Effect of Heat Treatment on Pore Architecture and Associated Property Charges in Plasma Sprayed TBCs

Plasma sprayed TBCs exhibit many interlamellar pores, voids and microcracks. These microstructural features are primarily responsible for the low global stiffnesses and the low thermal conductivities commonly exhibited by such coatings. The pore architecture thus has an important influence on such thermophysical properties. In the present work, the effect of heat treatment (at temperatures up to 1400C, for times of up to 100 hours) and coating purity on the pore architecture in detached YSZ top coats has been characterised by Mercury Intrusion Porosimetry (MIP) and BJH Analysis. While the overall porosity level (measured by densitometry) remained relatively unaffected (at around 10-12%) after the heat treatments concerned, there were substantial changes in the pore size distribution and the (inter-connected) specific surface area, although these changes occurred less rapidly with coatings produced using high purity powders. Fine pores (<~50 nm) rapidly disappeared, while the specific surface area dropped dramatically, particularly at high treatment temperatures (>~1300C). These changes are thought to be associated with improved inter-splat bonding and increased contact area, leading to disappearance of much of the very fine inter-splat porosity. These microstructural changes are reflected in sharply increased stiffness and thermal conductivity. Measured thermal conductivity data are compared with predictions from a recently-developed analytical model [1], using the deduced inter-splat contact area results as input parameters. Good agreement is obtained, suggesting that the model captures the main geometrical effects and the porosity architecture measurements reflect the most significant microstructural changes. REF.1. Golosnoy, IO, Tsipas, SA and Clyne, TW, An Analytical Model For Simulation Of Heat Flow In Plasma Sprayed Thermal Barrier Coating, J. Thermal Spray Techn., 14 (2005) 205-214

Properties and Performance of High-Purity Thermal Barrier Coatings

It has been found that reducing the level of impurity oxides (particularly SiO2 and Al2O3) in 7YSZ, from about 0.2 wt% to below 0.1 wt% raises the sintering resistance and the phase stability of plasma-sprayed coatings. The implications for the usage of these coatings at elevated temperatures are examined. It is concluded that using relatively high-purity powder of this type is likely to confer substantial benefits in terms of the thermomechanical stability of the coatings under service conditions

Microenvironment-mediated cancer dormancy : insights from metastability theory

Dormancy is an evolutionarily conserved protective mechanism widely observed in nature. A pathological example is found during cancer metastasis, where cancer cells disseminate from the primary tumor, home to secondary organs, and enter a growth-arrested state, which could last for decades. Recent studies have pointed toward the microenvironment being heavily involved in inducing, preserving, or ceasing this dormant state, with a strong focus on identifying specific molecular mechanisms and signaling pathways. Increasing evidence now suggests the existence of an interplay between intracellular as well as extracellular biochemical and mechanical cues in guiding such processes. Despite the inherent complexities associated with dormancy, proliferation, and growth of cancer cells and tumor tissues, viewing these phenomena from a physical perspective allows for a more global description, independent from many details of the systems. Building on the analogies between tissues and fluids and thermodynamic phase separation concepts, we classify a number of proposed mechanisms in terms of a thermodynamic metastability of the tumor with respect to growth. This can be governed by interaction with the microenvironment in the form of adherence (wetting) to a substrate or by mechanical confinement of the surrounding extracellular matrix. By drawing parallels with clinical and experimental data, we advance the notion that the local energy minima, or metastable states, emerging in the tissue droplet growth kinetics can be associated with a dormant state. Despite its simplicity, the provided framework captures several aspects associated with cancer dormancy and tumor growth

Simulation of failure of air plasma sprayed thermal barrier coating due to interfacial and bulk cracks using surface-based cohesive interaction and extended finite element method

This article describes a method of predicting the failure of a thermal barrier coating system due to interfacial cracks and cracks within bulk coatings. The interfacial crack is modelled by applying cohesive interfaces where the thermally grown oxide is bonded to the ceramic thermal barrier coating. Initiation and propagation of arbitrary cracks within coatings are modelled using the extended finite element method. Two sets of parametric studies were carried out, concentrating on the effect of thickness of the oxide layer and that of initial cracks within the ceramic coating on the growth of coating cracks and the subsequent failures. These studies have shown that a thicker oxide layer creates higher tensile residual stresses during cooling from high temperature, leading to longer coating cracks. Initial cracks parallel to the oxide interface accelerate coating spallation, and simulation of this process is presented in this article. By contrast, segmented cracks prevent growth of parallel cracks which can lead to spallation

