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Cytomimetic engineering of hepatocyte morphogenesis and function by substrate-based presentation of acellular E-cadherin
Semler, E. J., A. Dasgupta, et al. (2005), Tissue Eng 11(5-6): 734-50.
Abstract: Although cadherin-mediated intercellular contacts can be integral to the maintenance of functionally competent hepatocytes in vitro, the ability to engineer hepatocellular differentiated function via acellular E-cadherin has yet to be thoroughly explored. To investigate the potential of substrate-presented, acellular E-cadherin to modulate hepatocellular self-assembly and functional fate, rat hepatocytes were cultured at sparse densities on surfaces designed to display recombinant E-cadherin/Fc chimeras. On these substrates, hepatocytes were observed to recognize microdisplayed E-cadherin/Fc and responded by modulating the spatial distribution of the intracellular cadherin-complexing protein beta-catenin. Substrate-presented E-cadherin/Fc was also found to markedly alter patterns of hepatocyte morphogenesis, as cellular spreading and two-dimensional reorganization were significantly inhibited under these conditions, leading to multicellular aggregates that were considerably more three-dimensional in nature. Increasing cadherin exposure was also associated with elevated levels of albumin and urea secretion, two markers of hepatocyte differentiation, over control cultures. This suggested that cell-substrate cadherin engagement established more functionally competent hepatocellular phenotypes, coinciding with the notion that E-cadherin is a differentiation-inducing ligand for these cells. The morphogenetic and function-promoting effects of substrate-bound E-cadherin/Fc were further enhanced under conditions in which protein A was utilized as an anchoring molecule to present cadherin molecules, suggesting that ligand mobility may play an important role in the effective establishment of cell-to-substrate cadherin interactions. Interestingly, the percent increase in function detected for conditions of high cadherin exposure versus control cultures was found to be substantially higher at extremely low cell densities. This observation indicated that hepatocytes respond to substrate-presented E-cadherin even in the absence of native intercellular interactions and associated juxtacrine signaling. The incorporation of acellular E-cadherin on biomaterial substrates may thus potentially present a means to prevent hepatocellular dedifferentiation by maintaining liver-specific function in otherwise severely functionally repressive culture conditions.

Cytotoxic effects of residual chemicals from polymeric biomaterials for artificial soft intraocular lenses
Chirila, T. V., L. N. Walker, et al. (1991), J Cataract Refract Surg 17(2): 154-62.
Abstract: Development of improved hydrogels for soft intraocular lenses, based on 2-hydroxyethyl methacrylate monomer, requires the use of various other monomers and polymerization additives which have potential ocular toxicity. Three monomers, 2-hydroxyethyl methacrylate, methyl methacrylate, and 2-ethoxyethyl methacrylate, as well as two common inhibitors, hydroquinone and 4-methoxyphenol, were subjected to in vitro cytotoxicity assays as aqueous solutions at different concentrations. A new polymerization initiator, 2,2'-azo-bis-(2,4-dimethyl valeronitrile), was thermally decomposed in water at different concentrations and the products were also assayed for cytotoxicity. Assays were based on incubation with human choroidal fibroblasts. Cell death was evaluated by trypan blue dye exclusion, DNA synthesis inhibition, and lactate dehydrogenase tests. While methyl methacrylate and 2-ethoxyethyl methacrylate were found nontoxic, the other chemicals displayed high cytotoxicity. However, when extracts of synthesized poly(2-hydroxyethyl methacrylate) specimens, differentially treated after polymerization, were subjected to the same assays it was found that toxicity from residual 2-hydroxyethyl methacrylate monomer was lost during steam sterilization and storage in water because of the removal of the monomer through aqueous washing. The lack of toxicity in these specimens suggests that residual contents of inhibitor and initiator are too low to cause toxic effects on choroidal fibroblasts. It is concluded that hydrogels have low cytotoxic effects in vitro.

