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Pharmacokinetic behaviour of ACP gel, an autocrosslinked hyaluronan derivative, after intraperitoneal administration
Renier, D., P. Bellato, et al. (2005), Biomaterials 26(26): 5368-74.
Abstract: Autocrosslinked polysaccharide (ACP) gel is a fully biocompatible cross-linked derivative of hyaluronic acid, which has prolonged in vivo residence time and improved mechanical properties with respect to native hyaluronan for use in various surgical applications. The objective of this study was to assess the pharmacokinetic behaviour of ACP gel in dogs after intraperitoneal administration. Seven beagle dogs received intraperitoneal injections of tritium-labelled ACP gel. Blood samples were taken, and urine and faeces were collected until sacrifice, scheduled at various time points from 3 to 192 h after administration. Organs were removed from the animals at autopsy. Bodily fluid and organ samples were analysed for total and non-volatile radioactivity. Non-volatile radioactivity slowly appeared in plasma, with a median T(max) of 12 h, and then declined with a mean half-life of 69 h. Total radioactivity in plasma peaked later and declined more slowly, consistent with the formation of tritiated water. Little non-volatile radioactivity was found in any organs except the liver, where about 16% of the dose was present 72 h after administration, and the intestines, where the presence of radioactivity was probably due to a retention effect. A minor amount of non-volatile radioactivity was also found in the bone marrow. In summary, ACP gel administered into the peritoneal cavity is removed slowly by active initial catabolism at the injection site, and is then catabolised by well described physiological pathway of hyaluronan degradation with final release of simple molecules such as CO(2) and H(2)O. Given its in vivo residence time, ACP gel may be considered an ideal implantable surgical device.

Pharmacological activity of peroral chitosan-insulin nanoparticles in diabetic rats
Ma, Z., T. M. Lim, et al. (2005), Int J Pharm 293(1-2): 271-80.
Abstract: The objective of the present study was to evaluate the effects of formulation parameters on the in vivo pharmacological activity of the chitosan-insulin nanoparticles. Chitosan-insulin nanoparticles were prepared by ionotropic gelation at pH 5.3 and 6.1 and denoted as F5.3 np and F6.1 np, respectively. F5.3 np and F6.1 np administered orally at insulin doses of 50 U/kg and/or 100 U/kg were effective at lowering the serum glucose level of streptozotocin-induced diabetic rats. The 100 U/kg-dose F5.3 np sustained the serum glucose at pre-diabetic levels for at least 11 h. In comparison, F6.1 np had a faster onset of action (2h versus 10h) but lower efficiency. The effectiveness of peroral F5.3 np and F6.1 np in lowering the serum glucose level of streptozotocin-induced diabetic rats was ascribed to the local effect of insulin in intestine. Confocal micrographs showed strong interaction between rat intestinal epithelium and chitosan nanoparticles 3h post-oral administration.

Phase diagram of the system sodium alginate/water: a model for biofilms
Borchard, W., A. Kenning, et al. (2005), Int J Biol Macromol 35(5): 247-56.
Abstract: Sodium alginate is a polyelectrolyte consisting of the monomer units beta-D-mannuronate and alpha-L-guluronate. Mainly based on the theory of Khokhlow et al., the state diagram of the binary system alginate/water has been calculated using different sets of parameters like degree of ionization, degree of polymerization and interaction function. The calculations comprise miscibility gaps, liquidus curves, eutectic points and the behaviour at temperatures below the melting point of water. Also gel and swelling curves have been treated, where gels are physically crosslinked. The DSC diagram of a 0.5 by wt.% polymer sol shows a double melting peak, which is explained by a heterogeneity above 0 degrees C. The crystallization of water seems to concentrate the gelled system irreversibly.

