum combination of organic acid and calcium phosphate compound for components of a chitosan-bonded bone-filling paste. β-tricalcium phosphate was decomposed by malic acid and malonic acid, but these two acids did not decompose synthetic hydroxyapatite and ashed bovine bone. Assessment of ion release from a set paste containing either synthetic hydroxyapatite or ashed bovine bone indicated that only calcium ions were appreciably released after storing and stirring the set paste in physiologic saline for 7 days. © 1996 John Wiley & Sons, Inc.
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    A method for determination of the anisotropic properties of biomembranes (1996)
    Hoboken, NJ : Wiley-Blackwell
    Journal of Biomedical Materials Research 32 (1996), S. 125-132 
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    ISSN: 0021-9304
    Keywords: Chemistry ; Polymer and Materials Science
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Medicine , Technology
    Notes: A methodology was developed for potential determination of the anisotropic properties of biomembranes. This method is based on the theoretical discretization of a continuous membrane used for finite element analysis and the simultaneous measurement of the displacement of nodes on the surface of a membrane. From the given loads and measured nodal displacements, one can assemble the resulting stiffness matrix and approximate the material properties associated with the membrane. Mathematical estimations and computer simulations were performed to determine the perturbation of load and displacement errors on the resulting material properties. The results indicated that the material properties are particularly sensitive to displacement errors. The displacement measurements may require an accuracy of 20 μm for a 4 × 4 cm2 specimen. Significant inaccuracies occur close to the points of load application. © 1996 John Wiley & Sons, Inc.
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    In vivo characterization of a fluoropassivated gelatin-impregnated polyester mesh for hernia repair (1996)
    Hoboken, NJ : Wiley-Blackwell
    Journal of Biomedical Materials Research 32 (1996), S. 293-305 
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    ISSN: 0021-9304
    Keywords: Chemistry ; Polymer and Materials Science
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Medicine , Technology
    Notes: The present study was undertaken to evaluate a new prototype mesh that consists of a knitted polyester structure treated with a fluoropolymer and impregnated with gelatin. The Fluoropassiv® mesh, as well as two controls, the Surgipro™ polypropylene mesh and the Gore-Tex® expanded polytetrafluoroethylene patch, were used for the repair of experimentally induced abdominal hernias in piglets and followed for scheduled implantation periods of 4, 15, and 60 days. At the sacrifice the mesh and surrounding tissue were excised for histological assessment of the healing sequence, for the identification of changes in hematologic and immunological characteristics, and for the measurement of the mechanical properties. After cleaning to remove the encroaching tissue, the explanted devices were monitored for biostability by infrared spectroscopy (FTIR) and differential scanning calorimetry (DSC). The present study has demonstrated that the Fluoropassiv® mesh provides adequate mechanical strength and compares favorably with the two controls. No exacerbated systemic or in situ hematologic or immunological reactions were observed with either the meshes or the patch material. Histological studies revealed that thick collagenous and vascularized tissue were well anchored to the three biomaterials as early as 15 days after implantation. The degree of tissue penetration differed depending on the device. Chemically, they proved stable over time. © 1996 John Wiley & Sons, Inc.
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    Osteogenic differentiation of cultured marrow stromal stem cells on the surface of bioactive glass ceramics (1996)
    Hoboken, NJ : Wiley-Blackwell
    Journal of Biomedical Materials Research 32 (1996), S. 341-348 
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    ISSN: 0021-9304
    Keywords: Chemistry ; Polymer and Materials Science
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Medicine , Technology
    Notes: To investigate the significance of apatite-wollastonite-containing glass ceramic (AW ceramic) surfaces and the biological apatite layer formed on these surfaces, rat marrow cell culture, which shows osteogenic differentiation, was carried out on four different culture substrata (control culture dish, two AW ceramics, each having a different surface roughness, and a ceramic on which an apatite layer was formed. A culture period of 2 weeks in the presence of β-glycerophosphate, ascorbic acid, and dexamethasone resulted in abundant mineralized nodule formations that were positive for alkaline phosphatase (ALP) stain on all substrata. The stain on the apatite-formed AW ceramic was the most intense, the enzyme activity being about twice that of the control culture dish, which had the lowest stain and activity of the four substrata. Northern blot analysis of bone Gla protein (BGP) showed the same tendency, that is, the amount of BGP mRNA from cultured cells on the apatite-formed AW ceramics was the highest and the mRNA on the control dish was the lowest. These data indicate that the glass ceramic surface promotes osteoblastic differentiation and that the promotion can be further enhanced by the formation of a biological apatite layer on the ceramic surface. © 1996 John Wiley & Sons, Inc.
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    Preparation of bioactive Ti and its alloys via simple chemical surface treatment (1996)
    Hoboken, NJ : Wiley-Blackwell
    Journal of Biomedical Materials Research 32 (1996), S. 409-417 
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    ISSN: 0021-9304
    Keywords: Chemistry ; Polymer and Materials Science
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Medicine , Technology
    Notes: A simple chemical method was established for inducing bioactivity of Ti and its alloys. When pure Ti, Ti-6Al-4V, Ti-6Al-2Nb-Ta, and Ti-15Mo-5Zr-3Al substrates were treated with 10M NaOH aqueous solution and subsequently heat-treated at 600°C, a thin sodium titanate layer was formed on their surfaces. Thus, treated substrates formed a dense and uniform bonelike apatite layer on their surfaces in simulated body fluid (SBF) with ion concentrations nearly equal to those of human blood plasma. This indicates that the alkali- and heat-treated metals bond to living bone through the bonelike apatite layer formed on their surfaces in the body. The apatite formation on the surfaces of Ti and its alloys was assumed to be induced by a hydrated titania which was formed by an ion exchange of the alkali ion in the alkali titanate layer and the hydronium ion in SBF. The resultant surface structure changed gradually from the outermost apatite layer to the inner Ti and its alloys through a hydrated titania and titanium oxide layers. This provides not only the strong bonding of the apatite layer to the substrates but also a uniform gradient of stress transfer from bone to the implants. The present chemical surface modification is therefore expected to allow the use the bioactive Ti and its alloys as artificial bones even under load-bearing conditons. © 1996 John Wiley & Sons, Inc.
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    Difference in adhesion and proliferation of fibroblast between Langmuir-Blodgett films and cast surfaces of poly(γ-benzyl L-glutamate)/poly(ethylene oxide) diblock copolymer (1996)
    Hoboken, NJ : Wiley-Blackwell
    Journal of Biomedical Materials Research 32 (1996), S. 425-432 
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    ISSN: 0021-9304
    Keywords: Chemistry ; Polymer and Materials Science
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Medicine , Technology
    Notes: Block copolymers consisting of poly(γ-benzyl L-glutamate) and poly(ethylene oxide) as the hydrophobic and hydrophilic components, respectively were prepared. Cell attachment onto the surfaces of block copolymers fabricated either as well-defined ordered Langmuir-Blodgett (LB) films or solvent cast microphase-separated structures was studied. On ordered LB surfaces, adherent fibroblasts were larger than on the microphase-separated cast surfaces within 15 min. The difference in cell adhesion between LB films and cast surfaces increased with increasing PEO contents in block copolymer. Adherent cells increased with an increase in surface pressure of LB films in any polymer. Phase-contrast microphotographs of adherent cells showed rapid and extensive morphologic changes associated with the LB surface as compared to cast film surfaces. The number of cells grown on the LB surface is greater than that on the cast film. © 1996 John Wiley & Sons, Inc.
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    Bone morphogenetic protein encapsulated with a biodegradable and biocompatible polymer (1996)
    Hoboken, NJ : Wiley-Blackwell
    Journal of Biomedical Materials Research 32 (1996), S. 433-438 
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    ISSN: 0021-9304
    Keywords: Chemistry ; Polymer and Materials Science
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Medicine , Technology
    Notes: To develop a controlled release system for bone morphogenetic protein (BMP), poly(DL-lactide-co-glycolide) (PLGA) capsules containing BMP were prepared by an interfacial precipitation method using a water-in-oil-in-water emulsion. The surface morphology, particle size distribution, and hydrolytic degradation rate of the PLGA capsules were examined. The encapsulation yield and release rate of BMP in vitro were measured using fluorescein isothiocyanate-labeled BMP. The amount of BMP released from PLGA capsules increased between days 3 and 5. In addition, the effectiveness of BMP encapsulated in PLGA to induce bone formation in vivo was also examined by subcutaneous implantation in rats. Complete digestion of the capsules and new bone formation including bone marrow were identified by histologic examination of harvested tissues at 3 weeks after implantation. These results demonstrated that encapsulation of BMP with PLGA could be a promising method to induce bone in clinics. © 1996 John Wiley & Sons, Inc.
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    Effect of calcium phosphate ceramics on Gram-negative bacteria resistant to antibiotics (1996)
    Hoboken, NJ : Wiley-Blackwell
    Journal of Biomedical Materials Research 32 (1996), S. 473-479 
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    ISSN: 0021-9304
    Keywords: Chemistry ; Polymer and Materials Science
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Medicine , Technology
    Notes: This paper discusses the results of an experimental study on the effect of biphase calcium phosphate ceramics (BCPC) on laboratory-isolated polyresistant Gram-negative bacteria. Monitoring of this effect in a dynamical regimen was carried out upon Enterobacter cloacae 313, Klebsiella pneumoniae 227, Serratia marcescens 206, Klebsiella oxytoca 202, as well as on the standard strain Klebsiella pneumoniae 52145 (Institute Pasteur, Paris). The results show a significant antimicrobial effect of the ceramics. Antimicrobial properties are manifested during direct contact with BCPC and these depend on the quantity and grain size of the particles, as well as on the microbiological characteristics of the test microorganisms, and particularly on their cell size. © 1996 John Wiley & Sons, Inc.
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    Announcements (1996)
    Hoboken, NJ : Wiley-Blackwell
    Journal of Biomedical Materials Research 32 (1996), S. 493-493 
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    ISSN: 0021-9304
    Keywords: Chemistry ; Polymer and Materials Science
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Medicine , Technology
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1002/jbm.1996.820320302
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    In vitro properties of a chitosan-bonded self-hardening paste with hydroxyapatite granules (1996)
    Hoboken, NJ : Wiley-Blackwell
    Journal of Biomedical Materials Research 32 (1996), S. 527-532 
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    ISSN: 0021-9304
    Keywords: Chemistry ; Polymer and Materials Science
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Medicine , Technology
    Notes: A new self-hardening paste was made by using a combination of chitosan, hydroxyapatite (HA) granules, ZnO, and CaO. The sol was made by dissolving 0.1 g of chitosan in a solution of 0.1 g malic acid and 2.0 mL physiological saline solution. Mixed with 0.03 g of CaO and 0.04 g of ZnO powders was 2.77 g (55 wt %) of HA granules which had a homogeneous pore distribution and a porosity of 35-48%. The size of the granules was set for 0.1-0.3 mm. Kneading and setting of the paste generated a little amount of heat (32.8°C) as compared with the heat produced by polymethyl-methacrylate (PMMA) bone cement (114.5°C). The pH value of chitosan-HA-hardened composite after setting was nearly equal to that of human plasma (pH 7.4), while that of PMMA bone cement maintained an acid pH of 4.7. Hydroxyapatite granules less than 0.1 mm, 0.1-0.3 mm, or 0.3-0.6 mm were set using chitosan sol. The size of the granules did not influence the compressive strength of the set chitosan-HA-hardened composite. The greatest compressive strength of chitosan-HA-hardened composite was obtained by using 55 wt % of HA granules. The strength of the chitosan-HA-hardened composite was comparable to that of the cancellous bone derived from tibial eminentia, but was considerably lower than that of PMMA bone cement. © 1996 John Wiley & Sons, Inc.
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    Effect of calcium alginate on cellular wound healing processes modeled in vitro (1996)
    Hoboken, NJ : Wiley-Blackwell
    Journal of Biomedical Materials Research 32 (1996), S. 561-568 
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    ISSN: 0021-9304
    Keywords: Chemistry ; Polymer and Materials Science
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Medicine , Technology
    Notes: Although the clinical experience with calcium alginate has been generally good, well-controlled studies examining the effect of such dressings on the processes of wound healing have not been conducted. The healing of cutaneous ulcers requires the development of a vascularized granular tissue bed, filling of large tissue defects by dermal regeneration, and the restoration of a continuous epidermal keratinocyte layer. These processes were modeled in vitro in the present study, utilizing human dermal fibroblast, microvascular endothelial cell (HMEC), and keratinocyte cultures to examine the effect of calcium alginate on the proliferation and motility of these cultures, and the formation of capillarylike structures by HMEC. This study demonstrates that the calcium alginate tested increased the proliferation of fibroblasts but decreased the proliferation of HMEC and keratinocytes. In contrast, the calcium alginate decreased fibroblast motility but had no effect on keratinocyte motility. There was no significant effect of calcium alginate on the formation of capillarylike structures by HMEC. The effects of calcium alginate on cell proliferation and migration may have been mediated by released calcium ions. These results suggest that the calcium alginate tested may improve some cellular aspects of normal wound healing, but not others. © 1996 John Wiley & Sons, Inc.
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    Preparation of purified atactic polypropylene and polyvinyl methyl ether surfaces for thrombogenicity studies (1996)
    Hoboken, NJ : Wiley-Blackwell
    Journal of Biomedical Materials Research 32 (1996), S. 193-202 
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    ISSN: 0021-9304
    Keywords: Chemistry ; Polymer and Materials Science
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Medicine , Technology
    Notes: Commercial samples of atactic polypropylene (aPP) and polyvinyl methyl ether (PVME) were purified and spin-cast onto glass coverslips with a view to using these as model surfaces in thrombogenicity studies. These materials differ from polyvinyl alcohol (PVA) in a single functional group and are similarly amorphous: with the same backbone they have a hydroxyl, a methoxy, or a methyl group. The objective was to understand the role of the hydroxyl group in the platelet reactivity of PVA. Surface characterization showed that they were chemically pure (as determined by X-ray photoelectron spectroscopy) but not smooth (as determined by scanning electron microscopy or interferometry), presumably due to the difficulties of spin-casting optically clear films from hot solutions (aPP or polyethylene [PE]) or because of imperfect adhesion to the saline-treated substrate (PVME). PVME was also γ-irradiated to insolubilize it. Fewer platelets adhered to PVA than to PVME or to aPP and PE, but roughness effects and limited data preclude definitive conclusions regarding the effect of functional groups. Less protein was found on PVA than on the hydrophobic surfaces, but the significance of this observation is unclear. Further studies with more sensitive protocols are called for to examine the extent of platelet activation and its relationship to surface chemistry. © 1996 John Wiley & Sons, Inc.
