High-throughput organ-on-chip platform with integrated programmable fluid flow and real-time sensing for complex tissue models in drug development workflows.

Drug development suffers from a lack of predictive and human-relevant in vitro models. Organ-on-chip (OOC) technology provides advanced culture capabilities to generate physiologically appropriate, human-based tissue in vitro, therefore providing a route to a predictive in vitro model. However, OOC technologies are often created at the expense of throughput, industry-standard form factors, and compatibility with state-of-the-art data collection tools. Here we present an OOC platform with advanced culture capabilities supporting a variety of human tissue models including liver, vascular, gastrointestinal, and kidney. The platform has 96 devices per industry standard plate and compatibility with contemporary high-throughput data collection tools. Specifically, we demonstrate programmable flow control over two physiologically relevant flow regimes: perfusion flow that enhances hepatic tissue function and high-shear stress flow that aligns endothelial monolayers. In addition, we integrate electrical sensors, demonstrating quantification of barrier function of primary gut colon tissue in real-time. We utilize optical access to the tissues to directly quantify renal active transport and oxygen consumption via integrated oxygen sensors. Finally, we leverage the compatibility and throughput of the platform to screen all 96 devices using high content screening (HCS) and evaluate gene expression using RNA sequencing (RNA-seq). By combining these capabilities in one platform, physiologically-relevant tissues can be generated and measured, accelerating optimization of an in vitro model, and ultimately increasing predictive accuracy of in vitro drug screening.

Theoretical study on the possible use of SiC microparticles as photothermal agents for the heating of bacteria.

Gold nanoparticles exhibiting surface plasmon resonances have been considered as photothermal agents for the selective destruction of bacteria by visible to near-infrared radiation. Here, we consider theoretically the possible complementary use of sub-micron silicon carbide (SiC) particles as photothermal agents for the heating of bacteria by pulsed mid-infrared (MIR) radiation. A SiC microparticle can exhibit surface phonon resonances in the MIR. Similar to the effect of surface plasmon resonances in gold nanoparticles, this could lead to enhanced absorption at the resonant wavelength and strong heating of the microparticle locally. If the heating is sufficient, this might lead to damage of bacterial cells adjacent to SiC particles. We estimate the heating of sub-micron SiC particles in a water medium under various pulse lengths of radiation at wavelength 10.6 µm. Noting that SiC is being investigated as a biocompatible material that could be functionalized for biomedical applications, and that an appropriately roughened SiC surface could be expected to exhibit similar surface phonon resonances, we speculate that enhanced heating under MIR radiation may be useful for in vitro sterilization of such surfaces.

Fibronectin- and collagen-mimetic ligands regulate bone marrow stromal cell chondrogenesis in three-dimensional hydrogels.

Modification of tissue engineering scaffolds with bioactive molecules is a potential strategy for modulating cell behavior and guiding tissue regeneration. While adhesion to RGD peptides has been shown to inhibit in vitro chondrogenesis, the effects of extracellular matrix (ECM)-mimetic ligands with complex secondary and tertiary structures are unknown. This study aimed to determine whether collagen- and fibronectin-mimetic ligands would retain biologic functionality in three-dimensional (3D) hydrogels, whether different ECM-mimetic ligands differentially influence in vitro chondrogenesis, and if effects of ligands on differentiation depend on soluble biochemical stimuli. A linear RGD peptide, a recombinant fibronectin fragment containing the seven to ten Type III repeats (FnIII7-10) and a triple helical, collagen mimetic peptide with the GFOGER motif were covalently coupled to agarose gels using the sulfo-SANPAH crosslinker, and bone marrow stromal cells (BMSCs) were cultured within the 3D hydrogels. The ligands retained biologic functionality within the agarose gels and promoted density-dependent BMSC spreading. Interactions with all adhesive ligands inhibited stimulation by chondrogenic factors of collagen Type II and aggrecan mRNA levels and deposition of sulfated glycosaminoglycans. In medium containing fetal bovine serum, interactions with the GFOGER peptide enhanced mRNA expression of the osteogenic gene osteocalcin whereas FnIII7-10 inhibited osteocalcin expression. In conclusion, modification of agarose hydrogels with ECM-mimetic ligands can influence the differentiation of BMSCs in a manner that depends strongly on the presence and nature of soluble biochemical stimuli.

Social physique anxiety and disordered eating: what's the connection?

Social physique anxiety (SPA) is highly correlated with other body image measures that have been considered to be important in understanding eating disorders. However, SPA has not been directly studied with respect to eating disorders. Thus, the purpose of this investigation was to examine the link between SPA and measures of eating disorder symptomatology to determine if SPA should be considered as an additional risk factor in the prediction of eating disturbances. One hundred and sixty female undergraduates completed questionnaires measuring body mass index (BMI), social physique anxiety (SPAS), anorexic symptoms (EAT), bulimic symptoms (BULIT-R), depression (CES-D), self-esteem (SES) and obligatory exercise (OEQ). Regression analyses revealed that SPA and depression were the psychological correlates that predicted bulimic symptomatology and that SPA, depression, and obligatory exercise predicted anorexic symptomatology; all variables were positively related to eating disorder symptoms. Overall, the results indicate that social physique anxiety appears to be a useful construct for understanding eating disorder symptoms in female undergraduates.

Psychosocial antecedents of athletic injury: the effects of life stress and social support on female collegiate gymnasts.

The article presents information from two studies of a research program investigating psychosocial antecedents of athletic injury. Study 1 describes the development of the Life Events Survey for Collegiate Athletes (LESCA). The LESCA demonstrated good content validity and provided a stable measure of life stress. The LESCA's validity and the moderating effects of social support were explored in the second study. The LESCA provided a construct-valid measure of life stress and was a better predictor of athletic injury than the Social and Athletic Readjustment Rating Scale. Social support moderated the stress-injury relationship in such a way that LESCA negative life stress accounted for 11% to 22% of injury variances in low-support conditions; LESCA positive life stress accounted for 14% to 20% of injury variances in high-support conditions. Mechanisms underlying the stress-injury relationship and directions for future research are discussed with respect to the model outlined by M. B. Andersen and J. M. Williams in 1988.