Phase shifting speckle interferometry for determination of strain and Young's modulus of mineralized biological materials: a study of tooth dentin compression in water
Zaslansky, P., J. D. Currey, et al. (2005), J Biomed Opt 10(2): 024020.
Abstract: Mineralized biological materials have complex hierarchical graded structures. It is therefore difficult to understand the relations between their structure and mechanical properties. We report the use of electronic speckle pattern-correlation interferometry (ESPI) combined with a mechanical compression apparatus to measure the strain and Young's modulus of root dentin compressed under water. We describe the optomechanical instrumentation, experimental techniques and procedures needed to measure cubes as small as 1 x 1 x 2 mm. Calibration of the method is performed using aluminum, which shows that the measurements are accurate within 3% of the compression modulus reported for standard aluminum 6061. Our results reveal that the compression moduli of root dentin from the buccal and lingual sides of the root are quite different from the moduli of the interproximal sides. Root dentin from interproximal locations is found to have an average modulus of 21.3 GPa, which is about 40% stiffer than root dentin from the buccal and lingual locations, found to have a modulus of 15.0 GPa. Our approach can be used to map deformations on irregular surfaces, and measure strain on wet samples of varying sizes. This can be extended to the study of other biological materials including bone and synthetic biomaterials.

Phase transformations in a model mesenchymal tissue
Newman, S. A., G. Forgacs, et al. (2004), Phys Biol 1(1-2): 100-9.
Abstract: Connective tissues, the most abundant tissue type of the mature mammalian body, consist of cells suspended in complex microenvironments known as extracellular matrices (ECMs). In the immature connective tissues (mesenchymes) encountered in developmental biology and tissue engineering applications, the ECMs contain varying amounts of randomly arranged fibers, and the physical state of the ECM changes as the fibers secreted by the cells undergo fibril and fiber assembly and organize into networks. In vitro composites consisting of assembling solutions of type I collagen, containing suspended polystyrene latex beads (approximately 6 microm in diameter) with collagen-binding surface properties, provide a simplified model for certain physical aspects of developing mesenchymes. In particular, assembly-dependent topological (i.e., connectivity) transitions within the ECM could change a tissue from one in which cell-sized particles (e.g., latex beads or cells) are mechanically unlinked to one in which the particles are part of a mechanical continuum. Any particle-induced alterations in fiber organization would imply that cells could similarly establish physically distinct microdomains within tissues. Here we show that the presence of beads above a critical number density accelerates the sol-gel transition that takes place during the assembly of collagen into a globally interconnected network of fibers. The presence of this suprathreshold number of beads also dramatically changes the viscoelastic properties of the collagen matrix, but only when the initial concentration of soluble collagen is itself above a critical value. Our studies provide a starting point for the analysis of phase transformations of more complex biomaterials including developing and healing tissues as well as tissue substitutes containing living cells.

Phase transition behavior, protein adsorption, and cell adhesion resistance of poly(ethylene glycol) cross-linked microgel particles
Nolan, C. M., C. D. Reyes, et al. (2005), Biomacromolecules 6(4): 2032-9.
Abstract: Thermoresponsive poly(N-isopropylacrylamide) (pNIPAm) microgel particles cross-linked with various concentrations of PEG diacrylates of 3 different PEG chain lengths were synthesized via free-radical precipitation polymerization in order to investigate the phase transition and protein adsorption behavior as the hydrophilicity of the network is increased. Photon correlation spectroscopy (PCS) reveals that, as the concentration of PEG cross-linker incorporated into the particles is increased, an increase in the temperature and breadth of the phase transition occurs. Qualitative differences in particle density using isopycnic centrifugation confirm that higher PEG concentrations result in denser networks. The efficient incorporation of PEG cross-linker was confirmed with (1)H NMR, and variable temperature NMR studies suggest that, in the deswollen state, the longer PEG cross-links protrude from the dense globular network. This behavior apparently manifests itself as a decrease in nonspecific protein adsorption with increasing PEG length and content. Furthermore, when electrostatically attached to a glass surface, the particles containing the longer chain lengths exhibited enhanced nonfouling behavior and were resistant to cell adhesion in serum-containing media. The excellent performance of these particulate films and the simplicity with which they are assembled suggests that they may be applicable in a wide range of applications where nonfouling coatings are required.