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    Shrinkage temperature versus protein extraction as a measure of stabilization of photooxidized tissue (1996)
    Hoboken, NJ : Wiley-Blackwell
    Journal of Biomedical Materials Research 32 (1996), S. 209-214 
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    ISSN: 0021-9304
    Keywords: Chemistry ; Polymer and Materials Science
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Medicine , Technology
    Notes: A rise in thermal denaturation temperature has been utilized as an indication of stabilization of collagen-containing materials such as pericardial tissue and porcine heart-valve leaflets following treatment with glutaraldehyde, Denacol™, or other chemical agents. In contrast, stabilization of bovine pericardial tissue by dye-mediated photooxidation does not result in a significant rise in shrinkage temperature comparable with these treated materials. It was therefore hypothesized that a rise in shrinkage temperature is not a necessary indication for tissue stabilization. A sensitive protein extraction assay has been developed which can be used to monitor the stabilization of pericardial tissue by a variety of treatment methods, including photooxidation. A reduction in extractable protein, as analyzed by polyacrylamide gel electrophoresis, is noted for pericardial tissue treated with photooxidation, glutaraldehyde, or Denacol™. Loss of extractable protein, as a function of treatment time, correlates well with a significant rise in shrinkage temperature for pericardium treated with glutaraldehyde or Denacol™ but not with photooxidation. This difference is attributed to the stabilization processes of glutaraldehyde and Denacol™, which involve extensive crosslinking and polymer formation within and in addition to the native pericardial matrix, leading to a rise in matrix complexity and thermal stability. In contrast, photooxidation is a catalytic process involving modification and crosslink formation within existing matrix components, resulting in a material with little added matrix complexity. © 1996 John Wiley & Sons, Inc.
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    Sterility, mechanical properties, and molecular stability of polylactide internal-fixation devices treated with low-temperature plasmas (1996)
    Hoboken, NJ : Wiley-Blackwell
    Journal of Biomedical Materials Research 32 (1996), S. 227-235 
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    ISSN: 0021-9304
    Keywords: Chemistry ; Polymer and Materials Science
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Medicine , Technology
    Notes: The effect of low-temperature plasma on sterility, molecular, mechanical, and crystalline properties of poly(L-lactide), poly (L/D-lactide) and poly (L/DL-lactide) was investigated. Polymers were treated for 15 and 30 min at 100 W with nitrogen, argon, oxygen, and carbon dioxide plasma. All polymers treated with oxygen or carbon dioxide plasma were rendered sterile after 15 min of treatment. Only 70% of the samples treated under similar conditions with nitrogen or argon plasma were sterile. Extension of the exposure time to 30 min and increasing power to 200 W did not improve sterilization efficiency. Plasma sterilization, under the conditions used, caused no significant decrease or increase in overall molecular weight or polydispersity of the polylactides used. In most instances the effect of plasma sterilization was to slightly increase the overall molecular weight of the polymers studied. Treatment with argon plasma led to a more consistent increase in molecular weight than did treatment with nitrogen, oxygen, or carbon dioxide. Analysis of the surface (skin) of a poly(L-lactide) injection-molded rod following plasma sterilization indicated an increase in molecular weight as related to the interior (core) of the rod. Comparison of Mark-Houwink plots for the surface and interior of poly(L-lactide) injection-molded rods following plasma sterilization indicated an increase in chain branching for the surface relative to the interior of the rod. Generally the highly crystalline poly(L-lactide) was less susceptible to change upon plasma treatment than was the less crystalline poly(L/D-lactide) and poly(L/DL-lactide). The mechanical properties (shear strength, bending strength, and moduli) of the polylactides were not affected by plasma treatment. The overall melting temperature and the heat of melting of polylactides studied were not affected by plasma treatment. The melting temperature of the skin of the samples was about 1°C higher than the melting temperature of the core due to the chain orientation upon injection-molding. Plasma treatment of the polylactides reduced the melting temperature of the skin by 3°C to 5°C due to the crosslinking or branching at the surface layer. © 1996 John Wiley & Sons, Inc.
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    Measurement of bacterial growth rates on polymers (1996)
    Hoboken, NJ : Wiley-Blackwell
    Journal of Biomedical Materials Research 32 (1996), S. 271-278 
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    ISSN: 0021-9304
    Keywords: Chemistry ; Polymer and Materials Science
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Medicine , Technology
    Notes: A video microscope system and a mathematical model were developed to observe and model the early stage of bacterial growth on polymer surfaces. Glass slides were coated with polyorthoester, poly(L-lactic acid), and polysulfone, and inserted into a laminar flow cell to expose them to bacterial cultures of Staphylococcus epidermidis, Pseudomonas aeruginosa, or Escherichia coli. The free energy of adhesion (ΔFadh) was determined from contact-angle measurements. The microscopic observations along with the mathematical model allowed measurement of the rates of adhesion, release, and growth. The growth rate of P. aeruginosa on the various surfaces correlated to the ΔFadh. The growth rates of all species on all of the surfaces were slower than the growth rates of the bacteria in suspension. The mathematical model is valid for early growth before the bacteria form a complete monolayer, and is useful in predicting and modeling early growth of bacteria on implanted biomaterials. © 1996 John Wiley & Sons, Inc.
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    Immediate bone forming capability of prefabricated osteogenic hydroxyapatite (1996)
    Hoboken, NJ : Wiley-Blackwell
    Journal of Biomedical Materials Research 32 (1996), S. 481-492 
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    ISSN: 0021-9304
    Keywords: Chemistry ; Polymer and Materials Science
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Medicine , Technology
    Notes: We employed culture technology, which provides bone tissue in vitro, to expand and promote the osteogenic ability of marrow cells in porous hydroxyapatite (HA). Marrow cells were obtained from rat femur and cultured in a standard medium for 10 days, then trypsinized to make composites of HA and the cells. An additional 2-week culture (subculture) was done for the composite in a standard medium with or without the addition of dexamethasone (Dex). The 2-week subcultured composites were implanted into subcutaneous sites of syngeneic rats. These implants were harvested and prepared for the biochemical analysis of alkaline phosphatase activity and bone Gla protein content, as well as histological analysis of decalcified and undecalcified sections. In Dextreated composites, high alkaline phosphatase activity could be detected 1 week after implantation and was maintained until 8 weeks after implantation. The bone Gla protein content could also be detected 1 week after implantation, followed by a steady increase with the passage of time until 8 weeks after implantation. The histological analysis showed active bone formation even 1 week after implantation. The bone formation was evidenced by active osteoblast lining and the appearance of calcein labeling following calcein injection 1 week after implantation. Thus, Dex-treated subcultured marrow cells in pore regions of HA showed a high osteogenic response immediately after transplantation. In contrast, Dex-untreated composite did not show bone formation and contained traces of these biochemical parameters. These results indicate that the inherent osteogenic ability of marrow stromal stem cells in pore regions of HA can be stimulated using tissue culture technology; and thus, formed osteogenic HA can show immediate osteoblastic activity in in vivo situations, suggesting the applicability of the HA in clinical situations. © 1996 John Wiley & Sons, Inc.
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    Enhanced healing of segmental tibial defects in sheep by a composite bone substitute composed of tricalcium phosphate cylinder, bone morphogenetic protein, and type IV collagen (1996)
    Hoboken, NJ : Wiley-Blackwell
    Journal of Biomedical Materials Research 32 (1996), S. 505-512 
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    ISSN: 0021-9304
    Keywords: Chemistry ; Polymer and Materials Science
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Medicine , Technology
    Notes: Diaphyseal segmental defects in the tibia of 18 sheep were used to evaluate the healing potential of a composite bone substitute device (CBS) composed of a tricalcium phosphate cylinder (TCP), naturally occurring sheep bone morphogenetic protein (sBMP), and type IV collagen. A total of 100 mg of sBMP and 20 mg of type IV collagen in the high-dose group (CBSH), and 13 mg of sBMP and 2.5 mg of type IV collagen in the low-dose group (CBSL) were adsorbed to TCP cylinders, respectively. TCP cylinders impregnated with type IV collagen alone (TCPC) were used as control. A significantly larger area and more highly integrated intensity of newly formed external callus between CBSH and CBSL or TCPC group were quantified by computerized image analyzer at both 3 and 6 weeks. A torsion test showed that the maximal torque capacity, maximal angular deformation, and bone stiffness of healed osteotomized tibia with implants recovered 117-125% in CBSH, 72-109% in CBSL, and 63-80% in TCPC, compared with the corresponding contralateral tibia at 16 weeks. A healing superiority of the segmental bone defects replaced by the implants was demonstrated in the CBSH group. Thus, the composite bone substitute device defined in this study was shown to possess osteoinductivity, osteoconductivity, and mechanical strength. © 1996 John Wiley & Sons, Inc.
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    Subchondral bone and cartilage repair with bioactive glasses, hydroxyapatite, and hydroxyapatite-glass composite (1996)
    Hoboken, NJ : Wiley-Blackwell
    Journal of Biomedical Materials Research 32 (1996), S. 543-551 
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    ISSN: 0021-9304
    Keywords: Chemistry ; Polymer and Materials Science
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Medicine , Technology
    Notes: The repair of an osteochondral defect in rabbit femur was studied with three kinds of bioactive glasses (BG), hydroxyapatite (HA), and hydroxyapatite-glass (HAG) composite. Seventy-two osteochondral defects were created in 18 rabbits. Sixty-four cylinders were implanted and eight defects were left empty as controls. Histomorphometry, scanning electron microscopy (SEM) and energy dispersive X-ray analysis (EDXA) were used for evaluation. Small osteochondral defects in rabbit femur found to heal themselves by regeneration. The three BGs, HA, and HAG led to direct lamellar bone repair of subchondral bone and restoration of articular surfaces mostly with hyalinelike cartilage in 12 weeks. However, the composition of the materials affects their behavior. Chondrogenesis took place earlier with the BGs than with HA. HAG degraded too much, glass 14 was too reactive and brittle, and the high alumina content in glass 11 disturbed its bone-bonding ability. Glass 7 and HA were the most balanced in the repair process. A special preparation method was used to retain soft tissues fairly unchanged and enable them to the observed together with hard tissues in SEM analysis. © 1996 John Wiley & Sons, Inc.
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    Effects of Ca and H2O2 added to RPMI on the fretting corrosion of Ti6Al4V (1996)
    Hoboken, NJ : Wiley-Blackwell
    Journal of Biomedical Materials Research 32 (1996), S. 519-526 
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    ISSN: 0021-9304
    Keywords: Chemistry ; Polymer and Materials Science
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Medicine , Technology
    Notes: Titanium and its alloys have demonstrated considerable success in various surgical procedures including orthopedic, dental, and cardiovascular surgery. However, particulate debris from corrosion and wear is present in a considerable quantity in tissue local to the implant. This study evaluated the effect of Ca, since it is present in both serum and bone, and H2O2, since it is produced through local inflammation, on the amount of titanium release. Four sets of Ti6Al4V plates and Ti6Al4V screws were used. Each set was designated to one of four solutions: RPMI (cell culture growth media), RPMI with CaCl2, RPMI with CaCO3, and RPMI with H2O2. A fretter was used to cause corrosion by creating micromotion between two screws and a two-hole plate of Ti6Al4V. After fretting for 72 h, weight loss of the plate and screws and the amount of Ti and vanadium (V) in solution was used to assess the amount of fretting corrosion which had occurred. Results of weight loss and Ti in solution indicated that the presence of H2O2 increased the amount of particulate debris produced in RPMI as compared with RPMI alone. The addition of CaCl2 to RPMI also increased both weight loss and Ti in solution compared with RPMI alone. The addition of CaCO3, however, did not give values significantly different from RPMI alone. Comparison of weight loss and Ti in solution indicated that the increase in fretting corrosion was not different between RPMI with CaCl2 and RPMI with H2O2. The particulate wear debris from the four solutions was black in color and the size of the particulate produced was compared using a Coulter Multisizer. The results indicated that particles produced in the four solutions were not different, with mean values between 1.324 and 1.100 μm, and they were similar in size to the particulate found in tissues surrounding failed total hip replacements. In order to better understand the role of Ca in the fretting corrosion of Ti6Al4V, energy dispersive x-ray analysis (EDXA) using SEM was used to determine elemental composition of one countersink surface of a plate which had been run four times in RPMI with CaCl2. The presence of Ca in the bulk was not significant (% composition 〈 0.5%). However, Ca was present in two surface particles which were examined at a magnification of 55,000, with a Ca % composition of 63.2% and 19.2%. While results from this study indicate that both soluble Ca(CaCl2) and H2O2 increase the fretting corrosion of Ti6Al4V, the insoluble form of Ca, which would be found in bone and hydroxyapatite, has no effect. These data indicate that it is important to specify the media used in corrosion, dissolution, and elution experiments. © 1996 John Wiley & Sons, Inc.
