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Rheological characterization and turbidity of riboflavin-photosensitized changes in alginate/GDL systems
Baldursdottir, S. G. and A. L. Kjoniksen (2005), Eur J Pharm Biopharm 59(3): 501-10.
Abstract: Riboflavin (RF) in combination with light, in the wavelength range of 310-800 nm, is used to induce degradation of alginic acid gels. Light irradiation of alginate solutions in the presence of RF under aerobic conditions causes scission of the polymer chains. In the development process of a new drug delivery system, RF photosensitized degradation of alginic acid gels is studied by monitoring changes in the turbidity and rheological parameters of alginate/glucono-delta-lactone (GDL) systems with different concentrations of GDL. Addition of GDL induces gel formation of the samples by gradually lowering the pH-value of the system. The turbidity is measured and the cloud point determined. The turbidity starts to increase after shorter times with enhanced concentration of GDL. Enhanced viscoelasticity is detected with increasing GDL concentration in the post-gel regime, but small differences are detected at the gel point. The incipient gel is 'soft' and has an open structure independent on the GDL concentration. In the post-gel regime solid-like behavior is observed, this is more distinct for the systems with high GDL concentrations. The effect of photosensitized RF on alginate/GDL systems decreases with increasing amount of GDL in the system. The same trend is detected whether the systems are irradiated in the pre-gel or in the post-gel regime.

Rheological characterization of an artificial synovial fluid
Casentini, G., L. Di Paola, et al. (2005), Int J Artif Organs 28(7): 711-7.
Abstract: Rheological measurements on two classes of artificial synovial fluids have been carried out in the attempt to get a suitable but cheap lubricant for wear tests of prosthetic materials. Fluids of both classes are solutions of hyaluronic acid (HA) that, for one class, is dissolved into a simple Ringer solution whereas, for the other class, into a mixture of human serum and Ringer solution. Similar rheological properties have been observed for both classes of fluids. Experimental results have been interpreted by two classical models that are commonly used in the literature to describe the rheological behavior of colloidal systems and of polymer solutions with high entanglement density, respectively. The quality of correlations shows that, at high HA concentrations, entangled structures are largely present and cannot be neglected.

Rheological characterization of in situ cross-linkable hyaluronan hydrogels
Ghosh, K., X. Z. Shu, et al. (2005), Biomacromolecules 6(5): 2857-65.
Abstract: This report investigates the rheological properties of cross-linked, thiol-functionalized HA (HA-DTPH) hydrogels prepared by varying the concentration and molecular weight (MW) of the cross-linker, poly(ethylene glycol) diacrylate (PEGDA). Hydrogels were subsequently cured for either short-term (hours) or long-term (days) and subjected to oscillatory shear rheometry (OSR). OSR allows the evaluation and comparison of the shear storage moduli (G'), an index of the total number of effective cross-links formed in the hydrogels. While the oscillatory time sweep monitored the evolution of G' during in situ gelation, the stress and frequency sweeps measured the G' of preformed and subsequently cured hydrogels. From stress sweeps, we found that, for the hydrogels, G' scaled linearly with PEGDA concentration and was independent of its MW. Upon comparison with the classical Flory's theory of elasticity, stress sweep tests on short-term cured hydrogels revealed the simultaneous, but gradual, formation of spontaneous disulfide cross-links in the hydrogels. Results from time and frequency sweeps suggested that the formation of a stable, three-dimensional network depended strictly on PEGDA concentration. Results from the equilibrium swelling of hydrogels concurred with those obtained from oscillatory stress sweeps. Such a detailed rheological characterization of our HA-DTPH-PEGDA hydrogels will aid in the design of biomaterials targeted for biomedical or pharmaceutical purposes, especially in applications involving functional tissue engineering.

Rheometric study of the gelation of chitosan in aqueous solution without cross-linking agent
Montembault, A., C. Viton, et al. (2005), Biomacromolecules 6(2): 653-62.
Abstract: A new process of formation of chitosan physical hydrogels in aqueous solution, without any organic solvent or cross-linking additive, was studied. The three conditions required for the physical gelation were an initial polymer concentration over C*, a critical value of the balance between hydrophilic and hydrophobic interactions, and a physicochemical perturbation responsible for a bidimensional percolating mechanism. The time necessary to reach the gel point was determined by rheometry, and gelations were compared according to different initial conditions. Thus, we investigated the influence of the polymer concentration and the degree of acetylation (DA) of chitosan on gelation. The number of junctions per unit volume at the gel point varied with the initial polymer concentration, i.e., the initial number of chain entanglements per unit volume or the number of gel precursors. The time to reach the gel point decreased with both higher DAs and concentrations. For a chitosan of DA = 36.7%, a second critical initial concentration close to 1.8% (w/w) was observed. Above this concentration, the decrease of the time to reach the gel point was higher and fewer additional junctions had to be formed to induce gelation. To optimize these physical hydrogels, to be used for cartilage regeneration, their final rheological properties were studied as a function of their degree of acetylation and their polymer concentration. Our results allowed us to define the most appropriate gel for the targeted application corresponding to a final concentration of chitosan in the gel of near 1.5% (w/w) and a DA close to 40%.

