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Mechanical loading modulates cartilage homeostasis through the control of matrix synthesis and catabolism. However, the mechanotransduction pathways through which chondrocytes detect different loading conditions remain unclear. The present study investigated the influence of cyclic compression on intracellular Ca2+ signalling using the well-characterised chondrocyte-agarose model. Cells labelled with Fluo4 were visualised using confocal microscopy following a period of 10 cycles of compression between 0% and 10% strain. In unstrained agarose constructs, not subjected to cyclic compression, a subpopulation of approximately 45% of chondrocytes exhibited spontaneous global Ca2+ transients with mean transient rise and fall times of 19.4 and 29.4 sec, respectively. Cyclic compression modulated global Ca2+ signalling by increasing the percentage of cells exhibiting Ca2+ transients (population modulation) and/or reducing the rise and fall times of these transients (transient shape modulation). The frequency and strain rate of compression differentially modulated these Ca2+ signalling characteristics providing a potential mechanism through which chondrocytes may distinguish between different loading conditions. Treatment with apyrase, gadolinium and the P2 receptor blockers, suramin and basilen blue, significantly reduced the percentage of cells exhibiting Ca2+ transients following cyclic compression, such that the mechanically induced upregulation of Ca2+ signalling was completely abolished. Thus cyclic compression appears to activate a purinergic pathway involving the release of ATP followed by the activation of P2 receptors causing a combination of extracellular Ca2+ influx and intracellular Ca2+ release. Knowledge of this fundamental cartilage mechanotransduction pathway may lead to improved therapeutic strategies for the treatment of cartilage damage and disease.

| Point-of-care (POC) diagnostics is playing an increasingly important role in public health, environmental monitoring, and food safety analysis. Smartphones, alone or in conjunction with add-on devices, have shown great capability of data collection, analysis, display, and transmission, making them popular in POC diagnostics. In this article, the state-ofthe-art advances in smartphone-based POC diagnostic technologies and their applications in the past few years are outlined, ranging from in vivo tests that use smartphone's built-in/external sensors to detect biological signals to in vitro tests that involves complicated biochemical reactions. Novel techniques are illustrated by a number of attractive examples, followed by a brief discussion of the smartphone's role in telemedicine. The challenges and perspectives of smartphonebased POC diagnostics are also provided.

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. Inspired by daily hand-writing, innovative and ubiquitously available pens can be employed to write conductive patterns on multiple substrates; such a low-cost, fast, and user-friendly direct writing paradigm has recently aroused remarkable research interest as a promising electronics prototyping strategy. In this review, state-of-art advances in techniques for direct writing of electronics are presented, and pros and cons of each fabrication route are discussed. Emerging applications of pen-based writing electronics are also summarized. Based on these, fi nal conclusions, limitations and challenges, as well as ongoing perspectives are illustrated. a polyester-based tattoo-like integrated epidermal electronic system has been developed that can perform real-time muscle movement, heart activities, and brain-wave detection without the engagement of expensive and bulky medical instrumentations, holding promises to empower doctors to timely monitor vital signs of patients in a simple and effi cient way. [ 3 ] For these applications, the ideal electronics should be low-cost, easily accessible, high-performance, rapid prototyping, and user friendly etc. Consequently, increasing attention has been devoted to discovering several factors closely related to fl exible electronics (e.g., substrates, conductive materials, and manufacturing techniques) for fabricating electronics with increased performance and decreased cost. [ 7 ] Among them, the development of fast and cost-effective fabrication strategies has drawn close attentions for realizing lowcost fl exible electronics. [8][9][10] Recently, various techniques have been developed to fabricate fl exible electronics, such as coating, [ 11,12 ] sputtering, [ 13 ] and printing techniques (e.g., gravure printing, [ 14 ] fl exo printing, [ 15 ] offset printing, [ 16 ] inkjet printing, [ 17 ] and screen printing [ 18 ] ). Specifi cally, printing techniques enable rapid prototyping of components and devices with accurate three-dimensional (3D) structures, thus facilitating achievement of functional 3D electronics. [19][20][21] Based on a newly developed embedded 3D printing system, the fabrication of strain and pressure sensors has been demonstrated to be viable within highly stretchable silicon polymer substrates, exhibiting huge potential for the production of fl exible electronics and wearable devices with arbitrary constructs and unique functions. [ 6 ] However, these sophisticated techniques may not live up to the emerging demand of low cost, easy accessibility and rapid prototyping for fl exible electronics fabrication, since the long processing period of coating, the high energy consumption of sputtering, and the inevitable enrollment of expensive professional equipment of printing are all intractable issues that can hardly be overlooked. [ 22,23 ] As an alternative technique and inspired from day-to-day hand writing, various writing instruments, such as brush pen, [ 22,24,25 ] pencil, [26][27][28][29] fountain pen, [ 30,31 ] and ball pen, [32][33][34][35] have been re...

In this work, untreated bovine cortical bones (BCBs) were exposed to a range of heat treatments in order to determine at which temperature the apatite develops an optimum morphology comprising porous nano hydroxyapatite (nanoHAp) crystals. Rectangular specimens (10 mm × 10 mm × 3–5 mm) of BCB were prepared, being excised in normal to longitudinal and transverse directions. Specimens were sintered at up to 900 °C under ambient pressure in order to produce apatites by two steps sintering. The samples were characterized by thermogravimetric analysis, X-ray diffraction (XRD), and scanning electron microscopy (SEM) attached to an energy-dispersive X-ray spectroscopy detector. For the first time, morphology of the HAp particles was predicted by XRD, and it was verified by SEM. The results show that an equiaxed polycrystalline HAp particle with uniform porosity was produced at 900 °C. It indicates that a porous nanoHAp achieved by sintering at 900 °C can be an ideal candidate as an in situ scaffold for load-bearing tissue applications.