Obstacles in Haemocompatibility Testing

Abstract

ISO 10993-4 is an international standard describing the methods of testing of medical devices for interactions with blood for regulatory purpose. The complexity of blood responses to biomaterial surfaces and the variability of blood functions in different individuals and species pose difficulties in standardisation. Moreover, in vivo or in vitro testing, as well as the clinical relevance of certain findings, is still matter of debate. This review deals with the major remaining problems, including a brief explanation of surface interactions with blood, the current ISO 10993 requirements for testing, and the role of in vitro test models. The literature is reviewed on anticoagulation, shear rate, blood-air interfaces, incubation time, and the importance of evaluation of the surface area after blood contact. Two test categories deserve further attention: complement and platelet function, including the effects on platelets from adhesion proteins, venipuncture, and animal derived- blood. The material properties, hydrophilicity, and roughness, as well as reference materials, are discussed. Finally this review calls for completing the acceptance criteria in the ISO standard based on a panel of test results.

Are there sufficient standards for the in vitro hemocompatibility testing of biomaterials?

“…Unsolved concerns are also the lacking standards for anticoagulation or reference materials. Thus, variations between studies hardly enable a classification of hemocompatible and nonhemocompatible materials [51].…”

“…Unfortunately, these materials are not frequently used, in part not commercially available and may also not represent current state-of-theart technology. As a consequence, a variety of references aside of the recommended materials (filler free polydimethylsiloxan, low density polyethylene, polyvinylchloride, polyurethane, cellulose and expanded polytetrafluorethylen) have been applied in recent studies [51,100,101].…”

“…Alternatively, acceptance criteria can be applied with comparison to a predicate type material. The criteria can be expressed as percentage of baseline and should, at least, include hemolysis, thrombosis (platelet covered surface area), platelet retention/count as well as coagulation time [51].…”

6-Deoxy-6-aminoethyleneamino cellulose: synthesis and study of hemocompatibility

“…Therefore, hemocompatibility evaluation of amino cellulose is an indispensable prerequisite for their biomedical application. [10][11][12][13] Complexity of blood and cell interaction with biomaterials resulted in establishment of different in vivo and in vitro test models. In this study, several aspects of primary and secondary hemostasis were taken into consideration and effects on respective markers assayed in vitro.…”

A critical review of cell culture strategies for modelling intracortical brain implant material reactions

“…The most relevant studies using whole blood or blood plasma utilize human blood samples, although in some instances non-human derived blood is used [107]. In this latter scenario applicability to human implants is limited due to the complex nature and species specificity of immune responses (see Braune et al [110], and van Oeveren [111] for more details on specific immunity).…”