923 resultados para Molecular, Cellular, and Tissue Engineering


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Brugada syndrome (BS) is a genetic disease identified by an abnormal electrocardiogram ( ECG) ( mainly abnormal ECGs associated with right bundle branch block and ST-elevation in right precordial leads). BS can lead to increased risk of sudden cardiac death. Experimental studies on human ventricular myocardium with BS have been limited due to difficulties in obtaining data. Thus, the use of computer simulation is an important alternative. Most previous BS simulations were based on animal heart cell models. However, due to species differences, the use of human heart cell models, especially a model with three-dimensional whole-heart anatomical structure, is needed. In this study, we developed a model of the human ventricular action potential (AP) based on refining the ten Tusscher et al (2004 Am. J. Physiol. Heart Circ. Physiol. 286 H1573 - 89) model to incorporate newly available experimental data of some major ionic currents of human ventricular myocytes. These modified channels include the L-type calcium current (ICaL), fast sodium current (I-Na), transient outward potassium current (I-to), rapidly and slowly delayed rectifier potassium currents (I-Kr and I-Ks) and inward rectifier potassium current (I-Ki). Transmural heterogeneity of APs for epicardial, endocardial and mid-myocardial (M) cells was simulated by varying the maximum conductance of IKs and Ito. The modified AP models were then used to simulate the effects of BS on cellular AP and body surface potentials using a three-dimensional dynamic heart - torso model. Our main findings are as follows. (1) BS has little effect on the AP of endocardial or mid-myocardial cells, but has a large impact on the AP of epicardial cells. (2) A likely region of BS with abnormal cell AP is near the right ventricular outflow track, and the resulting ST-segment elevation is located in the median precordium area. These simulation results are consistent with experimental findings reported in the literature. The model can reproduce a variety of electrophysiological behaviors and provides a good basis for understanding the genesis of abnormal ECG under the condition of BS disease.

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Adipose tissue forms when basement membrane extract ( Matrigel (TM)) and fibroblast growth factor-2 (FGF-2) are added to our mouse tissue engineering chamber model. A mouse tumor extract, Matrigel is unsuitable for human clinical application, and finding an alternative to Matrigel is essential. In this study we generated adipose tissue in the chamber model without using Matrigel by controlled release of FGF-2 in a type I collagen matrix. FGF-2 was impregnated into biodegradable gelatin microspheres for its slow release. The chambers were filled with these microspheres suspended in 60 mu L collagen gel. Injection of collagen containing free FGF-2 or collagen containing gelatin microspheres with buffer alone served as controls. When chambers were harvested 6 weeks after implantation, the volume and weight of the tissue obtained were higher in the group that received collagen and FGF-2 impregnated microspheres than in controls. Histologic analysis of tissue constructs showed the formation of de novo adipose tissue accompanied by angiogenesis. In contrast, control groups did not show extensive adipose tissue formation. In conclusion, this study has shown that de novo formation of adipose tissue can be achieved through controlled release of FGF-2 in collagen type I in the absence of Matrigel.

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Sulfate is an essential ion required for numerous functions in mammalian physiology. Due to its hydrophilic nature, cells require sulfate transporters on their plasma membranes to allow entry of sulfate into cells. In this study, we identified a new mouse Na+-sulfate cotransporter (mNaS2), characterized its tissue distribution and determined its cDNA and gene (Slc13a4) structures. mNaS2 mRNA was expressed in placenta, brain, lung, eye, heart, testis, thymus and liver. The mouse NaS2 cDNA spans 3384 nucleotides and its open frame encodes a protein of 624 amino acids. Slc13a4 maps to mouse chromosome 6131 and contains 16 exons, spanning over 40 kb in length. Its 5'-flanking region contains CART- and GC-box motifs and a number of putative transcription factor binding sites, including GATA-1, MTF-1, STAT6 and HNF4 consensus sequences. This is the first study to define the tissue distribution of mNaS2 and resolve its cDNA and gene structures, which will allow us to investigate mNaS2 gene expression in vivo and determine its role in mammalian physiology.