Alginate hydrogels for in vivo bone regeneration : the immune competence of the animal model matters

Biomaterials with tunable biophysical properties hold great potential for tissue engineering. The adaptive immune system plays an important role in bone regeneration. Our goal is to investigate the regeneration potential of cell-laden alginate hydrogels depending on the immune status of the animal model. Specifically, the regeneration potential of rat mesenchymal stromal cell (MSC)-laden, void-forming alginate hydrogels, with a stiffness optimized for osteogenic differentiation, is studied in 5 mm critical-sized femoral defects, in both T-cell deficient athymic RNU nude rats and immunocompetent Sprague Dawley rats. Bone volume fraction, bone mineral density and tissue mineral density are higher for athymic RNU nude rats 6 weeks post-surgery. Additionally, these animals show a significantly higher number of total cells and cells with non-lymphocyte morphology at the defect site, while the number of cells with lymphocyte-like morphology is lower. Hydrogel degradation is slower and the remaining alginate fragments are surrounded by a thicker fibrous capsule. Ossification islands originating from alginate residues suggest that encapsulated MSCs differentiate into the osteogenic lineage and initiate the mineralization process. However, this effect is insufficient to fully bridge the bone defect in both animal models. Alginate hydrogels can be used to deliver MSCs and thereby recruit endogenous cells through paracrine signaling, but additional osteogenic stimuli are needed to regenerate critical-sized segmental femoral defects

In vivo microCT-based time-lapse morphometry reveals anatomical site-specific differences in bone (re)modeling serving as baseline parameters to detect early pathological events

The bone structure is very dynamic and continuously adapts its geometry to external stimuli by modeling and remodeling the mineralized tissue. In vivo microCT-based time-lapse morphometry is a powerful tool to study the temporal and spatial dynamics of bone (re)modeling. Here an advancement in the methodology to detect and quantify site-specific differences in bone (re)modeling of 12-week-old BALB/c nude mice is presented. We describe our method of quantifying new bone surface interface readouts and how these are influenced by bone curvature. This method is then used to compare bone surface (re)modeling in mice across different anatomical regions to demonstrate variations in the rate of change and spatial gradients thereof. Significant differences in bone (re)modeling baseline parameters between the metaphyseal and epiphyseal are shown, as well as cortical and trabecular bone of the distal femur and proximal tibia. These results are validated using conventional static in vivo microCT analysis. Finally, the insights from these new baseline values of physiological bone (re)modeling were used to evaluate pathological bone (re)modeling in a pilot breast cancer bone metastasis model. The method shows the potential to be suitable to detect early pathological events and track their spatio-temporal development in both cortical and trabecular bone. This advancement in (re)modeling surface analysis and defined baseline parameters according to distinct anatomical regions will be valuable to others investigating various disease models with site-distinct local alterations in bone (re)modeling.ER

Osmotic pressure modulates single cell cycle dynamics inducing reversible growth arrest and reactivation of human metastatic cells

Biophysical cues such as osmotic pressure modulate proliferation and growth arrest of bacteria, yeast cells and seeds. In tissues, osmotic regulation takes place through blood and lymphatic capillaries and, at a single cell level, water and osmoregulation play a critical role. However, the effect of osmotic pressure on single cell cycle dynamics remains poorly understood. Here, we investigate the effect of osmotic pressure on single cell cycle dynamics, nuclear growth, proliferation, migration and protein expression, by quantitative time-lapse imaging of single cells genetically modified with fluorescent ubiquitination-based cell cycle indicator 2 (FUCCI2). Single cell data reveals that under hyperosmotic stress, distinct cell subpopulations emerge with impaired nuclear growth, delayed or growth arrested cell cycle and reduced migration. This state is reversible for mild hyperosmotic stress, where cells return to regular cell cycle dynamics, proliferation and migration. Thus, osmotic pressure can modulate the reversible growth arrest and reactivation of human metastatic cells