Cytotoxicity of colloidal CdSe and CdSe/ZnS nanoparticles
Kirchner, C., T. Liedl, et al. (2005), Nano Lett 5(2): 331-8.
Abstract: Cytotoxicity of CdSe and CdSe/ZnS nanoparticles has been investigated for different surface modifications such as coating with mercaptopropionic acid, silanization, and polymer coating. For all cases, quantitative values for the onset of cytotoxic effects in serum-free culture media are given. These values are correlated with microscope images in which the uptake of the particles by the cells has been investigated. Our data suggest that in addition to the release of toxic Cd(2+) ions from the particles also their surface chemistry, in particular their stability toward aggregation, plays an important role for cytotoxic effects. Additional patch clamp experiments investigate effects of the particles on currents through ion channels.

Cytotoxicity of substances leached or dissolved from pulp capping materials
Cavalcanti, B. N., S. M. Rode, et al. (2005), Int Endod J 38(8): 505-9.
Abstract: AIM: To evaluate the cytotoxic effects of substances leached or dissolved from pulp capping materials on human pulp fibroblasts. METHODOLOGY: The substances were applied to cell cultures in conditioned media. The experimental groups were: GI (control; n = 24)--cultures treated with fresh medium; GII (n = 24)--cultures treated with calcium hydroxide cement; GIII (n = 24)--cultures treated with adhesive resin and GIV (n = 24)--cultures treated with 37% orthophosphoric acid. The media were conditioned by placing the crude materials in contact with fresh culture medium for 1 h. The cytotoxicity analysis was performed using the Trypan blue dye exclusion assay at times of 0, 6, 12 and 24 h for cell viability assay, and at 1, 3, 5 and 7 days for survival assay. Data were treated by anova (P < 0.05) and Tukey's test (P < 0.05). RESULTS: GI and II presented similar cell viability and cell growth. GIII and IV exhibited statistically significant lower percentages of cell viability: GIV only at the 0 h experimental time, whereas in GIII this viability markedly diminished reaching values of 10% by 12 h. Cell growth was impaired only in cultures of GIII. CONCLUSIONS: Substances dissolved from the adhesive system tested were cytotoxic for human dental pulp fibroblasts in culture, whilst substances leached from calcium hydroxide were biocompatible.

Dacron vascular biomaterial triggers macrophage ectoenzyme activity without change in cell membrane fluidity
Chignier, E., J. Guidollet, et al. (1993), J Biomed Mater Res 27(8): 1087-94.
Abstract: Biomaterials induce an inflammatory reaction characterized by a rapid recruitment at the implantation site of polymorphonuclear cells and macrophages. In the course of the inflammatory response, the cellular activation triggers expression of a number of enzymes, such as 5'-nucleotidase, which is widely distributed in animal cell membranes as an ectoenzyme. It is now well established that 5'-nucleotidase activity decreases following the contact of inflammatory cells with foreign particles. In this paper we investigate a possible correlation between the enzymatic activities and the dynamic properties of the cell membrane bilayer. Dacron pieces were introduced into rats' peritoneal cavities for a period of 6 h, after which the peritoneal cells were harvested, and various enzyme assays performed, including those for cytoplasmic, lysosomal, and ectoenzymes. In parallel, we studied cell membrane fluidity, using fluorescence polarization of 1-(4-trimethylammoniumphenyl)-6-phenyl-1,3,5-hexatriene (TMA-DPH), and cellular ultrastructural alteration resulting from the cell-biomaterial interactions using scanning and transmission electron microscopy. Our results show that: 1) macrophages spread around the Dacron fibers with cytoplasmic finger-like projections, but no phagolysosomes, 2) 5'-nucleotidase levels decrease with surgical trauma in comparison with the resident cell exudate, 3) implantation of biomaterials slightly modify the 5'-nucleotidase levels observed in the sham animal, 4) no differences in the anisotropy values indicating that membrane lipid order within the cells could not account for the observed decrease of 5'-nucleotidase activity. Thus, we can suggest that 5'-nucleotidase expression may reflect a particular feature of cell activation without a phagocytic process.