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The dynamics of drop formation and pinch-off have been investigated for a series of low viscosity elastic fluids possessing similar shear viscosities, but differing substantially in elastic properties. On initial approach to the pinch region, the viscoelastic fluids all exhibit the same global necking behavior that is observed for a Newtonian fluid of equivalent shear viscosity. For these low viscosity dilute polymer solutions, inertial and capillary forces form the dominant balance in this potential flow regime, with the viscous force being negligible. The approach to the pinch point, which corresponds to the point of rupture for a Newtonian fluid, is extremely rapid in such solutions, with the sudden increase in curvature producing very large extension rates at this location. In this region the polymer molecules are significantly extended, causing a localized increase in the elastic stresses, which grow to balance the capillary pressure. This prevents the necked fluid from breaking off, as would occur in the equivalent Newtonian fluid. Alternatively, a cylindrical filament forms in which elastic stresses and capillary pressure balance, and the radius decreases exponentially with time. A (0+1)-dimensional finitely extensible nonlinear elastic dumbbell theory incorporating inertial, capillary, and elastic stresses is able to capture the basic features of the experimental observations. Before the critical "pinch time" t(p), an inertial-capillary balance leads to the expected 2/3-power scaling of the minimum radius with time: R-min similar to(t(p)-t)(2/3). However, the diverging deformation rate results in large molecular deformations and rapid crossover to an elastocapillary balance for times t>t(p). In this region, the filament radius decreases exponentially with time R-min similar to exp[(t(p)-t)/lambda(1)], where lambda(1) is the characteristic time constant of the polymer molecules. Measurements of the relaxation times of polyethylene oxide solutions of varying concentrations and molecular weights obtained from high speed imaging of the rate of change of filament radius are significantly higher than the relaxation times estimated from Rouse-Zimm theory, even though the solutions are within the dilute concentration region as determined using intrinsic viscosity measurements. The effective relaxation times exhibit the expected scaling with molecular weight but with an additional dependence on the concentration of the polymer in solution. This is consistent with the expectation that the polymer molecules are in fact highly extended during the approach to the pinch region (i.e., prior to the elastocapillary filament thinning regime) and subsequently as the filament is formed they are further extended by filament stretching at a constant rate until full extension of the polymer coil is achieved. In this highly extended state, intermolecular interactions become significant, producing relaxation times far above theoretical predictions for dilute polymer solutions under equilibrium conditions. (C) 2006 American Institute of Physics

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We have demonstrated the successful production of titanium phosphate glass microspheres in the size range of ~10-200 µm using an inexpensive, efficient, easily scalable process and assessed their use in bone tissue engineering applications. Glasses of the following compositions were prepared by melt-quench techniques: 0.5P2O5-0.4CaO-(0.1 - x)Na2O-xTiO2, where x = 0.03, 0.05 and 0.07 mol fraction (denoted as Ti3, Ti5 and Ti7 respectively). Several characterization studies such as differential thermal analysis, degradation (performed using a novel time lapse imaging technique) and pH and ion release measurements revealed significant densification of the glass structure with increased incorporation of TiO2 in the glass from 3 to 5 mol.%, although further TiO2 incorporation up to 7 mol.% did not affect the glass structure to the same extent. Cell culture studies performed using MG63 cells over a 7-day period clearly showed the ability of the microspheres to provide a stable surface for cell attachment, growth and proliferation. Taken together, the results confirm that 5 mol.% TiO2 glass microspheres, on account of their relative ease of preparation and favourable biocompatibility, are worthy candidates for use as substrate materials in bone tissue engineering applications.

