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Hydroxypropyl chitosan bearing beta-cyclodextrin cavities: synthesis and slow release of its inclusion complex with a model hydrophobic drug
Prabaharan, M. and J. F. Mano (2005), Macromol Biosci 5(10): 965-73.
Abstract: Hydroxypropyl chitosan-graft-carboxymethyl beta-cyclodextrin (HPCH-g-CM beta-CD) was synthesized by grafting CM beta-CD onto HPCH using water soluble 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide (EDC) as the condensing agent. Due to the presence of hydrophobic beta-CD rings onto the HPCH backbone, this polymer can be used as a matrix for controlled drug release. The adsorption of a hydrophobic model drug, ketoprofen, by HPCH-g-CM beta-CD microparticles (using tripolyphosphate as an ionic crosslinking agent) fitted well in the Langmuir isotherm equation. The drug dissolution profile showed that HPCH-g-CM beta-CD microparticles provided a slower release of the entrapped ketoprofen than chitosan, and the release behavior was influenced by the pH value of the medium. These results suggest that beta-CD grafted with chitosan derivatives may become a potential biodegradable delivery system to control the release of hydrophobic drugs with pH-responsive capability.

Hydroxypropyl methylcellulose (HPMC) lubricant facilitates insertion of porous spherical orbital implants
de Silva, D. J. and J. M. Olver (2005), Ophthal Plast Reconstr Surg 21(4): 301-2.
Abstract: The insertion of an orbital implant in the posterior Tenon's space or in the eviscerated sclera must be smooth, without entrapment or dragging of adjacent soft tissue. Anterior Tenon's fascia and conjunctiva must be closed without undue tension that could lead to subsequent postoperative implant exposure. Current methods to prevent tissue drag include passing the implant via a cut "thumb" from a surgeon's glove, the use of a prepackaged rigid plastic funnel, or a specialized orbital implant introducing forceps, e.g., Carter sphere injector. We recommend also coating the porous implant with an inert semisynthetic viscoelastic polymer, thus enabling easy placement. We illustrate this in a typical case.

Hylan gel biomaterial: dermal and immunologic compatibility
Larsen, N. E., C. T. Pollak, et al. (1993), J Biomed Mater Res 27(9): 1129-34.
Abstract: Hylan, a hyaluronan derivative, was chemically cross-linked with divinyl sulfone to produce a water-insoluble gel. This gel was fragmented into a gel slurry and evaluated for particle size, biocompatibility, and residence times in selected tissues. Hylan gels used in this study are made up of pseudoplastic, deformable gel particles with greater elasticity (at all frequencies) and greater viscosity (shear rates, 0.01 sec-1) than the water soluble hylan polymer. Hylan gel was injected intradermally and subdermally in mice and was found to produce a minimal reaction at 24 h; thereafter (up to 7 weeks) there was no significant tissue reaction. Intradermal injection of [3H]-hylan gel in guinea pigs revealed a minimal tissue reaction after 1 week, and measurement of radioactivity in the tissue at 1, 2, and 4 weeks revealed only a slight decrease in the total amount of injected radioactivity. The immunogenic activity of hylan gel was evaluated in rabbits; unmodified hylan gel, degraded hylan gel, and hylan gel ovalbumin conjugate were used to immunize rabbits. No antibody production to any hylan gel sample was detected, although control rabbits immunized with ovalbumin developed titers > 400 of antiovalbumin antibodies by day 21, as measured by the passive cutaneous anaphylaxis assay (PCA). Last, serum from owl monkeys (Aotus trivirgatus) in which hylan gel had been placed intravitreally for up to 3 years contained no detectable anti-hylan gel antibodies (PCA assay). Skin tests on these monkeys were also negative.

Hypericin in the dark inhibits key steps of angiogenesis in vitro
Martinez-Poveda, B., A. R. Quesada, et al. (2005), Eur J Pharmacol 516(2): 97-103.
Abstract: Photoactivated hypericin has a potent cytotoxic effect over a wide range of cells. However, very recently hypericin has been shown to have antitumoral and antimetastatic effects in the dark. The aim of this study was to test whether hypericin in the dark affects angiogenesis. Different in vitro assays were used to study the potential effects of this compound on key steps of angiogenesis, namely, a colorimetric assay of cell proliferation/viability, a tubular formation on Matrigel assay, zymographic assays for gelatinases and urokinase, a wound assay for migration and a fluorometric assay for invasion through Matrigel. In this report, we show for the first time that hypericin kept in the dark inhibits several key steps of the angiogenic process, namely, bovine endothelial cell proliferation, formation of tubular-like structures on Matrigel, migration and invasion, as well as extracellular matrix degrading urokinase.