Optical quantification of intracellular mass density and cell mechanics in 3D mechanical confinement

Biophysical properties of cells such as intracellular mass density and cell mechanics are known to be involved in a wide range of homeostatic functions and pathological alterations. An optical readout that can be used to quantify such properties is the refractive index (RI) distribution. It has been recently reported that the nucleus, initially presumed to be the organelle with the highest dry mass density (ρ) within the cell, has in fact a lower RI and ρ than its surrounding cytoplasm. These studies have either been conducted in suspended cells, or cells adhered on 2D substrates, neither of which reflects the situation in vivo where cells are surrounded by the extracellular matrix (ECM). To better approximate the 3D situation, we encapsulated cells in 3D covalently-crosslinked alginate hydrogels with varying stiffness, and imaged the 3D RI distribution of cells, using a combined optical diffraction tomography (ODT)-epifluorescence microscope. Unexpectedly, the nuclei of cells in 3D displayed a higher ρ than the cytoplasm, in contrast to 2D cultures. Using a Brillouin-epifluorescence microscope we subsequently showed that in addition to higher ρ, the nuclei also had a higher longitudinal modulus (M) and viscosity (η) compared to the cytoplasm. Furthermore, increasing the stiffness of the hydrogel resulted in higher M for both the nuclei and cytoplasm of cells in stiff 3D alginate compared to cells in compliant 3D alginate. The ability to quantify intracellular biophysical properties with non-invasive techniques will improve our understanding of biological processes such as dormancy, apoptosis, cell growth or stem cell differentiation. <br

An early myeloma bone disease model in skeletally mature mice as a platform for biomaterial characterization of the extracellular matrix

Multiple myeloma (MM) bone disease is characterized by osteolytic bone tissue destruction resulting in bone pain, fractures, vertebral collapse, and spinal cord compression in patients. Upon initial diagnosis of MM, almost 80% of patients suffer from bone disease. Earlier diagnosis and intervention in MM bone disease would potentially improve treatment outcome and patient survival. New preclinical models are needed for developing novel diagnostic markers of bone structural changes as early as possible in the disease course. Here, we report a proof-of-concept, syngeneic, intrafemoral MOPC315.BM MM murine model in skeletally mature BALB/c mice for detection and characterization of very early changes in the extracellular matrix (ECM) of MM-injected animals. Bioluminescence imaging (BLI) in vivo confirmed myeloma engraftment in 100% of the animals with high osteoclast activity within 21 days after tumor cell inoculation. Early signs of aggressive bone turnover were observed on the outer bone surfaces by high-resolution microcomputed tomography (microCT). Synchrotron phase contrast-enhanced microcomputer tomography (PCE-CT) revealed very local microarchitecture differences highlighting numerous active sites of erosion and new bone at the micrometer scale. Correlative backscattered electron imaging (BSE) and confocal laser scanning microscopy allowed direct comparison of mineralized and nonmineralized matrix changes in the cortical bone. The osteocyte lacunar-canalicular network (OLCN) architecture was disorganized, and irregular-shaped osteocyte lacunae were observed in MM-injected bones after 21 days. Our model provides a potential platform to further evaluate pathological MM bone lesion development at the micro- and ultrastructural levels. These promising results make it possible to combine material science and pharmacological investigations that may improve early detection and treatment of MM bone disease

Sintering Kinetics of Plasma-Sprayed Zirconia TBCs

A model of the sintering exhibited by EB-PVD TBCs, based on principles of free energy minimization, was recently published by Hutchinson et al. In the current paper, this approach is applied to sintering of plasma-sprayed TBCs and comparisons are made with experimental results. Predictions of through-thickness shrinkage and changing pore surface area are compared with experimental data obtained by dilatometry and BET analysis respectively. The sensitivity of the predictions to initial pore architecture and material properties are assessed. The model can be used to predict the evolution of contact area between overlying splats. This is in turn related to the through-thickness thermal conductivity, using a previously-developed analytical model