The finite deformation of porous elastomers was studied by means of the numerical simulation of a... more The finite deformation of porous elastomers was studied by means of the numerical simulation of a representative volume element of the microstructure. The size and the discretization of the volume element were selected to obtain an exact response (to a few percent) of the plane-strain deformation of a material made up of a random and isotropic dispersion of circular cylindrical voids embedded in an incompressible neo-Hookean matrix. Three different loading modes (in-plane isotropic deformation, uniaxial elongation, and uniaxial traction) were simulated, and the corresponding stress-strain curves as well as the evolution of the microstructure with deformation were presented for materials with an initial porosity of 5, 10 and 20%. The numerical results were compared with the available homogenization models for the finite deformation of porous elastomers. It was found that the second-order estimate with field fluctuations of Lo´pez-Pamie´s and Ponte Castan˜eda led to very good approximations to the numerical results in most cases, and significant differences were only found under conditions of highly constrained deformation. The sources of these differences were discussed in the light of the changes in the microstructure provided by the numerical simulations.
The process leading to irreversible fibrotic constriction of the bronchioles was studied in two c... more The process leading to irreversible fibrotic constriction of the bronchioles was studied in two cases of bronchiolitis obliterans (BO) after bone marrow transplantation. Because lysyl oxidase (LOX) is the main collagen cross-linking enzyme that might account for irreversible fibrosis, its expression was studied together with expression of extracellular matrix (ECM) proteins. Characteristic types of lesions could be distinguished on the basis of histological and immunohistological criteria. An inflammatory stage was characterised by infiltration restricted to the bronchioles by lymphocytes and dendritic cells. A fibro-inflammatory stage was characterised by the coexistence of a persistent immune cellular lesion pattern with further focal modelling of a sub-epithelial neo-synthesised connective matrix. LOX expression was observed at the tips of intra-luminal fibrotic protrusions, together with tenascin and cellular fibronectin. A fibrotic stage was characterised by dense ECM deposits spreading throughout the peri-bronchiolar connective tissue, resulting in bronchiole obliteration and final disappearance. In contrast to reversible cases of fibrosis, persistence of long-term LOX expression reflecting continuing fibrosing activity might account for the irreversible status of BO. Our two cases illustrated that, at inflammatory and fibro-inflammatory stages, BO may be stabilised by immunosuppressive treatment, while the persistence of LOX expression in the fibrotic stage might correspond to a disease that becomes irreversible and fatal.
A micromechanics framework for the development of continuum-level constitutive models for the lar... more A micromechanics framework for the development of continuum-level constitutive models for the large-strain deformation of porous hyperelastic materials is presented. A kinematically admissible deformation field is assumed which enables the derivation of a strain energy density function for the porous material. The strain energy density function depends on the properties of the incompressible hyperelastic matrix material, the initial level of porosity, and the macroscopic deformation. Differentiation of the strain energy density function, with respect to deformation, provides an expression for the stress–strain behavior of the porous hyperelastic material. Example calculations are carried out for porous hyperelastic materials with a Neo–Hookean matrix. The constitutive model is used to predict the stress–strain behavior of the pore-containing matrix as a function of initial porosity and macroscopic loading conditions. Predictions of the dependence of the small-strain elastic response on porosity are compared to various estimates of effective elastic moduli for porous materials found in the literature. Constitutive model predictions of the small to large-strain deformation behavior compare well with results from numerical three-dimensional micromechanical multi-void cell models.
Journal of Materials Science-materials in Medicine, 2005
Cartilage engineering consists of re-constructing functional cartilage by seeding chondrocytes in... more Cartilage engineering consists of re-constructing functional cartilage by seeding chondrocytes in suitable biomaterials in vitro. The characteristics of neocartilage differ upon the type of biomaterial chosen. This study aims at determining the appropriate scaffold material for articular cartilage reconstruction using non articular chondrocytes harvested from rat sternum. For this purpose, the use of polysaccharide hydrogels such as alginate (AA) and hyaluronic acid (HA) was investigated. Several ratios of AA/HA were used as well as three derivatives obtained by chemical modification of HA (HA-C18, HA-C122.3, HA-C122.5-TEG0.5). Sternal chondrocytes were successfully cultured in 3D alginate and alginate/HA scaffolds. HA retention in alginate beads was found to be higher in beads seeded with cells than in beads without cells. HA-C18 improved HA retention in beads but inhibited the chondrocyte synthesis process. Cell proliferation and metabolism were enhanced in all biomaterials when beads were mechanically agitated. Preliminary results have shown that the chondrocyte neo-synthesised matrix had acquired articular characteristics after 21 days culture.