Dacron-urethane composite: a new biomaterial for osseous contour reconstruction
Leake, D. L. (1974), J Prosthet Dent 32(2): 182-7.

Damage accumulation, fatigue and creep behaviour of vacuum mixed bone cement
Jeffers, J. R., M. Browne, et al. (2005), Biomaterials 26(27): 5532-41.
Abstract: The behaviour of bone cement under fatigue loading is of interest to assess the long-term in vivo performance. In this study, uniaxial tensile fatigue tests were performed on CMW-1 bone cement. Acoustic emission sensors and an extensometer were attached to monitor damage accumulation and creep deformation respectively. The S-N data exhibited the scatter synonymous with bone cement fatigue, with large pores generally responsible for premature failure; at 20 MPa specimens failed between 2 x 10(3) and 2 x 10(4) load cycles, while at 7 MPa specimens failed from 3 x 10(5) load cycles but others were still intact after 3 x 10(6) load cycles. Acoustic emission data revealed a non-linear accumulation of damage with respect to time, with increasing non-linearity at higher stress levels. The damage accumulation process was not continuous, but occurred in bursts separated by periods of inactivity. Damage in the specimen was located by acoustic emissions, and allowed the failure site to be predicted. Acoustic emission data were also used to predict when failure was not imminent. When this was the case at 3 million load cycles, the tests were terminated. Creep strain was plotted against the number of load cycles and a linear relationship was found when a double logarithmic scale was employed. This is the first time a brand of cement has been characterised in such detail, i.e. fatigue life, creep and damage accumulation. Results are presented in a manner that allows direct comparison with published data for other cements. The data can also be used to characterise CMW-1 in computational simulations of the damage accumulation process. Further evidence is provided for the condition-monitoring capabilities of the acoustic emission technique in orthopaedic applications.

Decompressive hemicraniectomy with duraplasty: a treatment for large-volume ischemic stroke
Tazbir, J., M. T. Marthaler, et al. (2005), J Neurosci Nurs 37(4): 194-9.
Abstract: Increased intracranial pressure (ICP) is a cause of death and disability in neurological patients. Patients experiencing malignant stroke of the middle cerebral artery (MCA) have a high mortality related to cerebral edema, increased ICP, and subsequent cerebral herniation. Decompressive hemicraniectomy with duraplasty is a surgical option for those experiencing large volume MCA stroke. When decompressive hemicraniectomy with duraplasty is performed, functional outcomes improve if the MCA stroke candidate is younger, the onset of increased ICP occurred less than 24 hours before surgery, and surgery is performed before clinical signs of herniation syndrome occur. The level of care required for these patients makes nursing care challenging.

Decreased accumulation of S. epidermidis RP 62 A on to stainless steel in comparison with other biomaterials
Konig, D. P., J. M. Schierholz, et al. (2000), J Hosp Infect 44(1): 75-6.

Decreased bacterial adhesion to surface-treated titanium
Del Curto, B., M. F. Brunella, et al. (2005), Int J Artif Organs 28(7): 718-30.
Abstract: Osteointegrative dental implants are widely used in implantology for their well-known excellent performance once implanted in the host. Remarkable bacterial colonization along the transgingival region may result in a progressive loss of adhesion at gum-implant interface and an increase of the bone area exposed to pathogens. This phenomenon may negatively effect the osteointegration process and cause, in the most severe cases, implant failure. The presence of bacteria at implant site affect the growth of new bone tissue and consequently, the achievement of a mechanically stable bone-implant interface, key parameters for a suitable implant osteointegration. In the present work, a novel surface treatment has been developed and optimized in order to convert the amorphous titanium oxide in a crystalline layer enriched in anatase capable of providing not only antibacterial properties but also of stimulating the precipitation of apatite when placed in simulated body fluid. The collected data have shown that the tested treatment results in a crystalline anatase-type titanium oxide layer able to provide a remarkable decrease in bacterial attachment without negatively effecting cell metabolic activity. In conclusion, the surface modification treatment analyzed in the present study might be an elegant way to reduce the risk of bacterial adhesion and increase the lifetime of the transgingival component in the osteointegrated dental implant.