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    Effects of batch to batch variations and test methodology on degree of crystallinity and melting temperature of UHMW-PE as measured by differential scanning calorimetry (1996)
    Hoboken, NJ : Wiley-Blackwell
    Journal of Biomedical Materials Research 32 (1996), S. 619-626 
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    ISSN: 0021-9304
    Keywords: Chemistry ; Polymer and Materials Science
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Medicine , Technology
    Notes: The thermal and structural analysis of a total 22 batches from three medical grade ultrahigh molecular weight polyethylene (UHMW-PE) resins was determined using the DSC method. Batch to batch variations of approximately 5% were obtained for the melting temperature and the degree of crystallinity. The variations correlated both to the changes caused by γ-irradiation sterilization and subsequent aging, and to the differences in DSC results obtained from various laboratories on materials believed to exhibit essentially similar clinical performances. Varying the sample weight from 4.4 to 27.1 mg resulted in a significant relative increase of 5% in the degree of crystallinity. The study shows that the standard double melting/recrystallisation procedure for DSC evaluation produces variations in the melting behaviors of approximately the same magnitude as those indicated by batch lot or sterilization/aging. © 1996 John Wiley & Sons, Inc.
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    A bibliography of monographic works on biomaterials and biocompatibility: Update (1996)
    Hoboken, NJ : Wiley-Blackwell
    Journal of Biomedical Materials Research 33 (1996), S. 107-113 
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    ISSN: 0021-9304
    Keywords: Chemistry ; Polymer and Materials Science
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Medicine , Technology
    Notes: This bibliography serves as an update to another by the same title that covered the years 1973 through 1992 and was published in Volume 4 of the Journal of Applied Biomaterials in 1993. The monographs listed here were published between 1992 and 1995. Both bibliographies are indexed as a combined work by conference titles, series titles, and name of associated corporate bodies including professional society, research institute, and government agency names. © 1996 John Wiley & Sons, Inc.
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    Masthead (1996)
    Hoboken, NJ : Wiley-Blackwell
    Journal of Biomedical Materials Research 33 (1996) 
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    ISSN: 0021-9304
    Keywords: Chemistry ; Polymer and Materials Science
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Medicine , Technology
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1002/jbm.1996.820330201
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    Apatite formation on silica gel in simulated body fluid: Its dependence on structures of silica gels prepared in different media (1996)
    Hoboken, NJ : Wiley-Blackwell
    Journal of Biomedical Materials Research 33 (1996), S. 145-151 
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    ISSN: 0021-9304
    Keywords: Chemistry ; Polymer and Materials Science
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Medicine , Technology
    Notes: It has been shown that the prerequisite for glasses and glass-ceramics to bond to living bone is the formation of a layer of biologically active bonelike apatite on their surfaces. The hydrated silica formed on the surfaces of glasses and glass-ceramics plays an important role in nucleating the apatite. In the present study, the structure of the hydrated silica responsible for the apatite nucleation was investigated in an accellular simulated body fluid with ion concentrations nearly equal to those of human blood plasma. Three kinds of porous silica gels were prepared by hydrolysis and polycondensation of tetraethoxysilane in pure water or in aqueous solution containing polyethylene glycol or polyacrylic acid. The silica gels prepared in aqueous solution containing polyethylene glycol or polyacrylic acid had micron-size interconnected pores, whereas the gel prepared in pure water did not. All the gels contained a large volume of nanometer-size pores, almost the same amounts of silanol groups and D2 defect, and showed a high dissolution rate of the silica. Despite this, only the gel prepared in the solution containing polyethylene glycol formed the apatite on its surface in the simulated body fluid. This indicates that only a certain type of structural unit of the silanol group is responsible for the apatite nucleation. © 1996 John Wiley & Sons, Inc.
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    Poly(2-hydroxyethyl methacrylate) particles for management of hemorrhage of complicated origin: Treatment of hemobilia (1996)
    Hoboken, NJ : Wiley-Blackwell
    Journal of Biomedical Materials Research 33 (1996), S. 193-197 
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    ISSN: 0021-9304
    Keywords: Chemistry ; Polymer and Materials Science
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Medicine , Technology
    Notes: Poly(2-hydroxyethyl methacrylate) (PHEMA) particles of cylindrical and spherical shape were developed as a preparation for tumor treatment or control of hemorrhage by blocking their blood supply. In this report, PHEMA particles were used for the management of hemobilia, that is, bleeding into biliary passages. The origin of hemobilia in 31 patients was localized by selective angiography. With the objective of prophylaxy of hemorrhage, selective embolization with PHEMA particles of the branches of the hepatic artery responsible for the supply of blood to the focus of damage was used in 18 patients. This low-trauma method allowed either a complete control of bleeding or, at least, intraoperative blood loss was reduced more than twice. Histological investigation of the occluded blood vessels showed that the thrombus was attached to the particles and was reinforced by the porous structure of the polymer. A hypercoagulation reaction was observed in the postembolization period. This allowed correction of the hypocoagulation in the hemostasis system. © 1996 John Wiley & Sons, Inc.
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    Fabrication and selective surface modification of 3-dimensionally textured biomedical polymers from etched silicon substrates (1996)
    Hoboken, NJ : Wiley-Blackwell
    Journal of Biomedical Materials Research 33 (1996), S. 205-216 
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    ISSN: 0021-9304
    Keywords: Chemistry ; Polymer and Materials Science
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Medicine , Technology
    Notes: A new method is described for producing biomedically relevant polymers with precisely defined micron scale surface texture in the x, y, and z planes. Patterned Si templates were fabricated using photolithography to create a relief pattern in photoresist with lateral dimensions as small as I μm. Electroless Ni was selectively deposited in the trenches of the patterned substrate. The Ni served as a resilient mask for transferring the patterns onto the Si substrate to depths of up to 8.5 μm by anisotropic reactive ion etching with a fluorine-based plasma. The 3-dimensional (3-D) textured silicon substrates were used as robust, reusable molds for pattern transfer onto poly(dimethyl siloxane), low density poly(ethylene), poly(L-lactide), and poly(glycolide) by either casting or injection molding. The fidelity of the pattern transfer from the silicon substrates to the polymers was 90 to 95% in all three planes for all polymers for more than 60 transfers from a single wafer, as determined by scanning electron microscopy and atomic force microscopy. Further, the 3-D textured polymers were selectively modified to coat proteins either in the trenches or on the mesas by capillary modification or selective coating techniques. These selectively patterned 3-D polymer substrates may be useful for a variety of biomaterial applications. © 1996 John Wiley & Sons, Inc.
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    Influence of enamel prophylaxis on wettability of three commercially available orthophosphoric acids (1996)
    Hoboken, NJ : Wiley-Blackwell
    Journal of Biomedical Materials Research 33 (1996), S. 269-274 
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    ISSN: 0021-9304
    Keywords: Chemistry ; Polymer and Materials Science
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Medicine , Technology
    Notes: An in vitro study was performed to assess the wettability of orthophosphoric acid after different procedures for cleaning the enamel surface. Ninety noncarious third molars were randomly distributed into three groups with different enamel surface treatments: an air-powder polisher unit, prophylaxis pastes, and no enamel surface cleaning. Three commercially available orthophosphoric acids were used, and there were 10 teeth in each group. Acid viscosity values and contact-angle measurements were obtained. Each enamel surface was also examined with the scanning electron microscope. Results suggested that the surface treatment with which the best spreading of the acid solution was attained was the air-powder polisher. The least spreading of the acid was obtained with prophylaxis pastes, in which contact angles were even higher than those obtained on the untreated enamel surface. The 3M acid solution was the one that showed the best spreading onto the enamel surface. © 1996 John Wiley & Sons, Inc.
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    Masthead (1996)
    Hoboken, NJ : Wiley-Blackwell
    Journal of Biomedical Materials Research 33 (1996) 
    Details
    ISSN: 0021-9304
    Keywords: Chemistry ; Polymer and Materials Science
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Medicine , Technology
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    URL: http://dx.doi.org/10.1002/jbm.1996.820330401
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    Characterization of silane-treated hydroxyapatite powders for use as filler in biodegradable composites (1996)
    Hoboken, NJ : Wiley-Blackwell
    Journal of Biomedical Materials Research 30 (1996), S. 231-238 
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    ISSN: 0021-9304
    Keywords: Chemistry ; Polymer and Materials Science
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Medicine , Technology
    Notes: Hydroxyapatite (HA) powder was treated with different silane adhesion promoters, to optimize its performance as a filler in polymer composites. The silane coupling agents investigated possessed vinyl, methacryloxy, primary amine, secondary amine, and diamine functionality. The different coatings were evaluated with respect to their influence on ionic exchange. X-ray photoelectron spectroscopy revealed the presence of a few monolayers thin silane films on HA powder. Silane coupling agents were able to bond chemically on the HA surface because a thin coating remained after washing of the powder with water. The water stability of this bond was evaluated by successive extractions and was judged limited, especially in the case of the hydrophilic aminosilanes. Zeta-potential measurements indicated the “transparency” of the coatings for ionic transport, that was corroborated by two in vitro dissolution studies, in Gomori's Tris-maleate buffer, and in simulated body fluid. However, aminosilane coatings could delay the release of calcium and phosphate ions during the first 2 days of immersion of treated HA powder in Gomori's buffer. © 1996 John Wiley & Sons, Inc.
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    Performance of small diameter synthetic vascular prostheses with confluent autologous endothelial cell linings (1996)
    Hoboken, NJ : Wiley-Blackwell
    Journal of Biomedical Materials Research 30 (1996), S. 221-229 
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    ISSN: 0021-9304
    Keywords: Chemistry ; Polymer and Materials Science
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Medicine , Technology
    Notes: Autologous grafts are superior to their synthetic counterparts for grafting arteries smaller than 6-mm diameter both in terms of acute thrombogenicity and chronic intimal hyperplasia. Endothelial cell (EC) coating of the blood contacting surface may reduce thrombogenicity of synthetic small diameter vascular prostheses. In this study, the survival of EC monolayers on synthetic 4-mm diameter arterial prostheses over short-term implantations (≤6 weeks) was examined. Graft types examined were expanded polytetrafluoroethylene (ePTFE) and microporous polyurethane (PU). Lumenal coverage with ECs was achieved by culturing ovine ECs on prostheses treated by either physical adsorption or covalent binding of ovine fibronectin (Fn). An ovine carotid interposition model was used to examine the performance of EC coated ePTFE and microporous PU over implantation periods of 1, 3, and 6 weeks. Outcomes assessed at the end of each experiment were graft patency, area covered by ECs, and thrombus free surface area (TFSA). Fn concentration, cell density at the time of coating and prostacyclin production in vitro were similar for both graft types. Occlusion occurred more frequently in unseeded grafts compared with EC coated grafts over 3 and 6 week implantation periods; however, the difference was not significant (p = 0.099). In prostheses precoated with ECs, approximately 40-60% of the surface area remained covered with endothelial-like cells following the first postoperative week. Recovery of EC layers occurred rapidly thereafter with 80-90% coverage at 3 weeks. TFSA remained low in comparison to EC cover in these prostheses until between 3 and 6 weeks postoperatively, suggesting a lag phase in recovery of EC function of seeded cells. In contrast, EC cover of unseeded prostheses only achieved 10-30% at 3 weeks, primarily by pannus EC ingrowth from the adjacent artery. TFSA of unseeded grafts increased in direct proportion to EC cover over time suggesting that there was no lag phase in function of these ingrowing cells. © 1996 John Wiley & Sons, Inc.
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    Effect of high external pressures on the vibrational spectra of biomedical materials: Calcium hydroxyapatite and calcium fluoroapatite (1996)
    Hoboken, NJ : Wiley-Blackwell
    Journal of Biomedical Materials Research 30 (1996), S. 239-244 
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    ISSN: 0021-9304
    Keywords: Chemistry ; Polymer and Materials Science
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Medicine , Technology
    Notes: Infrared and Raman spectra of the principal mineral component of human hard tissue, calcium hydroxyapatite, Ca10(PO4)6(OH)2, or HAP, and the analogous calcium fluoroapatite, Ca10(PO4)6F2, or FAP, have been recorded, using a diamond-anvil cell, at pressures ranging from ambient to 30 kbar. For FAP, the absence of any discontinuities in the slopes of the v (cm-1) versus P (kbar) plots for the observed bands indicates that no pressure-induced structural transition occurs in this material throughout the pressure range investigated. For the internal vibrational modes of HAP, however, there are distinct breaks at ∼20 kbar in the v versus P plots, suggesting the occurrence of a structural change at this pressure. The OH stretching mode of HAP shifts to higher wave numbers with increasing pressure while the associated OH librational mode shifts in the opposite direction. The pressure-induced structural transition in HAP is reversible and occurs at ∼22 kbar upon decompression. Further evidence for a structural change taking place at ∼20 kbar was provided by a parallel pressure-tuning Raman study. Hydrogen bonding does not occur, or is very weak, in HAP. © 1996 John Wiley & Sons, Inc.
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    Contribution of vascular catheter material to the pathogenesis of infection: Depletion of complement by silicone elastomer in vitro (1996)
    Hoboken, NJ : Wiley-Blackwell
    Journal of Biomedical Materials Research 30 (1996), S. 245-250 
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    ISSN: 0021-9304
    Keywords: Chemistry ; Polymer and Materials Science
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Medicine , Technology
    Notes: We previously have shown that vascular catheters made of silicone elastomer carry a greater risk of subcutaneous infection with Staphylococcus aureus than do polyurethane (PU), polyvinylchloride (PVC), or Teflon® catheters. We further have shown that there is greater inflammation surrounding silicone catheters than there is surrounding catheters made of the other materials, suggesting that silicone produces a greater chemotactic gradient than do the other materials. This study used a functional complement opsonization assay and radioimmunoassays to compare the relative abilities of silicone, polyurethane, and polyvinylchloride to activate complement. Serum incubated in silicone catheters for 24 h had less than 30% of the opsonizing ability of fresh serum while ≥78% of the opsonizing ability remained with serum incubated in PU or PVC catheters. Measurement of C3a des Arg, C4a des Arg, C5a des Arg, and SC5b-9 demonstrated that the loss of opsonizing ability was due to 10-fold greater alternate pathway complement activation by silicone than by PU or PVC. This finding suggests that excessive complement activation by silicone may explain the greater inflammation seen around silicone catheters in vivo and also might play a role in silicone's creating a greater risk of infection. © 1996 John Wiley & Sons, Inc.
