PLGA microspheres are widely studied for controlled release drug delivery applications, and many models have been proposed to describe PLGA degradation and erosion and drug release from the bulk polymer. Autocatalysis is known to have a complex role in the dynamics of PLGA erosion and drug transport and can lead to size-dependent heterogeneities in otherwise uniformly bulk-eroding polymer microspheres. The aim of this review is to highlight mechanistic, mathematical models for drug release from PLGA microspheres that specifically address interactions between phenomena generally attributed to autocatalytic hydrolysis and mass transfer limitation effects. Predictions of drug release profiles by mechanistic models are useful for understanding mechanisms and designing drug release particles.

Trouble at the hive: Neonicotinoid pesticides cause mortality and decline in insect pollinators. One repeatedly noted effect is a reduction in bee colony size. However, the mechanism behind this reduction is unclear. Crall et al. performed complex real-time monitoring of bumblebee behavior within their nests (see the Perspective by Raine). Neonicotinoid exposure reduced nurse and caretaking behaviors, which affected productivity and harmed colony thermoregulation. These changes in behavior acted together to decrease colony viability, even when exposure was nonlethal. Science , this issue p. 683 ; see also p. 643

Diabetic nephropathy, a kidney complication arising from diabetes, is the leading cause of death in diabetic patients. Unabated, the growing epidemic of diabetes is increasing instances of diabetic nephropathy. Although the main causes of diabetic nephropathy have been determined, the mechanisms of their combined effects on cellular and tissue function are not fully established. One of many damages of diabetic nephropathy is the development of fibrosis within the kidneys, termed mesangial expansion. Mesangial expansion is an important structural lesion that is characterized by the aberrant proliferation of mesangial cells and excess production of matrix proteins. Mesangial expansion is involved in the progression of kidney failure in diabetic nephropathy, yet its causes and mechanism of impact on kidney function are not well defined. Here, we review the literature on the causes of mesangial expansion and its impacts on cell and tissue function. We highlight the gaps that still remain and the potential areas where bioengineering studies can bring insight to mesangial expansion in diabetic nephropathy.

Two finite difference discretization schemes for approximating the spatial derivatives in the diffusion equation in spherical coordinates with variable diffusivity are presented and analyzed. The numerical solutions obtained by the discretization schemes are compared for five cases of the functional form for the variable diffusivity: (I) constant diffusivity, (II) temporally-dependent diffusivity, (III) spatially-dependent diffusivity, (IV) concentration-dependent diffusivity, and (V) implicitly-defined, temporally- and spatially-dependent diffusivity. Although the schemes have similar agreement to known analytical or semi-analytical solutions in the first four cases, in the fifth case for the variable diffusivity, one scheme produces a stable, physically reasonable solution, while the other diverges. We recommend the adoption of the more accurate and stable of these finite difference discretization schemes to numerically approximate the spatial derivatives of the diffusion equation in spherical coordinates for any functional form of variable diffusivity, especially cases where the diffusivity is a function of position.

The 2019 novel coronavirus, SARS-CoV-2, is a pathogen of critical significance to international public health. Knowledge of the interplay between molecular-scale virus-receptor interactions, single-cell viral replication, intracellular-scale viral transport, and emergent tissue-scale viral propagation is limited. Moreover, little is known about immune system-virus-tissue interactions and how these can result in low-level (asymptomatic) infections in some cases and acute respiratory distress syndrome (ARDS) in others, particularly with respect to presentation in different age groups or pre-existing inflammatory risk factors. Given the nonlinear interactions within and among each of these processes, multiscale simulation models can shed light on the emergent dynamics that lead to divergent outcomes, identify actionable “choke points” for pharmacologic interventions, screen potential therapies, and identify potential biomarkers that differentiate patient outcomes. Given the complexity of the problem and the acute need for an actionable model to guide therapy discovery and optimization, we introduce and iteratively refine a prototype of a multiscale model of SARS-CoV-2 dynamics in lung tissue. The first prototype model was built and shared internationally as open source code and an online interactive model in under 12 hours, and community domain expertise is driving regular refinements. In a sustained community effort, this consortium is integrating data and expertise across virology, immunology, mathematical biology, quantitative systems physiology, cloud and high performance computing, and other domains to accelerate our response to this critical threat to international health. More broadly, this effort is creating a reusable, modular framework for studying viral replication and immune response in tissues, which can also potentially be adapted to related problems in immunology and immunotherapy.