Hypersensitivity to metallic biomaterials: a review of leukocyte migration inhibition assays
Hallab, N., J. J. Jacobs, et al. (2000), Biomaterials 21(13): 1301-14.
Abstract: Metal hypersensitivity is a well-established phenomenon occurring in a variety of domestic and workplace settings. Degradation products of metallic biomaterials may mediate metal hypersensitivity. However, little is known about the short- and long-term pharmacodynamics and bioavailability of circulating metal degradation products in vivo. Mechanisms by which in vivo metal sensitivity reactions occur have not been well characterized and the degree to which metal sensitivity may be a predisposing factor for eliciting an overaggressive immune response remains clinically unpredictable. In vitro leukocyte migration inhibition assays have been used for investigating cell-mediated hypersensitivity reactions to biomaterial and biomaterial degradation products. This review provides a historical and technical summary of four in vitro techniques used for determination of leukocyte migration activity: (1) membrane migration or Boyden chamber, (2) capillary tube, (3) leukocyte migration using agarose technique, and (4) collagen gels. It is difficult to determine which, if any, of these techniques is singularly best suited for the investigation of suspected biomaterial-related symptoms in patients. However, Boyden chamber membrane migration testing is recommended for clinical investigations, principally because a high degree of standardized investigator independent materials and methodologies is necessary for compiling and comparing the results of patients tested at various times over the length of an extended study. Ultimately, in vitro migration inhibition testing has the potential to provide a reliable means for predicting some complications and thus enhancing the outcome for patients receiving metallic implants. Continuing improvements in migration inhibition testing methods, used alone or in combination with other immunologic assays, will likely improve assessment of patients susceptible to biomaterial antigen-induced delayed-type hypersensitivity responses.

Hyphenated chromatographic methods for biomaterials
Al-Dirbashi, O. Y. and K. Nakashima (2000), Biomed Chromatogr 14(6): 406-21.
Abstract: The improvement in hyphenated analytical techniques has significantly widened their applications to the analysis of biomaterials. In this article, we discuss recent advances in applications of hyphenated chromatographic techniques including capillary electrophoresis to the analyses of biological samples. As tools of separation, gas chromatography, high-performance liquid chromatography and capillary electrophoresis are considered with special emphasis on applications utilizing the hyphenation of these methods to mass spectrometry. Moreover, applications using other detection methods such as Fourier transform infrared spectroscopy hyphenated to gas chromatography and photodiode array detector combined with high-performance liquid chromatography or capillary electrophoresis are also discussed. Owing to their high sensitivity, luminescence-based detection systems such as laser-induced fluorescence and chemiluminescence are also included in this review.

Identification of apolipoprotein A-I as a major adsorbate on biomaterial surfaces after blood or plasma contact
Cornelius, R. M., J. Archambault, et al. (2002), Biomaterials 23(17): 3583-7.
Abstract: Apolipoprotein A-I is the major protein component of HDL. It is reported in this communication that apo A-I is a significant component of the protein layer adsorbed from blood or plasma to a variety of biomaterial surfaces, including hydrophobic and hvdrophilic polymers, liposomes, a heparinized surface, and a polysulfone hemodialyzer membrane. Evidence in support of this conclusion from SDS-PAGE and immunoblots of proteins eluted from the surfaces after blood or plasma contact is presented. Whether the presence of apo A-I on these surfaces results from the uptake of the free protein or HDL particles remains to be determined. It appears that apolipoprotein A-I and/or HDL deposition may be an important effect in blood-biomaterial interactions generally, and one that has been largely overlooked.

Image analysis in the evaluation of biomaterials
Hunt, J. A., D. G. Vince, et al. (1993), J Biomed Eng 15(1): 39-45.
Abstract: An examination regime, based on a computer-aided image analysis system, has been developed for the quantitative evaluation of the local tissue response to biomaterials. This procedure involves the immunoenzymic staining of tissue sections using monoclonal antibodies specific for certain inflammatory cell types. An avidin-biotin-horseradish peroxidase staining method is used to identify antibody binding sites and the sections are assayed using a computer-aided image analysis system. This regime facilitates the rapid and accurate measurement of 30 cell related parameters in sections stained for macrophages, polymorphonuclear leucocytes, and other cells.

