Schematic representation of oxygen content inside organs. The human body is composed of numerous oxygen gradients and organ-specific microenvironments that require microphysiological systems to study oxygen exchange in a tunable and controllable manner. The brain contains neurons, astrocytes, and pericytes situated above and within the basal lamina. Oxygen crosses the endothelium to reach brain cells via the capillary lumen. A tumor creates new vasculature as it grows (neoangiogenesis), while the core of the tumor continues to become more hypoxic. The lung receives oxygen in air, which then binds to hemoglobin molecules after crossing through the epithelium and interstitial space. For the liver, oxygen rich blood travels from the portal vein toward the central vein, providing nutrients to sinusoidal endothelial cells, stellate cells in the perisinusoidal space, and hepatocytes. The kidney contains oxygen gradients within each renal medulla and from the inner papilla to the renal cortex. The intestine has a steep oxygen gradient from the microvasculature underneath the crypt-villus axis to the bacteria populated lumen. The skin is an oxygen barrier with the epidermis at very low oxygen. The heart contains numerous levels of oxygen as oxygen-poor blood flows into the vena cava and oxygen-rich blood exits via the aorta.