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    In vitro platelet adhesion to nonionic and ionic hydrogels with different water contents (1996)
    Hoboken, NJ : Wiley-Blackwell
    Journal of Biomedical Materials Research 30 (1996), S. 295-304 
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    ISSN: 0021-9304
    Keywords: Chemistry ; Polymer and Materials Science
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Medicine , Technology
    Notes: To investigate in vitro platelet adhesion to hydrogels, using electron-beam irradiation, polymer reaction, and radical polymerization, hydrogels were synthesized to have a wide range of water content. The nonionic synthesized hydrogels include polyacrylamide (PAAm), poly(vinyl alcohol) (PVA), poly(ethylene glycol) (PEG), poly(N-vinyl pyrrolidone), and poly(methoxy-PEG methacrylate) while the ionic hydrogels were crosslinked poly(AAm-acrylic acid) and poly(AAm-dimethylaminoethyl methacrylate) copolymers. Adhesion of washed rabbit platelets to these hydrogels were studied in phosphate-buffered saline for 30 min. In the case of PVA and PAAm hydrogels, platelet adhesion also was conducted in the presence of proteins. The protein sorption into PVA hydrogel was studied by fluorescent spectroscopy. It was found that all the nonionic hydrogels exhibited a lower level of platelet adhesion than did conventional hydrophobic polymers, such as medical-grade poly(vinyl chloride), polyurethane, and silicone, and they exhibited the minimum platelet adhesion at a water content of around 90%. PAAm and PEG hydrogels had the weakest interaction with platelets when the water content was lower than 90%. PVA hydrogel showed the highest platelet adhesion in the low-water-content region, but the platelet adhesion was greatly reduced in the presence of proteins. Significant protein sorption was noted when the water content of PVA hydrogel was as high as 80%. Introduction of a positive charge into the PAAm hydrogel promoted platelet adhesion whereas the negative charge introduced into the hydrogel slightly reduced the number of adhered platelets. © 1996 John Wiley & Sons, Inc.
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    Pillared-surface microstructure and soft-tissue implants: Effect of implant site and fixation (1996)
    Hoboken, NJ : Wiley-Blackwell
    Journal of Biomedical Materials Research 30 (1996), S. 305-312 
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    ISSN: 0021-9304
    Keywords: Chemistry ; Polymer and Materials Science
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Medicine , Technology
    Notes: Previous work with subcutaneous implants in a rat animal model has shown that pillarlike surface microstructure will reduce fibrosis and enhance blood vessel approximation to the implant surface when compared with nontextured controls. This study was designed to determine the effect of microtissue anatomy and implant site on the observed response, as well as the effect of implant fixation. The lateral posterior sites were found to contain a fat pad which produced a dramatically reduced fibrosis for the microstructured implants compared with smooth controls. Although significant differences between pillar-microstructured implants and controls were found for most sites, neither fascia nor muscle reduces the level of cellular response to the same degree as fat. Suture fixation of the implants did not produce a significantly different response in these tests. The occupation of the interpillar spaces by fat and moderation of interfacial shear forces is proposed as a mechanism to explain these results. © 1996 John Wiley & Sons, Inc.
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    Biocompatible coatings for luminal and outer surfaces of small-caliber artificial grafts (1996)
    Hoboken, NJ : Wiley-Blackwell
    Journal of Biomedical Materials Research 30 (1996), S. 321-330 
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    ISSN: 0021-9304
    Keywords: Chemistry ; Polymer and Materials Science
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Medicine , Technology
    Notes: Luminal and outer surfaces and small-caliber vascular grafts at an early implantation period may require completely opposite cellular responses: minimal cellular adhesion and fibrin formation for a luminal surface versus potent cellular adhesion and migration and matrix generation for an outer surface. Differentiated biocompatible design of luminal and outer surfaces into small-caliber artificial grafts may lead to successful healing. We molecularly designed photocurable extracellular matrices (ECMs): photocurable chondroitin sulfate (CS) and hyaluronic acid (HA) for the luminal surface coating and photocurable gelatin for the outer surface coating. All of them were partially derivatized with photodimerizable groups such as thymine, cinnamate, and coumarin groups and converted to produce water-insoluble gels upon ultraviolet irradiation. In vitro study showed that platelet adhesion on photogelled CS and HA was significantly reduced, whereas endothelial cells adhered well on photogelled gelatin. These materials were individually coated and photogelled onto respective surfaces of artificial grafts (inner diameter [ID], 5 mm). During acute-phase implantation into dogs for up to 1 week, minimal cell adhesion was observed on the luminal surface, which was uniformly covered by photogelled CS or HA. Heparin impregnation of photocured ECM reduced fibrin formation. On the other hand, enhanced tissue ingrowth was noted at the outer surface. Although these ECM-coated grafts need further improvement in molecular design and coating techniques, photocurable ECMs may contribute to successful healing and a high patency rate of small-caliber artificial grafts. © 1996 John Wiley & Sons, Inc.
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    Confocal laser-scanning microscopy for determining the structure of and keratinocyte infiltration through collagen sponges (1996)
    Hoboken, NJ : Wiley-Blackwell
    Journal of Biomedical Materials Research 30 (1996), S. 331-339 
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    ISSN: 0021-9304
    Keywords: Chemistry ; Polymer and Materials Science
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Medicine , Technology
    Notes: The development of artificial skin substitutes based on cultured cells and biomaterials such as collagen requires an understanding of cellular interactions with the substrate. In this study, human keratinocytes were cultured on the surface of collagen sponges, and confocal laser-scanning microscopy (CLSM) was used to assess both the microstructure of the sponge, and the cell morphology and distribution throughout the sponge. It was found that the pore size increased with increasing depth into the sponge. Both pore size and fiber thickness increased during incubation for up to 10 days at 37°C in culture medium in the absence of cells. This latter effect was not observed when the sponges were incubated in distilled water. Keratinocytes penetrated into the sponge even after only 3 days in culture. By 10 days in culture, the cells had penetrated to the maximum depth that could be examined (120 μm from the sponge surface). In the presence of cells, the inner structure of the collagen sponge had altered after 10 days in culture, with the collagen fibers becoming thicker, and pore geometry less regular. The mechanism responsible for this is unknown at present. Although the presence of the keratinocytes increases distortion of the sponge structure, factors from the medium itself also contribute to this effect. CLSM is a powerful tool for assessing cellular interactions with bioimplants, providing both qualitative and quantitative information. It offers many advantages over scanning electron microscopy (SEM) and histological techniques. CLSM minimizes the time-consuming, extensive preparation of samples required with the latter two methods, and allows noninvasive serial optical sectioning of intact samples. © 1996 John Wiley & Sons, Inc.
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    Light and electron microscopic studies of bone-titanium interface in the tibiae of young and mature rats (1996)
    Hoboken, NJ : Wiley-Blackwell
    Journal of Biomedical Materials Research 30 (1996), S. 523-533 
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    ISSN: 0021-9304
    Keywords: Chemistry ; Polymer and Materials Science
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Medicine , Technology
    Notes: Bone-titanium contact was examined in young and mature rats on various days after insertion of pure titanium into the tibia. Under light microscopy, on the 14th day, lamellar mature bone was initially formed, and was seen to make direct contact with the titanium in both groups. In young rats on the 28th day, bone-titanium contact was greater than that in mature animals. On 1-μm sections, an amorphous zone 0.5-1.0 μm thick was found around the titanium, and a slender cell layer lay parallel to the implant, forming the superficial layer of the amorphous zone. Ultrastructurally, these slender cells were identified as osteoblastlike cells and made direct contact with the implant via a 20-50-nm thin amorphous zone. Below this cell layer, a collagen-containing, poorly mineralized zone was present and bordered by lamellar bone with a lamina limitans-like structure. However, this cell layer was absent in places, and therefore the thick amorphous zone without slender cell layer consisted ultrastructurally of a 20-50-nm thin amorphous zone and a poorly mineralized zone bordered by the lamellar bone. Sometimes this poorly mineralized zone was absent, and in such cases, the lamellar bone contacted the titanium by the thin amorphous zone formed on the lamina limitans-like structure. Thus, although bone was seen to make contact with the titanium implant, ultrastructurally a 20-50-nm thin amorphous zone, a slender cell layer, and/or a poorly mineralized zone were interposed between the bone and titanium. © 1996 John Wiley & Sons, Inc.
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    Interactions of osteoblasts and macrophages with biodegradable and highly porous polyesterurethane foam and its degradation products (1996)
    Hoboken, NJ : Wiley-Blackwell
    Journal of Biomedical Materials Research 32 (1996), S. 355-366 
    Details
    ISSN: 0021-9304
    Keywords: Chemistry ; Polymer and Materials Science
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Medicine , Technology
    Notes: The macrophage cell line J774, primary rat osteoblasts, and the osteoblast cell line MC3T3-E1 were used to examine the biocompatibility of a newly developed polyesterurethane foam and the possible use of this structure as bone-repair materials. The newly developed, biodegradable, and highly porous (pore size 100-150 μm) DegraPol/btc® polyesterurethane foam was found to exhibit good cell compatibility; the cell-to-substrate interactions induced neither cytotoxic effects nor activation of macrophages. Osteoblasts and macrophages exhibited normal cell morphology. No signs of cell damage were detected using scanning electron microscopy (SEM). No significant increase in the production of tumor necrosis factor-α (TNF-α) or nitric oxide (NO) was detected in macrophages. Compared with cells cultured on tissue culture polystyrene (TCPS), macrophages exhibited relatively high cell attachment (150% of TCPS) but significantly high doubling time (about 8 days) compared with TCPS (4.6 days). Primary rat osteoblasts and the osteoblast cell line exhibited relatively high attachment (140% and 180% of TCPS, respectively) and a doubling time of about 5 days, compared with TCPS (6 days and 8.8 days, respectively). Eight days after cell seeding, osteoblasts exhibited a confluent cell multilayer and migrated into the pores of the polymer. In addition they produced high concentrations of collagen type I, the main protein of the bone, and expressed increasing alkaline phosphatase activity and osteocalcin production throughout the 12 days of the experiment. During degradation of these polymers, small crystalline particles of short-chain poly[(R)-3-hydroxybutyric acid] (M n ≈ 2300) (PHB-P) are released. Therefore PHB-P (diameter, 2-20 μm), as possible degradation products of the polymer, are investigated here for their effects on macrophages and osteoblasts. Results obtained in the present study clearly indicate that macrophages and, to a lesser degree, osteoblasts have the ability to take up (phagocytose) PHB-P. At low concentrations particles of PHB failed to induce cytotoxic effects or to activate macrophages. Osteoblasts showed only limited PHB-P phagocytosis and no signs of cellular damage. At high concentrations of PHB-P, this process was accompanied by cytotoxic effects in macrophages (〉200 pg PHB-P/cell) and to a lesser extent in osteoblasts (〉400 pg PHB-P/cell). © 1996 John Wiley & Sons, Inc.
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    Improved blood compatibility of segmented polyurethanes by polymeric additives having phospholipid polar groups. I. Molecular design of polymeric additives and their functions (1996)
    Hoboken, NJ : Wiley-Blackwell
    Journal of Biomedical Materials Research 32 (1996), S. 391-399 
    Details
    ISSN: 0021-9304
    Keywords: Chemistry ; Polymer and Materials Science
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Medicine , Technology
    Notes: To improve the blood compatibility of a segmented polyurethane (SPU), 2-methacryloyloxyethyl phosphorylcholine (MPC) polymer was blended with the SPU. The MPC was copolymerized with cyclohexyl methacrylate (CHMA) or 2-ethylhexyl methacrylate (EHMA), and the MPC polymers obtained could be dissolved in the same solvent as the SPU (Tecoflex® 60). The blended membranes composed of SPU and MPC polymers were prepared by a solvent evaporation method. A small amount of MPC polymer in the blended membrane leached out after immersion in water for 10 days. The X-ray photo electron spectra indicated that the MPC moieties were located at the surface of the SPU membrane blended with poly(MPC-co-CHMA). On the other hand, the poly-(MPC-co-EHMA) was located homogeneously in the SPU membrane. The mechanical properties of the SPU membrane, as determined by tensile stress-strain measurements, changed very little even after addition of the MPC polymers. Blood compatibility of the blended membrane was evaluated by blood-cell adhesion on the surface when the membranes were placed in contact with rabbit whole blood or platelet-rich plasma. The addition of MPC polymer in the SPU membrane dramatically reduced cell adhesion. It is concluded that the blending of the MPC polymer in the SPU membrane is an effective method for imparting nonthrombogenicity. © 1996 John Wiley & Sons, Inc.
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    Endotoxin rejection by ultrafiltration through high-flux, hollow fiber filters (1996)
    Hoboken, NJ : Wiley-Blackwell
    Journal of Biomedical Materials Research 32 (1996), S. 467-471 
    Details
    ISSN: 0021-9304
    Keywords: Chemistry ; Polymer and Materials Science
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Medicine , Technology
    Notes: The efficacy of endotoxin (ET) rejection of four hollow fiber membranes with comparable sieving properties was evaluated in an ultrafiltration experiment. The solution conditioned with type I lipopolysaccharide (LPS) from Escherichia coli, 80,000 endotoxin units (EU)/L, was filtered through polyesterpolymer alloy (PEPA), polymethyl methacrylate (PMMA), polyacrylonitrile (PAN), and polysulfone (PS) membranes. The ET activity of the filtrate was not detectable in PEPA and PMMA, 6.4 ± .04 (mean ± SD) EU/L in PAN, and 10.3 ± 1.1 EU/L in PS. The ET activity of the filtrate of type II LPS from Acinetobacter solution, 80,000 EU/L, was not detectable in PEPA, 3.7 ± 0.4 EU/L in PMMA, 16.5 ± 1.5 EU/L in PAN, and 20.7 ± 1.4 EU/L in the PS filter. The order of the rejection capability coincided with the adsorptive capacity as shown by the decrement in ET levels of solutions filled within the filter modules in the adsorption equilibrium experiment. In conclusion complete rejection of ET molecules can be achieved by ultrafiltration through hydrophobic membranes having a high adsorptive capacity in addition to an appropriate sieving property for ET molecules. © 1996 John Wiley & Sons, Inc.
