Multi-assay assessment of cytotoxicity reveals multiple mechanisms of action in 3D microtissues.

Cell viability assays are an integral component of toxicology and high-throughput drug screening studies; however, many assays rely on a single biomarker of cell death which provides an incomplete assessment of cell viability. Here, we introduce an innovative approach that combines data from multiple assays using a linear mixed effects regression model and principal component analysis. We explored the cytotoxic response of various assay-treatment combinations using four assays with distinct mechanisms of action and seven different treatments across three types of microtissue cultures.

Polarization in Raman spectroscopy helps explain bone brittleness in genetic mouse models.

Raman spectroscopy (RS) has been extensively used to characterize bone composition. However, the link between bone biomechanics and RS measures is not well established. Here, we leveraged the sensitivity of RS polarization to organization, thereby assessing whether RS can explain differences in bone toughness in genetic mouse models for which traditional RS peak ratios are not informative.

Partial removal of pore and loosely bound water by low-energy drying decreases cortical bone toughness in young and old donors.

With an ability to quantify matrix-bound and pore water in bone, (1)H nuclear magnetic resonance (NMR) relaxometry can potentially be implemented in clinical imaging to assess the fracture resistance of bone in a way that is independent of current X-ray techniques, which assess bone mineral density as a correlate of bone strength. Working towards that goal, we quantified the effect of partial dehydration in air on the mechanical and NMR properties of human cortical bone in order to understand whether NMR is sensitive to water-bone interactions at low energy and whether such interactions contribute to the age-related difference in the toughness of bone. Cadaveric femurs were collected from male and female donors falling into two age groups: 21-60 years of age (young) and 74-99 years of age (old).