In 1984, low-density polyethylene (LDPE) and polymethylsiloxane (PDMS), two primary reference materials (PRM), were made available by the National Heart, Lung, and Blood Institute (NHLBI) as discriminatory tools for the validation of standardized and novel in vitro and in vivo tests in the evaluation of biomaterials. This article reviews the results and conclusions obtained by several studies investigating the hemocompatibility, in vitro biocompatibility, inflammatory response, and in vivo tissue reactions of these two reference materials. Variable results obtained with LDPE and PDMS in ex vivo hemocompatibility studies were attributed to the type of animal model used, the flow velocity of the circulating blood, the time of exposure, and the methodology used to measure blood cell adhesion or activation at the surface of the materials. In contrast, both the LDPE and PDMS appeared to be suitable reference materials when used in in vitro biocompatibility, inflammatory response, and in vivo studies. However, caution must be taken when interpreting the results, because gamma sterilization of these two materials as well as their origin (for example PDMS) are two critically important factors. In conclusion, we see a definite need for standardized hemocompatible parameters and better high-quality hemocompatibility studies on PRM. This review also suggests other materials as potential PRM candidates, namely, Biomer and Intramedic polyethylene.

Membranes made from 4 commercial poly(carbonate urethanes): Carbothane (CB), Chronoflex (CF), Corethane 80A (CT80), and Corethane 55D (CT55), and from 2 poly(ether urethanes): Tecoflex (TF) and Tecothane (TT) were prepared by solution casting and sterilized by either ethylene oxide (EO) or gamma radiation. Their biocompatibility was evaluated in vitro in terms of proliferation, cell viability, and adhesion characteristics of human umbilical veins (HUVEC), monocytes (THP-1), and skin fibroblasts, and by measuring complement activation through the generation of the C3a complex. Their hemocompatibility was determined by measuring the level of radiolabeled platelet, neutrophil, and fibrin adhesion in an ex vivo arteriovenous circuit study in piglets as well as via an in vitro hemolysis test. The results of this study showed no endothelial cell proliferation on any of the materials. The cell viability study revealed that the CB, CF, and TF membranes sterilized by EO maintained the highest percentage of monocyte viability after 72 h of incubation (>70%) while none of the gamma-sterilized membranes displayed any cell viability. The fibroblast adhesion and C3a generation assays revealed that none of the materials supported any cell adhesion or activated complement, regardless of the sterilization method. The hemolysis test also confirmed that the 4 poly(carbonate urethanes) were hemolytic while none of the poly(ether urethanes) were. Finally, the ex vivo study revealed that significantly more platelets adhered to the CB and CT55 membranes while the levels of neutrophil and fibrin deposition were observed to be similar for all 6 materials. In conclusion, the study identified the CF and TF membranes as having superior biocompatibility and hemocompatibility compared to the other polyurethanes.

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