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Immobilization of human thrombomodulin on biomaterials: evaluation of the activity of immobilized human thrombomodulin
Kishida, A., Y. Ueno, et al. (1994), Biomaterials 15(14): 1170-4.
Abstract: Thrombomodulin (TM) is a newly described endothelial cell associated protein that functions as a potent natural anticoagulant by converting thrombin from a procoagulant protease to an anticoagulant. In this study, the immobilization of hTM was investigated in detail using surface modified polymers. As the basis of immobilization, poly(acrylic acid) (PAAc) surface-grafted poly(ethylene) (PAAc-g-PE) film was used with the expectation of increasing the immobilization amount of hTM. The effect of the immobilization reaction on the hTM activities, and the comparison of the activities of the immobilized hTM with the free hTM, were studied.

Immobilization of human thrombomodulin onto biomaterials. Comparison of immobilization methods and evaluation of antithrombogenicity
Kishida, A., Y. Ueno, et al. (1994), Asaio J 40(3): M840-5.
Abstract: Human thrombomodulin (hTM), which is a newly described endothelial cell associated protein that functions as a potent natural anticoagulant by converting thrombin from a procoagulant protease to an anticoagulant, was immobilized on to various substrates by two immobilization methods. As the substrates of immobilization, poly(acrylic acid) surface grafted poly(ethylene) (PAAc-g-PE) film, poly(vinylamine) surface grafted poly(ethylene) film, and PAAc surface grafted nylon were used. For immobilization, simultaneous preactivation methods were used. The effect of the immobilization reaction on hTM activities, the comparison of the activities of immobilized hTM with those of free hTM, and the effect of the thrombin incorporation on antithrombogenic activity were studied. The hTM immobilized onto PAAc-g-PE by preactivation showed the highest antithrombogenic activity. The thrombin incorporation affected protein C activation activity but not the fibrinogen clotting time. hTM immobilized nylon showed greater antithrombogenicity in vitro.

Immobilization of TiO2 nanopowder on glass beads for the photocatalytic decolorization of an azo dye C.I. Direct Red 23
Daneshvar, N., D. Salari, et al. (2005), J Environ Sci Health A Tox Hazard Subst Environ Eng 40(8): 1605-17.
Abstract: TiO2 supported on glass beads was prepared and its photocatalytic activity was determined by photooxidation of the commercial textile dye, C.I. Direct Red 23, in aqueous solution illuminated by a UV-C lamp (30 W). The progress of photocatalytic decolorization of the C.I. Direct Red 23 was studied by measuring the absorbance at lambda(max) = 507 nm by UV Vis spectrophotometer. The experiments indicated that both UV light and TiO2 were needed for the effective destruction of the dye. The effect of pH on the rate of decolorization efficiency was followed in the pH range 2-12. Acidic pH range was found to favor the decolorization rate. The addition of a proper amount of hydrogen peroxide improved the decolorization, whereas the excess hydrogen peroxide quenched the formation of hydroxyl radicals (*OH). The electrical energy consumption per order of magnitude for photocatalytic decolorization of the dye was lower in the UV/TiO2/H2O2 process than that in the UV/TiO2 process. In the real wastewater sample the efficiency of the method was determined by measuring the changes in the absorption spectra of the dye solution during photodegradation. Our results indicated that during the photooxidation process, the decolorization efficiency was more than 80% at irradiation time of 3 h.

Immobilized gellan sulfate surface for cell adhesion and multiplication: development of cell-hybrid biomaterials using self-produced fibronectin
Miyamoto, K., A. Kanemoto, et al. (2002), Int J Biol Macromol 30(2): 75-80.
Abstract: A new concept for cell-hybrid biomaterial is proposed in which human unbilical vein endothelial cells (HUVEC) are adhered to an immobilized gellan sulfate (GS) surface. Extra domain A containing fibronectin (EDA(+)FN) released from HUVEC is necessary for cell adhesion and multiplication. The material design in this study is based on these self-released cell adhesion proteins. The interaction between GS and EDA(+)FN was evaluated using the affinity constant (KA); the value obtained was 1.03x10(8) (M(-1)). These results suggest that the adhesion of HUVEC to GS may be supported by the adhesion of EDA(+)FN to GS. We also found that this new material adheres to HUVEC, allowing the reintroduction of EDA(+)FN, which is self-produced by the cell. This material is relatively easy to produce, not requiring the usual coating of adhesion proteins in pretreatment.