Imaging appearance of some forms of Shiseido brand
Keni, S. P. and K. W. Altman (2005), Am J Rhinol 19(4): 421-2.

Immediate extraction site grafting: materials and clinical objectives
Bader, H. (2005), Dent Today 24(7): 86-9; quiz 89.

Immediate implant placement: diagnosis, treatment planning and treatment steps/or successful outcomes
Becker, W. (2005), J Calif Dent Assoc 33(4): 303-10.
Abstract: Diagnosis and treatment planning are key factors in achieving successful outcomes after placing and restoring implants placed immediately after tooth extraction. The efficacy of immediate implant placement has been established and shown to be predictable if reasonable guidelines are followed. Some or all of the following suggestions, depending on individual circumstances should be considered when evaluating a patient for dental implants: thorough medical and dental histories, clinical photographs, study casts, periapical and panogram radiographs, as well as a linear tomography or computerized tomography of the proposed implant sites. Reasons for tooth extraction include, but are not limited to, insufficient crown to root ratios, remaining root length, periodontal attachment levels, periodontal health of teeth adjacent to the proposed implant sites, unrestorable caries, root fractures with large endodontic posts, root resorption, teeth with deep furcation invasions being considered as abutments for fixed partial dentures, and questionable teeth in need of endodontic retreatment. Teeth requiring root amputations, hemisections or advanced periodontal procedures may have a questionable prognosis, and patients should be given the implant option before these procedures are implemented. Similarly, nonvital teeth, fractured at the gingival margin with roots shorter than 13 mm should be considered for the implant option. This review will describe the steps for immediate implant placement at the time of extraction as well as the "gap" and socket preservation.

Immediate/early function of Branemark System TiUnite implants in fresh extraction sockets in maxillae and posterior mandibles: an 18-month prospective clinical study
Vanden Bogaerde, L., B. Rangert, et al. (2005), Clin Implant Dent Relat Res 7 Suppl 1: S121-30.
Abstract: BACKGROUND: The advantages of placing implants in fresh extraction sockets and putting them in immediate/early function are many. A predicable protocol opens the possibility of performing a single surgical procedure, giving the patient a temporary prosthesis immediately, and minimizing the shrinkage of hard tissue and soft tissue recession. PURPOSE: The aim of the present study was to develop a strict protocol for and to evaluate the feasibility of immediate/ early function on implants placed in fresh extraction sockets located in maxillae and posterior mandibles, including defects around the implants treated according to a regenerative procedure. MATERIALS AND METHODS: Nineteen patients were treated after tooth extraction according to an immediate function protocol and were observed for 18 months. Fifty Mk IV TiUnite (Nobel Biocare AB, Goteborg, Sweden) implants were installed in partially edentulous areas in maxillae (n = 17) and posterior mandibles (n = 5). Implants were installed directly into the alveoli, and the temporary prostheses were connected immediately after surgery (n = 11) or within 7 days, that is, an "early function" procedure (n = 11). Thirteen implants did not require any type of regenerative procedure, whereas the remaining 37 implants had filling with autogenous bone, 4 of which also had a resorbable membrane. Standardized intraoral radiographs were taken for evaluation of marginal bone level, and 38 of the implants were systematically checked by resonance frequency analysis. RESULTS: All patients were followed for 18 months, and none of the 50 implants failed. However, one implant showed signs of failure after 6 weeks, but once the occlusal load was removed, the implant regained its stability completely, no longer demonstrated symptoms, and could be used successfully for prosthetic rehabilitation. The mean value of the implant stability quotient was 60 at baseline (range 45-75) and 63 after 6 months (range 46-75). The marginal bone resorption was 0.9 mm (SD 1.1 mm; n = 48) 18 months after implant insertion (1 year after final prosthesis). CONCLUSION: The immediate placement of implants into fresh extraction sockets combined with immediate/early function procedures seems to be a safe and reliable procedure when using a strict protocol.

