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A study of the relationship between mass and physical strength of keratin bars in vivo
Peplow, P. V. and G. J. Dias (2004), J Mater Sci Mater Med 15(11): 1217-20.
Abstract: A study was undertaken of the changes in the mass and physical properties of keratin bars implanted subcutaneously in adult rats. A very gradual decrease occurred in vivo in the dry weight of the bars over the period of the study (up to 18 weeks). The elastic modulus of the bars decreased abruptly when present in vivo between 3 and 6 weeks. At the same time there was an increase in the number of cavitations and fissures at the surface of the bars, and an increase in a central internal region of the bars where there was a disorganisation in structure of the polymer. A biocompatible material showing such changes in vivo is likely to be suitable for a variety of medical and surgical applications in which it provides a framework for cell invasion.

A study on reference standard for cytotoxicity assay of biomaterials
Oshima, H. and M. Nakamura (1994), Biomed Mater Eng 4(4): 327-32.
Abstract: The objective of the present study was to find a standard substance for use as a reference in the cytotoxicity assay of biomaterials, as an alternative to animal experiments in recent years. Eight kinds of rubber were made in a plate shape to keep their surface area at 1 cm2 against 10 ml of extract volume. They were extracted by the following three extraction methods (a) dynamic extraction at 200 rpm gyration on alumina balls at 37 degrees C for 24 h; (b) static extraction at 37 degrees C for 24 h and (c) extraction by heating in an autoclave at 121 degrees C for 60 min. At the end of each period each extract was examined for cell viability based on an evaluation by neutral red uptake. These methods were repeated up to seven times. Two kinds of chemicals were also tested. The extracts obtained were used to treat human gingival fibroblasts that have been cultured with DMEM supplemented with 5% fetal bovine serum into a 96 well tissue culture plate by 1 x 10(5) cells/ml, in an incubator aerated with 5% CO2, and 95% humidified air at 37 degrees C for 48 h. The extracts of ethylene-propylene, butyl, nitrile rubbers, and two kinds of chemicals yielded strong cytotoxicity in all three kinds of extraction methods, while chloroprene, fluorine-contained, isoprene, India, and silicone rubbers showed little cytotoxicity. The results obtained by the three kinds of extraction methods revealed no differences in the order of cytotoxicity of the materials tested.(ABSTRACT TRUNCATED AT 250 WORDS)

A synergistic chlorhexidine/chitosan combination for improved antiplaque strategies
Decker, E. M., C. von Ohle, et al. (2005), J Periodontal Res 40(5): 373-7.
Abstract: BACKGROUND: The minor efficacy of chlorhexidine (CHX) on other cariogenic bacteria than mutans streptococci such as Streptococcus sanguinis may contribute to uneffective antiplaque strategies. METHODS AND RESULTS: In addition to CHX (0.1%) as positive control and saline as negative control, two chitosan derivatives (0.2%) and their CHX combinations were applied to planktonic and attached sanguinis streptococci for 2 min. In a preclinical biofilm model, the bacteria suspended in human sterile saliva were allowed to attach to human enamel slides for 60 min under flow conditions mimicking human salivation. The efficacy of the test agents on streptococci was screened by the following parameters: vitality status, colony-forming units (CFU)/ml and cell density on enamel. The first combination reduced the bacterial vitality to approximately 0% and yielded a strong CFU reduction of 2-3 log(10) units, much stronger than CHX alone. Furthermore, the first chitosan derivative showed a significant decrease of the surface coverage with these treated streptococci after attachment to enamel. CONCLUSIONS: Based on these results, a new CHX formulation would be beneficial unifying the bioadhesive properties of chitosan with the antibacterial activity of CHX synergistically resulting in a superior antiplaque effect than CHX alone.