Immobilized metal ion affinity adsorption and immobilized metal ion affinity chromatography of biomaterials. Serum protein affinities for gel-immobilized iron and nickel ions
Porath, J. and B. Olin (1983), Biochemistry 22(7): 1621-30.
Abstract: Immobilized metal ion affinity adsorption (IMA adsorption) is a collective term that is proposed to include all kinds of adsorptions whereby metal atoms or ions immobilized on a polymer cause or dominate the interaction at the sorption sites. IMA chromatography is one of the most powerful methods available to date for protein fractionation although this is not as yet widely recognized. This study deals with the theoretical aspects of IMA adsorption and its practical applications as exemplified by the various results reported here. The synthesis of iminodiacetate-substituted agarose (IDA-agarose) and tris(carboxymethyl)ethylenediamine-agarose (TED-agarose) is described. Many types of metal ions can easily be immobilized on these gel derivatives to form IMA adsorbents. We have not observed any damage to the proteins during the adsorption-desorption process. After performance of an experiment, the gels can easily be regenerated and can be loaded with the same or a different metal ion for an ensuing experiment. Specific adsorption is demonstrated for serum proteins on immobilized Ni(II) and Fe(III). Ligand-specific desorption (affinity elution) is also demonstrated by including in the buffer system certain solutes which are similar to or identical with some particular amino acids found in proteins. High concentrations of certain salts that affect the structure of water, such as Na2SO4, promote coordinate covalent bonding of proteins by a mechanism that is apparently similar to that found in hydrophobic interactions. Neutral detergents and aquoorganic solvents may be used. This opens up the possibility for the fractionation of membrane components. The IMA-adsorption method could also be expanded to other areas besides protein fractionation.

Immobilized N-alkylated polyethylenimine avidly kills bacteria by rupturing cell membranes with no resistance developed
Milovic, N. M., J. Wang, et al. (2005), Biotechnol Bioeng 90(6): 715-22.
Abstract: Several critical mechanistic and phenomenological aspects of the microbicidal surface coatings based on immobilized hydrophobic polycations, previously developed by us, are addressed. Using Escherichia coli (Gram-negative) and Staphylococcus aureus (Gram-positive) bacteria, remarkable bactericidal action (up to a 10(9)-fold reduction in live bacteria count in the surface-exposed solution and a 100% inactivation of the surface-adhered bacteria) of an amino-glass slide covalently derivatized with N-hexyl,methyl-polyethylenimine (PEI) is found to be due to rupturing bacterial cell membranes by the polymeric chains. The bacteria fail to develop noticeable resistance to this lethal action over the course of many successive generations. Finally, the immobilized N-alkyl-PEI, while deadly to bacteria, is determined to be harmless to mammalian (monkey kidney) cells.

Immune responses in mice of beta-galactosidase adsorbed or encapsulated in poly(lactic acid) and poly(lactic-co-glycolic acid) microspheres
Stivaktakis, N., K. Nikou, et al. (2005), J Biomed Mater Res A 73(3): 332-8.
Abstract: The immune response induced in mice by beta-galactosidase (beta-gal) adsorbed or encapsulated on poly(lactic acid) (PLA) and poly(lactic-co-glycolic acid) (PLGA) microspheres was investigated. The encapsulated protein elicited higher antibody response than the protein adsorbed on the microspheres in the case of the PLA microspheres. However, the encapsulated protein elicited weaker antibody response than the adsorbed protein in the case of the PLGA (50:50) microspheres, probably because, in this case, the encapsulation process adversely affected protein immunogenicity. In the case of adsorbed beta-gal, higher antibody response was obtained with the PLA microspheres than with the PLGA (50:50) microspheres. This may be related to the lower rate of beta-gal desorption from the PLA microspheres. Based on the immunoglobulin G1/immunoglobulin G2a ratios and the stimulation indices for interferon-gamma and interleukin-4, beta-gal encapsulated or adsorbed on PLA microspheres induced a Th(1)-biased immune response whereas beta-gal encapsulated or adsorbed on PLGA (50:50) microspheres induced a Th(2)-biased immune response. The results obtained indicate that more potent immune responses are obtained when the protein is encapsulated than adsorbed on the microspheres, providing that the encapsulation process does not adversely affect protein immunogenicity. Also, the type of polymer used to prepare the microspheres, but not the method of protein association with the microspheres, may affect the type of immune response.