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    Masthead (1996)
    Hoboken, NJ : Wiley-Blackwell
    Journal of Biomedical Materials Research 32 (1996) 
    Details
    ISSN: 0021-9304
    Keywords: Chemistry ; Polymer and Materials Science
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Medicine , Technology
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1002/jbm.1996.820320301
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    Pharmacologic inhibition of particulate-induced bone resorption (1996)
    Hoboken, NJ : Wiley-Blackwell
    Journal of Biomedical Materials Research 31 (1996), S. 91-96 
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    ISSN: 0021-9304
    Keywords: Chemistry ; Polymer and Materials Science
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Medicine , Technology
    Notes: In this study, a rat calvaria/macrophage co-culture model was used to study the effects of various agents upon bone resorption induced by macrophage exposure to bone cement particles. The experimental group consisted of calvaria bone disks set in tissue culture medium on stainless-steel platforms into wells with macrophages adherent to the bottom which are exposed to the particles. Tumor necrosis factor α (TNF-α), prostaglandin E2 (PGE2), and calcium 45 (Ca45) were released in significant amounts in this system. Interleukin 1α (IL-1α) was not detected. Indomethacin inhibited the production of PGE2, but did not affect TNF release or inhibit the release of Ca45. Anti-TNF antibody neutralized the presence of TNF to undetectable levels, but did not affect PGE2 release or inhibit Ca45 release. The addition of calcitonin did not inhibit Ca45 release by calvaria. In contrast, the addition of disodium pamidronate, a member of the bisphosphonate family, was effective in inhibiting the release of Ca45 even after 96 h of incubation. In prior studies, incubation of calvaria in conditioned medium from macrophages exposed to cement particles led to resorption through a mechanism which is dependent upon TNF production by macrophages, and PGE2 production by cells in bone. In this two-way system, in which macrophages and cells in bone are allowed to interact, this dependency was no longer evident. Pamidronate was the only agent tested which suppressed the increase in bone resorption associated with macrophage exposure to bone cement particles to levels which were not significantly different from unexposed calvaria. By delaying or preventing bone resorption associated with macrophage exposure to bone cement particles, bisphosphonates may have a clinical role in cemented joint arthroplasty by decreasing the rate or incidence of aseptic loosening and prolonging implant longevity. © 1996 John Wiley & Sons, Inc.
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    In vitro cell response to differences in poly-L-lactide crystallinity (1996)
    Hoboken, NJ : Wiley-Blackwell
    Journal of Biomedical Materials Research 31 (1996), S. 17-30 
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    ISSN: 0021-9304
    Keywords: Chemistry ; Polymer and Materials Science
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Medicine , Technology
    Notes: Many different processing techniques are currently being used to produce tissue regeneration devices from polyesters in the polylactide/polyglycolide family. While it is generally well recognized that processing techniues influence buil mechanical and degradation properties of these materials, the effects on surface properties are relatively less well studied. We thus investigated the effects of processing conditons that are known to change bulk properties, but not composition, on the surface properties of poly-L-lactide (PLLA). Specifically, we investigated the role of bulk crystallinity of PLLA substrates on several physicochemical aspects of the surface and on the attachment, morphology, and differentiated function of cultured primary hepatocytes and growth of 3T3 fibroblasts. We fabricated smooth, clear PLLA films of 13-37% crystallinity. Glancing angle X-ray diffraction indicated that low crystallinity films lacked order in the first 50 A of the surface while relatively high crystallinity films had detectable order in this range. In other aspects, the surfaces of all PLLA substrates appeared identical with XPS, SEM, and advancing contact angle analysis, but contact angle hysteresis was slightly greater for more crystalline films. Although the physicochemical properties of the surfaces appeared almost identical, we observed differences in cell behavior on less crystalline versus more crystalline films. Hepatocytes formed spheroids on all PLLA substrates, but spheroid formation was faster (24-48 h) on crystalline substrates. Quantitative image analysis was used to assess the average cell area as a function of time in culture, and our data confirm previous reports that retention of differentiated function is inversely related to cell spreading where function was assessed by P-450 enzyme activity. In addition, the growth rate of 3T3 fibroblasts was lower on crystalline substrates than on amorphous substrates. An important conclusion from this work is that processing techniques that lead to seemingly inconsequential changes in bulk and surface properties of these polymers may influence biological response. © 1996 John Wiley & Sons, Inc.
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    A study of the influence of biphase calcium phosphate ceramics on bacterial strains: In vitro approach (1996)
    Hoboken, NJ : Wiley-Blackwell
    Journal of Biomedical Materials Research 31 (1996), S. 219-226 
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    ISSN: 0021-9304
    Keywords: Chemistry ; Polymer and Materials Science
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Medicine , Technology
    Notes: An in vitro study of the influence of Biphase Calcium Phosphate Ceramics (BCPCs) on bacterial strains is presented. The test procedures were carried out in saline test solution to which different quantities (2,4,50,100, and 200 mg) of BCPCs(samples A and B) were added. The influence of BCPCs on standard bacterial strains has been determined by measuring bacterial contamination using the plate count method.The testing method was validated with membrane filtration and direct inoculation in culture media of sediment and supernatant. The test demonstrated reduction of the bacterial cell population in from 1 to 24 h in all experiments. The antibacterial effect revealed the specific inherent properties of the BCPCs under investigation. © 1996 John Wiley & Sons, Inc.
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    Quantitative assessment of apatite formation via a biomimetic method using quartz crystal microbalance (1996)
    Hoboken, NJ : Wiley-Blackwell
    Journal of Biomedical Materials Research 31 (1996), S. 243-249 
    Details
    ISSN: 0021-9304
    Keywords: Chemistry ; Polymer and Materials Science
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Medicine , Technology
    Notes: Quantitative assessment of hydroxyapatite formation on a gold surface via the biomimetic method, composed of a nucleation step in a simulated body fluid (SBF) containing glass powders and a subsequent apatite growth step in glass powder-free SBF, was made using a quartz crystal microbalance (QCM) technique. The frequency change of the QCM linearly increased with increasing soaking time, and largely depended on the nucleation period. The growth rates, defined as daily increase in thickness, increased monotonicly with an increasing nucleation period of up to 96 h, thereafter being constant at 2.0 μm/day. The growth rate of the apatite layer increased with increasing temperature of the SBF: 0.9, 2.0, and 3.8 μm/day at 25, 37, and 50°C, respectively. The Arrhenius-type activation energy for the growth of apatite was 47.3 kJ/mol. The QCM method was found to be a very powerful tool for quantitative, in situ measurement of precipitation and growth of apatite in real time. © 1996 John Wiley & Sons, Inc.
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    Conjugates of insulin with copolymers of N-(2-hydroxypropyl) methacrylamide: Effects on smooth muscle cell proliferation (1996)
    Hoboken, NJ : Wiley-Blackwell
    Journal of Biomedical Materials Research 31 (1996), S. 265-272 
    Details
    ISSN: 0021-9304
    Keywords: Chemistry ; Polymer and Materials Science
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Medicine , Technology
    Notes: The hypothesis that an elevated plasma insulin level contributes to an increase in coronary heart disease has led to studies of the mitogenic effect of native insulin and its conjugates on smooth muscle cells (SMC). In this study, insulin was covalently attached to two water-soluble polymers containing N-(2-hydroxypropyl)methacrylamide using the mixed anhydride method. The first polymer was a copolymer of N-(2-hydroxypropyl)methacrylamide and N-methacryloyldiglycine. The second one was a terpolymer of two of the above-given monomers and R-(-)-1-methyl-2-methacryloylamidoethyl 2-acetamido-2-deoxy-β-D-glucopyranoside. Insulin conjugates were isolated and characterized, and the mitogenic effect on SMC was investigated. The results showed that only conjugates of insulin and terpolymers bearing pendant N-acetyl-glucosamine groups do not have a mitogenic effect on SMC while maintaining the hypoglycemic activity of insulin. This finding suggests that some inter- or intramolecular interactions of coupled insulin with the sugar moiety(ies) attached to the polymer backbone contribute to the observed effects. © 1996 John Wiley & Sons, Inc.
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    Masthead (1996)
    Hoboken, NJ : Wiley-Blackwell
    Journal of Biomedical Materials Research 31 (1996) 
    Details
    ISSN: 0021-9304
    Keywords: Chemistry ; Polymer and Materials Science
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Medicine , Technology
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1002/jbm.1996.820310201
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    Complement activation by IgG immobilized on methylated silicon (1996)
    Hoboken, NJ : Wiley-Blackwell
    Journal of Biomedical Materials Research 31 (1996), S. 305-312 
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    ISSN: 0021-9304
    Keywords: Chemistry ; Polymer and Materials Science
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Medicine , Technology
    Notes: Activation of the complement system by immobilized IgG on methylated silicon was studied by ellipsometry/antibody-, ELISA-, and RIA techniques after exposure to human serum at 37°C for up to 1 h. The IgG-covered surfaces rapidly activated the complement system and the combined results suggest an initial classical pathway activation. Complement factor 1q (C1q) and IgG were antibody-detectable on the surfaces for serum incubations up to 5 min but not thereafter. Anti-C3c and anti-properdin bound to the surfaces at all serum incubation times. Experiments with 125I-IgG preadsorbed to surfaces, or added to normal-, EGTA-, and EDTA-sera, showed that IgG was not displaced from the protein film by serum. © 1996 John Wiley & Sons, Inc.
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    Local accumulation of titanium released from a titanium implant in the absence of wear (1996)
    Hoboken, NJ : Wiley-Blackwell
    Journal of Biomedical Materials Research 31 (1996), S. 227-234 
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    ISSN: 0021-9304
    Keywords: Chemistry ; Polymer and Materials Science
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Medicine , Technology
    Notes: Titanium and its alloys, like the majority of metallic implant materials, release passive metal dissolution products. This raises the issues of amount and fate, i.e. transport, storage, and/or excretion of these metal dissolution products. In this paper we document titanium levels in tissues local to a commercially pure titanium implant in the absence of wear; compare these values to control tissues; and determine the relative contribution of the local accumulation to total release. Titanium fiber felts were implanted into the tibia of rabbits for periods up to 1 year. Bone and muscle tissue samples near the implant were collected. Using electrothermal atomic absorption spectrophotometry the samples were analyzed for titanium content.Compared to controls, titanium levels in the bone near the implant were elevated at 1-, 4-, and 12-month postoperative time points. The 12-month time point had higher periprosthetic bone titanium levels than both the 1- and the 4-month implant groups. Titanium levels in muscle tissue near the felt also indicated release was occurring. The data support the hypothesis that metal species released from titanium implants in the absence of wear have a limited solubility. As a result, they tend to remain in an area local to the implant. © 1996 John Wiley & Sons, Inc.
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    Thermomechanical investigation of poly(methylmethacrylate) containing an organobismuth radiopacifying additive (1996)
    Hoboken, NJ : Wiley-Blackwell
    Journal of Biomedical Materials Research 31 (1996), S. 339-343 
    Details
    ISSN: 0021-9304
    Keywords: Chemistry ; Polymer and Materials Science
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Medicine , Technology
    Notes: Previously we demonstrated the feasibility of using up to 24% triphenylbismuth (TPB) as a radiopaque, monomer-miscible additive for dental acrylic resins. In this study we examined the influence of TPB on thermomechanical properties of a representative polymethylmethacrylate (PMMA) ambient-cured resin used for temporary dental crowns and bridges. TPB (0%, 5%, 15% or 30% w/w) was dissolved in the monomer component, added to the powder component, and allowed to cure in rectangular molds. After 1 h they were either stored at 23°C for 23 h, or heated for 5 min at either 40°C or 50°C, and then stored for 23 h. They were then scanned from -10° to 125°C in a dynamic mechanical thermal analyzer using the three-point bending mode of deformation at 1-Hz frequency.The onset to the glass-transition temperature (Tg) is decreased by 13° to 32°C by addition of TPB, while the storage modulus (E′) at 25°C is either unchanged or is slightly increased. TPB did not interfere with the curing reaction, and postcure heating at 40°C had no effect on either E′ or Tg. However, heating at 50°C generally increased Tg but had very little effect on E′ throughout the 0-50°C operating temperature range. TPB crystals were observed to have precipitated at TPB levels above 8%. These crystals, dispersed throughout the PMMA, act as reinforcing fillers. This reinforcement can account for the lack of a decrease in E′, as would be expected if TPB had a plasticizing effect below Tg. However, even at 5%, a concentration at which all the TPB remains dissolved in the solid polymer, no decrease in E′ was observed. This implies that TPB exerts an antiplasticizing effect at temperatures below 50°C, possibly by occupying free volume among the polymer chains.It is concluded that TPB, in amounts adequate to impart diagnostic levels of radiopacity, is unlikely to adversely affect the clinical utility of PMMA-based dental acrylic resins. © 1996 John Wiley & Sons, Inc.