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Alpha-modified minimum essential medium (αMEM) has been found to cross-link a 1% gellan gum solution, resulting in the formation of a self-supporting hydrogel in 1:1 and 5:1 ratios of polysaccharide: αMEM. Rheological data from temperature sweeps confirm that in addition to orders of magnitude differences in G' between 1% gellan and 1% gellan with αMEM, there is also a 20°C increase in the temperature at which the onset of gelation takes place when αMEM is present. Frequency sweeps confirm the formation of a true gel; mechanical spectra for mixtures of gellan and αMEM clearly demonstrate G' to be independent of frequency. It is possible to immobilize cells within a three-dimensional (3D) gellan matrix that remain viable for up to 21 days in culture by adding a suspension of rat bone marrow cells (rBMC) in αMEM to 1% gellan solution. This extremely simple approach to cell immobilization within 3D constructs, made possible by the fact that gellan solutions cross-link in the presence of millimolar concentrations of cations, poses a very low risk to a cell population immobilized within a gellan matrix and thus indicates the potential of gellan for use as a tissue engineering scaffold. © 2007 Sage Publications.

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Scaffolds derived from processed tissues offer viable alternatives to synthetic polymers as biological scaffolds for regenerative medicine. Tissue-derived scaffolds provide an extracellular matrix (ECM) as the starting material for wound healing and the functional reconstruction of tissues, offering a potentially valuable approach for the replacement of damaged or missing tissues. Additionally, acellular tissue may provide a natural microenvironment for host-cell migration and the induction of stem cell differentiation to contribute to tissue regeneration. There are a number of processing methods that aim to stabilize and provide an immunologically inert tissue scaffold. Furthermore, these tissue-processing methods can often be applied to xenogenic transplants because the essential components of the ECM are often maintained between species. In this study, we applied several tissue-processing protocols to the cornea in order to obtain a decellularized cornea matrix that maintained the clarity and mechanical properties of the native tissue. Histology, mechanical testing and electron microscopy techniques were used to assess the cell extraction process and the organization of the remaining ECM. In vitro cell seeding experiments confirmed the processed corneas’ biocompatibility.

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Porous 3D polymer scaffolds prepared by TIPS from PLGA (53:47) and PS are intrinsically hydrophobic which prohibits the wetting of such porous media by water. This limits the application of these materials for the fabrication of scaffolds as supports for cell adhesion/spreading. Here we demonstrate that the interior surfaces of polymer scaffolds can be effectively modified using atmospheric air plasma (AP). Polymer films (2D) were also modified as control. The surface properties of wet 2D and 3D scaffolds were characterised using zeta-potential and wettability measurements. These techniques were used as the primary screening methods to assess surface chemistry and the wettability of wet polymer constructs prior and after the surface treatment. The surfaces of the original polymers are rather hydrophobic as highlighted but contain acidic functional groups. Increased exposure to AP improved the water wetting of the treated surfaces because of the formation of a variety of oxygen and nitrogen containing functions. The morphology and pore structure was assessed using SEM and a liquid displacement test. The PLGA and PS foam samples have central regions which are open porous interconnected networks with maximum pore diameters of 49 μm for PLGA and 73 μm for PS foams. (Figure Presented) © 2007 Wiley-VCH Verlag GmbH & Co. KGaA.

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Hydrogen bonds play important roles in maintaining the structure of proteins and in the formation of most biomolecular protein-ligand complexes. All amino acids can act as hydrogen bond donors and acceptors. Among amino acids, Histidine is unique, as it can exist in neutral or positively charged forms within the physiological pH range of 5.0 to 7.0. Histidine can thus interact with other aromatic residues as well as forming hydrogen bonds with polar and charged residues. The ability of His to exchange a proton lies at the heart of many important functional biomolecular interactions, including immunological ones. By using molecular docking and molecular dynamics simulation, we examine the influence of His protonation/deprotonation on peptide binding affinity to MHC class II proteins from locus HLA-DP. Peptide-MHC interaction underlies the adaptive cellular immune response, upon which the next generation of commercially-important vaccines will depend. Consistent with experiment, we find that peptides containing protonated His residues bind better to HLA-DP proteins than those with unprotonated His. Enhanced binding at pH 5.0 is due, in part, to additional hydrogen bonds formed between peptide His+ and DP proteins. In acidic endosomes, protein His79β is predominantly protonated. As a result, the peptide binding cleft narrows in the vicinity of His79β, which stabilizes the peptide - HLA-DP protein complex. © 2014 Bentham Science Publishers.