This review describes the role of bone cells and their surrounding matrix in maintaining bone strength through the process of bone remodelling. Subsequently, this work focusses on how bone formation is guided by mechanical forces and fluid shear stress in particular. It has been demonstrated that mechanical stimulation is an important regulator of bone metabolism. Shear stress generated by interstitial fluid flow in the lacunar-canalicular network influences maintenance and healing of bone tissue. Fluid flow is primarily caused by compressive loading of bone as a result of physical activity. Changes in loading, e.g. due to extended periods of bed rest or microgravity in space are associated with altered bone remodelling and formation in vivo. In vitro, it has been reported that bone cells respond to fluid shear stress by releasing osteogenic signalling factors such as nitric oxide and prostaglandins. This work focusses on the application of in vitro models to study the effects of fluid flow on bone cell signalling, collagen deposition and matrix mineralization. Particular attention is given to in vitro set-ups which allow long-term cell culture and the application of low fluid shear stress. In addition, this review explores what mechanisms influence the orientation of collagen fibres which determine the anisotropic properties of bone. A better understanding of these mechanisms could facilitate the design of improved tissue-engineered bone implants or more effective bone disease models.

Several computational models based on experimental techniques and theories have been proposed to describe cytoskeleton (CSK) mechanics. Tensegrity is a prominent model for force generation, but it cannot predict mechanics of individual CSK components, nor explain the discrepancies from the different single cell stimulating techniques studies combined with cytoskeleton-disruptors. A new numerical concept that defines a multi-structural 3D finite element (FE) model of a single-adherent cell is proposed to investigate the biophysical and biochemical differences of the mechanical role of each cytoskeleton component under loading. The model includes prestressed actin bundles and microtubule within cytoplasm and nucleus surrounded by the actin cortex. We performed numerical simulations of atomic force microscopy (AFM) experiments by subjecting the cell model to compressive loads. The numerical role of the CSK components was corroborated with AFM force measurements on U2OS-osteosarcoma cells and NIH-3T3 fibroblasts exposed to different cytoskeleton-disrupting drugs. Computational simulation showed that actin cortex and microtubules are the major components targeted in resisting compression. This is a new numerical tool that explains the specific role of the cortex and overcomes the difficulty of isolating this component from other networks in vitro. This illustrates that a combination of cytoskeletal structures with their own properties is necessary for a complete description of cellular mechanics.

Microfluidic systems are increasingly being used for the culture and study of dissociated cells because they require only minute amounts of materials while enabling drug screening and chemotaxis studies down to the single cell level. However, the culture of organized tissue, such as brain slices, has been more difficult to adapt to microfluidic devices. Here, we present a microfluidic system, comprising (i) a perfusion chamber for the culture of organotypic slices that is compatible with high resolution imaging on inverted microscopes, and (ii) a novel transparent microfluidic probe (MFP) for the localized microperfusion of the brain tissue. The MFP is made in poly(dimethylsiloxane), features six micrometre-scale apertures and can be assembled within a few hours in a standard laboratory. Each aperture can indiscriminately be used either for the injection or aspiration of solutions, giving rise to many possible combinations. The MFP was successfully used for the perfusion of a small number of cells in a brain slice with concurrent confocal fluorescence imaging of the perfused dye and sub-cellular structures within the tissue.

Microfluidics are expected to revolutionize the healthcare industry especially in developing countries since it would bring portable, easy-to-use, self-contained diagnostic devices to places with limited access to healthcare. To date, however, microfluidics has not yet been able to live up to these expectations. One non-negligible factor can be attributed to inaccessible prototyping methods for researchers in low-resource settings who are unable to afford expensive equipment and/or obtain critical reagents and, therefore, unable to engage and contribute to microfluidics research. In this paper, we present methods to create microfluidic devices that reduce initial costs from hundreds of thousands of dollars to about $6000 by using readily accessible consumables and inexpensive equipment. By including the scientific community most embedded and aware of the requirements of healthcare in developing countries, microfluidics will be able to increase its reach in the research community and be better informed to provide relevant solutions to global healthcare challenges.

The Sertoli cell ectoplasmic specialization (ES) is a specialized domain of the calcium‐dependent Sertoli cell‐spermatid junctional complex. Not only is it associated with the mechanical adhesion of the cells, but it also plays a role in the morphogenesis and differentiation of the developing germ cells. Abnormal or absent Sertoli ESs have been associated with step‐8 spermatid sloughing and subsequent oligospermia. With a micropipette pressure transducing system (MPTS) to measure the force needed to detach germ cells from Sertoli cells, this study examined, for the first time, the strength of the junction between Sertoli cells and spermatids and between Sertoli cells and spermatocytes. The mean force needed to detach spermatocytes from Sertoli cells was 5.25 × 10⁻⁷ pN, prestep‐8 spermatids from Sertoli cells was 4.73 × 10⁻⁷ pN, step‐8 spermatids from Sertoli cells was 8.82 × 10⁻⁷ pN, and spermatids plus EDTA was 2.16 × 10⁻⁷ pN. These data confirm the hypothesis that step‐8 spermatids are more firmly attached to Sertoli cells than are spermatocytes and pre‐step‐8 spermatids and that calcium chelation reduces binding strength between Sertoli cells and spermatids. The MPTS is a useful tool in studying the various molecular models of the Sertoli‐germ cell junctional strength and the role of reproductive hormones and enzymes in coupling and uncoupling of germ cells from Sertoli cells.

One of the most important areas of research on microfluidic technologies focuses on the identification and characterisation of novel materials with enhanced properties and versatility. Here we present a fast, easy and inexpensive microstructuration method for the fabrication of novel, flexible, transparent and biocompatible microfluidic devices. Using a simple hot press, we demonstrate the rapid (30 s) production of various microfluidic prototypes embossed in a commercially available soft thermoplastic elastomer (sTPE). This styrenic block copolymer (BCP) material is as flexible as PDMS and as thermoformable as classical thermoplastics. It exhibits high fidelity of replication using SU-8 and epoxy master molds in a highly convenient low-isobar (0.4 bar) and iso-thermal process. Microfluidic devices can then be easily sealed using either a simple hot plate or even a room-temperature assembly, allowing them to sustain liquid pressures of 2 and 0.6 bar, respectively. The excellent sorption and biocompatibility properties of the microchips were validated via a standard rhodamine dye assay as well as a sensitive yeast cell-based assay. The morphology and composition of the surface area after plasma treatment for hydrophilization purposes are stable and show constant and homogenous distribution of block nanodomains (∼22° after 4 days). These domains, which are evenly distributed on the nanoscale, therefore account for the uniform and convenient surface of a “microfluidic scale device”. To our knowledge, this is the first thermoplastic elastomer material that can be used for fast and reliable fabrication and assembly of microdevices while maintaining a high and stable hydrophilicity.