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    Bone regeneration with resorbable polymeric membranes. III. Effect of poly(L-lactide) membrane pore size on the bone healing process in large defects (1996)
    Hoboken, NJ : Wiley-Blackwell
    Journal of Biomedical Materials Research 31 (1996), S. 385-394 
    Details
    ISSN: 0021-9304
    Keywords: Chemistry ; Polymer and Materials Science
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Medicine , Technology
    Notes: Poly(l-lactide) membranes of various pore sizes: microporous, medium pore size (10-20 μm), and large pore size (20-200 μm) were implanted in 15 mature New Zealand female rabbits to cover a 10-mm diaphyseal defect created in the radius. Five rabbits were implanted with each membrane. No internal fixation was used, as it was assumed that the intact ulna splints the radius adequately. Postoperative radiographs revealed the formation of hematoma within the bone defect. At the 2nd week after surgery, the hematoma was resorbed and the formation of new bone was noted radiologically either at the ends of the bone fragments or as osteophytes on the proximal and distal edges of the membrane. At 4 weeks, the newly formed bone was growing centripetally from the fragment ends. The bone regeneration took place in the majority of the cases under investigation, regardless of the pore size of the polymeric membranes used. There were, however, some differences in the intensity of the bone regeneration process. Although at 2 weeks after surgery bone formation was seen radiographically in all animals, at 6 months five rabbits of five, four rabbits of five, and three rabbits of five implanted respectively with microporous membrane, medium pore-size membrane, and large pore-size membrane showed complete regeneration of bone within the defects. It is suggested that the primary function of the membrane used to cover bone defects is to preserve the osteogenic components present in the space under the membrane from escaping and support the growth of cells within the “medullary cavity” formed by the tubular implant. © 1996 John Wiley & Sons, Inc.
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    Announcement (1996)
    Hoboken, NJ : Wiley-Blackwell
    Journal of Biomedical Materials Research 31 (1996), S. 437-437 
    Details
    ISSN: 0021-9304
    Keywords: Chemistry ; Polymer and Materials Science
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Medicine , Technology
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1002/jbm.1996.820310302
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    Preparation of stable aqueous solution of keratins, and physiochemical and biodegradational properties of films (1996)
    Hoboken, NJ : Wiley-Blackwell
    Journal of Biomedical Materials Research 31 (1996), S. 439-444 
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    ISSN: 0021-9304
    Keywords: Chemistry ; Polymer and Materials Science
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Medicine , Technology
    Notes: A stable aqueous solution of reduced keratins was prepared by extracting the proteins from wool (Corriedale) with a mixture of urea, mercaptanol, surfactant, and water at 40-60°C. Sodium dodecyl sulfate was especially effective as a surfactant, not only in promoting extraction but also in stabilizing the aqueous protein solution. The proteins had the following constants: MW, 52,000-69,000 daltons; cysteine content, 8-9 mol %; pl about 6.7. A clear film was readily prepared from a keratin solution containing glycerol. The film was insoluble in water and organic solvents including dimethyl sulfoxide. The keratin film was permeable to glucose, urea, and sodium chloride. The keratin film was degraded in vitro (by trypsin) and in vivo (by subcutaneous embedding in mice). © 1996 John Wiley & Sons, Inc.
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    Novel fracture toughness test using a notchless triangular prism (NTP) specimen (1996)
    Hoboken, NJ : Wiley-Blackwell
    Journal of Biomedical Materials Research 31 (1996), S. 457-463 
    Details
    ISSN: 0021-9304
    Keywords: Chemistry ; Polymer and Materials Science
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Medicine , Technology
    Notes: The aim of this study was to develop and validate a new method for determining the fracture toughness of materials and adhesive interfaces. The new test specimen is a notchless triangular prism (NTP) which, when placed in the testing holder, achieves a configuration similar to that of the standard chevron-notched short rod (CNSR) specimen. It can be cast, ground, or simply machined easily and reproducibly without cutting an initial notch. Finite element analysis of a modeled NTP specimen loaded in tension showed a stress distribution similar to a CNSR specimen. A very good correlation was obtained between the NTP and CNSR fracture toughness values of poly(methyl methacrylate) during a calibration study. Fracture toughness values similar to those reported in the literature were obtained for several dental materials and one adhesive interface using the NTP test. The fracture patterns were indicative of plane strain conditions during testing. All bulk specimens and most of the adhesive specimens showed crack arrest, which suggested a stable, well-controlled testing procedure. These results suggest that the NTP fracture toughness test can be used to determine the fracture mechanics of bulk materials and adhesive interfaces. © 1996 John Wiley & Sons, Inc.
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    Characterization of apatite layer formation on P2O5-CaO, P2O5-CaO-Na2O, and P2O5-CaO-Na2O-Al2O3 glass hydroxyapatite composites (1996)
    Hoboken, NJ : Wiley-Blackwell
    Journal of Biomedical Materials Research 31 (1996), S. 481-486 
    Details
    ISSN: 0021-9304
    Keywords: Chemistry ; Polymer and Materials Science
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Medicine , Technology
    Notes: P2O5-based glass hydroxyapatite (HA) composites denoted HA-2 oxide, HA-3 oxide, and HA-4 oxide, were immersed in Hank's balanced salt solution for a period of 1, 2, 3, and 4 weeks at 37°C in nonagitated condition for in vitro evaluation. A surface layer was precipitated on the composites that was analyzed using scanning electron microscopy (SEM), X-ray photoelectron spectroscopy, and thin film X-ray diffractometry (TF-XRD). SEM micrographs showed complete coverage of the composite surface by crystallites after immersion of 1 week in the solution, which grew thicker with respect to immersion time. The binding energies measured by XPS indicated apatite formation and the presence of carbonate on the composite surface, showing the newly formed layer was a carbonated apatite. Confirmation of the formed apatite layer was obtained by TF-XRD. © 1996 John Wiley & Sons, Inc.
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    Simultaneous assessment of bioprosthetic heart valve biomechanical properties and collagen crimp length (1996)
    Hoboken, NJ : Wiley-Blackwell
    Journal of Biomedical Materials Research 31 (1996), S. 503-509 
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    ISSN: 0021-9304
    Keywords: Chemistry ; Polymer and Materials Science
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Medicine , Technology
    Notes: A new morphologic method is described for the simultaneous quantitation of porcine aortic valve collagen crimp length and the assessment of biomechanical properties. This method utilizes the simultaneous real-time video recording of collagen crimp morphology and acquisition of crimp length data through the combination of polarized light microscopy and morphometry. We felt that the development of this method was warranted, due to the fundamental role played by collagen in porcine aortic valve performance. The development of this method involved the design and fabrication of a uniaxial microtensile stage, suitable for mounting on a standard microscope stage. The validation of our test method was accomplished by a comparison of untreated and glutaraldehyde-treated porcine aortic valve leaflet tissue, because the biomechanical and morphologic characteristics of the native and fixed aortic valve have been extensively studied. The method described in this communication enables the collection of morphologic and biomechanical data from a single tissue specimen, eliminating the need for independent studies of multiple specimens. Furthermore, this method obviates the need for making assumptions, which may be difficult to verify, concerning the homogeneity of different test specimens with respect to their morphology and corresponding mechanical response to different experimental conditions. © 1996 John Wiley & Sons, Inc.
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    Protein adsorption to a bioactive glass with special reference to precorrosion (1996)
    Hoboken, NJ : Wiley-Blackwell
    Journal of Biomedical Materials Research 31 (1996), S. 525-531 
    Details
    ISSN: 0021-9304
    Keywords: Chemistry ; Polymer and Materials Science
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Medicine , Technology
    Notes: The protein adsorption properties of the bioactive glass S53P4 were studied using albumin, IgG, and fibrinogen solutions (1 mg/mL) as well as diluted plasma, serum, and 1:1:1 mixtures of albumin, IgG, and fibrinogen. The bioactive glass granules (315-500 μm) were used in the experiments without pretreatments or as precorroded with an Si-rich or a Ca,P-rich layer. The protein adsorption properties of S53P4 were compared to a commercial bioactive glass (Bioglass®), an inert glass, an experimental glass ceramic, titanium (Ti), and hydroxyapatite (HA). The untreated S53P4 bound in Tris-buffered saline mainly albumin from diluted plasma and serum and the 1:1:1 (1 mg of each) mixture of albumin, IgG, and fibrinogen. No binding of fibrinogen was observed. The omission of NaCl from the buffer used in the experiments increased the number of proteins bound by the S53P4. Most of the albumin bound by the glass could be detached with 0.5-1M NaCl speaking for electrostatic protein bonding. The protein adsorption properties of Bioglass® resembled those of S53P4. The Ca,P-rich layer glass, the inert glass, the glass ceramic, HA, and Ti all bound several plasma and serum proteins, including fibrinogen. The Si-rich layer glass showed protein binding properties resembling the untreated glass more than the Ca,P-rich layer glass. The protein adsorption test used in the present study revealed differences in the protein adsorption properties of the studied materials, which may reflect differences in their surface potentials. It also functioned in registration of corrosion-induced changes in the surface properties of the S53P4. As judged by the protein adsorption properties, the untreated S53P4 could have a higher biocompatibility than the two precorroded glasses. Precorrosion, especially the formation of the Ca,P-rich layer, increased the number of proteins bound by the S53P4. Thus, a precorroded glass as compared to the untreated glass could be a better carrier of specific proteins that may be used to improve the biocompatibility of the bioactive glass. © 1996 John Wiley & Sons, Inc.
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    Masthead (1996)
    Hoboken, NJ : Wiley-Blackwell
    Journal of Biomedical Materials Research 31 (1996) 
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    ISSN: 0021-9304
    Keywords: Chemistry ; Polymer and Materials Science
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Medicine , Technology
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1002/jbm.1996.820310401
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    Activation of osteoclast-mediated bone resorption by the supernatant from a rabbit synovial cell line in response to polyethylene particles (1996)
    Hoboken, NJ : Wiley-Blackwell
    Journal of Biomedical Materials Research 32 (1996), S. 3-9 
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    ISSN: 0021-9304
    Keywords: Chemistry ; Polymer and Materials Science
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Medicine , Technology
    Notes: It is unknown whether the soluble factors produced from cells activated by wear particles in the fibrous tissue around failed joint prostheses really activate osteoclastic bone resorption. In this study, the activation of osteoclast-mediated bone resorption by the products from a rabbit synovial cell line (HIG-82) stimulated by various particles was investigated using rabbit unfractionated bone cells cultured on a dentin slice. The HIG cells were challenged with the following laboratory-made particles: high-density polyethylene (PE), cobalt alloy (Co-Cr), titanium alloy (Ti6Al4V), pure titanium (Ti), and sintered hydroxyapatite (HA). The size of each particle was 〈2 μm. The supernatants from HIG cells cultured with the appropriate concentration of wear particles were added to unfractionated bone cells on a dentin slice, and then resorbed areas were determined for each particle. Interestingly, resorbed areas significantly increased only when the culture medium from HIG cells with PE particles was added to unfractionated bone cells. This study demonstrates that PE particles stimulate the rabbit synovial cells to produce soluble factors that induce osteoclast-mediated bone resorption. Moreover, this experimental model is a useful method sensitively to evaluate the effects of soluble factors from the cells stimulated by particulate biomaterials from joint prostheses on osteoclastic bone resorption. © 1996 John Wiley & Sons, Inc.
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    Material-induced up-regulation of leukocyte CD11b during whole blood contact: Material differences and a role for complement (1996)
    Hoboken, NJ : Wiley-Blackwell
    Journal of Biomedical Materials Research 32 (1996), S. 29-35 
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    ISSN: 0021-9304
    Keywords: Chemistry ; Polymer and Materials Science
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Medicine , Technology
    Notes: Material-induced thrombogenicity is in part a consequence of leukocyte activation. To evaluate and compare material-induced platelet damage, we have expanded our in vitro flow cytometric immunoassay to include assessment of leukocyte activation. We have used a very simple system whereby fresh, heparinized whole blood contacts materials for 1 h at 37°C under low shear. Unlike other tests that focus on adherent leukocytes, this assay evaluates the leukocytes in the whole blood drained from the tube (1.57 mm internal diameter, 25 cm length) after material contact. We demonstrate that whole blood contact with a polyvinyl alcohol (PVA) hydrogel surface leads to a twofold up-regulation in CD11b surface expression of all monocytes and neutrophils. The activation is metal-ion dependent and highly material dependent in that blood contact with polyethylene and Silastic™ surfaces leads to minimal activation. The shedding of L-selection as a marker of leukocyte activation was found to be unsuitable in our assay given its ease of shedding in resting heparinized whole blood. Further, plasma levels of complement components Bb and sC5b-9 (ELISA assays) were significantly elevated only after blood contact with PVA hydrogel surfaces (9.4 μg/mL sC5b-9 and 9.6 μg/mL Bb). Use of recombinant soluble human CR1 (sCR1) to inhibit the action of the C3 and C5 convertases completely inhibited sC5b-9 levels in whole blood after contact with PVA hydrogel surfaces and inhibited CD11b up-regulation by over 70%, suggesting that material-induced leukocyte activation is partially mediated by C5a production. © 1996 John Wiley & Sons, Inc.
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    Platelet-polymer interactions: Morphologic and intracellular free calcium studies of individual human platelets (1996)
    Hoboken, NJ : Wiley-Blackwell
    Journal of Biomedical Materials Research 32 (1996), S. 65-76 
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    ISSN: 0021-9304
    Keywords: Chemistry ; Polymer and Materials Science
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Medicine , Technology
    Notes: Light and electron microscopic methods were used to correlate changes in platelet morphology with levels of internal free calcium in platelets adhering to Formvar, Pellethane, and 14% SO3 Pellethane. Free calcium levels were elevated when platelets initially activated in response to contact with the polymer substrates. With buffer containing 1 mM CA2+, representative of in vivo plasma calcium levels, platelets activating on the sulfonated substrate exhibited significantly higher intracellular free calcium levels compared to those on Formvar and Pellethane. Furthermore, the intracellular free calcium remained elevated in these platelets which failed to spread normally on the sulfonated substrate. In contrast, the platelets adherent on Formvar and Pellethane achieved normal fully spread morphologies with correspondingly low or resting calcium levels. Our results indicate that the addition of the sulfonated group to Pellethane affected internal platelet calcium regulation to cause an abnormal spreading response. The nonviable platelet morphologies observed on sulfonated Pellethane compare to other dead cell morphologies caused by abnormally elevated levels of intracellular free Ca2+. © 1996 John Wiley & Sons, Inc.
