A reliable in vitro dynamic test method to evaluate device thrombogenicity is very important for the improvement of the design and safety of blood-contacting medical devices, while reducing the use of animal studies. In this study, a recirculating flow loop system was developed for thrombogenicity testing, using donor sheep blood anticoagulated with Anticoagulant Citrate Dextrose Solution A (ACDA) and used within 24–36 hr postdraw. Immediately before testing, the blood was recalcified and heparinized to a donor-specific target concentration. The heparinization level was based on a static pretest, in which latex tubes were incubated at room temperature for 30 min in blood with a series of heparin concentrations and evaluated for thrombus deposition. For dynamic testing, blood was recirculated at room temperature through a polyvinyl chloride (PVC) tubing loop containing a test material for 1 hr at 200 ml/min using a roller pump. Nine materials were investigated: a negative control (polytetrafluoroethylene [PTFE]), a positive control (latex), and seven commonly used biomaterials including PVC, two silicones with different formulations (Q-Sil and V-Sil), nylon, polyurethane (PU), high-density polyethylene (HDPE), and polyether block amide (PEBAX). The results showed that latex was significantly more thrombogenic than all the other materials (p < 0.05), PVC and Q-Sil exhibited intermediate thrombogenicity with significantly more thrombus surface coverage and thrombus weight than PTFE (p < 0.05), whereas PTFE and the rest of the biomaterials had little to no thrombus deposition. In summary, the test loop system was able to effectively differentiate materials with different thrombogenic potentials.
From the U.S. Food and Drug Administration, Silver Spring, Maryland.
Submitted for consideration April 2018; accepted for publication in revised form January 2019.
Disclosure: The authors have no conflicts of interest to report.
This work was supported financially by funding from the FDA Center for Devices and Radiological Health Critical Path program. This project was also supported in part by an appointment to the Research Participation Program at the FDA, administered by the Oak Ridge Institute for Science and Education through an interagency agreement between the U.S. Department of Energy and FDA.
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Correspondence: Qijin Lu, 10903 New Hampshire Ave, Bldg. 62–2204, Silver Spring, MD 20903-0002. Email: Qijin.Lu@fda.hhs.gov.