A Microfluidic Model of Ischemia/Reperfusion Injury Arterial

Background: Cardiovascular diseases are the most common cause of mortality in the Western world. Ischemia is associated with a variety of cardiovascular diseases. Although restoring blood flow is critical to prevent cellular damage, rapid reperfusion increases tissue damage, even in tissues that were not affected by the ischemia. A variety of animal models have been developed to investigate Ischemia/Reperfusion (IR) injury. However, they are often expensive and do not mimic well human physiology, additionally, there is an ethical problem with animal experiments. We propose to develop a microfluidic cell culture device that offers an alternative in vitro system for recapitulating certain features of human IR injury.

Methods: Microfluidic device were prepared from polydimethylsiloxane via replica molding based on a 3D printed mold. The channels were precoated with fibronectin and then Human Umbilical Vein Endothelial cells were cultured in them. Fibrin clots were fabricated by using a water-in-oil emulsion of a fibrinogen solution mixed with thrombin. Two hours after cell seeding clots were injected into the channel to create an emboli obstructed channel. We then dissolved the emboli via using tissue plasminogen activator (tPA). Cells morphology and inflammation factor were monitored after 5 hours post restoration of flow.

Results: We were able to grow HUVEC inside microfluidic channel and replicate a fibrin clot obstruction of flow. Altogether, a method which replicates embolism and clot lysis on a chip that contains live endothelial cells was developed.

Conclusion: By proper design, microfluidic models can be developed that can replicate important feature of IR.