Abstract
According to ISO 10993-4, shear-dependent processes must be considered in the blood compatibility testing of cardiovascular implants, which demands controlled and physiological flow conditions in the test environment. For very small test objects such as coronary stents with a diameter below 5 mm, this is difficult to achieve, as previous test methods are either unable to represent the required flow velocities in small-lumen sample chambers, or can only do so under high pump shear stress, which in extreme cases can mask the effects of the tiny test objects. In this paper, we present a novel concept for dynamic in vitro models based on pneumatically generated blood flow (AirDrive technology), which can achieve flow rates and velocities up to 450 ml min(-1) or 930 mm s(-1), respectively. This allows for hemocompatibility testing of coronary stents under physiologically high flow rates without generating major shear stress from the pump mechanism. In an initial feasibility study, single coronary stents with different surface finishes (polished/unpolished) were subjected to flow velocities of up to 560 mm s(-1) in a 3.2 mm diameter sample chamber. Blood samples were collected before and after perfusion, and haematological and coagulation markers were analysed. Unpolished stents elicited higher shear-induced blood responses than polished stents. This demonstrates that our experimental setup is highly sensitive and enables precise and robust investigation of blood compatibility under physiologically relevant flow conditions, even for the smallest objects under investigation. To show the superiority of this novel model in creating high flow rates while maintaining minimal blood damage, the AirDrive system was compared to the commonly used roller pump closed-loop system, with the former exhibiting significantly less blood damage. This further confirms that the AirDrive technology we present in this paper is of the highest value for developmental or regulatory testing of blood compatibility of small- and medium-sized test objects.