Phase-contrast imaging of thin biomaterials
Baruchel, J., A. Lodini, et al. (2001), Biomaterials 22(12): 1515-20.
Abstract: The necessity of information about the inner microscopical features of low absorbing materials is one of the most important goals in the structural research field. So far, non destructive analysis have been performed using contact radiography giving the scope for great advances in the production and application of new materials. However, the nature of interaction, namely X-ray absorption, limited the observations only to materials having sufficient heavy elements content. The adoption of a different X-ray interaction with matter which involves refractive properties of materials is at the basis of phase-contrast imaging. The novel method allows the use of high X-ray energies, for a deeper penetration and a lower released dose, without losing any information on the nature of the sample. A demonstration study, performed at the third generation European Synchrotron Radiation Facility (ESRF)-Grenoble, to show the potential of the new technique applied to biomaterials characterization is presented here. The test samples are a commercial matrix barrier (GUIDOR) intended to aid the healing process after periodontal surgery and a hydroxyapatite thin slab originally deposited by plasma spray technique on a TA6V alloy substrate. Phase-contrast images showed significant advantages revealing features that have negligible absorption contrast. The technique can be successfully used for the characterization of biomaterials.

Phase-contrast microtomography of thin biomaterials
Rustichelli, F., S. Romanzetti, et al. (2004), J Mater Sci Mater Med 15(9): 1053-7.
Abstract: Phase-contrast microtomography, performed at the beamline ID 22 of the European Synchrotron Radiation Facility (ESRF, Grenoble, France), is demonstrated for high-resolution 3-D imaging of a hydroxyapatite sample. The technique, which relies on phase contrast imaging, gives the possibility to observe features inside samples with negligible absorption contrast. The positive results obtained suggest a possible future investigation of the influence of the distribution of pores and defects inside biomaterial coatings, on the growth of osteoblast cells.

pH-dependence of the properties of hydrophobically modified polyvinylamine
Chen, X., Y. Wang, et al. (2005), Langmuir 21(25): 11673-7.
Abstract: A series of N-alkyl or N-benzyl substituted polyvinylamines (PVAm) were prepared and the properties of aqueous solutions were measured as functions of pH. The polymer solutions showed almost no surface activity under acidic conditions whereas surface tension was reduced to 40-50 mN/m around pH 9. Increasing either the degree of hydrophobic substitution or the hydrophobic chain length lowered the pH at which surface tension lowering was observed. Hydrophobic substitution also shifted plots of the degree of ionization versus pH toward lower pH which means lower pH values were required to achieve a given value of polymer charging. The hydrophobically modified PVAm associated in water giving species whose apparent diameter measured by dynamic light scattering decreased with increasing pH, whereas the electrophoretic mobilities of the associated species increased with decreasing pH. Although many hydrophobically modified and pH sensitive polymers have been described in the literature for applications in biomaterials, drug release and as pH sensitive surfactants, the hydrophobically modified PVAms are particularly attractive because they are easily prepared from commercially available polyvinylamines.

Phenotypic characteristics of joint fluid cells from patients with continuous joint effusion after total knee arthroplasty
Niki, Y., H. Matsumoto, et al. (2006), Biomaterials 27(8): 1558-65.
Abstract: Joint effusion after total joint arthroplasty (TJA) is a manifestation of inflammatory reactions within the prosthetic joint. Among the various causes for joint effusion following TJA, deep infection (DI), wear particle-induced synovitis (PS) and metal sensitivity to the implant should be excluded as soon as possible, as these may result in the failure of TJA. The present study analyzed joint fluid cells from patients after total knee arthroplasty (TKA) using fluorescence-activated cell sorter (FACS), and examined the feasibility of using FACS to exclude the possibility of biomaterial-related complication. A total of 72TKAs from 64 patients suffering from joint effusion were examined in this study. Joint fluid was aspirated in outpatient clinics and applied to FACS. The results indicated that patients could be clearly classified into four types based on forward/side scatter profiles. Analysis of specific CD markers revealed that leukocytes were selectively recruited from blood to inflamed prosthetic joints. Dominant cell types were CD16+neutrophils in DI and increased rheumatoid activity, CD14+macrophages in PS, and CD3+CD45RO+T cells in metal sensitivity. These findings suggest the feasibility of diagnosing joint effusion by analyzing dominant cell type recruited using FACS. In conclusion, FACS may offer a useful tool for analyzing joint fluid cells from post-TJA patients and for excluding biomaterial-related complication following TJA.