Defensins impair phagocytic killing by neutrophils in biomaterial-related infection
Kaplan, S. S., R. P. Heine, et al. (1999), Infect Immun 67(4): 1640-5.
Abstract: The implantation of foreign material carries a risk of infection which frequently is resistant to all treatment short of removing the implant. We have previously shown that these materials activate neutrophils by contact, leading to production of oxygen free radicals accompanied by release of granule products. Such activation further results in depletion of local host defenses, including the capacity of biomaterial-activated neutrophils to kill bacteria. Among the granule products released from neutrophils are small cationic antibacterial peptides (human neutrophil peptides [HNP]) known as defensins. Here we tested the hypothesis that defensins, released from activated neutrophils onto the surface of biomaterials, might play a role in the deactivation of subsequent neutrophil populations. Incubation of neutrophils with purified HNP resulted in a dose-related impairment of stimulus-induced oxygen radical production and of phagocytic killing. Furthermore, fresh neutrophils added to biomaterial-associated neutrophils exhibited impaired phagocytic killing. This impairment could be abrogated by antibody to HNP but not by an irrelevant antibody. Taken together, these observations support the idea that neutrophils activated at a material surface can create, by means of HNP release, an environment hostile to their microbicidal function and that of their infiltrating brethren.

Degenerative mineralization in the fibrous capsule of silicone breast implants
Legrand, A. P., G. Marinov, et al. (2005), J Mater Sci Mater Med 16(5): 477-85.
Abstract: The formation of a fibrous capsule made of long collagen fibers surrounding breast implants represents an unavoidable phenomenon as the patient's reaction to the presence of a foreign body. Depending upon the size and shape of the implants and the chemicals percolating through the shell, this fibrous capsule is continuously remodeled. The compaction of the foreign debris in the vicinity of the silicone shell is followed by the loss of cellular activity, shrinkage and necrosis. Calcification is the ultimate step. These phenomena were illustrated in the analysis of 18 explanted breast prostheses after 20 or more years of implantation. The degenerative mineralization was shown in scanning electron microscopy and light microscopy. The minerals proved to be bone-like hydroxyapatite by X-ray diffraction and Solid State NMR analysis. Whatever the characteristics of any sophisticated new model of breast implant, phenomenon of mineralization might be minimized but it is very unlikely that it would be totally eliminated.

Degradability of polysaccharides multilayer films in the oral environment: an in vitro and in vivo study
Etienne, O., A. Schneider, et al. (2005), Biomacromolecules 6(2): 726-33.
Abstract: Biomedical devices and modified biomaterial surfaces constitute an expanding research domain in the dental field. However, such oral applications have to face a very particular environment containing specific physiological conditions and specific enzymes. To evaluate their suitability in the development of novel oral applications, the degradability of polyelectrolyte multilayer films made of the natural polysaccharides chitosan and hyaluronan (CHI/HA) was investigated in vitro and in vivo in a rat mouth model. The films were either native or cross-linked using a water-soluble carbodiimide (EDC) in combination with N-hydroxysulfosuccinimide. The in vitro degradation of the films by different enzymes present in the oral environment, such as lysozyme and amylase, was followed by quartz crystal microbalance measurements and confocal laser scanning microscopy observations after being film labeled with CHI(FITC). Whereas native films were subjected to degradation by all the enzymes, cross-linked films were more resistant to enzymatic degradation. Films were also put in contact with whole saliva, which induced a slow degradation of the native films over an 18 h period. The in vivo degradation of the films deposited on polymer disks and sutured in the rat mouth was followed over a 3 day period. Whereas film degradation is fast for native films, it is much slower for the cross-linked ones. More than 60% of these films remained on the disks after 3 days in the mouth. Taken together, these results suggest that the multilayer films made of natural polysaccharides are of high potential interest for oral applications, especially as drug release systems, offering various degradation rates and consequent release characteristics.