Ring-reinforced prosthesis for paracolostomy hernia
de Ruiter, P. and A. B. Bijnen (2005), Dig Surg 22(3): 152-6.
Abstract: BACKGROUND: The reported recurrence rate after paracolostomy hernia repair, with or without mesh, varies between 47 and 100%. We developed a polypropylene mesh prosthesis with a central opening, reinforced with a polypropylene ring, that can be implanted suprafascially through a mucocutaneous incision. METHODS: The results of a consecutive series of 46 patients with paracolostomy hernia, who were implanted with this prosthesis between October 1988 and November 2000 in 12 hospitals, were analyzed. The mean follow-up was 5 (range 1-13) years. RESULTS: The early infection rate was 4.3%. Two patients were lost to follow-up. The late infection rate was 2.3%. Seven patients (15.9%) developed a recurrent parastomal hernia and were all reoperated. The prosthesis was definitively removed in 10 patients. CONCLUSION: Although implantation of this new prosthesis is not without complications, it offers the lowest reported recurrence rate until now.

Rising to the surface: the technology of polymeric surfaces on biomaterials
Williams, D. (1998), Med Device Technol 9(8): 6-8, 10, 12.
Abstract: The properties of a piece of plastic may generally be highly appropriate for a medical application except that its surface may not be optimal. Some of the many ways in which the surfaces of biomaterials can be modified so that the main bulk properties are undisturbed and specialist surface properties exist in a thin, often invisible, layer are described in this article.

Risk of thrombosis with the use of sirolimus-eluting stents for percutaneous coronary intervention (from registry and clinical trial data)
Bavry, A. A., D. J. Kumbhani, et al. (2005), Am J Cardiol 95(12): 1469-72.
Abstract: We conducted a meta-analysis on 6 studies in 2,963 patients who had coronary artery disease and received a sirolimus-eluting stent or a bare metal stent for revascularization. Compared with bare metal stents, sirolimus-eluting stents did not appear to increase the risk for thrombosis up to 13.5 months after coronary intervention (risk ratio 0.49, 95% confidence interval 0.22 to 1.12, p = 0.09).

Role of adult mesenchymal stem cells in bone tissue engineering applications: current status and future prospects
Mauney, J. R., V. Volloch, et al. (2005), Tissue Eng 11(5-6): 787-802.
Abstract: Mesenchymal stem cells (MSCs) have been demonstrated as an attractive cell source for tissue-engineering applications because of their ability to be easily isolated and expanded from adult bone marrow aspirates and their versatility for pluripotent differentiation into mesenchymal tissues. This review highlights advances and progress in bone reconstruction techniques for both the repair of site-specific bone defects and the attenuation of musculoskeletal disease symptoms associated with osteoporosis and osteogenesis imperfecta. Despite the enormous potential benefits of MSCs within these approaches, conventional tissue culture methods limit the clinical utility of these cells because of the gradual loss of both their proliferative and differentiation potential during ex vivo expansion. Novel strategies to overcome these limitations are discussed including cultivation in the presence of basic fibroblastic growth factor 2, induction of ectopotic telomerase expression, and ex vivo expansion on various collagenous biomaterials. In addition, this review also outlines mechanistic theories on the potential role of MSC-extracellular matrix interactions in mediating the retention of MSC proliferative and differentiation capacity after ex vivo expansion on collagenous biomaterials.