pH-induced self-assembly and capsules of sodium alginate
Cao, Y., X. Shen, et al. (2005), Biomacromolecules 6(4): 2189-96.
Abstract: In this investigation, we used a kind of polyelectrolyte, sodium alginate, as a model biomacromolecule to investigate the aggregation behaviors in aqueous solution after partial protonation of carboxylate groups in the alginate molecules. It is demonstrated that the alginate assemblies with core-shell structure can be generated by the partial protonation of carboxylate groups in sodium alginate chains using the protons released gradually from the reaction of K(2)S(2)O(8) with water at 70 degrees C in aqueous solution. The partial cross-linked alginate assemblies are pH sensitive and can change to hollow structure in the medium with relatively high pH value. This approach avoids use of block or grafted copolymers as the precursors or any other template to prepare assemblies and capsules, and provides a functional surface for subsequent chemical reaction at the surface (e.g., for binding biomolecules and for surface grafting). Such unique assemblies are also expected to be useful in biomedical fields.

Phospholipid polymer surfaces reduce bacteria and leukocyte adhesion under dynamic flow conditions
Patel, J. D., Y. Iwasaki, et al. (2005), J Biomed Mater Res A 73(3): 359-66.
Abstract: Persistence of infection can occur when the host immune response is compromised because of the presence of a foreign implant. Surface modification of biomaterials with phospholipid polymers may enhance biocompatibility and reduce incidence of infection by impeding bacterial and leukocyte adhesion. A rotating disk model, which generates shear stress from 0 to 18 dynes/cm(2), was used to characterize adhesion of neutrophils, monocytes, and bacteria in phosphate-buffered saline (PBS) or 25% human serum on polyethylene terephthalate surfaces coated with a phospholipid polymer, poly[omega-methacryloyloxyalkyl phosphorylcholine (MAPC)-co-n-butyl methacrylate (BMA)]. The material designated PMB30 contains a methylene chain length, (CH(2))(n), of n = 2, whereas PMHB30 contains a chain length of n = 6. In PBS, bacterial adhesion was shear stress dependent with the lowest bacterial density observed on PMB30. However, the presence of serum proteins eliminated shear stress and surface chemistry effects in addition to bacterial adhesion reduced to <10% of adhesion in PBS. Trends for leukocyte adhesion in serum demonstrated shear dependence with PMB30 exhibiting the lowest cell density throughout the range of shear stresses. In conclusion, modification of the polyethylene terephthalate surfaces with phospholipid polymers resulted in reduced bacterial and leukocyte adhesion. Furthermore, shortening the methylene chain length of the MAPC copolymer most effectively reduced adhesion.

Phosphorylcholine is favorable for antibody production from hybridoma cells
Montano, X., A. L. Lewis, et al. (2005), Biotechnol Bioeng 90(6): 770-4.
Abstract: Growth of antibody-secreting hybridomas requires special conditions such as serum-free defined media containing growth factors and vitamins. However, the surface on which these cells can proliferate has been shown to play an important role. Phosphorylcholine (PC)-based polymers are zwitterionic compounds with nonbiofouling properties. These polymers are characterized by having reduced protein absorption properties. Our aim was to determine whether well-established hybridoma cell lines were able to proliferate and produce measurable amounts of monoclonal antibodies when grown on PC-polymer-coated surfaces. Comparative experiments using four well-known hybridoma cell lines (PAb421, PAb246, PAb1801 which recognize p53, and PAb280 which recognizes SV40 small t antigen) grown on PC-polymer-coated, uncoated, and two commercially available tissue culture plates showed that PC-polymer-coated plates were more efficient than uncoated plates in sustaining cell growth and monoclonal antibody production/secretion as defined by growth assays and ELISA. Also, results demonstrated that PC-polymer-coated plates were able to perform better than commercially available plates. These observations suggest that PC polymers could be used as an alternative, efficient surface coating to grow hybridoma cell lines and allow detectable antibody secretion.