Immobilization and stabilization of biomaterials for biosensor applications
D'Souza, S. F. (2001), Appl Biochem Biotechnol 96(1-3): 225-38.
Abstract: Biosensors are finding applications in a variety of analytical fields. A biosensor basically consists of a transducer in conjunction with a biologically active molecule that converts a biochemical signal into a quantifiable electric response. The specificity of the biosensor depends on the selection of the biomaterial. Enzymes, antibodies, DNA, receptors, organelles, microorganisms as well as animal and plant cells or tissues have been used as biologic sensing materials. Advances in biochemistry, molecular biology, and immunochemistry are expected to lead to a rapid expansion in the range of biologic recognition elements to be used in the field of biosensors. Biomaterials that are stable and function even in highly acidic, alkaline, hydrophobic, or oxidizing environments as well as stable to high temperature and immune to toxic substrates in the processing stream will play an important role. Techniques for immobilization of the biomaterials have played a significant role in the biosensor field. Immobilization not only brings about the intimate contact of the biologic catalysts with the transducer, but also helps in the stabilization of the biologic system, thus enhancing its operational and storage stability. A number of techniques have been developed in our laboratory for the immobilization of enzymes, multienzyme systems, cells, and enzyme-cell conjugates. Some of these aspects that are of significance in biosensor applications have been highlighted.

Immobilization of alpha-glucosidase in chitosan coated polygalacturonic acid
Dincer, A., B. Okutucu, et al. (2005), Prep Biochem Biotechnol 35(2): 103-11.
Abstract: Crude alpha-glucosidase from Baker's yeast was immobilized in polygalacturonic acid beads and coated with chitosan. Chemical and physical characterization were performed by using p-nitrophenyl-alpha-D-glucopyranoside (pNPG) as an artificial substrate. Operation, thermal, pH, and strorage stabilities of the free and immobilized enzyme were also examined. The stabilities of immobilized enzyme were found to be better than that of the free enzyme. Furthermore, the hydrolysis rate of the chitosan coated alpha-glucosidase polygalacturonic acid beads were studied. In conclusion, the enzyme beads appear to have good characteristics and offer the prospect that this system may find application in enzyme immobilization, in addition to controlled drug release studies.

Immobilization of beta-fructofuranosidase from Aspergillus japonicus on chitosan using tris(hydroxymethyl)phosphine or glutaraldehyde as a coupling agent
Cheng, T. C., K. J. Duan, et al. (2005), Biotechnol Lett 27(5): 335-8.
Abstract: A partially purified beta-fructofuranosidase from Aspergillus japonicus was covalently immobilized on to chitosan beads using either glutaraldehyde or tris(hydroxymethyl)phosphine (THP) as a coupling agent. Compared with the glutaraldehyde-immobilized and the free enzyme, the THP-immobilized enzyme had the highest thermal stability with 78% activity retained after 12 days at 37 degrees C. The THP-immobilized enzyme also had higher reusability than that immobilized by glutaraldehyde, 75% activity was retained after 11 batches (or 11 days) at 37 degrees C for the THP immobilized enzyme system. Less yield (48%) of fructooligosaccharides (FOS) were produced by the THP-immobilized enzyme compared with the free enzyme system (58%) from 50 (w/v) sucrose at 50 degrees C.

Immobilization of glucose oxidase onto gelatin for biosensor construction
Emregul, E., S. Sungur, et al. (2005), J Biomater Sci Polym Ed 16(4): 505-19.
Abstract: The properties of a glucose biosensor made by immobilization of glucose oxidase onto gelatin in a layer of electrochemically deposited polyaniline have been investigated. Glucose oxidase was immobilized within gelatin cross-links with chromium(III) acetate. The glucose oxidase biosensor was developed by forming a polyaniline-deposited electrode surface as support for the immobilized enzyme gel, in order to increase its durability. The polyaniline/gelatin/glucose oxidase biosensor has been characterized using chemical and electrochemical methods. Temperature, pH, cross-linking agent concentration, enzyme concentration, kinetic properties, reusability and the effect of electro-active compounds were among the parameters studied. The response time of the glucose oxidase biosensor is 90 s, the detection limit is below 1 mmol/dm3 and the sensor can be used 20 times within a 2-month period without losing its stability.

Immobilization of heavy metals in contaminated soil using nonhumus-humus soil and hydroxyapatite
Misra, V. and S. D. Pandey (2005), Bull Environ Contam Toxicol 74(4): 725-31.