Degradable and highly porous polyesterurethane foam as biomaterial: effects and phagocytosis of degradation products in osteoblasts
Saad, B., G. Ciardelli, et al. (1998), J Biomed Mater Res 39(4): 594-602.
Abstract: Recently, a new class of biodegradable PHB-based polyesterurethane (DegraPol/btc) has been prepared and found to exhibit favorable cell and tissue compatibility. The present study has been designed to evaluate the response of primary isolated rat tibia osteoblasts to small crystalline particles of short-chain poly[(R)-3-hydroxybutyric acid] (PHB-P diameter: 2-20 microm), of fluorescent-labeled analogs (DPHP-P), and of lysine methyl ester as possible degradation products of DegraPol/btc. Observations made using confocal microscopy clearly indicate that osteoblasts have the capability of taking up PHB-P particles. Although in single-cell analysis the number of DPHB-P-positive osteoblasts gradually increased up to 16 days, the fluorescence intensity per osteoblast increased only during the first 4 h after DPHB-P incubation, and then it retained the 4 h level up to 16 days. No significant change in the production levels of collagen type I and osteocalcin was detectable after treatment with low concentrations of PHB-P for up to 32 days. In contrast, a time- and dose-dependent alteration of the alkaline phosphatase (ALP) activity was found. Maximal activity was measured after 4 days of treatment with 2 microg of PHB-P/mL (170% of control cells). Rat peritoneal macrophages co-cultured with osteoblasts in a transwell culture system mimicked the observed PHB-P induced ALP elevation. Therefore, the PHB-P-induced ALP increase could be the result of direct or indirect stimulation of osteoblasts, possibly via soluble factors produced by contaminating osteoclasts. Taken collectively, the data demonstrate that osteoblasts are capable of phagocytosing PHB-P and that this process is accompanied at low PHB-P concentrations by dose- and time-dependent alteration of alkaline phosphatase activity but not of collagen type I or osteocalcin.

Degradable thiol-acrylate photopolymers: polymerization and degradation behavior of an in situ forming biomaterial
Rydholm, A. E., C. N. Bowman, et al. (2005), Biomaterials 26(22): 4495-506.
Abstract: Degradable thiol-acrylate photopolymers are a new class of biomaterials capable of rapidly polymerizing under physiological conditions upon exposure to UV light, with or without added photoinitiators, and to depths exceeding 10 cm. These materials are formed in situ, and the versatility of their chemistry affords a high degree of control over the final material properties. For example, variations in monomer mole fractions directly affect the final network molecular structure, varying the time required to achieve complete mass loss from 25 to 100 days, the molecular weight distributions of the degradation products, and the swelling ratios and compressive moduli throughout degradation. Additionally, varying the mole fraction of multifunctional thiol monomer in the initial reaction mixture controls the concentration of reactive sites in the network available for post-polymerization modification of the polymer.

Degradation of 4-chlorophenol by microwave irradiation enhanced advanced oxidation processes
Zhihui, A., Y. Peng, et al. (2005), Chemosphere 60(6): 824-7.
Abstract: In this work the synergistic effects of several microwave assisted advanced oxidation processes (MW/AOPs) were studied for the degradation of 4-chlorophenol (4-CP). The efficiencies of the degradation of 4-CP in dilute aqueous solution for a variety of AOPs with or without MW irradiation were compared. The results showed that the synergistic effects between MW and H2O2, UV/H2O2, TiO2 photocatalytic oxidation (PCO) resulted in a high degradation efficiency for 4-CP. The potential of MW/AOPs for treatment of industrial wastewater is discussed.