Photoablative inlay laser in situ keratomileusis (PAI-LASIK) in the rabbit model
Peyman, G. A., C. F. Beyer, et al. (2005), J Cataract Refract Surg 31(2): 389-97.
Abstract: PURPOSE: To evaluate the suitability, biocompatibility, and efficacy of a proprietary hydrogel photoablative inlay (PAI) for use during laser in situ keratomileusis (LASIK). SETTING: Laboratory study, Tulane University Health Sciences Center, New Orleans, Louisiana, USA. METHODS: Eight rabbits (1 eye each) underwent the PAI-LASIK procedure; 4 eyes had a disk-shaped inlay and 4, a donut-shaped inlay. Preoperatively, the hydrogel material was ablated with a programmed correction of 5.0 diopters of hyperopia or myopia. RESULTS: The eyes were followed for 1 to 16 months. No eye showed signs of rejection or extrusion of the PAI. There was no significant difference in corneal clarity or the healing rate between eyes with donut-shaped PAIs and those with disk-shaped PAIs. One eye with a donut-shaped PAI had minimal corneal haze. The remaining inlays did not opacify or fracture during ablation. CONCLUSION: The hydrogel material can be used for the proposed PAI-LASIK procedure.

Photocatalytic degradation of azo dyes by nitrogen-doped TiO2 nanocatalysts
Liu, Y., X. Chen, et al. (2005), Chemosphere 61(1): 11-8.
Abstract: This study examined the photocatalytic degradation of three azo dyes, acid orange 7 (AO7), procion red MX-5B (MX-5B) and reactive black 5 (RB5) using a new type of nitrogen-doped TiO2 nanocrystals. These newly developed doped titania nanocatalysts demonstrated high reactivity under visible light (lambda>390 nm), allowing more efficient usage of solar light. The doped titania were characterized by X-ray diffraction (XRD) and transmission electron microscopy (TEM). Experiments were conducted to compare the photocatalytic activities of nitrogen-doped TiO2 nanocatalysts and commercially available Degussa P25 powder using both UV illumination and solar light. It is shown that nitrogen-doped TiO2 after calcination had the highest photocatalytic activity among all three catalysts tested, with 95% of AO7 decolorized in 1 h under UV illumination. The doped TiO2 also exhibited substantial photocatalytic activity under direct sunlight irradiation, with 70% of the dye color removed in 1h and complete decolorization within 3 h. Degussa P25 did not cause detectable dye decolorization under identical experimental conditions using solar light. The decrease of total organic carbon (TOC) and evolution of inorganic sulfate (SO4(2-)) ions in dye solutions were measured to monitor the dye mineralization process.

Photocatalytic degradation of surfactants with immobilized TiO2: comparing two reaction systems
Lizama, C., C. Bravo, et al. (2005), Environ Technol 26(8): 909-14.
Abstract: The photocatalytic degradation of two industrial-grade surfactants, sodium lauryl sulphate (SLS) and sodium dodecylbenzenesulphonate (SDDBS), were achieved using TiO2 immobilised on glass Raschig rings and inside a bent tube of glass, using two different photoreactors in recirculation batch mode with a black light fluorescent tube as irradiation source. The influence of parameters pH, recalculation flow, airflow and number of treatment units were determined. For comparison purposes, the energetic cost of treatment was determined for both reaction systems as the figure-of-merit EE/O, showing that titania supported on glass Raschig rings is a more efficient system than the inner coated spring with TiO2, but this condition is strongly dependent on the surfactant identity. The best conditions for surfactants elimination were used to carry out the treatment of solutions containing two commercial detergents, reaching an 80% of removal in 60 min of irradiation.

Photocatalytic one-electron oxidation of biphenyl derivatives strongly coupled with the TiO2 surface
Tachikawa, T., S. Tojo, et al. (2004), Langmuir 20(7): 2753-9.
Abstract: One-electron oxidation of various biphenyl derivatives such as biphenyl (BP), 4-hydroxybiphenyl (HBP), 4,4'-biphenol (DHBP), 4-methoxy-4'-hydroxybiphenyl (MHBP), 4-cyano-4'-hydroxybiphenyl (CNHBP), 4-biphenylmethanol (BPM), and 4-biphenylethanol (BPE) adsorbed on the surface of TiO2 powder slurried in acetonitrile has been investigated by time-resolved diffuse reflectance spectroscopy. From the Langmuir adsorption isotherms for BP and HBP, it is suggested that the OH group plays an important role in adsorbing on the surface ofTiO2. The spectroscopic characteristics of charge transfer complexes of substrates and the TiO2 surface have been studied by steady-state diffuse reflectance spectroscopy. The high efficiency of a one-electron oxidation reaction was observed for hydroxyl-substituted BPs (HBP, DHBP, MHBP, CNHBP), compared with BPM and BPE, indicating that the strength of the electronic coupling element (H(DA)) between the electron acceptor and donor is a key factor in the one-electron oxidation of a substrate adsorbed on the TiO2 powder. The effects of the distance between the electron donor and the acceptor on the electronic coupling element are also discussed.