Role of an alginate lyase for alginate transport in mucoid Pseudomonas aeruginosa
Jain, S. and D. E. Ohman (2005), Infect Immun 73(10): 6429-36.
Abstract: The opportunistic pathogen Pseudomonas aeruginosa secretes a capsule-like polysaccharide called alginate that is important for evasion of host defenses, especially during chronic pulmonary disease of patients with cystic fibrosis (CF). Most proteins for alginate biosynthesis are encoded by the 12-gene algD operon. Interestingly, this operon also encodes AlgL, a lyase that degrades alginate. Mutants lacking AlgG, AlgK, or AlgX, also encoded by the operon, synthesize alginate polymers that are digested by the coregulated protein AlgL. We examined the phenotype of an DeltaalgL mutation in the highly mucoid CF isolate FRD1. Generating a true DeltaalgL mutant was possible only when the algD operon was under the control of a LacI(q)-repressed trc promoter. Upon induction of alginate production with isopropyl-beta-D-thiogalactopyranoside, the DeltaalgL mutant cells were lysed within a few hours. Electron micrographs of the DeltaalgL mutant showed that alginate polymers accumulated in the periplasm, which ultimately burst the bacterial cell wall. The requirement of AlgL in an alginate-overproducing strain led to a new model for alginate secretion in which a multiprotein secretion complex (or scaffold, that includes AlgG, AlgK, AlgX, and AlgL) guides new polymers through the periplasm for secretion across the outer membrane. In this model, AlgL is bifunctional with a structural role in the scaffold and a role in degrading free alginate polymers in the periplasm.

Role of E-cadherin molecules in spheroid formation of hepatocytes adhered on galactose-carrying polymer as an artificial asialoglycoprotein model
Takei, R., D. Suzuki, et al. (2005), Biotechnol Lett 27(16): 1149-56.
Abstract: The role of E-cadherin in the spheroid formation of hepatocytes adhered on the poly(N-p-vinylbenzyl-D-lactonamide) (PVLA) as a model ligand for asialoglycoprotein receptors (ASGP-R) of hepatocytes was studied. Expression of E-cadherin was increased in round hepatocytes adhered on a high-coating density of PVLA (100 microg/ml), and also in flat ones adhered on a low-coating density of PVLA (1 microg/ml) in the presence of epidermal growth factor (EGF). Hepatocyte spheroids formed on the high-coating density of PVLA in the presence of EGF after 48 h were inhibited by an anti-E-cadherin monoclonal antibody (ECCD-1). From immunofluorescence and confocal laser microscopy, E-cadherin was localized in the intercellular boundaries and concentrated at the inside surface of aggregated cells. As a result, E-cadherin could play an important role in hepatocyte assembly.

Role of extracellular matrix in regulation of staurosporine-induced apoptosis in breast cancer cells
Vasaturo, F., C. Malacrino, et al. (2005), Oncol Rep 13(4): 745-50.
Abstract: Autocrine and paracrine mechanisms modulate the synthesis and secretion of extracellular matrix (ECM); moreover, each component of the ECM is capable of modulating the synthesis and release of other ECM molecules. Therefore, the synthesis of ECM glycoprotein fibronectin and laminin was studied in the human breast cancer cell lines MCF7 and MDA MB 23, plated on different ECM. Our results showed that the cells plated on a fibronectin substrate increased laminin synthesis: this event correlated with an increase in alpha2 and alpha3 integrin subunits. Staurosporine-induced apoptosis was then analyzed in the cell lines plated on different ECM. Staurosporine treatment determined the apoptosis of 35 and 33% respectively of MDA MB 231 and MCF7; these values increased to 60 and 64% in cells plated on laminin, to 48 and 63% in cells plated on fibronectin and to 64 and 69% in cells plated on matrigel. Moreover, staurosporine treatment decreased bcl-2 expression in the cells plated on fibronectin and laminin. Yet, staurosporine treatment determined PARP cleavage and PARP partial disappearance when the cells were plated on matrigel. Finally, a partial loss of function mutant Ras protein that activated only Raf pathway, was expressed in MCF7, in order to identify whether the increase of apoptosis induced by extracellular matrix involved the Raf/MAP kinase pathway. The increase of apoptosis of the cells plated on matrigel suggested that the activation of the Raf pathway is probably involved in the decrease of survival on matrigel. These data demonstrate that the modification of ECM modulates the apoptotic process of breast cancer cells and suggest that it is worthwhile to dissect the role of ECM in the control of apoptotic process.

Role of glucose side chains with serotype-specific polysaccharide in the cariogenicity of Streptococcus mutans
Nakano, K., R. Nomura, et al. (2005), Caries Res 39(4): 262-8.
Abstract: Previously, we isolated and characterized a new Streptococcus mutans strain (serotype k) from human blood and oral cavity samples, and found that the serological properties of serotype k strains were similar to those of a gluA-inactivated mutant strain of MT8148 (MT8148GD). MT8148GD showed significantly lower sucrose-dependent adhesion to glass surfaces, sucrose-independent adhesion to saliva-coated hydroxyapatite, dextran-binding activity, and cell-associated glucosyltransferase (GTF) activity than the parent strain. Further, Western blot analysis revealed reduced GTFB and GTFC expression in serotype k strains as compared to MT8148, though the caries-inducing activities of MT8148GD and a serotype k oral isolate in rats were similar to that of MT8148. We conclude that a glucose side-chain defect in the serotype-specific polysaccharide of S. mutans may be associated with its cariogenicity, though to a lesser extent than its other major surface proteins.

