Microsystems Models of Pathophysiology

In this chapter, we focus on the use of microsystems to study disease pathology. There is an urgent need for new model systems, both to elucidate disease mechanisms and to develop new therapies, but existing model systems for many diseases still lack the ability to recapitulate critical disease processes or the ability to quantify those processes. Microsystems have the unique ability to replicate the length scales and transport properties that are observed in vivo and thus provide the opportunity to recapitulate many of the critical cell-cell and cell-microenvironment interactions that are crucial in health and disease. Moreover, microsystems provide the ability to directly control these cellular interactions and to perturb them in real time while allowing high spatiotemporal resolution imaging of pathogenesis. For these reasons, this field is exploding with model systems being developed for an enormous range of diseases. Here, we address the problem of developing microsystems models of disease from the perspective of the biological and physiological challenges to studying some specific pathologies, and we discuss how microsystems have been used to address those challenges. After a brief introduction, the chapter is divided into four sections. In the first section, we discuss vascular and hematologic pathologies, including thrombosis, sickle cell disease, malaria, and atherosclerosis. Next, we move on to pathologies of various organs, including the lungs, the kidneys, the liver, and the brain. In the third section, we discuss the challenges of developing "tumor-in-a dish" models that allow us to study tumorigenesis and metastasis. Finally, we conclude with some thoughts on what the field has accomplished thus far, where the major challenges still lie in the development of microsystems models of pathology, and what are some of the opportunities for the future of this field.