Abstract
There is a large gap between conventional 2D cell cultures and inside the body where cells reside in 3D microenvironments that are comprised of a complex set of cellular, chemical, and physical cues and are dynamically fed by blood vessels. This physiological gap raises various challenges in basic cell biology, drug testing, and cellular therapeutics because cells in traditional dish cultures respond very differently than in the body. Recent advances in microsystems technology and tissue engineering have led to the development of organ-on-a-chip microsystems that reconstitute key functional units of organs. By mimicking natural tissue architecture and microenvironmental chemical and physical signals within microfluidic devices, this technology realizes tissue-level functionality in vitro that cannot be recapitulated with conventional culture methods. Since the physiological microenvironments in living systems are mostly microfluidic in nature, microfluidic systems facilitate engineering of cellular microenvironments. Microfluidic systems allow for control of local chemical gradients and dynamic mechanical forces, which play important roles in organ development and function. Organ-on-a-chip technology has great potential to facilitate drug discovery and development, to model human physiology and disease, to model pharmacokinetics and pharmacodynamics, and to replace animal models for efficacy and toxicity testing. Here, I describe current strategies to engineer vascular networks within microfluidic devices and to develop vascularized organ-on-a-chip microsystems. The vascular system is responsible for transporting nutrients and oxygen as well as blood cells and removing waste products, which is essential to maintain cellular viability and function in organs. Current conventional cell culture methods, however, lack the vasculature. For larger cell aggregates or organoids, diffusive transport of nutrients and oxygen is insufficient to support their growth and function. Thus, engineering perfusable vascular networks that can deliver nutrients and blood cells to cell constructs or tissues could be a useful platform to recapitulate cellular microenvironments and tissue-level cell functions. By faithfully recapitulating the complexity of cellular microenvironment including the vasculature in the body, it has been possible to create more reliable in vitro systems to predict responses in humans.