Immuno-capture of Cryptosporidium parvum using micro-well array
Taguchi, T., H. Takeyama, et al. (2005), Biosens Bioelectron 20(11): 2276-82.
Abstract: A glass slide and micro-well array chip on which anti-Cryptosporidium parvum antibody was immobilized were used for the rapid capture and detection of C. parvum. Biotinylated anti-C. parvum antibodies were spotted onto the streptavidin-coated glass slides. C. parvum oocysts were captured specifically on the spot when more than 73 ng of anti-C. parvum antibody was applied onto the glass slide. However, C. parvum oocysts captured on the glass slide were detached by repeating washing steps. To improve the capture efficiency of oocysts, capture was performed in a micro-well format consisting of 1024 wells/2.5 mm2 (32 x 32 wells) fabricated as a chip by photolithography. Instead of a flat surface on a glass slide, each well was 30 microm in diameter and 10 microm in depth. Streptavidin was also immobilized onto the micro-well array. The biotinylated anti-C. parvum antibodies were immobilized efficiently onto the chip using a buffer containing 20% methanol. Using this technique C. parvum oocysts were stably captured onto the chip after repeated washing procedures. These data show that the newly designed micro-well array technique described here is useful for antibody-mediated C. parvum capture.

Immunogold electron microscopy in situ end-labeling (EM-ISEL): assay for biomaterial DNA damage detection
Assad, M., N. Lemieux, et al. (1997), Biomed Mater Eng 7(6): 391-400.
Abstract: We have evaluated a genotoxicity assay that combines in situ end-labeling, colloidal gold tagging and electron microscopy in order to adapt it to the measurement of in vitro biomaterial-induced genotoxicity. Human lymphocytes were cultured in semi-physiological medium which had been previously exposed to biomaterial extracts of commercially pure titanium following ISO standards. In order to visualize the location of induced DNA strand breaks, cells were then exposed to exonuclease III which partially digests and amplifies lesions by releasing nucleotides at free 3' hydroxyl ends from nicked double-stranded DNA. The resulting single-stranded DNA was allowed to hybridize with short oligonucleotides of random sequences including biotinylated dUTP. After random priming using Escherichia coli DNA polymerase I, incorporation of biotin-dUTP was detected by immunogold binding to the chromatin. Cells exposed to a mutagenic concentration of methyl methanesulfonate, as a positive control, showed a significantly higher and stronger gold staining than both titanium-exposed and unexposed specimens. This assay allows a precise localization and quantification of both in vitro DNA breakage and DNA repair. It could provide a powerful tool for rapid assessment of the genotoxic potential of new biomaterials.

Immunomodulation and biomaterials
Tetta, C., G. Camussi, et al. (1993), Biomater Artif Cells Immobilization Biotechnol 21(2): 253-63.

Impact and temporal trends of percutaneous coronary intervention in the drug-eluting stent versus bare metal stent eras
Thompson, C. A., A. V. Kaplan, et al. (2005), Am J Cardiol 96(5): 668-72.
Abstract: Limited published data exist about how the introduction of drug-eluting stents (DESs) has affected the technical aspects of percutaneous coronary intervention and in-hospital patient outcomes in clinical practice. A total of 2,215 consecutive patients who underwent percutaneous coronary intervention for de novo coronary artery disease were divided into 2 cohorts: the pre-DES era (May 1, 2002 to April 30, 2003) and the DES era (May 1, 2003 to April 30, 2004). The procedural success rates (94.9% vs 96.4%, respectively; p = 0.075) and the in-hospital major adverse events (6.4% vs 5.7%, respectively; p = 0.53) were similar between the pre-DES and DES eras. The DES percentage of use increased from 49.5% in the first quarter to 84.1% in the final quarter of the first year after the introduction of this technology (p <0.0001). The results of our study have shown that despite more complex percutaneous coronary intervention procedures with tendencies for more complete lesion coverage and anatomic revascularization, the procedural success and in-hospital outcomes have been comparable since the introduction of DESs.

