Porous zirconia scaffold modified with mesoporous bioglass coating

Porous yttria-stabilized zirconia (YSZ) has been regarded as a potential candidate for bone substitute as its high mechanical strength. However, porous YSZ bodies are biologically inert to bone tissue. It is therefore necessary to introduce bioactive coatings onto the walls of the porous structures to enhance the bioactivity. In this study, the porous zirconia scaffolds were prepared by infiltration of Acrylonitrile Butadiene Styrene (ABS) scaffolds with 3 mol% yttria stabilized zirconia slurry. After sintering, a method of sol-gel dip coating was involved to make coating layer of mesoporous bioglass (MBGs). The porous zirconia without the coating had high porosities of 60.1% to 63.8%, and most macropores were interconnected with pore sizes of 0.5-0.8mm. The porous zirconia had compressive strengths of 9.07-9.90MPa. Moreover, the average coating thickness was about 7μm. There is no significant change of compressive strength for the porous zirconia with mesoporous biogalss coating. The bone marrow stromal cell (BMSC) proliferation test showed both uncoated and coated zirconia scaffolds have good biocompatibility. The scanning electron microscope (SEM) micrographs and the compositional analysis graphs demonstrated that after testing in the simulated body fluid (SBF) for 7 days, the apatite formation occurred on the coating surface. Thus, porous zirconia-based ceramics were modified with bioactive coating of mesoporous bioglass for potential biomedical applications

Triethylphosphite as a network forming agent enhances in-vitro biocompatibility and corrosion protection of hybrid organic-inorganic sol-gel coatings for Ti6Al4V alloys

The biocompatibility and life of metallic implants can be enhanced through improving the biocompatibility and corrosion protection characteristics of the coatings used with these materials. In this study, triethylphosphite (TEP) was used to introduce phosphorus into organic-inorganic hybrid silica based sol gel coatings prepared using γ-methacryloxypropyltrimethoxysilane and tetramethylorthosilicate. Addition of TEP dramatically increased the rate of intermolecular condensation and resulted in materials showing greater cross linking. Protein (fibrinogen) uptake, osteoblast in vitro biocompatibility and corrosion resistance was enhanced in coatings containing TEP. Although higher concentrations of phosphorus supported the greatest improvement in biocompatibility, a compromise in the phosphorus concentration used would be required if corrosion resistance was most desirable parameter for optimisation. Films prepared by dip coating on Ti6Al4V alloys from these sols offer a promising alternative to wholly metallic prostheses

The automated multi-stage substructuring system for NASTRAN

The substructuring capability developed for eventual installation in Level 16 is now operational in a test version of NASTRAN. Its features are summarized. These include the user-oriented, Case Control type control language, the automated multi-stage matrix processing, the independent direct access data storage facilities, and the static and normal modes solution capabilities. A complete problem analysis sequence is presented with card-by-card description of the user input

Cosmological Deformation of Lorentzian Spin Foam Models

We study the quantum deformation of the Barrett-Crane Lorentzian spin foam model which is conjectured to be the discretization of Lorentzian Plebanski model with positive cosmological constant and includes therefore as a particular sector quantum gravity in de-Sitter space. This spin foam model is constructed using harmonic analysis on the quantum Lorentz group. The evaluation of simple spin networks are shown to be non commutative integrals over the quantum hyperboloid defined as a pile of fuzzy spheres. We show that the introduction of the cosmological constant removes all the infrared divergences: for any fixed triangulation, the integration over the area variables is finite for a large class of normalization of the amplitude of the edges and of the faces.Comment: 37 pages, 7 figures include

Phase-field modeling of pitting and mechanically-assisted corrosion of Mg alloys for biomedical applications

A phase-field model is developed to simulate the corrosion of Mg alloys in body fluids. The model incorporates both Mg dissolution and the transport of Mg ions in solution, naturally predicting the transition from activation-controlled to diffusion-controlled bio-corrosion. In addition to uniform corrosion, the presented framework captures pitting corrosion and accounts for the synergistic effect of aggressive environments and mechanical loading in accelerating corrosion kinetics. The model applies to arbitrary 2D and 3D geometries with no special treatment for the evolution of the corrosion front, which is described using a diffuse interface approach. Experiments are conducted to validate the model and a good agreement is attained against in vitro measurements on Mg wires. The potential of the model to capture mechano-chemical effects during corrosion is demonstrated in case studies considering Mg wires in tension and bioabsorbable coronary Mg stents subjected to mechanical loading. The proposed methodology can be used to assess the in vitro and in vivo service life of Mg-based biomedical devices and optimize the design taking into account the effect of mechanical deformation on the corrosion rate. The model has the potential to advocate further development of Mg alloys as a biodegradable implant material for biomedical applications

Phase-field modeling of pitting and mechanically-assisted corrosion of Mg alloys for biomedical applications.