A synthetic glycosaminoglycan mimetic binds vascular endothelial growth factor and modulates angiogenesis
Rouet, V., Y. Hamma-Kourbali, et al. (2005), J Biol Chem 280(38): 32792-800.
Abstract: In a previous study, we showed that in situ injection of glycosaminoglycan mimetics called RGTAs (ReGeneraTing Agents) enhanced neovascularization after skeletal muscular ischemia (Desgranges, P., Barbaud, C., Caruelle, J. P., Barritault, D., and Gautron, J. (1999) FASEB J. 13, 761-766). In the present study, we showed that the RGTA OTR4120 modulated angiogenesis in the chicken embryo chorioallantoic membrane assay, in a dose-dependent manner. We therefore investigated the effect of OTR4120 on one of the most specific angiogenesis-regulating heparin-binding growth factors, vascular endothelial growth factor 165 (VEGF165). OTR4120 showed high affinity binding to VEGF165 (Kd = 2.2 nm), as compared with heparin (Kd = 15 nm), and potentiated the affinity of VEGF165 for VEGF receptor-1 and -2 and for neuropilin-1. In vitro, OTR4120 potentiated VEGF165-induced proliferation and migration of human umbilical vein endothelial cells. In the in vivo Matrigel plug angiogenesis assay, OTR4120 in a concentration as low as 3 ng/ml caused a 6-fold increase in VEGF165-induced angiogenesis. Immunohistochemical staining showed a larger number of well differentiated VEGFR-2-expressing-cells in Matrigel sections of OTR4120-treated plug than in control sections. These findings indicate that OTR4120 enhances the VEGF165-induced angiogenesis and therefore may hold promise for treating disorders characterized by deficient angiogenesis.

A synthetic multicellular system for programmed pattern formation
Basu, S., Y. Gerchman, et al. (2005), Nature 434(7037): 1130-4.
Abstract: Pattern formation is a hallmark of coordinated cell behaviour in both single and multicellular organisms. It typically involves cell-cell communication and intracellular signal processing. Here we show a synthetic multicellular system in which genetically engineered 'receiver' cells are programmed to form ring-like patterns of differentiation based on chemical gradients of an acyl-homoserine lactone (AHL) signal that is synthesized by 'sender' cells. In receiver cells, 'band-detect' gene networks respond to user-defined ranges of AHL concentrations. By fusing different fluorescent proteins as outputs of network variants, an initially undifferentiated 'lawn' of receivers is engineered to form a bullseye pattern around a sender colony. Other patterns, such as ellipses and clovers, are achieved by placing senders in different configurations. Experimental and theoretical analyses reveal which kinetic parameters most significantly affect ring development over time. Construction and study of such synthetic multicellular systems can improve our quantitative understanding of naturally occurring developmental processes and may foster applications in tissue engineering, biomaterial fabrication and biosensing.

A system-on-chip digital pH meter for use in a wireless diagnostic capsule
Hammond, P. A., D. Ali, et al. (2005), IEEE Trans Biomed Eng 52(4): 687-94.
Abstract: This paper describes the design and implementation of a system-on-chip digital pH meter, for use in a wireless capsule application. The system is organized around an 8-bit microcontroller, designed to be functionally identical to the Motorola 6805. The analog subsystem contains a floating-electrode ISFET, which is fully compatible with a commercial CMOS process. On-chip programmable voltage references and multiplexors permit flexibility with the minimum of external connections. The chip is designed in a modular fashion to facilitate verification and component re-use. The single-chip pH meter can be directly connected to a personal computer, and gives a response of 37 bits/pH, within an operating range of 7 pH units.

A technique for measuring the thermal conductivity and evaluating the "apparent conductivity" concept in biomaterials
Arkin, H., K. R. Holmes, et al. (1989), J Biomech Eng 111(4): 276-82.
Abstract: A simple technique for measuring thermal conductivity of biomaterials is described. The method is based on depositing a pulse of heat into the material of choice, and fitting the subsequent local temperature decay to that predicted by a theoretical model. This transient method is most suitable in situations where frequent measurements of the thermal conductivity are desired. The method was evaluated by calculating the thermal conductivity of several inert materials. The measured conductivities compared well with published values. The developed technique was also used to examine the applicability of the "apparent conductivity" index to combine both conductive and blood-convective thermal effects in living, blood perfused tissues. Using both simulated and experimental results, it was shown that the changes in the apparent conductivity are highly correlated with changes in blood flow. However, quantitative application of this index must be restricted to conditions that are similar to those which existed at the time the apparent conductivity was measured.

A technique for the fabrication of an immediate mandibular surgical stent securing a skin graft
Tomsett, K. L., M. S. Chambers, et al. (2005), J Prosthet Dent 93(4): 395-7.
Abstract: Patients who receive a skin graft following an ablative mandibular procedure may require an immediate intraoral surgical stent. This article describes an efficient and accurate method of fabricating an immediate mandibular surgical stent in the operating room setting.

A templating route to nanoporous chitosan materials
Liu, Y., J. Tang, et al. (2005), Carbohydr Res 340(18): 2816-20.
Abstract: Nanoporous chitosan materials in both membrane and bulk form with pore diameter ranges of 10-50nm were prepared by a novel emulsion-mediated templating method. Considering the biocompatibility and versatility of chitosan, the nanoporous chitosan material is expected to have a wide variety of applications in the biotechnological and biomaterials areas.

