The development of advanced techniques of fabrication of three-dimensional (3D) microenvironments for the study of cell growth and proliferation has become one of the major motivations of material scientists and bioengineers in the past decade. Here, we present a novel residueless 3D structuration technique of poly(dimethylsiloxane) (PDMS) by water-in-PDMS emulsion casting and subsequent curing process in temperature-/pressure-controlled environment. Scanning electron microscopy and X-ray microcomputed tomography allowed us to investigate the impact of those parameters on the microarchitecture of the porous structure. We demonstrated that the optimized emulsion casting process gives rise to large-scale and highly interconnected network with pore size ranging from 500 μm to 1.5 mm that turned out to be nicely adapted to 3D cell culture. Experimental cell culture validations were performed using SaOS-2 (osteosarcoma) cell lines. Epifluorescence and deep penetration imaging techniques as two-photon confocal microscopy unveiled information about cell morphology and confirmed a homogeneous cell proliferation and spatial distribution in the 3D porous structure within an available volume larger than 1 cm³. These results open alternative scenarios for the fabrication and integration of porous scaffolds for the development of 3D cell culture platforms.

We analytically study the influence of boundaries on distant localized patterns generated by a Turing instability. To this end, we use the Swift-Hohenberg model with arbitrary boundary conditions. We find that the bifurcation diagram of these localized structures generally involves four homoclinic snaking branches, rather than two for infinite or periodic domains. Second, steady localized patterns only exist at discrete locations, and only at the center of the domain if their size exceeds a critical value. Third, reducing the domain size increases the pinning range.

We consider the transition between the steady vertical path and the oscillatory path of two-dimensional bodies moving under the effect of buoyancy in a viscous fluid. Linearization of the Navier–Stokes equations governing the flow past the body and of Newton’s equations governing the body dynamics leads to an eigenvalue problem, which is solved numerically. Three different body geometries are then examined in detail, namely a quasi-infinitely thin plate, a plate of rectangular cross-section with an aspect ratio of 8, and a rod with a square cross-section. Two kinds of eigenmodes are observed in the limit of large body-to-fluid mass ratios, namely ‘fluid’ modes identical to those found in the wake of a fixed body, which are responsible for the onset of vortex shedding, and four additional ‘aerodynamic’ modes associated with much longer time scales, which are also predicted using a quasi-static model introduced in a companion paper. The stability thresholds are computed and the nature of the corresponding eigenmodes is investigated throughout the whole possible range of mass ratios. For thin bodies such as a flat plate, the Reynolds number characterizing the threshold of the first instability and the associated Strouhal number are observed to be comparable with those of the corresponding fixed body. Other modes are found to become unstable at larger Reynolds numbers, and complicated branch crossings leading to mode switching are observed. On the other hand, for bluff bodies such as a square rod, two unstable modes are detected in the range of Reynolds number corresponding to wake destabilization. For large enough mass ratios, the leading mode is similar to the vortex shedding mode past a fixed body, while for smaller mass ratios it is of a different nature, with a Strouhal number about half that of the vortex shedding mode and a stronger coupling with the body dynamics.

Biological and histopathological techniques identified osteoclasts and macrophages as targets of zoledronic acid (ZA), a therapeutic agent that was detrimental for patients in the French OS2006 trial. Conventional and multiplex immunohistochemistry of microenvironmental and OS cells were performed on biopsies of 124 OS2006 patients and 17 surgical (“OSNew”) biopsies respectively. CSF-1R (common osteoclast/macrophage progenitor) and TRAP (osteoclast activity) levels in serum of 108 patients were correlated to response to chemotherapy and to prognosis. TRAP levels at surgery and at the end of the protocol were significantly lower in ZA+ than ZA− patients (p_adj = 0.0011; 0.0132). For ZA+-patients, an increase in the CSF-1R level between diagnosis and surgery and a high TRAP level in the serum at biopsy were associated with a better response to chemotherapy (p = 0.0091; p = 0.0251). At diagnosis, high CD163+ was associated with good prognosis, while low TRAP activity was associated with better overall survival in ZA− patients only. Multiplex immunohistochemistry demonstrated remarkable bipotent CD68+/CD163+ macrophages, homogeneously distributed throughout OS regions, aside osteoclasts (CD68+/CD163−) mostly residing in osteolytic territories and osteoid-matrix-associated CD68−/CD163+ macrophages. We demonstrate that ZA not only acts on harmful osteoclasts but also on protective macrophages, and hypothesize that the bipotent CD68+/CD163+ macrophages might present novel therapeutic targets.

Gradients of concentration and temperature across exothermic chemical fronts propagating in free-surface solution layers can initiate Marangoni-driven convection. We investigate here the dynamics arising from such a coupling between exothermic autocatalytic reactions, diffusion, and Marangoni-driven flows. To this end, we numerically integrate the incompressible Navier-Stokes equations coupled through the tangential stress balance to evolution equations for the concentration of the autocatalytic product and for the temperature. A solutal and a thermal Marangoni numbers measure the coupling between reaction-diffusion processes and surface-driven convection. In the case of an isothermal system, the asymptotic dynamics is characterized by a steady fluid vortex traveling at a constant speed with the front, deforming and accelerating it [L. Rongy and A. De Wit, J. Chem. Phys. 124, 164705 (2006)]. We analyze here the influence of the reaction exothermicity on the dynamics of the system in both cases of cooperative and competitive solutal and thermal effects. We show that exothermic fronts can exhibit new unsteady spatio-temporal dynamics when the solutal and thermal effects are antagonistic. The influence of the solutal and thermal Marangoni numbers, of the Lewis number (ratio of thermal diffusivity over molecular diffusivity), and of the height of the liquid layer on the spatio-temporal front evolution are investigated.

Atherosclerotic plaques develop at particular sites in the arterial tree, and this regional localisation depends largely on haemodynamic parameters (such as wall shear stress; WSS) as described in the literature. Plaque rupture can result in heart attack or stroke and hence understanding the development and vulnerability of atherosclerotic plaques is critically important. The purpose of this study is to characterise the haemodynamics of blood flow in the mouse aortic arch using numerical modelling. The geometries are digitalised from synchrotron imaging and realistic pulsatile blood flow is considered under rigid wall assumptions. Two cases are considered; arteries with and without plaque. Mice that are fed under fat diet present plaques in the aortic arch whose size is dependent on the number of weeks under the diet. The plaque distribution in the region is however relatively constant through the different samples. This result underlines the influence of the geometry and consequently of the wall shear stresses for plaque formation with plaques growing in region of relative low shear stresses. A discussion of the flow field in real geometry in the presence and absence of plaques is conducted. The presence of plaques was shown to alter the blood flow and hence WSS distribution, with regions of localised high WSS, mainly on the wall of the brachiocephalic artery where luminal narrowing is most pronounced. In addition, arch plaques are shown to induce recirculation in the blood flow, a phenomenon with potential influence on the progression of the plaques. The oscillatory shear index and the relative residence time have been calculated on the geometry with plaques to show the presence of this recirculation in the arch, an approach that may be useful for future studies on plaque progression.