Use of simple and complex in vitro models for multiparameter characterization of human blood-material/device interactions

Abstract

Medical devices, intended for blood contacting applications, undergo extensive in vitro testing followed by animal and clinical feasibility studies. Besides the use of materials known to be intrinsically blood-compatible, the surface of such devices is often modified with a coating in order to improve the performance characteristics during blood exposure. In vitro evaluation of blood-device interactions accompanies the product development cycle from the early design phase using basic material geometries until final finished-product testing. Specific test strategies can vary significantly depending on the end application, the particular study objectives and variables of interest, and cost. To examine the degree to which findings derived from two different in vitro approaches complement one another, this report contrasts findings from a simple multipass loop model with findings from a simulated cardiopulmonary bypass (CPB) model. The loop model consists of tubular test materials, with and without surface modification, formed into valved Chandler loops. The CPB model has an oxygenator with and without surface modification connected to a reservoir and a blood pump. The surface modifications studied in this report are the Carmeda® BioActive Surface and Duraflo® II heparin coatings. Common blood parameters in the categories of coagulation, platelets, hematology, and immunology were monitored in each model. Ideal models employ the optimal level of complexity to study the design variables of interest and to meet practical cost considerations. In the case of medical device design studies, such models should also be predictive of performance. In the more complex and realistic simulated CPB model, experimental design and cost factors prevented easy/optimum manipulation of critical variables such as blood donor (use of paired samples) and heparin level. Testing in the simpler loop model, on the other hand, readily offered manipulation of these variables, and produced findings which overlapped with observations from the more complex CPB model. Thus, the models described here complimented one another. Moreover, conclusions from consistent findings, such as favorable responses associated with the heparin coatings, between the two models were considered to be more robust.