Testing biomaterials for application in artificial organs: impact of procedures, donor and patient properties.

Many factors can affect the characterisation of biomaterials during testing. These include drugs administered prior to testing and shear stress on blood cells induced by different blood flows and specific blood donor conditions. Some of the misconceptions in testing are described here and serve to indicate that a systems approach, and not only individual test parameters, is best when testing for biocompatibility. "Methodology is everything and the devil is in the details", remarked Paul Simmons, the current president of the International Society for Stemcell Research, in an article in Nature magazine [1]. The article refers to current problems related to the reproducibility of data in stem cell research. Reproducibility in in vitro testing is also mandatory when selecting polymers for medical device applications. Many mechanical and physical engineers are surprised when they realise the enormous standard deviations (sometimes between 50 and 100%) of data found in biological or physiological investigations of biomaterials. The reasons for this are the complexity of physiological parameters such as the nature of blood originating from a variety of donors and hour-to-hour and day-to-day physiological differences. As a consequence, standardisation is a condition sine qua non in biomaterial testing, and knowledge of possible pitfalls is absolutely necessary. Therefore ISO 10993-4, Biological Evaluation of Medical Devices, Selection of Tests for Interaction With Blood, [2] provides a practical tool, including a decision tree for use in the selection of appropriate polymers for biomaterial applications. However, the interested reader finds in Section 3.1 of ISO 10993-4 the definition of blood-device interaction: "Any interaction between blood or any component of blood and a device, resulting in effects on blood, or on any organ or tissue, or on the device". A note added to this definition further clarifies: "Such effects may or may not have clinically significant or undesirable consequences." This prompts one to ask if effects leading to undesirable consequences that are not clinically significant would be helpful to the polymer chemist. This article provides some observations and examples of the misconceptions and pitfalls that exist in testing biomaterials for biocompatibility.