Design and in silico validation of a human body on a chip for toxicity assessment of drugs to prevent graft-versus-host disease

Toxicity assessment of novel drugs requires the development of models that provide information about the behavior of the cells and the drugs. Current cytotoxicity assays rely on data generated in vitro under static conditions, different from the conditions in the human body, where everything is dynamic and connected. Here we designed a body-on-a-chip and validated its utility to provide in silico information to better design in vitro cytotoxicity assays under dynamic conditions. We focus on cellular and structural features of the integrated main organs affected by systemic toxicity (heart, liver and kidneys), assuming passive mixer conditions for drug-blood interactions using the physicochemical characteristics of a model immuno-modulating drug such as sirolimus or rapamycin. Velocity, pressure and concentration fields were characterized to calculate the values of shear stress, vortex formation and mixing degree.Clinical Relevance — Chronic diseases are highly prevalent in our society and predicted to become the main burden within the next decade. The most long-term successful treatment for most of them is transplantation of the affected organ. However, the risk of developing graft-versus-host disease is still a limitation for this therapeutic approach despite the availability of drugs to modulate the immune system to tolerate the donor’s presence. Therefore, the toxicity assessment of novel immune drugs for organs of interest is a high priority.