A phase-field model is developed to simulate the corrosion of Mg alloys in body fluids. The model incorporates both Mg dissolution and the transport of Mg ions in solution, naturally predicting the transition from activation-controlled to diffusion-controlled bio-corrosion. In addition to uniform corrosion, the presented framework captures pitting corrosion and accounts for the synergistic effect of aggressive environments and mechanical loading in accelerating corrosion kinetics. The model applies to arbitrary 2D and 3D geometries with no special treatment for the evolution of the corrosion front, which is described using a diffuse interface approach. Experiments are conducted to validate the model and a good agreement is attained against in vitro measurements on Mg wires. The potential of the model to capture mechano-chemical effects during corrosion is demonstrated in case studies considering Mg wires in tension and bioabsorbable coronary Mg stents subjected to mechanical loading. The proposed methodology can be used to assess the in vitro and in vivo service life of Mg-based biomedical devices and optimize the design taking into account the effect of mechanical deformation on the corrosion rate. The model has the potential to advocate further development of Mg alloys as a biodegradable implant material for biomedical applications. STATEMENT OF SIGNIFICANCE: A physically-based model is developed to simulate the corrosion of bioabsorbable metals in environments that resemble biological fluids. The model captures pitting corrosion and incorporates the role of mechanical fields in enhancing the corrosion of bioabsorbable metals. Model predictions are validated against dedicated in vitro corrosion experiments on Mg wires. The potential of the model to capture mechano-chemical effects is demonstrated in representative examples. The simulations show that the presence of mechanical fields leads to the formation of cracks accelerating the failure of Mg wires, whereas pitting severely compromises the structural integrity of coronary Mg stents. This work extends phase-field modeling to bioengineering and provides a mechanistic tool for assessing the service life of bioabsorbable metallic biomedical devices

Nanostructured Mg-ZK50 Sheets Fabricated for Potential Use for Biomedical Applications

Magnesium (Mg) alloys are widely used in biomedical applications thanks to their combination of exceptional mechanical properties, biocompatibility, and biodegradability. Mg-ZK alloy series; for instance, ZK40, ZK60 and ZK61; is an example of the most commonly used Mg bio-alloy. Zirconium (Zr) acts as a grain refiner when added to Mg, which manipulates the material structure by producing a refined internal structure and enhancing its properties. In addition, when Zinc (Zn) is added to a Mg-Zr alloy, strength is improved. Therefore, given the favorable properties of ZK alloys in biomedical applications, the current research aimed for the fabrication and the evaluation of a new ZK alloy with a new composition; ZK50, as a potential biomaterial for biomedical applications. Three stages were implemented in order to achieve the objective of this study. In the first stage, ball milling process was used to synthesize nanostructured Mg-ZK50 alloy from elemental powders (Mg, Zr, and Zn). The produced powders (BM) were studied using SEM, XRD and TEM to determine the internal structure refinement as well as the phase development due to milling. In the second stage, Powder-in-Tube (PIT) rolling process followed by annealing was applied to produce consolidated thin sheets from the BM powders. Accordingly, in the third stage, the effect of annealing on the internal structure, mechanical properties, corrosion behavior and cytotoxicity was evaluated. The mechanical milling of the elemental powders produced a nanostructured alloyed powder after 45 hrs of milling with a crystallite size of 8.83 nm, which is considered the finest internal structure for Mg and Mg based alloys to date. Afterwards, nanostructured thin sheets were successfully produced using PIT at 300 °C with 67% reduction percent. The modulus of the sheets was found matching to that of human bones. It is worthy to note that annealing was found to have a detrimental effect on the corrosion behavior of the alloy. However, a hydroxyapatite layer was formed which indicated that the produced sheets induced osteoinductivity of the bone. Moreover, cytotoxicity of the sheets was not affected by the sheets and all the produced sheets showed an acceptable toxicity level within the cells. In conclusion, the produced Mg-ZK50 nanostructured alloyed sheets are considered a new potential biomaterial for orthopedic implants that induces osteoinductivity and prevent stress shielding

Accurate determination and application of local strain for studying tissues with gradients in mechanical properties