Impact of coronary culprit lesion calcium in patients undergoing paclitaxel-eluting stent implantation (a TAXUS-IV sub study)
Moussa, I., S. G. Ellis, et al. (2005), Am J Cardiol 96(9): 1242-7.
Abstract: Randomized clinical trials have shown that paclitaxel-eluting stents significantly reduce restenosis after percutaneous coronary intervention. The impact of lesion calcification on the efficacy of paclitaxel-eluting stents is unknown. In the TAXUS-IV trial, 1,314 patients who underwent percutaneous coronary intervention were randomly assigned to a bare-metal or paclitaxel-eluting stent. By core laboratory analysis, 247 lesions (19%) were moderately or severely calcified. At the 9-month angiographic follow-up examination, the paclitaxel-eluting stent had significantly reduced the amount of late loss compared with the control stent (0.26 +/- 0.56 vs 0.51 +/- 0.48 mm, p = 0.015) within the analysis segment in the calcific lesions. The analysis segment restenosis rate was similar in patients with calcified and noncalcified lesions after paclitaxel-eluting stent implantation (7.5% vs 8.0%, respectively; p = 1.0). The rate of ischemia-driven target lesion revascularization (TLR) at 1 year was reduced by 56% in patients with calcified lesions (11.9% vs 5.1%, p = 0.09) and by 75% in noncalcified lesions (15.7% vs 4.3%, p <0.0001). By interaction testing, the efficacy of the paclitaxel-eluting stent in reducing TLR at 1 year was similar in the calcified and noncalcified lesions (p = 0.30). Moreover, by multivariate analysis, implantation of the paclitaxel-eluting stent was a powerful independent predictor of freedom from TLR, with similar hazard ratios for efficacy in calcified and noncalcified lesions (0.30 and 0.26, respectively). In conclusion, implantation of paclitaxel-eluting stents in patients with de novo coronary lesions significantly reduced restenosis in patients with and without calcified lesions.

Impact of heat on nanocrystalline silver dressings. Part I: Chemical and biological properties
Taylor, P. L., A. L. Ussher, et al. (2005), Biomaterials 26(35): 7221-9.
Abstract: Thermal stability of heat-treated nanocrystalline silver dressings was investigated using chemical techniques and biological assays. Dressings were heat-treated for 24h at temperatures from 23 to 110 degrees C. Bactericidal efficacy of heat-treated dressings was measured using a log reduction assay, while antibacterial longevity was determined via plate-to-plate transfer corrected zone of inhibition assays. Over the temperature range tested, biological activity dropped from excellent to negligible. Biological longevity results showed that controlled release properties of the dressings were significantly reduced by heat treatments above 75 degrees C. These data illustrate nanocrystalline silver sensitivity to heat. Further, it was clear that dressing efficacy is determined by total available soluble silver, not total silver in the dressing. It was determined that the quantity of soluble silver decreased significantly with increased heat treatment temperatures. These results should be considered in developing new nanocrystalline drug delivery systems.

Impact of heat on nanocrystalline silver dressings. Part II: Physical properties
Taylor, P. L., O. Omotoso, et al. (2005), Biomaterials 26(35): 7230-40.
Abstract: This work explores the effects of elevated temperature on the physical and chemical properties of nanocrystalline silver, and relates it to previously observed thermally induced changes in biological activity [Taylor PL et al. Biomaterials, in press, doi:10.1016/j.biomaterials.2005.05.040]. Microstructural evolution of nanocrystalline silver dressings, heat-treated for 24 h at temperatures from 23 to 110 degrees C, was studied in detail using X-ray diffraction (XRD), scanning electron microscopy (SEM), and X-ray photoelectron spectroscopy (XPS). These analyses indicated that silver nanocrystalline coatings undergo significant changes in structure when exposed to elevated temperature. XRD analysis showed a rapid increase in crystallite size above 75 degrees C along with decomposition of crystalline silver oxide (Ag2O) at the onset of crystallite growth. SEM imaging showed a loss of fine features and sintering of the structure at elevated temperatures. The XPS data indicated that silver-oxygen bonds disappeared completely, with the initial decomposition occurring between 23 and 37 degrees C, and total oxygen in the coating decreased from 16-17% to 6.5% over the temperature range of 75-110 degrees C. A comparison of these results to the data of Taylor et al. [Biomaterials, in press, doi:10.1016/j.biomaterials.2005.05.040] indicates that the unique biological properties of nanocrystalline silver are related to its nanostructure. This should guide future development of therapeutic nanocrystalline silver delivery systems.