Degradation of biomaterials by phagocyte-derived oxidants
Sutherland, K., J. R. Mahoney, 2nd, et al. (1993), J Clin Invest 92(5): 2360-7.
Abstract: Polymers used in implantable devices, although relatively unreactive, may degrade in vivo through unknown mechanisms. For example, polyetherurethane elastomers used as cardiac pacemaker lead insulation have developed surface defects after implantation. This phenomenon, termed "environmental stress cracking," requires intimate contact between polymer and host phagocytic cells, suggesting that phagocyte-generated oxidants might be involved. Indeed, brief exposure of polyetherurethane to activated human neutrophils, hypochlorous acid, or peroxynitrite produces modifications of the polymer similar to those found in vivo. Damage to the polymer appears to arise predominantly from oxidation of the urethane-aliphatic ester and aliphatic ether groups. There are substantial increases in the solid phase surface oxygen content of samples treated with hypochlorous acid, peroxynitrite or activated human neutrophils, resembling those observed in explanted polyetherurethane. Furthermore, both explanted and hypochlorous acid-treated polyetherurethane show marked reductions in polymer molecular weight. Interestingly, hypochlorous acid and peroxynitrite appear to attack polyetherurethane at different sites. Hypochlorous acid or activated neutrophils cause decreases in the urethane-aliphatic ester stretch peak relative to the aliphatic ether stretch peak (as determined by infrared spectroscopy) whereas peroxynitrite causes selective loss of the aliphatic ether. In vivo degradation may involve both hypohalous and nitric oxide-based oxidants because, after long-term implantation, both stretch peaks are diminished. These results suggest that in vivo destruction of implanted polyetherurethane involves attack by phagocyte-derived oxidants.

Degradation of trichloroethylene by photocatalysis in an internally circulating slurry bubble column reactor
Jeon, J. H., S. D. Kim, et al. (2005), Chemosphere 60(8): 1162-8.
Abstract: The effects of initial trichloroethylene (TCE) concentration, recirculating liquid flow rate and gas velocity on photodegradation of TCE have been determined in an internally circulating slurry bubble column reactor (0.15m-ID x 0.85 m-high). Titanium dioxide (TiO2) powder was employed as a photocatalyst and the optimum loading of TiO2 in the present system is found to be approximately 0.2 wt%. The stripping fraction of TCE by air flow increases but photodegradation fraction of TCE decreases with increasing the initial TCE concentration, recirculating liquid flow rate and gas velocity. The average removal efficiency of TCE is found to be approximately 97% in an internally circulating slurry bubble column reactor.

Degradation resistance of some candidate composite biomaterials
McKenna, G., G. W. Bradley, et al. (1979), J Biomed Mater Res 13(5): 783-98.
Abstract: The degradation resistance of matrix, fiber and composite systems which we have been studying as candidate orthopedic materials has been examined in two appropriate environments. Both resistance to steam sterilization in an autoclave environment and resistance to a simulated physiologic solution have been studied. In the autoclave study, samples were placed in a pressure cooker at 123 degrees C for differing amounts of time and tested for retention of mechanical properties. Results indicate that most of the materials tested could be autoclaved several times, as long as autoclave times did not exceed 1 hr. Longer autoclave times result in an accelerated degradation and loss of strength of all materials except the polypropylene. Polysulfone degrades after even the shortest autoclave duration. Resistance to the simulated physiologic environment was tested by measured retention of mechanical properties after immersion times in pseudo-extracellular fluid (PECF) at 37 degrees C for as long as three years. None of the materials showed any significant changes in properties after immersion in the PECF.

Degradative effects of conventional steam sterilization on biomaterial surfaces
Baier, R. E., A. E. Meyer, et al. (1982), Biomaterials 3(4): 241-5.
Abstract: Prior to implantation trials in animals, the effect of steam sterilization on the surface properties of metallic and coated biomaterials was studied. Pure germanium plates and cast surgical Vitallium discs and subperiosteal implants were treated to present three standard types of biomaterials surfaces prior to steam sterilization, ranging from scrupulously clean, high-energy metals to uniformly low-energy organic layers. Both before and after sterilization, the sample surfaces were characterized by a variety of nondestructive physiochemical techniques. The results indicate that steam sterilization is likely to compromise the properties of otherwise carefully prepared biomedical implants by depositing hydrophobic organic and hygroscopic salt contaminants over the implant surfaces.

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Last Modified: 8 February 2006