Determination of the mechanical behavior of materials requires an understanding of deformation during loading. While this is traditionally accomplished in engineering by examining a force displacement curve for a whole sample, these techniques implicitly ignore local geometric complexities and local material inhomogeneities commonly found in biologic tissues. Techniques such as normalized cross correlation have been classically applied to address this issue and resolve deformation at the local level; however, these techniques have proven unreliable when deformations become large, if the sample undergoes a rotation, and/or if strain fields become incompatible (e.g. at or near failure). Presented here is a toolbox of techniques that addresses the limitations of the prior state-of-the-art for localized strain estimation. The first algorithm, termed 2D direct deformation estimation (2D-DDE), directly incorporates concepts from mechanics into non-rigid registration algorithms from computer vision, eliminating the need to consider displacement fields, as required for all of the prior state-of-the-art techniques. This results in not only an improvement in accuracy and precision of deformation estimation, but also relaxes compatibility of the deformation fields. A second algorithm, 2D Strain Inference with Measures of Probable Local Elevation (2D-SIMPLE), incorporates the results of 2D-DDE with results from algorithms that enforce strain compatibility to develop a robust detector of strain concentrations. While tracking local strain in a vinylidene chloride sheet in tension, 2D-SIMPLE detected strain concentrations which predicted the initiation of a crack in the material and the progression of the crack tip. The third and fourth algorithms generalize the two dimensional algorithms to analyze three dimensional deformations in volumetric images (3D-DDE and 3D-SIMPLE, respectively). Lastly, the 2D-DDE algorithm is modified to estimate two dimensional surface deformation from multi-view imaging systems. The robustness and adaptability of these techniques was then validated and demonstrated on a wide variety of biomedical applications. Using 2D-DDE, a microscale compliant region was discovered at the tendon-to-bone attachment, local heterogeneity of partially mineralized scaffolds was revealed, and gradients in stiffness of partially mineralized nano-fiber scaffolds were demonstrated. Using 2D-SIMPLE, mechanisms of embryonic wound healing and associated strain localizations were elucidated. 3D-DDE confirmed the existence of strain gradients across chordae tendineae in beating murine hearts as well as demonstrated dramatic localized changes in wall deformation before and after myocardial infarction in murine hearts. 2D-DDE was also used to develop a model system to study the effects of applied stress versus the effects of applied strain on cells. The model system was first theorized by considering a system in which gradients of cross sectional area or scaffold shape were composed with gradients in material stiffness. By combining these gradients in novel ways, it was theoretically determined that stress and strain could be locally isolated. A tensile bioreactor was constructed, techniques for fabricating scaffolds with gradients in stiffness and gradients in cross sectional area were developed, and theoretical strain gradients were confirmed experimentally using 2D-DDE. The model system was then validated for in vitro cell studies. Cell adhesion, proliferation, and viability following a seven day loading protocol were explored. Methods for determining single cell responses, which could be correlated back to a specific stress or strain states, were developed using immunocytochemistry and 2D-DDE approaches. Future studies will apply this model system to determine precise mechanotransduction responses of cells. These studies are critical to optimize stem cell tissue engineering strategies as well inform cell mechanobiology mechanisms

Development And Analysis Of Next-Generation Polymeric And Bio-Ceramic Based Orthopedic Scaffolds By Advanced Manufacturing Techniques

Gliomas express mutant isocitrate dehydrogenases producing excessive amounts of D 2-hydroxyglutarate (D2HG) and releasing some of it into the environment. The immune surveillance is reduced as a result, however, the mechanisms behind lymphocyte suppression by the D2HG stereoisomer remain unknown. I incubated Jurkat T cells with D2HG at concentrations present within and surrounding gliomas, or its obverse L2HG stereoisomer, and quantified 2HG isomers within washed cells by TSPC derivatization with stable isotope-labeled D2HG and L2HG internal standards, HPLC separation, and mass spectrometry. D2HG was found in quiescent cells in double the amount of L2HG. External D2HG or L2HG increased the level of the provided stereoisomer in a transient, concentration-dependent process. IL-2 expression, even when maximally elicited by A23187 and PMA, was inhibited and ultimately abolished by exogenous D2HG in a concentration-dependent manner. Notably, a significant reduction occurred at just twice its basal intracellular level. In contrast, L2HG was only moderately inhibitory. IL-2 expression is regulated by increased intracellular Ca++ that stimulates Calcineurin to dephosphorylate cytoplasmic phospho-NFAT to enable its nuclear translocation. Besides, to induce IL-2, AP-1 complex which is downstream of ERK needs to ligate. D2HG inhibited p-ERK in Jurkat T cells, impairing the AP-1 complex. D2HG abolished expression of a stably-integrated NFAT-driven luciferase reporter, and this concentration-dependent inhibition precisely paralleled inhibition of IL-2. D2HG did not affect intracellular Ca++. Rather, surface Plasmon resonance showed D2HG, but not L2HG, bound Calcineurin. D2HG, but not L2HG, inhibited Ca++-dependent Calcineurin phosphatase activity. Thus, D2HG is a stereoselective Calcineurin phosphatase inhibitor that prevents NFAT dephosphorylation, and so abolishes IL-2 transcription in stimulated Jurkat cells. This occurs at D2HG concentrations found within and adjacent to gliomas independent of delayed epigenetic modulation of transcription