Biomedical Engineering Reference
In-Depth Information
ponents. The reason is that in vitro apparatus has an advantage as it allows the
user to control parameters such as time and temperature in a laboratory
environment. There are standardizations such as ASTM, BSI and ISO related to
in vitro cell culture cytotoxicity assays (Winn et al., 2006).
ISO 10993, Biological Evaluation of Medical Device ± Part 5: Test for in
vitro Toxicity, has been reviewed for a systematic look at the in vitro assess-
ment. The test is to be assessed with one or more of three tests, namely the
extract test, direct contact test and indirect contact test which is decided based
on the nature of part, potential portion of use and nature of use (ISO, 2009). Both
direct and indirect contact methods should be applied for adequate evaluation of
cell response because indirect contact methods pose the risk of providing results
that lead to misjudging the cytotoxicity test for implant material. Different
results of cytotoxicity from direct and indirect methods have been reported for
the same implant biomaterial (Muller, 2008).
Subsequently, these will lead to the preparation of the material and the cell
culture, and the manner of their interaction. Primarily, it is inevitable that two
parts of ISO 10993, Part 1: Evaluation and testing within a risk management
system (ISO, 2003) and Part 12: Sample preparation and reference material
(ISO, 2007), are to be carried out before implementation of Part 5. ISO 10993,
Part 5 is investigated after certain duration of the test and the results in toxicity
determination can be accordingly explored in four sections, i.e. cell morphology
damage, cell damage, cell growth and specific aspect of cellular metabolism.
ISO 10993 Part 12 is for the preparation of samples and selection of reference
material for medical device testing in accordance with one or more parts of the
ISO 10993 series (ISO, 2007).
ISO 10993 Part 4: Selection of tests for interaction with blood (ISO, 2002)
also offers advantages as the test can be conducted in the early development
phase of biomaterials. Part 4 investigates biomaterials in terms of their inter-
action with blood and its effects on the blood/tissue/organ or device. ISO 10993-
4 (ISO, 2002) provides a list of blood-circulating medical devices and the tests
(i.e. thrombosis, coagulation, platelets, haematology and complement system)
accordingly. The choice of one or more of these tests depends upon the system
conditions such as duration of blood±device contact, temperature, sterility, flow
conditions and the device characteristics in contact with blood as categorized in
ISO 10993-1 (ISO, 2003) (i.e. non-contact, external connecting and implant
devices).
Haemocompatibility tests can be applied to a single component of a device
for screening purposes. However, as mentioned before, it cannot provide
sufficient information of haemocompatibility of the complete device. Another
area of caution is the type of blood being used for the tests. The standard
suggests that human blood differs among individuals. If it is not absolutely
necessary, species of animal blood should be investigated according to ISO
10993-2.