Role of gut macrophages in mice orally contaminated with scrapie or BSE
Maignien, T., M. Shakweh, et al. (2005), Int J Pharm 298(2): 293-304.
Abstract: While there is a growing consensus on the understanding of the propagation pathways after oral infection of transmissible spongiform encephalopathy (TSE) agents and even if the central role of follicular dendritic cells is identified, little is known about the key players in the first steps of the infection and about the site of the disease development. We investigated the role of gut macrophages, which are capable of capturing aggregates of the prion protein. PLGA particles containing clodronate were designed in order to be orally administered and to target Peyer's patches for inducing gut-associated macrophages suicide in mice. Mice were subsequently infected with scrapie or BSE by the oral route. It was found that the efficacy of macrophage suppression in the Peyer's patches correlated well with an earlier appearance of PrPres in these formations and with a higher amount of PrPres at a later stage of the infection. Thus, the capture of infectious particles that have crossed the epithelial gut barrier and their elimination by macrophages seems to be a key event to restrict the amount of agent initiating the infection.

Role of HSP70i in regulation of biomaterial-induced activation of human monocytes-derived macrophages in culture
Bhardwaj, R. S., M. Eblenkamp, et al. (2001), J Mater Sci Mater Med 12(2): 97-106.
Abstract: The functioning of an implant depends on the material properties and the wound-healing process. The latter is led by an inflammatory reaction guided mainly by monocyte/macrophage activity. This in vitro study investigated human monocytes/macrophages in culture from 2 h to 10 days on silicone, polyurethane, teflon and TCPS. Analysis of cytokine release by ELISA showed that maturing macrophages have different capacities to produce cytokines TNFalpha, IL10, IL8 and GM-CSF. The long culture-mature macrophages on all polymers produced comparable low levels of TNFalpha, IL10 and IL8. Monocytes/macrophages on polyurethane and teflon, and those on silicone only in long culture-time produced high GM-CSF amounts, where as those on TCPS exhibited low levels of GM-CSF. FACS analysis revealed that HSP70i was highly inducible after short time culture yet this high level was maintained in long culture-mature macrophages on TCPS only, whereas on other polymers the mature macrophages showed a high reduction in HSP70i level, which demonstrated a high stress-response by cells on TCPS. Accordingly, CLSM-analysis revealed low nuclear NF-kappaB in cells on TCPS and high nuclear NF-kappaB in mature macrophages on silicone and polyurethane, showing a high cellular activation on the latter two polymers. This corresponded also to the high mitochondrial activity by XTT metabolism displayed by the mature macrophages on polyurethane >/= silicone > teflon > TCPS. These data show a correlation of (1) cytokines (TNFalpha, GM-CSF) and HSP70i, (2) NF-kappaB and HSP70i by monocytes/macrophages after contact with polymers. Thus, HSP70i might be a useful molecular candidate for exploring biomaterial-induced inflammatory reaction.

Role of omega-3 polyunsaturated fatty acids on cyclooxygenase-2 metabolism in brain-metastatic melanoma
Denkins, Y., D. Kempf, et al. (2005), J Lipid Res 46(6): 1278-84.
Abstract: Cyclooxygenase-2 (COX-2) is important in the progression of epithelial tumors. Evidence indicates that omega-6 PUFAs such as arachidonic acid (AA) promote the growth of tumor cells; however, omega-3 fatty acids [eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA)] inhibit tumor cell proliferation. We investigated the effects of omega-3 PUFA on the expression and function of COX-2 in 70W, a human melanoma cell line that metastasizes to the brain in nude mice. We show that 1) tumor necrosis factor-alpha upregulates the expression of both COX-2 mRNA and prostaglandin E2 (PGE2) production, and 2) omega-3 and omega-6 PUFA regulate COX-2 mRNA expression and PGE2 production. AA increased COX-2 mRNA expression and prostaglandin production in omega-6-stimulated 70W cells. Conversely, COX-2 mRNA expression decreased in cells incubated with EPA or DHA. AA increased Matrigel invasion 2.4-fold, whereas EPA or DHA did not. Additionally, PGE2 increased in vitro invasion 2.5-fold, whereas exposure to PGE3 significantly decreased invasion. Our results demonstrate that incubation of 70W cells with either AA or PGE2 increased invasiveness, whereas incubation with EPA or DHA downregulated both COX-2 mRNA and protein expression, with a subsequent decrease in Matrigel invasion. Taken together, these results indicate that omega-3 PUFA regulate COX-2-mediated invasion in brain-metastatic melanoma.