Neo-classical tokamak plasma theory predicts poloidal rotation driven by the temperature gradient... more Neo-classical tokamak plasma theory predicts poloidal rotation driven by the temperature gradient of a few km s −1 . In conventional aspect-ratio tokamak plasmas, e.g. on JET and DIII-D, apparent poloidal velocities considerably in excess of the neo-classical values have been measured, particularly in the presence of internal transport barriers, by means of charge-exchange recombination spectroscopy (CXRS) on the fully ionized C 6+ impurity ions. Comparison between such measurements and theoretical predictions requires careful corrections to be made for apparent 'pseudo' velocities, which can arise from the finite lifetime of the excited atoms in the magnetized plasma and the energy dependence of the charge-exchange excitation process. In present day spherical tokamak plasmas this correction is an order of magnitude smaller than on large conventional tokamaks, which operate at higher temperature and magnetic field, hence reducing any associated systematic uncertainties. On MAST measurements of toroidal and poloidal flows of the C 6+ impurities are available from high-resolution Doppler CXRS measurements, including appropriate corrections for the pseudo-velocities. Comparison of the measured C 6+ velocities with neo-classical theory requires calculation of the impurity flow, which differs from that of the bulk ions due to the respective diamagnetic contributions for each species and inter-species friction forces. Comparisons are made with the predictions of a recent neo-classical theory Collisional transport in a low collisionality plasma with strong rotation PhD Thesis University of Bristol, Newton and Helander 2006 Phys. Plasmas 13 102505), which calculates the full neo-classical transport matrix for bulk ions and a single impurity species for a strongly rotating plasma, as well as those of
Photoluminescence of NeO excimers produced in a Ne matrix by photodissociation of N2O with synchr... more Photoluminescence of NeO excimers produced in a Ne matrix by photodissociation of N2O with synchrotron radiation are reported. An anomalous blue-shift of the (1S → 1D) band was observed. Also, the spin-forbidden (1D → 3P) band was seen for the fust time in a matrix.
chronic wounds, the dermal matrix is insufficient to stimulate healing and assistance by external... more chronic wounds, the dermal matrix is insufficient to stimulate healing and assistance by external factors is needed for wound closure. Although the concept of the extracellular matrix directing wound healing is not new, ideas about how best to provide the extracellular matrix components required to 'jump-start' the healing process are still evolving. Historically, these strategies have included use of enzyme-inhibiting dressing materials, which bind matrix metalloproteinases and remove them from the chronic wound environment, or direct application of purified growth factors to stimulate fibroblast activity and deposition of neo-matrix. More recently, the application of a structurally intact, biochemically complex extracellular matrix, designed to provide the critical extracellular components of the dermis in a single application, has allowed for the reconstruction of new, healthy tissue and restoration of tissue integrity in the previously chronic wound. This review focuses on this third mechanism as an emerging tactic in effective wound repair. Intact extracellular matrix can quickly, easily, and effectively provide key extracellular components of the dermis necessary to direct the healing response and allow for the proliferation of new, healthy tissue. Its application may promote the healing of wounds that have been refractory to other, more conventional treatment strategies, and may eventually show utility when used earlier in wound healing treatment with the goal of preventing wounds from reaching a truly chronic, nonresponsive state.
Computer Methods in Biomechanics and Biomedical Engineering, 2011
Extracellular matrix (ECM) in chondrocytes-seeded agarose aggregates to form islands of matrix. T... more Extracellular matrix (ECM) in chondrocytes-seeded agarose aggregates to form islands of matrix. These islands need to coalesce to develop functional cartilage. Hence, macroscopic properties are determined by transport and aggregation of macromolecules at the microscale, which varies temporally and spatially. This study evaluates the importance of the mutual interaction between matrix components and matrix development.Fluorescence recovery after photobleaching measurements demonstrates that diffusivity depends on the presence and density of ECM. A reaction–diffusion model describing synthesis, transport and immobilisation of ECM predicts steep gradients in ECM around chondrocytes, resembling histology. Steric hindrance of diffusion by ECM is essential for the formation of these gradients. Finally, microscopic ECM concentration is linked with macroscopic mechanical properties. Construct softening is predicted when temporal and spatial variations in diffusivity are considered.In conclusion, non-constant diffusion renders significant effects on both the microscopic ECM development and the macroscopic mechanical properties of developing tissue-engineered cartilage.
