Minimal functional model of hemostasis in a biomimetic microfluidic system.

Biology is functional, and this function both inspires and puzzles. Inspiration from biology has led to the development of biomimetic systems—artificial systems that function by mimicking biology. Biomimetic systems have been successfully created in self-assembly, 2] materials, chemical synthesis, and surface chemistry. They often provide insight into the puzzles of biology, because to develop a biomimetic system, models of biology must be created and tested. In this paper we show how this approach can be extended to a dynamic, nonequilibrium chemical system. We describe a minimal model of hemostasis, then show how this model may be implemented with chemical reactions and used to create a functional microfluidic system that is capable of repairing itself by mimicking hemostasis. Hemostasis is a complex functional system that consists of approximately 80 coupled biochemical reactions that involve both soluble proteins and platelets. It is responsible for repairing damaged blood vessels and preventing excessive bleeding. It maintains blood in a fluid, clot-free state under normal conditions, but creates a localized solid clot in response to vascular damage. The complexity of hemostasis is associated with a finely tuned self-regulation, essential for its function. This self-regulation is believed to be the basis of two essential features of healthy hemostasis: 1) Hemostasis shows a threshold response. There is no response to small regions of internal vascular damage present throughout the circulatory system, but full response to substantial damage of a blood vessel; 2) hemostasis acts locally. A clot formed in the region of substantial damage is confined to that region. These two features are responsible for preventing excessive clotting that obstructs the blood flow and is associated with lifethreatening conditions such as deep-vein thrombosis. Self-regulation in hemostasis is thought to be the direct result of a delicate balance between the initiation and inhibition modules; the flow of blood is essential to achieving this balance. The network of interacting reactions in hemostasis is difficult to model; this difficulty is inherent to complex reaction networks. 12] The interactions between reactions and the role of fluid flow are difficult to model by