A thin carboxymethyl cellulose culture substrate for the cellulase-induced harvesting of an endothelial cell sheet
Ko, I. K., K. Kato, et al. (2005), J Biomater Sci Polym Ed 16(10): 1277-91.
Abstract: Engineered tissues constructed with two-dimensionally organized cells provide promising parts for reconstructing damaged tissues. Here we propose a new method for fabricating a 2D sheet made of an endothelial cell monolayer. First a culture substrate was prepared by treating the glass surface with an amine-terminated organosilicon derivative, followed by the covalent attachment of a thin carboxymethyl cellulose (CMC) layer. Fibronectin was immobilized onto the CMC-coated surface to promote cell adhesion. These surfaces were characterized step by step by means of contact angle measurement and X-ray photoelectron spectroscopy. Porcine aortic endothelial cells adhered to the culture substrate and consequently formed a confluent monolayer. When the substrate-cell composite was immersed in a cellulase solution, a cell sheet was spontaneously detached from the substrate due to enzymatic digestion of the CMC layer. The cell-cell connections were well preserved in the cell sheet, even after detachment from the substrate, most likely due to the fact that cellulase is harmless to mammalian cells. The cell sheet could be transferred to other culture dish with the aid of a hydrophilic membrane support, retaining the proliferation activity of the cells. The results obtained in this study demonstrate that cellulase treatment of the CMC layer is a rational and efficient method for obtaining a 2D cell sheet.

A three-layered nano-carbonated hydroxyapatite/collagen/PLGA composite membrane for guided tissue regeneration
Liao, S., W. Wang, et al. (2005), Biomaterials 26(36): 7564-71.
Abstract: Functional graded materials (FGM) provided us one new concept for guided tissue regeneration (GTR) membrane design with graded component and graded structure where one face of the membrane is porous thereby allowing cell growth thereon and the opposite face of the membrane is smooth, thereby inhibiting cell adhesion in periodontal therapy. The goal of the present study was to develop a three-layered graded membrane, with one face of 8% nano-carbonated hydroxyapatite/collagen/poly(lactic-co-glycolic acid) (nCHAC/PLGA) porous membrane, the opposite face of pure PLGA non-porous membrane, the middle layer of 4% nCHAC/PLGA as the transition through layer-by-layer casting method. Then the three layers were combined well with each other with flexibility and enough high mechanical strength as membrane because the three layers all contained PLGA polymer that can be easily used for practical medical application. This high biocompatibility and osteoconductivity of this biodegraded composite membrane was enhanced by the nCHAC addition, for the same component and nano-level crystal size with natural bone tissue. The osteoblastic MC3T3-E1 cells were cultured on the three-layered composite membrane, the primary result shows the positive response compared with pure PLGA membrane.

A tissue-engineered suburethral sling in an animal model of stress urinary incontinence
Cannon, T. W., D. D. Sweeney, et al. (2005), BJU Int 96(4): 664-9.
Abstract: OBJECTIVE: To create and evaluate the functional effects of a tissue-engineered sling in an animal model of stress urinary incontinence (SUI). MATERIALS AND METHODS: Twenty female Sprague-Dawley rats were divided into four equal groups: a control group (C) had no intervention before the leak-point pressure (LPP) was measured; a denervated group (D) had bilateral proximal sciatic nerve transection (PSNT) and periurethral dissection with no sling placed; group S had concomitant bilateral PSNT and a suburethral sling of small intestinal submucosa (SIS) placed; and group (M) had concomitant bilateral PSNT with implantation of a tissue-engineered sling. The suburethral sling was placed via a transabdominal approach with the sling sutured to the pubic bone. Tissue-engineered slings were prepared with muscle-derived cells obtained via the pre-plate technique and subsequently seeded for 2 weeks on a SIS scaffold. Suburethral slings were implanted 2 weeks before LPP testing, using the vertical-tilt method. RESULTS: Surgically placing a suburethral sling is feasible in the female rat, with few complications. LPPs from both sling groups (S and M) were not significantly different from untreated controls (C). The S, M and C groups all had significantly higher LPPs than group D. Importantly, no rat from either sling group (S and M) had signs of urinary retention. CONCLUSIONS: Placing tissue-engineered slings in an animal model of SUI resulted in LPP values that were not significantly different from those in untreated control or SIS (S) groups. These data show that incorporating muscle stem cells into SIS slings does not adversely alter the advantageous mechanical properties of the SIS sling in a model of SUI, and provide the basis for future functional studies of tissue-engineered sling materials with long-term retention.