Impact of intravascular ultrasound lesion characteristics on neointimal hyperplasia following sirolimus-eluting stent implantation
Kaneda, H., T. Koizumi, et al. (2005), Am J Cardiol 96(9): 1237-41.
Abstract: The effect of lesion characteristics on neointimal hyperplasia after sirolimus-eluting stent implantation was examined in 45 patients who underwent successful preinterventional intravascular ultrasound. There were no differences in neointimal hyperplasia between the moderate/severe calcified lesion group (calcium arc >120 degrees) and the non/mild calcified lesion group or between the positive vessel remodeling group (external elastic membrane area at the minimal lumen area site larger than that at the proximal reference site) and negative vessel remodeling group. No correlation between preinterventional plaque burden and neointimal hyperplasia was found. In patients who have coronary artery disease, sirolimus-eluting stents continue to demonstrate striking suppression of neointimal proliferation, irrespective of lesion characteristics previously associated with greater restenotic risk.

Impact of platelet glycoprotein IIb/IIIa Inhibition on the paclitaxel-eluting stent in patients with stable or unstable angina pectoris or provocable myocardial ischemia (a TAXUS IV substudy)
Teirstein, P. S., J. Kao, et al. (2005), Am J Cardiol 96(4): 500-5.
Abstract: Whether the benefits that glycoprotein IIb/IIIa inhibitors confer in patients who undergo bare metal stent implantation extend to drug-eluting stents is unknown. We performed a prespecified subgroup analysis of the TAXUS IV study population to examine the effect of procedural glycoprotein IIb/IIIa inhibition during paclitaxel-eluting stent implantation on periprocedural creatine kinase-MB (CK-MB) levels. Glycoprotein (GP) IIb/IIIa inhibitors were administered to 57.7% of patients who had been randomized to receive the TAXUS stent and to 56.7% of those who had been randomized to receive the control stent. Among patients who received the TAXUS stent, the rate of CK-MB increases of >3 times the normal level was 2.6-fold higher in those who received a GP IIb/IIIa inhibitor than in those who did not (11.4% vs 4.4%, p = 0.0015). Composite rates of major adverse cardiac events and target vessel failure were also higher at 1 month in the GP IIb/IIIa group. By multivariate analysis, use of GP IIb/IIIa inhibitors during stenting with the TAXUS stent was an independent predictor of CK-MB increases >3 times the normal level. Further studies are warranted.

Impact of sirolimus-eluting stents on outcomes of patients treated for acute myocardial infarction by primary angioplasty
Cheneau, E., S. W. Rha, et al. (2005), Catheter Cardiovasc Interv 65(4): 469-72.
Abstract: Sirolimus-eluting stents (SESs) are currently being used in patients undergoing percutaneous coronary intervention (PCI). SESs have not been evaluated in the treatment of acute myocardial infarction by primary angioplasty. We report our initial experience with SESs implanted during primary angioplasty. One hundred and three patients were treated within 12 hr after onset of acute myocardial infarction (AMI) with primary angioplasty and SES implantation. Those patients were compared to 504 patients treated with bare metal stents (BMSs). Angiographic success (TIMI flow grade 3 and residual stenosis < 50%) was completed in 98% of patients with SESs and no subacute stent thrombosis was reported. In-hospital outcomes were similar in the SES and BMS groups. At 6 months, major cardiac events were less frequent in the SES group than in the BMS group (9% vs. 24%, respectively; P < 0.001), driven by a lesser need for repeat revascularization with SESs (1% vs. 10.3% with BMSs; P = 0.014). Mortality at 6 months was 7% with SESs and 11% with BMSs (P = 0.14). SESs are safe and effective for the treatment of AMI by primary angioplasty. As compared to BMSs, SESs improve long-term outcome after AMI, mainly by reducing the need for repeat revascularization.