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    Initial hemocompatibility studies of titanium and zirconium alloys: Prekallikrein activation, fibrinogen adsorption, and their correlation with surface electrochemical properties (1996)
    Hoboken, NJ : Wiley-Blackwell
    Journal of Biomedical Materials Research 32 (1996), S. 77-85 
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    ISSN: 0021-9304
    Keywords: Chemistry ; Polymer and Materials Science
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Medicine , Technology
    Notes: Two novel metal alloys, Ti-13Nb-13Zr and Zr-2.5Nb, have been engineered for applications in orthopedic implants because of their favorable mechanical properties, corrosion resistance, and compatibility with bone and tissue. These alloys also have the ability to form a hard, abrasion-resistant, ceramic surface layer upon oxidative heat treatment (diffusion hardening, DH). Previous studies have indicated that these and other ceramics cause limited hemolysis and exhibit remarkable structural integrity after extended exposure to physiological environments. Such observations suggest that DH Ti-13Nb-13Zr and ZrO2/Zr-2.5Nb could be used successfully as components in blood-contacting devices. Materials intended for such applications must possess properties that do not elicit adverse physiological responses, such as the initiation of the coagulation cascade or thrombus formation. In the present study measurements of prekallikrein activation, fibrinogen adsorption from diluted human plasma, and the strength of fibrinogen attachment as judged by residence-time experiments were performed to evaluate the potential hemocompatibility of these materials. The results of the prekallikrein activation and fibrinogen-retention studies correlated well with two electrochemical properties of the alloys, the open circuit potential and reciprocal polarization resistance. The results indicate that both the original and treated Ti and Zr alloys activate prekallikrein and adsorb as well as retain fibrinogen in amounts similar to other materials used as components of blood-contacting devices. On the basis of these studies, these alloys appear to be promising candidates for cardiovascular applications and merit further investigation. © 1996 John Wiley & Sons, Inc.
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    Surface-induced mineralization: A new method for producing calcium phosphate coatings (1996)
    Hoboken, NJ : Wiley-Blackwell
    Journal of Biomedical Materials Research 32 (1996), S. 111-118 
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    ISSN: 0021-9304
    Keywords: Chemistry ; Polymer and Materials Science
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Medicine , Technology
    Notes: Calcium phosphate coatings were nucleated and grown from aqueous solution onto titanium metal substrates via surface-induced mineralization (SIM) processing techniques. This process is based on the observation that in nature organisms use biopolymers to produce ceramic composites, such as teeth, bones, and shells. The SIM process involves modification of a surface to introduce surface functionalization followed by immersion in aqueous supersaturated calcium phosphate solutions. This low-temperature process (〈100°C) has advantages over conventional methods of calcium phosphate deposition in that uniform coatings are produced onto complex-shaped and/or microporous samples. Additionally, because it is a low-temperature process, control of the phase and crystallinity of the deposited material can be maintained. © 1996 John Wiley & Sons, Inc.
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    Crystallization of experimental bioactive glass compositions (1996)
    Hoboken, NJ : Wiley-Blackwell
    Journal of Biomedical Materials Research 32 (1996), S. 119-124 
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    ISSN: 0021-9304
    Keywords: Chemistry ; Polymer and Materials Science
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Medicine , Technology
    Notes: Crystallization kinetics studies for six experimental glass formulations in the system Na2O-CaO-SiO2-P2O5 synthesized by wet chemistry were conducted by means of differential thermal analysis. These glasses had CaO/P2O5 and SiO2/(CaO + Na2O) ratios ranging from 8.74-3.38 and 0.92-3.03, respectively. Samples of each glass (n = 30 were heated from 23 to 1250°C under N2 atmosphere at heating rates ranging from 10 to 50°C/min. Glass-ceramics were obtained after heat treating the initial glasses at temperatures determined from their DTA exotherms. The activation energy of crystallization for each glass composition was calculated from an expression-relating log-heating rate and the reciprocal of the exothermic peak temperature. The compositions of the six glasses were significantly different (p = 0.05). The activation energy of crystallization (Q) values ranged from 196 to 782 kJ/mole. A correlation was obtained between Q and CaO/P2O5 and between Q and the Young's modulus (p 〈 0.001). Two of the six glasses exhibited bulk crystallization. X-ray diffraction studies showed that four of the six glasses exhibited different proportions of crystalline phases following heat treatment. These phases were wollastonite (CaSiO3), Na2CaSi3O9, combeite [Na4Ca3SI6O16(OH)2], and some unidentifiable phases. Two of the six bioceramic materials had a mixture of unknown crystalline phases. © 1996 John Wiley & Sons, Inc.
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    Human monocyte morphology is affected by local substrate charge heterogeneity (1996)
    Hoboken, NJ : Wiley-Blackwell
    Journal of Biomedical Materials Research 32 (1996), S. 133-142 
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    ISSN: 0021-9304
    Keywords: Chemistry ; Polymer and Materials Science
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Medicine , Technology
    Notes: Cells are sensitive to topological, chemical, and electrical properties of substrates on which they are grown. However, most studies of cell-surface interactions have neglected electrical effects or confounded them with other substrate properties. The use of nanofabrication technology has made it possible to fabricate optically transparent surfaces with controlled chemistry and topology, and with active, controllable surface charge density in domains as small as 1-4 μm. Human monocytes incubated on polystyrene with 3.3 μm-wide strip domains, alternately charged so as to maintain overall charge neutrality, show significant charge density and time-dependent increases (greater than twofold) in cell area and cell perimeter after challenge with a phagocytic trigger (human IgG opsonized zymosan particles). Additional ultrastructural studies on silicon dioxide substrates show charge-density-dependent qualitative morphological differences. These studies clearly demonstrate that human monocytes respond in vitro to local surface-charge heterogeneity in the absence of substrate topology and compositional variation. © 1996 John Wiley & Sons, Inc.
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    Control of cell adhesion, migration, and orientation on photochemically microprocessed surfaces (1996)
    Hoboken, NJ : Wiley-Blackwell
    Journal of Biomedical Materials Research 32 (1996), S. 165-173 
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    ISSN: 0021-9304
    Keywords: Chemistry ; Polymer and Materials Science
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Medicine , Technology
    Notes: Using surface-photochemistry - driven microprocessing, striped patterns of cell-adhesive and nonadhesive domains were prepared on tissue-culture dishes. The width of striped patterns ranged from 20 to 130 μm. When endothelial cells were cultured on such dimensionally well-defined surfaces, cells adhered, migrated, and proliferated only on cell-adhesive domains. Migration potentials such as tracks of moving cells and migration rates were determined using a time-lapse video recording apparatus under a phase-contrast microscope and a computer-assisted image analyzer. The migration track in the direction of the width of the stripe-pattern was limited to the size of the width, and effective migratory distance over 400 min of observation was considerably reduced, to almost half that for a nontreated surface, whereas migratory rate was not changed by surface processing, irrespective of the stripe-pattern width. After a 2-day culture, oriented patterned cellular sheets were obtained. Cells were elongated and aligned along the axis of the striped pattern. The degrees of orientation and elongation were enhanced with a decrease of the line width. At the narrowest surface domain, cells only migrated back and forth, and eventually they became highly elongated and oriented along the axis of the domain. These results indicated that the adhesion area, migrating direction, and orientation of cells can be controlled by this method with micron-order precision. This method provides quantitative information on the kinetics of the migration process and the morphogenesis of the microprocessed surface. © 1996 John Wiley & Sons, Inc.
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    Static and fatigue properties of two new low-viscosity PMMA bone cements improved by vacuum mixing (1996)
    Hoboken, NJ : Wiley-Blackwell
    Journal of Biomedical Materials Research 31 (1996), S. 451-456 
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    ISSN: 0021-9304
    Keywords: Chemistry ; Polymer and Materials Science
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Medicine , Technology
    Notes: With the objectives of reducing toxicity and improving the mechanical properties of the prior Sulfix®-6 cement, a new low-viscosity bone cement with a new catalyst (Sulfix®-60), and a gentamycin containing cement (Allofix-G®) were developed. Although static strength could be improved in comparison with the older Sulfix®-6 cement, investigations regarding improved fatigue strength and the influence of vacuum mixing on the mechanical properties were missing. Dynamic weakness was the major disadvantage of the older Sulfix®-6 cement. To investigate fatigue strength specimens of the new bone cements were tested with load guiding until breakage or 20 million cycles. In the three series, hand mixing, vacuum mixing, and vacuum mixing with additional pressurization were performed, respectively. Vacuum mixing led to increased fatigue stability from 6.3 to 9.1 MPa for Sulfix®-60, and from 6.3 to 8.2 MPa for Allofix-G®. Additional compression had no significant effect. A 200% increased fatigue strength was detectable in comparison with the older cement. In the four-point bending test, similar results were found. It could be proved that an increased polymerization rate achieved with the use of the new catalyst was responsible for the improved mechanical properties of the new bone cement Sulfix®-60. © 1996 John Wiley & Sons, Inc.
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    Biomechanical and histological analysis of an HA coated, arc deposited CPTi canine hip prosthesis (1996)
    Hoboken, NJ : Wiley-Blackwell
    Journal of Biomedical Materials Research 31 (1996), S. 465-474 
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    ISSN: 0021-9304
    Keywords: Chemistry ; Polymer and Materials Science
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Medicine , Technology
    Notes: The interfacial shear strength and bone tissue response was investigated for an arc deposited (AD) commercially pure titanium implant surface, with (AD/HA) and without (AD) plasma-sprayed hydroxyapatite (HA) coating. Ten purpose bred coonhounds received bilateral femoral stem implantation (AD and AD/HA) in the proximal femurs (hemiarthroplasty). The femoral prosthesis consisted of a modular CoCr alloy head, modular Ti-6A1-4V neck, and a 10-mm diameter cylindrical Ti-6A1-4V femoral stem. The AD surface had 30-35% greater surface roughness than the AD/HA surface. The HA coating had a purity greater than 90% and a crystallinity greater than 65%. After 6, 12, and 24 weeks, the implants were retrieved and analyzed with mechanical testing, qualitative and quantitative histology, and electron microscopy. The AD/HA implants had equivalent interfacial shear strengths to the AD implants at all time periods. The AD/HA implants had significantly greater linear bone contact than the AD implants. The 6-week implants had significantly thicker cortical bone than the 12- and 24-week implants. The HA coating was very stable in vivo, evidenced by no thickness reduction at any time period. Qualitatively, the AD/HA implants primarily had bone contacting the implant surface with little fibrous tissue present, and the AD implants had bone and fibrous tissue contacting the implant surface. The electron microscopy analysis showed that the mechanically tested implants exhibited a mixed failure mode at the bone, HA coating, and titanium interfaces. © 1996 John Wiley & Sons, Inc.
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    Bone bonding ability of an apatite-coated polymer produced using a biomimetic method: A mechanical and histological study in vivo (1996)
    Hoboken, NJ : Wiley-Blackwell
    Journal of Biomedical Materials Research 31 (1996), S. 487-494 
    Details
    ISSN: 0021-9304
    Keywords: Chemistry ; Polymer and Materials Science
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Medicine , Technology
    Notes: A 20-μm thick apatite layer was coated onto polyethersulfone (PES) rectangular plates by soaking them in simulated body fluid containing CaO-SiO2 based glass powder. Coated and uncoated PES plates (10 × 15 × 1.5 mm) were implanted in the tibiae of rabbits, which were sacrificed 8, 16, and 30 weeks thereafter, and the samples were examined histologically using contact microradiography (CMR), Giemsa surface staining, and a scanning electron microscope connected to an electron probe microanalyzer (SEM-EPMA). The tensile failure loads at the bone/implant interfaces were determined using the detaching test. The histological examinations showed excellent bone apposition on coated PES and the sign of degradation of the apatite layer at remodeling lacunae. The apatite layer underwent complete resorption and was replaced by bone in most areas of the bone/implant interface after 30 weeks. Bone did not bond directly to uncoated PES after each follow-up period. The failure loads between bone and coated PES at 8, 16, and 30 weeks after implantation were 1.17 ± 0.35, 2.36 ± 0.53, and 1.45 ± 0.48 kg, respectively. Those between bone and uncoated PES were nearly 0 kg at each postimplantation period. Failure during the detaching test occurred at the bone/apatite interface or near it after 8 weeks. After 16 weeks, it usually occurred at the apatite/PES interface or near it, and occasionally in the middle of the apatite layer. The apatite layer was hardly detected at the failured interface after 30 weeks. In this study, an apatite-coated PES produced using a biomimetic method was demonstrated to bond directly to bone without any intervening soft tissue, which indicates that this material possesses excellent bioactivity. © 1996 John Wiley & Sons, Inc.
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    Comparison of elasticities of components of a cardiac bioprosthesis leaflet (1996)
    Hoboken, NJ : Wiley-Blackwell
    Journal of Biomedical Materials Research 30 (1996), S. 47-52 
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    ISSN: 0021-9304
    Keywords: Chemistry ; Polymer and Materials Science
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Medicine , Technology
    Notes: The mechanoelastic behavior of calf pericardium employed in cardiac bioprostheses was compared with that of three types of thread (Nylon, Prolene, and silk) used to suture this biological tissue. The elastic limit (EL) of each material was determined by means of tensile tests and the mathematical functions that govern the stress/strain curves within the EL have been described. The first derivative of these functions for each point to the curves allowed the immediate calculation of the elastic modulus (EM), which was considered the best parameter for comparing the elasticities of the materials being assessed. It was observed that the deformation of the pericardium produced by the working stress of a pericardial leaflet was approximately 1000 times greater than that produced in the surgical threads. When the elasticities were compared on the basis of the EM, that of pericardium was 749.06, 626.95, and 1253.17 times greater than that of the Nylon, Prolene, and silk suture threads, respectively. These results demonstrate that the interaction between these materials (pericardium and the threads) could be generating detrimental forces that can diminish the durability of the leaflets of the bioprostheses constructed of calf pericardium. © 1996 John Wiley & Sons, Inc.
