Large scale 3-D phase-field simulation of coarsening in Ni-base superalloys

In this study we present a large scale numerical simulation of γ-γ′ microstructure evolution in Ni-base superalloy using the multi-phase field method in three dimensions. We numerically simulated precipitation hardening heat treatment cycles. Large scale three dimensional simulations are necessary in order to get sufficient statistics for predicting the morphological evolution, average γ′ precipitate size, precipitates size distribution over time and ripening exponent for a given temperature and composition. A detailed analysis of obtained result is presented emphasising the effect of elastic interaction on the coarsening kinetics in Ni-base superalloy. The study is performed using the phase-field modelling library “OpenPhase” which is based on a multi-phase field multi-component model

How multi-organ microdevices can help foster drug development

Multi-organ microdevices can mimic tissue-tissue interactions that occur as a result of metabolite travel from one tissue to other tissues in vitro. These systems are capable of simulating human metabolism, including the conversion of a pro-drug to its effective metabolite as well as its subsequent therapeutic actions and toxic side effects. Since tissue-tissue interactions in the human body can play a significant role in determining the success of new pharmaceuticals, the development and use of multi-organ microdevices presents an opportunity to improve the drug development process. The goals are to predict potential toxic side effects with higher accuracy before a drug enters the expensive phase of clinical trials as well as to estimate efficacy and dose response. Multi-organ microdevices also have the potential to aid in the development of new therapeutic strategies by providing a platform for testing in the context of human metabolism (as opposed to animal models). Further, when operated with human biopsy samples, the devices could be a gateway for the development of individualized medicine. Here we review studies in which multi-organ microdevices have been developed and used in a ways that demonstrate how the devices’ capabilities can present unique opportunities for the study of drug action. We also discuss the challenges that are inherent in the development of multi-organ microdevices. Among these are how to design the devices, and how to create devices that mimic the human metabolism with high authenticity. Since single organ devices are testing platforms for tissues that can later be combined with other tissues within multi-organ devices, we will also mention single organ devices where appropriate in the discussion

Mimicking Human Pathophysiology in Organ-on-Chip Devices

WOS: 000446973500007Convergence of life sciences, engineering, and basic sciences has opened new horizons for biologically inspired innovations, and a considerable number of organ-on-a-chip platforms have been developed for mimicking physiological systems of biological organs such as the brain, heart, lung, kidney, liver, and gut. Various biophysicochemical factors can also be introduced into such organ-on-a-chip platforms to study metabolic and systemic effects spanning from drug toxicity to different pathologic manifestations. There is also a pressing need to develop better disease models for common pathologies using variations of these platforms. This can be achieved by recapitulating the unique microenvironment of a disease to investigate the cause and development of abnormal conditions as well as the structural and functional changes resulting from such a pathology. In this review, the organ-on-a-chip platforms that have been developed to model different pathologies of neurodegenerative, cardiovascular, respiratory, hepatic, and digestive systems, along with cancer are summarized. Although the field is still in its infancy, it is anticipated that developing disease model-on-a-chip platforms will likely be a valuable addition to the field of disease modeling, pathology studies, and improved drug discovery.National Cancer Institute of the National Institutes of Health Pathway to Independence Award [K99CA201603]; Lush Prize; New England Anti-Vivisection Society (NEAVS); Mayo Clinic Professorship; NIHUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USA [R43CA221490, R01CA200399, R01CA183827, R01CA195503, R01CA216855]; Swiss National Science FoundationSwiss National Science Foundation (SNSF); FRQS postdoctoral fellowship (Quebec, Canada); NEAVS; American Fund for Alternatives to Animal Research (AFAAR)O.Y.-C. and S.H. contributed equally to this work. Y.S.Z. gratefully acknowledges funding from the National Cancer Institute of the National Institutes of Health Pathway to Independence Award (K99CA201603), the Lush Prize, and the New England Anti-Vivisection Society (NEAVS). A.Q.H. was supported by the Mayo Clinic Professorship and a Clinician Investigator award as well as the NIH (R43CA221490, R01CA200399, R01CA183827, R01CA195503, R01CA216855). S.H. acknowledges funding from the Swiss National Science Foundation. A.K.M. acknowledges FRQS postdoctoral fellowship (Quebec, Canada). S.M. acknowledges the NEAVS and the American Fund for Alternatives to Animal Research (AFAAR) for Postdoctoral Fellowship