Immobilization of hemoglobin at the galleries of layered niobate HCa2Nb3O10
Gao, L., Q. Gao, et al. (2005), Biomaterials 26(26): 5267-75.
Abstract: Hemoglobin (Hb) was intercalated at the galleries of layered niobate HCa(2)Nb(3)O(10) (HCNO). Two different kinds of layered phases of Hb-CNO composites Hb-CNO-1 and Hb-CNO-2 were obtained with the interlayer distances of 7.2 and 10.3nm in correspondence with the monolayer and bilayer arrangements of proteins between the niobate layers, respectively, based on the powder XRD pattern, HRTEM, UV-vis spectra and CHN analyses. FTIR spectra of Hb-CNO composites show that amide I and amide II bands were actually the same as those of the native Hb, which indicates that there is almost no structural change after immobilization. Michaelis-Menten model methods were used to study the peroxidatic activity of the reaction of 2-methoxyphenol and H(2)O(2) for the entrapped Hb in the galleries of HCNO. Compared to that of free Hb, the kinetic parameters of Hb-CNO k(cat), K(M) and k(cat)/K(M) were affected by the immobilization process. The immobilized Hb showed a higher relative activity than that of free Hb after incubated in phosphate buffer (pH = 7) at 80 degrees C for a period of time. The environments between the layers of HCNO are hydrophilic which will bind water tightly and help to stabilize the 'essential water' layer around the protein. So, immobilization of Hb between the layers of HCNO enhanced the activity of Hb in water-DMSO mixture.

Immobilization of heparin on a silicone surface through a heterobifunctional PEG spacer
Chen, H., Y. Chen, et al. (2005), Biomaterials 26(35): 7418-24.
Abstract: A novel method of immobilizing heparin on a silicone surface through a heterobifunctional PEG spacer was used yield well defined surfaces with highly active surface immobilized heparin and low non-specific protein adsorption. The heparin surface density achieved using this technique was 0.68 microg/cm2. Sessile drop water contact angles showed increased hydrophilicity of the silicone surface after PEG modification and a further decrease in the contact angles following the grafting of heparin. High specificity for ATIII with little fibrinogen adsorption was noted in plasma adsorption studies. This ATIII adsorption was mediated by the heparin layer, since surfaces modified with PEG only did not adsorb significant quantities of AT. The thrombin resistance of the heparin modified surfaces was demonstrably greater as measured by a chromogenic thrombin generation assay. The results suggest that the heterbifunctional PEG linker results in a high density of active heparin on the surfaces.

Immobilization of heparin on polylactide for application to degradable biomaterials in contact with blood
Seifert, B., T. Groth, et al. (1995), J Biomater Sci Polym Ed 7(3): 277-87.
Abstract: The poly-(D, L-lactide) RESOMER R208 (Boehringer-Ingelheim, Germany) was modified with heparin to improve the blood contacting properties of the material. The immobilization of herapin was carried out by covalent binding with glutaraldehyde as the coupling agent. The reaction conditions, such as temperature and time, were varied to optimize the binding of heparin. The efficiency of the immobilization was monitored with respect to the total amount of coupled herapin with a toluidine blue assay and the anticoagulant activity of immobilized heparin with a factor Xa assay. The hemocompatibility of the modified polylactide was estimated after blood-material contact by the activation of platelets measured with an enzyme immuno assay for GMP140. Immobilization at ambient temperature and a reaction time of 2 h resulted in maximal heparin binding, high anticoagulant activity, and low thrombogenicity. Since the remaining unsaturated aldehyde groups of the coupling agent may cause a low hemocompatibility of the material, washing of the heparinized polylactide was carried out with ethanol. However, it was shown that washing diminished the anticoagulant activity of heparin and increased the thrombogenicity. The prolonged storage of heparinized polylactide in phosphate buffered saline for 8 days demonstrated that small quantities of heparin were released but the hemocompatibility was further improved, indicated by an increasing anticoagulant potential and a decrease in platelet activation with incubation time. A comparison of polylactide, heparinized polylactide, polypropylene, and Pellethane with respect to platelet activation by GMP140 assay and scanning electron microscopy, revealed that the heparinization of polylactide substantially improved the hemocompatibility of RESOMER R208, making the material comparable to Pellethane.

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Last Modified: 8 February 2006