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    Preliminary biological evaluation of polyamidoamine (PAMAM) StarburstTM dendrimers (1996)
    Hoboken, NJ : Wiley-Blackwell
    Journal of Biomedical Materials Research 30 (1996), S. 53-65 
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    ISSN: 0021-9304
    Keywords: Chemistry ; Polymer and Materials Science
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Medicine , Technology
    Notes: PAMAM Starburst™ dendrimers are spherical macromolecules composed of repeating polyamidoamino units. They can be produced in successive “generations,” each with a defined size, molecular weight, and number of terminal amino groups. Because of these well-defined characteristics, PAMAMs are finding utility in a variety of applications, many of which are biological in nature. Little is known, however, about the biological behavior of the PAMAMs, which is critical to their use in vivo. Generation 3 (G3; MW = 5,147; 24 terminal amines), 5 (G5; MW = 21,563; 96 amines), and 7 (G7; MW = 87,227; 384 amines) PAMAMs were studied in V79 cells or in Swiss-Webster, mice for a number of biological properties, including (1) in vitro toxicity, (2) in vivo toxicity, (3) immunogenicity, and (4) biodistribution. Potential biological complications were observed only with G7 at the highest level tested. No evidence of immunogenicity was seen. The biodistribution properties of the Starburst™ dendrimers were rather unusual. G3 showed the highest accumulation in kidney tissue (∼15% ID/g over 48 h); G5 and G7 appeared to preferentially localize in the pancreas (peak levels ∼32% ID/g at 24 h, and ∼20% ID/g at 2 h, respectively). In addition, G7 showed extremely high urinary excretion, with values of 46 and 74% ID/g at 2 and 4 h, respectively. In general, the dendrimers did not exhibit properties that would preclude their use in biological applications. Depending on the situation (desired endpoint, dose, and generation used), however, the biodistribution of biological preparations should be carefully studied. © 1996 John Wiley & Sons, Inc.
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    Biomaterial-neutrophil interactions: Dysregulation of oxidative functions of fresh neutrophils induced by prior neutrophil-biomaterial interaction (1996)
    Hoboken, NJ : Wiley-Blackwell
    Journal of Biomedical Materials Research 30 (1996), S. 67-75 
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    ISSN: 0021-9304
    Keywords: Chemistry ; Polymer and Materials Science
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Medicine , Technology
    Notes: Biomaterial-associated infection results in increased morbidity and mortality, and may occur because of nonproductive premature activation of neutrophils resulting in impaired phagocyte function at the biomaterial surface in the event of bacterial challenge. To further explore the effects of this premature activation, we evaluated the supernatants of biomaterial associated neutrophils to determine whether soluble mediators were released, and the likely role of these mediators. We show that these supernatants contain a chemoattractant and thereby induce chemotaxis by fresh neutrophils. No evidence of enhanced oxidative free radical production by either unstimulated neutrophils or a primed response to other mediators occurs when neutrophils were incubated with these supernatants. We also examined the effect of adding fresh neutrophils to a biomaterial surface containing a previous inoculum of neutrophils, and observed that the fresh cells did not become stimulated to release reactive oxygen intermediates (ROI) and also exhibited impaired killing of staphylococci. These studies suggest that not only does the biomaterial surface activate the initial wave of neutrophils but that subsequent waves of neutrophils exhibit an impaired host-defense function. These results are consistent with the known impairment of host defense in the presence of biomaterials, and provide evidence for a long-term down-regulation of neutrophil function at biomaterial surfaces. © 1995 John Wiley & Sons, Inc.
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    Effect of the substitution of La2O3 for CaO on the bioactivity of 2.5CaO · 2SiO2 glass (1996)
    Hoboken, NJ : Wiley-Blackwell
    Journal of Biomedical Materials Research 32 (1996), S. 187-192 
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    ISSN: 0021-9304
    Keywords: Chemistry ; Polymer and Materials Science
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Medicine , Technology
    Notes: Glasses of the following composition were prepared: (2.5-x)CaO · x/3La2O3 · 2SiO2 (0 ≤ x ≤ 1). Their behavior when soaked in a simulated body fluid (SBF) was studied by means of electron microscopy (EM) equipped with an energy-dispersive system (EDS) for elemental analysis, IR spectroscopy, and x-ray diffraction. All the studied glasses react with SBF by forming a calcium phosphate layer. This layer appears to be increasingly thinner with increasing amounts of La2O3 substituted. The experimental results are in good agreement with mechanisms reported in the literature. Moreover they suggest that lanthanum oxide is retained in the layer below the phosphate. After 6 days of soaking, crystalline hydroxyapatite is formed in the case of La2O3 free glass. © 1996 John Wiley & Sons, Inc.
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    Use of p-nitrophenyl chloroformate chemistry to immobilize protein on orthopedic biomaterials (1996)
    Hoboken, NJ : Wiley-Blackwell
    Journal of Biomedical Materials Research 32 (1996), S. 203-208 
    Details
    ISSN: 0021-9304
    Keywords: Chemistry ; Polymer and Materials Science
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Medicine , Technology
    Notes: Biochemical surface modification involves covalently immobilizing biomolecules onto biomaterial surfaces to induce specific biological responses. This approach may be useful for enhancing the fixation of orthopedic implants. p-Nitrophenyl chloroformate (p-NPC) was used to immobilize protein on bulk samples of Co-Cr-Mo and Ti-6Al-4V. Activation of both materials was dependent on the concentration of p-NPC, with a maximum of approximately 1.5 active groups/nm2 of nominal surface area. Trypsin was used as a model protein because much is known about its structure and mode of action. Derivatization with 0.65 mg p-NPC/cm2 resulted in significantly greater enzymatic activity (7.4 BAEE [N-(α)-benzoyl-L-arginine ethyl ester hydrochloride] units) on the Co-Cr-Mo samples compared with higher concentrations of p-NPC (5 BAEE units) and with simple adsorption of trypsin (1.5 BAEE units). An activity of 10.5 BAEE units was measured on both adsorbed and p-NPC-activated Ti-6Al-4V, with the exception of samples derivatized with 1.95 mg p-NPC/cm2, on which activity was significantly lower (4 BAEE units). In probing the linkages between trypsin and biomaterial by treatment with chaotropic agents, guanidine hydrochloride (GuHCl) was observed to eliminate more enzymatic activity than was urea. On Co-Cr-Mo samples, GuHCl removed nearly all the trypsin activity, while urea significantly decreased the activity only at a concentration of 0.65 mg p-NPC/cm2. Treatment of Ti-6Al-4V samples with GuHCl caused a trend of decreasing activity with increasing concentration of p-NPC, whereas urea had no effect on immobilized trypsin activity. © 1996 John Wiley & Sons, Inc.
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  • 96
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    Effect of physical crosslinking methods on collagen-fiber durability in proteolytic solutions (1996)
    Hoboken, NJ : Wiley-Blackwell
    Journal of Biomedical Materials Research 32 (1996), S. 221-226 
    Details
    ISSN: 0021-9304
    Keywords: Chemistry ; Polymer and Materials Science
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Medicine , Technology
    Notes: We previously demonstrated that ultraviolet (UV) or dehydrothermal (DHT) crosslinking partially denatured fibers extruded from an insoluble type I collagen dispersion. In this study denaturation effects were evaluated by measuring collagen-fiber sensitivity to trypsin. Shrinkage-temperature measurements and sensitivity to collagenase served as indices of crosslinking. UV or DHT crosslinking increased the collagen-fiber shrinkage temperature, resistance to degradation in collagenase, and durability under load in collagenase. However, in trypsin solutions, solubility was significantly increased for UV (≈11%) or DHT (≈15%) crosslinked fibers compared with uncrosslinked fibers (≈4%). Size-exclusion chromatography indicated that no intact collagen α-chains were present in the soluble fraction of fibers exposed to trypsin (MW 〈1 kD). Interestingly, UV-crosslinked collagen fibers remained intact an order of magnitude longer (4840 ± 739 min) than DHT-crosslinked (473 ± 39 min) or uncrosslinked (108 ± 53 min) fibers when placed under load in trypsin solutions. These data indicate that mechanical loading during incubation in a trypsin solution measures denaturation effects not detected by the trypsin-solubility assay. Our results suggest that DHT-crosslinked collagen fibers should not be used as load-bearing implants. UV-crosslinked fibers may retain more native structure and should exhibit greater resistance to nonspecific proteases in vivo. © 1996 John Wiley & Sons, Inc.
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  • 97
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    Biocompatibility testing of NiTi screws using immunohistochemistry on sections containing metallic implants (1996)
    Hoboken, NJ : Wiley-Blackwell
    Journal of Biomedical Materials Research 32 (1996), S. 243-248 
    Details
    ISSN: 0021-9304
    Keywords: Chemistry ; Polymer and Materials Science
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Medicine , Technology
    Notes: NiTi is one of the most innovative concepts to have appeared in the field of metallic biomaterials in recent years but its biocompatibility remains controversial. We evaluated the biocompatibility of Nitinol screws using immunohistochemistry to observe the distribution of bone proteins during bone remodeling process around NiTi implant. Results were compared with screws made of Vitallium, c.p. titanium, Duplex austenitic-ferritic stainless steel (SAF), and Stainless Steel 316L. Screws were implanted in rabbit tibia for 3, 6, and 12 weeks. Embedding was performed in the hard resin Technovit, and for the immunohistochemical procedure undecalcified sections with bone-anchored implants could thus be used. The immunostaining method developed seemed to be a reliable technique to stain proteins in undecalcified sections. Biocompatibility results of the NiTi screws compared with the other screws showed a slower osteogenesis process characterized by no close contact between implant and bone, disorganized migration of osteoblasts around the implant, and a lower activity of osteonectin synthesis. © 1996 John Wiley & Sons, Inc.
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  • 98
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    Distribution of nickel and cobalt following dermal and systemic administration with in vitro and in vivo studies (1996)
    Hoboken, NJ : Wiley-Blackwell
    Journal of Biomedical Materials Research 32 (1996), S. 279-283 
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    ISSN: 0021-9304
    Keywords: Chemistry ; Polymer and Materials Science
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Medicine , Technology
    Notes: Contact dermatitis following skin contact with ionic metals occurs in about 15% of the human population, but systemic responses are not as common. It is generally believed that skin contact with metal ions leads to different biological processing compared with systemic contact. The purpose of the experiments presented here was to examine elimination of nickel and cobalt salts following skin application and following injection into the deep tissue of hamsters. In addition uptake of the metal by fibroblasts and by keratinocytes was examined in vitro. The data indicate that elimination of nickel and cobalt in the urine following systemic injection was rapid, as expected, but that elimination following skin application was delayed. Much of the metal was retained in the skin. Uptake of the metal by keratinocytes at low doses was greater than the uptake by the fibroblasts. At high doses the differences were not as great. Thus the conclusion is drawn that metal salts are retained in the skin for an extended period of time and could lead to prolonged antigen processing and consequent immune responses in the dermal tissue. Skin application leads to some systemic distribution but the systemic application did not lead to skin accumulation. © 1996 John Wiley & Sons, Inc.
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  • 99
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    Bilateral symmetry of biomechanical properties in rat femora (1996)
    Hoboken, NJ : Wiley-Blackwell
    Journal of Biomedical Materials Research 32 (1996), S. 285-288 
    Details
    ISSN: 0021-9304
    Keywords: Chemistry ; Polymer and Materials Science
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Medicine , Technology
    Notes: In many studies, bone healing and remodeling have been examined in various animal models using one femur as a control for the contralateral femur based on the assumption that they are bilaterally symmetrical. Symmetry studies have been limited mainly to geometrical properties. The purpose of this study was to determine whether or not there is symmetry in the mechanical properties of rat femora. Two strain gauges were attached to the anterior surface parallel to the long axis of explanted femora of retired female breeder and 120-day-old male Sprague Dawley rats. Femora were mechanically tested in cantilever bending and the strain values were recorded. Moments of inertia, cortical areas, and moduli of elasticity were determined from strains and cross-sectional properties. Female femora showed a bilateral strain difference of less than 2.2% and an elastic modulus difference of less than 8.7%. Males had less than 2.0% and 7.9% differences for strain and elastic moduli, respectively. Statistical analysis showed no significant difference between left and right femoral strain values for the females, but modulus differences were significantly different at the p = 0.05 level. There was no significant difference in strain and modulus values for the males, indicating mechanical and geometrical symmetry of their femora. © 1996 John Wiley & Sons, Inc.
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  • 100
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    In vivo testing of crosslinked polyethers. II. Weight loss, IR analysis, and swelling behavior after implantation (1996)
    Hoboken, NJ : Wiley-Blackwell
    Journal of Biomedical Materials Research 32 (1996), S. 321-331 
    Details
    ISSN: 0021-9304
    Keywords: Chemistry ; Polymer and Materials Science
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Medicine , Technology
    Notes: As reported in Part I (“In vivo testing of crosslinked polyethers. I. Tissue reactions and biodegradation,” J. Biomed. Mater. Res., this issue, pp. 307-320), microscopical evaluation after implantation of crosslinked (co)polyethers in rats showed differences in the rate of biodegradation, depending on the presence of tertiary hydrogen atoms in the main chain and the hydrophilicity of the polyether system. In this article (Part II) the biostability will be discussed in terms of weight loss, the swelling behavior, and changes in the chemical structure of the crosslinked polyethers after implantation. The biostability increased in the order poly(POx) 〈 poly(THF-co-OX) 〈 poly(THF) for the relatively hydrophobic polyethers. This confirmed our hypothesis that the absence of tertiary hydrogen atoms would improve the biostability. On the other hand, signs of biodegradation were observed for all polyether system studied. Infrared surface analysis showed that biodegradation was triggered by oxidative attack on the polymeric chain, leading to the formation of carboxylic ester and acid groups. It also was found that in the THF-based (co)polyethers, α-methylene groups were more sensitive than β-methylene groups. For a hydrophilic poly(THF)/PEO blend, an increase in surface PEO content was found, which might be due to preferential degradation of the PEO domains. © 1996 John Wiley & Sons, Inc.
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