In Vitro models for thrombogenicity testing of blood-recirculating medical devices.

INTRODUCTION: Blood-recirculating medical devices, such as mechanical circulatory support (MCS), extracorporeal membrane oxygenators (ECMO), and hemodialyzers, are commonly used to treat or improve quality of life in patients with cardiac, pulmonary, and renal failure, respectively. As part of their regulatory approval, guidelines for thrombosis evaluation in pre-clinical development have been established. In vitro testing evaluates a device's potential to produce thrombosis markers in static and dynamic flow loops. AREAS COVERED: This review focuses on in vitro static and dynamic models to assess thrombosis in blood-recirculating medical devices. A summary of key devices is followed by a review of molecular markers of contact activation. Current thrombosis testing guidance documents, ISO 10993-4, ASTM F-2888, and F-2382 will be discussed, followed by analysis of their application to in vitro testing models. EXPERT OPINION: In general, researchers have favored in vivo models to thoroughly evaluate thrombosis, limiting in vitro evaluation to hemolysis. In vitro studies are not standardized and it is often difficult to compare studies on similar devices. As blood-recirculating devices have advanced to include wearable and implantable artificial organs, expanded guidelines standardizing in vitro testing are needed to identify the thrombotic potential without excessive use of in vivo resources during pre-clinical development.