The finite deformation of porous elastomers was studied by means of the numerical simulation of a... more The finite deformation of porous elastomers was studied by means of the numerical simulation of a representative volume element of the microstructure. The size and the discretization of the volume element were selected to obtain an exact response (to a few percent) of the plane-strain deformation of a material made up of a random and isotropic dispersion of circular cylindrical voids embedded in an incompressible neo-Hookean matrix. Three different loading modes (in-plane isotropic deformation, uniaxial elongation, and uniaxial traction) were simulated, and the corresponding stress-strain curves as well as the evolution of the microstructure with deformation were presented for materials with an initial porosity of 5, 10 and 20%. The numerical results were compared with the available homogenization models for the finite deformation of porous elastomers. It was found that the second-order estimate with field fluctuations of Lo´pez-Pamie´s and Ponte Castan˜eda led to very good approximations to the numerical results in most cases, and significant differences were only found under conditions of highly constrained deformation. The sources of these differences were discussed in the light of the changes in the microstructure provided by the numerical simulations.
The process leading to irreversible fibrotic constriction of the bronchioles was studied in two c... more The process leading to irreversible fibrotic constriction of the bronchioles was studied in two cases of bronchiolitis obliterans (BO) after bone marrow transplantation. Because lysyl oxidase (LOX) is the main collagen cross-linking enzyme that might account for irreversible fibrosis, its expression was studied together with expression of extracellular matrix (ECM) proteins. Characteristic types of lesions could be distinguished on the basis of histological and immunohistological criteria. An inflammatory stage was characterised by infiltration restricted to the bronchioles by lymphocytes and dendritic cells. A fibro-inflammatory stage was characterised by the coexistence of a persistent immune cellular lesion pattern with further focal modelling of a sub-epithelial neo-synthesised connective matrix. LOX expression was observed at the tips of intra-luminal fibrotic protrusions, together with tenascin and cellular fibronectin. A fibrotic stage was characterised by dense ECM deposits spreading throughout the peri-bronchiolar connective tissue, resulting in bronchiole obliteration and final disappearance. In contrast to reversible cases of fibrosis, persistence of long-term LOX expression reflecting continuing fibrosing activity might account for the irreversible status of BO. Our two cases illustrated that, at inflammatory and fibro-inflammatory stages, BO may be stabilised by immunosuppressive treatment, while the persistence of LOX expression in the fibrotic stage might correspond to a disease that becomes irreversible and fatal.
A micromechanics framework for the development of continuum-level constitutive models for the lar... more A micromechanics framework for the development of continuum-level constitutive models for the large-strain deformation of porous hyperelastic materials is presented. A kinematically admissible deformation field is assumed which enables the derivation of a strain energy density function for the porous material. The strain energy density function depends on the properties of the incompressible hyperelastic matrix material, the initial level of porosity, and the macroscopic deformation. Differentiation of the strain energy density function, with respect to deformation, provides an expression for the stress–strain behavior of the porous hyperelastic material. Example calculations are carried out for porous hyperelastic materials with a Neo–Hookean matrix. The constitutive model is used to predict the stress–strain behavior of the pore-containing matrix as a function of initial porosity and macroscopic loading conditions. Predictions of the dependence of the small-strain elastic response on porosity are compared to various estimates of effective elastic moduli for porous materials found in the literature. Constitutive model predictions of the small to large-strain deformation behavior compare well with results from numerical three-dimensional micromechanical multi-void cell models.
Journal of Materials Science-materials in Medicine, 2005
Cartilage engineering consists of re-constructing functional cartilage by seeding chondrocytes in... more Cartilage engineering consists of re-constructing functional cartilage by seeding chondrocytes in suitable biomaterials in vitro. The characteristics of neocartilage differ upon the type of biomaterial chosen. This study aims at determining the appropriate scaffold material for articular cartilage reconstruction using non articular chondrocytes harvested from rat sternum. For this purpose, the use of polysaccharide hydrogels such as alginate (AA) and hyaluronic acid (HA) was investigated. Several ratios of AA/HA were used as well as three derivatives obtained by chemical modification of HA (HA-C18, HA-C122.3, HA-C122.5-TEG0.5). Sternal chondrocytes were successfully cultured in 3D alginate and alginate/HA scaffolds. HA retention in alginate beads was found to be higher in beads seeded with cells than in beads without cells. HA-C18 improved HA retention in beads but inhibited the chondrocyte synthesis process. Cell proliferation and metabolism were enhanced in all biomaterials when beads were mechanically agitated. Preliminary results have shown that the chondrocyte neo-synthesised matrix had acquired articular characteristics after 21 days culture.