A transmission electron microscopy examination of the interface between osteoblasts and metal biomaterials
Garvey, B. T. and R. Bizios (1995), J Biomed Mater Res 29(8): 987-92.
Abstract: Transmission electron microscopy was used to examine the interface between metal implant materials and bone cells. Specifically, neonatal rat calvaria osteoblasts were cultured on CoCrMo alloy and on 316L stainless steel discs (mechanically polished to a 0.3 micron finish) in Dulbecco's Modified Eagle Medium (supplemented with 10% fetal bovine serum, 50 micrograms/mL ascorbic acid, and 10 mM beta-glycerophosphate) under standard, sterile, cell culture conditions for 14 to 28 days. At the end of the prescribed time periods, the cells were fixed and embedded in resin before removing the metal substrates using an electrolytic dissolution technique and a 7% NaCl solution. Transmission electron microscopic examination of stained, ultrathin sections of the biological samples revealed an intact interface with microscopic details characteristic to the cell line and similar to those reported in the literature for animal and explant studies. The osteoblasts exhibited continuous contact and intimate apposition to both the CoCrMo and stainless steel substrate surfaces and grew in multilayered structures; an electron dense layer (composed of mucopolysaccharides and proteins) was observed at the surface of both substrates; collagen fibrils and mineralized foci were observed in the extracellular matrix interspersed among the multilayered osteoblasts.

A transmission electron microscopy study of mineralization in age-induced transparent dentin
Porter, A. E., R. K. Nalla, et al. (2005), Biomaterials 26(36): 7650-60.
Abstract: It is known that fractures are more likely to occur in altered teeth, particularly following restoration or endodontic repair; consequently, it is important to understand the structure of altered forms of dentin, the most abundant tissue in the human tooth, in order to better define the increased propensity for such fractures. Transparent (or sclerotic) dentin, wherein the dentinal tubules become occluded with mineral as a natural progressive consequence of aging, is one such altered form. In the present study, high-resolution transmission electron microscopy is used to investigate the effect of aging on the mineral phase of dentin. Such studies revealed that the intertubular mineral crystallites were smaller in transparent dentin, and that the intratubular mineral (larger crystals deposited within the tubules) was chemically similar to the surrounding intertubular mineral. Exit-wave reconstructed lattice-plane images suggested that the intratubular mineral had nanometer-size grains. These observations support a "dissolution and reprecipitation" mechanism for the formation of transparent dentin.

A versatile three-iodine molecular building block leading to new radiopaque polymeric biomaterials
Benzina, A., M. A. Kruft, et al. (1996), J Biomed Mater Res 32(3): 459-66.
Abstract: A methacrylic monomer containing three iodine atoms, 2- [2',3',5'-triiodobenzoyl]-ethyl methacrylate (compound 1), was prepared in pure form. Compound 1 can be reacted with other methacrylates, such as methyl methacrylate (MMA), and 2-hydroxyethyl methacrylate (HEMA) with high conversion. Typically, less than 0.5% of free monomer is left after polymerization. For example, compound 1 was reacted with MMA and HEMA in the molar ratio 7:73:20, respectively. This yielded a terpolymer with Tg = 86 degrees C, Mw = 47,000 g/ mol and Mn = 22,800 g/mol. This material was characterized by various physicochemical techniques, including gel permeation chromatography, differential scanning calorimetry, thermogravimetric analysis, and nuclear magnetic resonance (NMR) spectroscopy (1H at 400 MHz, DMSO-d6 solution). In addition the material was found to exhibit low surface thrombogenicity in vitro and a low propensity to activate contacting blood platelets. Furthermore it was found that the terpolymer is markedly radiopaque: even thin objects (< 0.5 mm) could be easily visualized using X-ray fluoroscopic techniques as are routinely used in the clinic, e.g., during coronary angiography. The combined results obtained with the present terpolymer (particularly its in vitro hemocompatibility and its radiopacity) leads to the suggestion that this type of polymer could be used as cardiovascular biomaterials, for instance for the construction of a new type of endovascular stents. These would be expected to show improved biocompatibility if compared with metallic stents which are currently used, for instance in conjunction with percutaneous transluminal coronary angioplasty (PTCA). A stent prototype, constructed from the present radiopaque terpolymer, is shown and discussed briefly.