Role of protein kinase C in the monocyte-derived macrophage-mediated biodegradation of polycarbonate-based polyurethanes
McBane, J., P. Santerre, et al. (2005), J Biomed Mater Res A 74(1): 1-12.

Role of the dialyzer membrane on the overall phosphate kinetics during hemodialysis
Katopodis, K. P., A. Chala, et al. (2005), Blood Purif 23(5): 359-64.
Abstract: BACKGROUND/AIM: We investigated the potential role of the membrane type on phosphate kinetics. METHODS: Six patients on dialysis (HD) were studied using modified cellulose (Hemophan), ethylene-vinyl alcohol (EVAL) and polyacrylonitrile (PAN). Total (TPR), extracellular (EPR) and intracellular (IPR) phosphate removal and effective dialyzer phosphate clearance (K(d)) were determined by the DDQ method. The intercompartment transfer coefficient (K(C)) was calculated using a mathematical model. Erythrocyte phosphate (P(ERY)) and 2,3-biphosphoglycerate (2,3-BPG) concentrations were determined before and after HD. RESULTS: TPR was 1.2+/-0.4, 1.10+/-0.4 and 1.09+/-0.4 g with Hemophan, EVAL and PAN, respectively (p=n.s.). EPR and IPR were independent of membrane type. There was no difference in K(C) between membranes (321+/-70, 338+/-92 and 341+/-83 ml/min, respectively). The P(ERY) and 2,3--BPG remained statistically insignificant for all membranes. CONCLUSION: Our results show that the type of membrane does not influence the kinetics of phosphate during dialysis, neither in the transfer from plasma to dialysate nor from the intra- to the extracellular compartment.

Role of tissue engineering in oral and maxillofacial reconstruction: findings of the 2005 AAOMS Research Summit
Feinberg, S. E., T. L. Aghaloo, et al. (2005), J Oral Maxillofac Surg 63(10): 1418-25.

Role of zinc in formulation of PLGA/PLA nanoparticles encapsulating betamethasone phosphate and its release profile
Ishihara, T., N. Izumo, et al. (2005), J Control Release 105(1-2): 68-76.
Abstract: The purpose of this study was to develop poly(D,L-lactic/glycolic acid) (PLGA) or poly(D,L-lactic acid) (PLA) nanoparticles of less than 200 nm in diameter that encapsulated water-soluble corticosteroid derivatives for sustained release and targeting to inflammatory sites. Nanoparticles were prepared with PLGA (or PLA), zinc, betamethasone phosphate and surfactant by an oil-in-water solvent diffusion method. With this method, the efficiency of encapsulating betamethasone phosphate in the nanoparticles and the particle size were significantly affected by various factors, such as the concentration of PLGA (or PLA) and the amount of zinc added. Nanoparticles ranging from 80 to 250 nm in diameter could be prepared, with a maximum betamethasone phosphate content of 8% (w/w). Betamethasone phosphate was gradually released from the nanoparticles in diluted serum, and the release rate depended on the glycolic/lactic acid ratio and on the molecular weight of PLGA or PLA. Betamethasone was gradually released over at least 8 days from murine macrophages that had internalized betamethasone phosphate-encapsulated nanoparticles in vitro, and the rate of release was slower than from nanoparticles prepared without zinc. These results suggest that zinc increases the efficiency of encapsulating betamethasone phosphate in nanoparticles and also promotes sustained release of betamethasone phosphate from the nanoparticles.

Root resorption and ankylosis associated with guided tissue regeneration
Cury, P. R., C. Furuse, et al. (2005), J Am Dent Assoc 136(3): 337-41.
Abstract: BACKGROUND: Root resorption and ankylosis have been reported rarely as sequelae to guided tissue regeneration (GTR). The authors describe a clinical case of root resorption following GTR that involved the use of a bioabsorbable membrane. CASE DESCRIPTION: Two years after GTR was performed on a Class II furcation defect, the clinical examination revealed root resorption reaching the pulp chamber. The furcation defect was filled with epithelium and connective tissue, which contained inflammatory infiltrate and fragments of the membrane. The authors also observed areas of the tooth that exhibited points of ankylosis and root resorption. CLINICAL IMPLICATIONS: Clinical trials have reported favorable clinical and histologic results with GTR. However, this case report, along with other case reports and studies in animals, suggests a high risk of root resorption and ankylosis after GTR, which could limit the indications for this technique.

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Last Modified: 8 February 2006