Neo-classical tokamak plasma theory predicts poloidal rotation driven by the temperature gradient... more Neo-classical tokamak plasma theory predicts poloidal rotation driven by the temperature gradient of a few km s −1 . In conventional aspect-ratio tokamak plasmas, e.g. on JET and DIII-D, apparent poloidal velocities considerably in excess of the neo-classical values have been measured, particularly in the presence of internal transport barriers, by means of charge-exchange recombination spectroscopy (CXRS) on the fully ionized C 6+ impurity ions. Comparison between such measurements and theoretical predictions requires careful corrections to be made for apparent 'pseudo' velocities, which can arise from the finite lifetime of the excited atoms in the magnetized plasma and the energy dependence of the charge-exchange excitation process. In present day spherical tokamak plasmas this correction is an order of magnitude smaller than on large conventional tokamaks, which operate at higher temperature and magnetic field, hence reducing any associated systematic uncertainties. On MAST measurements of toroidal and poloidal flows of the C 6+ impurities are available from high-resolution Doppler CXRS measurements, including appropriate corrections for the pseudo-velocities. Comparison of the measured C 6+ velocities with neo-classical theory requires calculation of the impurity flow, which differs from that of the bulk ions due to the respective diamagnetic contributions for each species and inter-species friction forces. Comparisons are made with the predictions of a recent neo-classical theory Collisional transport in a low collisionality plasma with strong rotation PhD Thesis University of Bristol, Newton and Helander 2006 Phys. Plasmas 13 102505), which calculates the full neo-classical transport matrix for bulk ions and a single impurity species for a strongly rotating plasma, as well as those of
Photoluminescence of NeO excimers produced in a Ne matrix by photodissociation of N2O with synchr... more Photoluminescence of NeO excimers produced in a Ne matrix by photodissociation of N2O with synchrotron radiation are reported. An anomalous blue-shift of the (1S → 1D) band was observed. Also, the spin-forbidden (1D → 3P) band was seen for the fust time in a matrix.
chronic wounds, the dermal matrix is insufficient to stimulate healing and assistance by external... more chronic wounds, the dermal matrix is insufficient to stimulate healing and assistance by external factors is needed for wound closure. Although the concept of the extracellular matrix directing wound healing is not new, ideas about how best to provide the extracellular matrix components required to 'jump-start' the healing process are still evolving. Historically, these strategies have included use of enzyme-inhibiting dressing materials, which bind matrix metalloproteinases and remove them from the chronic wound environment, or direct application of purified growth factors to stimulate fibroblast activity and deposition of neo-matrix. More recently, the application of a structurally intact, biochemically complex extracellular matrix, designed to provide the critical extracellular components of the dermis in a single application, has allowed for the reconstruction of new, healthy tissue and restoration of tissue integrity in the previously chronic wound. This review focuses on this third mechanism as an emerging tactic in effective wound repair. Intact extracellular matrix can quickly, easily, and effectively provide key extracellular components of the dermis necessary to direct the healing response and allow for the proliferation of new, healthy tissue. Its application may promote the healing of wounds that have been refractory to other, more conventional treatment strategies, and may eventually show utility when used earlier in wound healing treatment with the goal of preventing wounds from reaching a truly chronic, nonresponsive state.
Computer Methods in Biomechanics and Biomedical Engineering, 2011
Extracellular matrix (ECM) in chondrocytes-seeded agarose aggregates to form islands of matrix. T... more Extracellular matrix (ECM) in chondrocytes-seeded agarose aggregates to form islands of matrix. These islands need to coalesce to develop functional cartilage. Hence, macroscopic properties are determined by transport and aggregation of macromolecules at the microscale, which varies temporally and spatially. This study evaluates the importance of the mutual interaction between matrix components and matrix development.Fluorescence recovery after photobleaching measurements demonstrates that diffusivity depends on the presence and density of ECM. A reaction–diffusion model describing synthesis, transport and immobilisation of ECM predicts steep gradients in ECM around chondrocytes, resembling histology. Steric hindrance of diffusion by ECM is essential for the formation of these gradients. Finally, microscopic ECM concentration is linked with macroscopic mechanical properties. Construct softening is predicted when temporal and spatial variations in diffusivity are considered.In conclusion, non-constant diffusion renders significant effects on both the microscopic ECM development and the macroscopic mechanical properties of developing tissue-engineered cartilage.
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