A viscous bioerodible poly(ortho ester) as a new biomaterial for intraocular application
Einmahl, S., F. Behar-Cohen, et al. (2000), J Biomed Mater Res 50(4): 566-73.
Abstract: The biocompatibility of a viscous, hydrophobic, bioerodible poly(ortho ester) (POE) intended for intraocular application was investigated. POE was evaluated as a blank carrier and as containing modulators of degradation. Each formulation was injected intracamerally and intravitreally in rabbit eyes, and clinical and histological examinations were performed postoperatively for 2 weeks. In the case of intracameral injections, polymer biocompatibility appeared to depend on the amount injected in the anterior chamber. When 50 microL was administered, the polymer degraded within 2 weeks, and clinical observations showed good biocompatibility of POE with no toxicity to the ocular tissues or increase in intraocular pressure. The injection of a larger volume, 100 microL, of POE, appeared inappropriate because of direct contact of polymeric material with the corneal endothelium, and triggered reversible edema and inflammation in the anterior chamber of the eye that regressed after a few days. After intravitreal administration, POE was well tolerated and no inflammatory reaction developed during the observation period. The polymer degraded slowly, appearing as a round whitish bubble in the vitreous cavity. The presence of modulators of degradation both improved POE biocompatibility and prolonged polymer lifetime in the eye. POE appears to be a promising biomaterial for clinical intraocular application.

Ability of different biomaterials to enantioselectively catalyze oxidation and reduction reactions
Nagaoka, H. (2004), Biotechnol Prog 20(1): 128-33.
Abstract: We studied the ability of different biomaterials to enantioselectively catalyze oxidation or reduction reactions with the help of substrate rac-1-m or p-ArCH(OH)Me and the 1-o-ArC(O)Me derivatives. Apoenzyme (NAD(P)(+)-dependent secondary alcohol dehydrogenase(NAD(P)-E)) and cofactor (NAD(P)(+)) were activated by preincubating immobilized aqueous plant leaf (e.g., young wheat leaves), cereal tissue (wheat bran), vegetable (e.g., carrot), and seaweed (e.g., wakame seaweed) solutions, and the NAD(P)-E oxidized only (R)-isomers highly enantioselectively. Thus, greater than 99% ee(s) of (S)-isomers (1m-5m and 1p-5p) can be obtained from corresponding rac-1-m or p-ArCH(OH)Me. Further, immobilized chlorella cells and immobilized baker's yeast can reduce highly stereoselectively; greater than 99% ee(s) of (S)-isomers (1o-5o) can be obtained from corresponding 1-o-ArC(O)Me. Specific use of each isomer ((S)-6 and (R)-6) with greater than 99% ee(s) of racemic-1-2-NpCH(OH)Me becomes possible through selective use of NAD(P)-E eluted from artemisia vulgaris indica leaves and young wheat leaves. We suggest that the pH of the reaction media can determine not only the direction of NAD(P)-E, toward enantioselectively catalyzed oxidation (pH > 7.0) or reduction reaction (pH < 7.0), but also the regioselective reactivity of NAD(P)-E to the substrate o- (pH < 7.0), m-, and p-substituted groups (pH > 7.0). Thus, in comparison to current biocatalysts, several biomaterials can serve as asymmetric reagent bases, providing easily obtained, low-cost natural catalysts with stereoselectivity, regioselectivity, and substrate specificity that work under mild conditions for asymmetric synthesis of organic compounds.

About biomaterials and how they work in groin hernia repairs
Stoppa, R. (2003), Hernia 7(2): 57-60.

Abridged report of the committee to survey the needs and opportunities for the biomaterials industry
Barenberg, S. A. (1988), J Biomed Mater Res 22(12): 1267-91.

AC electrospray biomaterials synthesis
Yeo, L. Y., Z. Gagnon, et al. (2005), Biomaterials 26(31): 6122-8.
Abstract: A rapid, viable and safe fabrication method for biomaterials synthesis is reported using high-frequency AC electrospraying. We demonstrate its potential for polymeric nanoparticle fabrication, drug encapsulation in mono-dispersed micron-sized biodegradable polymer shells and the synthesis of 1microm biodegradable fibers with adjustable pore sizes as bioscaffolds for tissue/orthopaedic engineering and wound care therapy. The absence of charge in the ejected drops and fibers facilitates pulmonary drug delivery, polymer encapsulation and minimizes protein/DNA denaturing or compound ionization.

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Last Modified: 8 February 2006