Photocatalytic oxidation of sulfamethazine
Kaniou, S., K. Pitarakis, et al. (2005), Chemosphere 60(3): 372-80.
Abstract: The photocatalytic degradation of sulfamethazine (SMT), a sulfonamide drug, has been investigated in aqueous heterogeneous solutions containing n-type oxide semiconductors as photocatalysts. The disappearance of the organic molecule follows approximately a pseudo-first-order kinetics according to the Langmuir-Hinshelwood model. It was observed that, with TiO2 P-25 and ZnO as photocatalysts, quantitative degradation of the organic molecule occurs after 4 h. During this time the desulfurization of the substrate is complete, while only 30% of the nitrogen in the organic compound was recovered in the form of nitrate and ammonium ions, indicating that various other nitrogen-containing organic compounds remain in the solution. The addition of H2O2 leads, in the case of TiO2 P-25, to a twofold increase on the reaction rate, while a negative effect has been observed in the presence of ZnO. The initial apparent photonic efficiency (zeta0) of the photooxidation and the mineralization under various experimental conditions have been calculated.

Photocatalytic remediation of gamma-HCH contaminated soil induced by alpha-Fe2O3 and TiO2
Zhao, X., X. Quan, et al. (2004), J Environ Sci (China) 16(6): 938-41.
Abstract: Heterogeneous photocatalytic degradation of gamma-HCH on soil surfaces was carried out to evaluate the photocatalytic effectiveness of alpha-Fe2O3 and TiO2 toward degrading gamma-HCH on soil surfaces. After being spiked with gamma-HCH, soil samples were loaded with alpha-Fe2O3 or TiO2 and exposed to UV-light irradiation. Different catalyst loads, 0%, 2%, 5%, 7%, and 10% (wt.) alpha-Fe2O3; 0%, 0.5%, 1%, 2: (wt.)TiO2, were tested for up to 7 d irradiation. The effects of soil thickness, acidity, and humic substances were also investigated. The obtained results indicated that the gamma-HCH photodegradation follows the pseudo-first-order kinetics. The addition of alpha-Fe2O3 or TiO2 accelerates the photodegradation of gamma-HCH, while the photodegradation rate decreases when the content of alpha-Fe2O3 exceeds 7% (wt.). The degradation rate increases with the soil pH value. Humic substances inhibit the photocatalytic degradation of gamma-HCH. Pentachlorocyclohexene, tetrachlorocyclohexene, and trichlorobenzene are detected as photodegradation intermediates, which are gradually degraded with the photodegradation evolution.

Photocatalytic treatment of linear alkylbenzene sulfonate (LAS) in water
Mehrvar, M. and S. H. Venhuis (2005), J Environ Sci Health A Tox Hazard Subst Environ Eng 40(5): 1003-12.
Abstract: The photocatalytic degradation of aqueous linear alkylbenzene sulfonate (LAS) was studied. Two different photocatalysts, Degussa P25 TiO2 and Hombikat UV 100 TiO2, were used to degrade aqueous linear alkylbenzene sulfonate in slurry batch photoreactors. For a 100 mg/L LAS solution based on first-order rate constants, the optimum photocatalyst loading for Degussa P25 TiO2 was 4.0 g/L, while for Hombikat UV 100 TiO2 it was 2.0 g/L. The photoactivity of Degussa P25 TiO2 it was higher than that of Hombikat UV 100 TiO2 for the treatment of LAS. A mixture of both photocatalysts did not improve the LAS degradation rates in batch experiments. Combination of Degussa P25 TiO2 and 600 mg/L H2O2 along with irradiation with UV light at either 254 or 365 nm did not improve the LAS degradation rates over the photocatalytic or photolytic processes individually.

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Last Modified: 8 February 2006