Impact of stents and abciximab on survival from cardiogenic shock treated with percutaneous coronary intervention
Huang, R., J. Sacks, et al. (2005), Catheter Cardiovasc Interv 65(1): 25-33.
Abstract: This retrospective observational review compares patient characteristics and in-hospital and long-term outcomes of cohorts of patients undergoing percutaneous coronary intervention (PCI) for cardiogenic shock complicating acute myocardial infarction (MI) prior to the use of stents (as well as glycoprotein IIb/IIIa inhibitor and dual-antiplatelet therapy) with PCI in the stent era. Cardiogenic shock remains the leading cause of hospital mortality from acute MI. This is a report of consecutive patients with cardiogenic shock complicating acute MI, without mechanical complication, referred for emergency catheterization to a single operator at two consecutive Veterans Affairs medical centers over a 15-year period (1988 to August 2003). PCI was attempted in all 93 cases: 44 consecutive patients in the present era and 49 consecutive patients in the stent era. Patients with comparable extent of coronary disease, more ST elevation myocardial infarction, multiple areas of infarction, and greater comorbidity underwent PCI in the stent era. Nevertheless, PCI in the stent era was associated with higher rates of acute success and improved in-hospital survival. Kaplan-Meier curves and log-rank testing showed highly significant improvement in overall survival (P < 0.0001). Logistic regression of in-hospital survival demonstrated that stent use (colinear with glycoprotein IIb/IIIa use and dual-antiplatelet therapy) was significantly associated with survival in a model adjusting for extent of coronary disease and comorbidities (P = 0.007). Stents and abciximab have been associated with improved acute angiographic and procedural success of PCI for cardiogenic shock, leading to improved survival.

Impaction bone grafting with hydroxyapatite: increased femoral component stability in experiments using Sawbones
Fujishiro, T., T. Nishikawa, et al. (2005), Acta Orthop 76(4): 550-4.
Abstract: BACKGROUND: Substantial bone loss and bone defects increase the amount of allografting required in hip revision surgery. Thus, the use of a synthetic material to limit the amount of allograft tissue required for impaction grafting is desirable. We evaluated the potential of hydroxyapatite (HA) mixtures to provide initial mechanical stability to a polished tapered femoral stem. MATERIAL AND METHODS: We determined the initial stability of a polished tapered femoral stem after reconstructing a cavitary femoral bone defect by impaction bone grafting with cement in Sawbones composite femurs. Three types of graft material were tested for their ability to improve initial rotational stability. The graft materials investigated were pure allograft, a mixture of 50% allograft and 50% hydroxyapatite (HA), and pure HA. RESULTS: We found a statistically significant difference between the three groups as regards torsional micromotion and failure load. INTERPRETATION: Our findings suggest that reconstruction of femoral bone defects with pure HA or a mixture of allograft and HA provides adequate initial stability for femoral revision arthroplasty using impaction grafting.

Impairment of angiogenesis and cell migration by targeted aquaporin-1 gene disruption
Saadoun, S., M. C. Papadopoulos, et al. (2005), Nature 434(7034): 786-92.
Abstract: Aquaporin-1 (AQP1) is a water channel protein expressed widely in vascular endothelia, where it increases cell membrane water permeability. The role of AQP1 in endothelial cell function is unknown. Here we show remarkably impaired tumour growth in AQP1-null mice after subcutaneous or intracranial tumour cell implantation, with reduced tumour vascularity and extensive necrosis. A new mechanism for the impaired angiogenesis was established from cell culture studies. Although adhesion and proliferation were similar in primary cultures of aortic endothelia from wild-type and from AQP1-null mice, cell migration was greatly impaired in AQP1-deficient cells, with abnormal vessel formation in vitro. Stable transfection of non-endothelial cells with AQP1 or with a structurally different water-selective transporter (AQP4) accelerated cell migration and wound healing in vitro. Motile AQP1-expressing cells had prominent membrane ruffles at the leading edge with polarization of AQP1 protein to lamellipodia, where rapid water fluxes occur. Our findings support a fundamental role of water channels in cell migration, which is central to diverse biological phenomena including angiogenesis, wound healing, tumour spread and organ regeneration.

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Last Modified: 8 February 2006