Chondrocyte Deformations as a Function of Tibiofemoral Joint Loading Predicted by a Generalized High-Throughput Pipeline of Multi-Scale Simulations

Cells of the musculoskeletal system are known to respond to mechanical loading and chondrocytes within the cartilage are not an exception. However, understanding how joint level loads relate to cell level deformations, e.g. in the cartilage, is not a straightforward task. In this study, a multi-scale analysis pipeline was implemented to post-process the results of a macro-scale finite element (FE) tibiofemoral joint model to provide joint mechanics based displacement boundary conditions to micro-scale cellular FE models of the cartilage, for the purpose of characterizing chondrocyte deformations in relation to tibiofemoral joint loading. It was possible to identify the load distribution within the knee among its tissue structures and ultimately within the cartilage among its extracellular matrix, pericellular environment and resident chondrocytes. Various cellular deformation metrics (aspect ratio change, volumetric strain, cellular effective strain and maximum shear strain) were calculated. To illustrate further utility of this multi-scale modeling pipeline, two micro-scale cartilage constructs were considered: an idealized single cell at the centroid of a 100×100×100 μm block commonly used in past research studies, and an anatomically based (11 cell model of the same volume) representation of the middle zone of tibiofemoral cartilage. In both cases, chondrocytes experienced amplified deformations compared to those at the macro-scale, predicted by simulating one body weight compressive loading on the tibiofemoral joint. In the 11 cell case, all cells experienced less deformation than the single cell case, and also exhibited a larger variance in deformation compared to other cells residing in the same block. The coupling method proved to be highly scalable due to micro-scale model independence that allowed for exploitation of distributed memory computing architecture. The method’s generalized nature also allows for substitution of any macro-scale and/or micro-scale model providing application for other multi-scale continuum mechanics problems

Production and characterization of carbamazepine nanocrystals by electrospraying for continuous pharmaceutical manufacturing

In this paper, an electrospray technique followed by annealing at high temperatures was developed to produce nanocrystals of carbamazepine (CBZ), a poorly water-soluble drug, for continuous pharmaceutical manufacturing process. Electrospraying solutions of CBZ in methanol obeys the expected scaling law of current, which is I ∼ Q[superscript 1/2] (I, electrical current; Q, flow rate), for liquids with sufficiently high conductivity and viscosity. Lower flow rates during electrospraying were preferred to produce smaller diameters of monodisperse, dense CBZ nanoparticles. CBZ nanoparticles were predominantly amorphous immediately after electrospraying. Crystallization of CBZ nanoparticles was accelerated by annealing at high temperatures. CBZ nanocrystals with the most stable polymorph, form III, were obtained by annealing at 90°C, which is above the transition temperature, 78°C, for the enantiotropic CBZ form III and form I. The solubility and dissolution rates of CBZ nanocrystals increased significantly as compared with those of CBZ bulk particles. Therefore, electrospray technology has the potential to produce pharmaceutical dosage forms with enhanced bioavailability and can readily be integrated in a continuous pharmaceutical manufacturing process.Novartis-MIT Center for Continuous Manufacturin

Tribological behaviour of W-alloyed carbon-based coatings in dry and lubricated sliding contact

Carbon-based coatings with different W contents were deposited by direct current magnetron sputtering in reactive and non-reactive atmospheres. All deposited coatings have compact morphologies with amorphous (tungsten-free) or nanocrystalline structures (tungsten-doped). The latter one was indicated by very broad peaks in X-ray Diffraction spectra in the position of tungsten carbide suggesting W-carbide nanoparticles embedded in an amorphous carbon matrix. The hardness increased from 10 to 15 GPa with increasing W content. The coatings were tribological tested at dry and lubricated conditions with increasing temperature in a coating/steel configuration. In dry sliding, the friction coefficient increases with the increase of the temperature reaching values higher than 1.0. The friction is significantly lower in lubricated contact using three different oils: poly-alpha-olefin, paraffin and olive oil. The olive oil shows promising lubricating properties at the temperature lower than 70°C; however, at higher temperature, the coatings were quickly worn through

Temperature-dependent contact phenomena of PVD- and CVD-deposited DLC films sliding on the thin aluminium foil

This paper reports on tribological properties of magnetron-sputtered WC-C and chemical-vapour deposited diamond-like carbon films coated onto hard-metal surfaces when sliding on aluminium foil (0.2 mm nominal thickness) at different temperatures. The study addresses the evolution of the coefficient of friction at the interfaces of the coated hard metal and the aluminium foil under dry-lubrication conditions, in a ball-on-disc configuration. The wear mechanisms of the aluminium foil and the damage produced on the coated surfaces due to the sticking of aluminium were evaluated as a function of the deposited coating and the temperature at their interfaces. Aluminium-transfer to WC-C coated hard-metal surfaces during the sliding operation seemed to be a non-continuous process, which appeared after a certain number of sliding cycles. Temperatures above 70ºC accelerated the transfer of aluminium to the WC-C tool surfaces. Chemical-vapour-deposited diamond-like carbon films hindered the transfer of aluminium to the hard metal even at temperatures of around 125ºC. At greater temperatures, an aluminium--aluminium tribo-surface is formed at the interface, which increases the wear rate of the foils and rapidly degrades the quality of coatings of the hard-metal surfaces