Evaluation of Biocompatibility Using In Vitro Methods: Interpretation and Limitations - Tissue Engineering: Cell-Surface Interactions for Tissue Culture - page 119

1.1 Standards for Biocompatibility Testing of Biomaterials
The market for medical devices and therapies is large and steadily growing. The
global market for medical products and hospital supplies is over $220 billion [ 55 ].
Within this, the market for tissue engineering and cell therapy products is set to
grow from a respectable $8.3 billion in 2010 to nearly $32 billion by 2018 [ 52 ].
The global market for minimally invasive devices and instruments was worth
$14.8 billion in 2008, and could reach $23.0 billion in 2014 [ 14 ]. Orthopaedics is
one of the largest segments of the medical device sector. The global orthopaedic
instrumentation market is projected to surpass US $47 billion by the year 2015,
driven by an aging global population, the rising incidence of age-related conditions
such as osteoarthritis and sports-related injuries, and improving orthopaedic sur-
gical procedures [ 141 ]. As a result, industry is strongly motivated to take part in
the global competition and to enter this market or increase their share with new
products and solutions which are heavily advertised by companies as the best on
the market. In order to prevent fraud and negative consequences for the patients,
federal agencies and notified bodies (NBs) survey the medical devices market and
assess the performance of each device.
One premise of these products is that they have to fulfil criteria such as bio-
compatibility, and its assessment according to standard test methods has been one
objective approach by which the NBs evaluate these products. These standards test
methods have been included as an instrument by federal agencies and NBs to be
able to assess the performance of each device and to prevent fraud and negative
consequences to the patients from new medical devices entering the market. In the
early 1980s the standards organization American Standards and Test Methods
international (ASTM international) developed the first standards for testing
cytotoxicity and skin irritation based on industrial needs and the demand of NBs
[ 6 , 7 , 9 ]. The catalogue of standard tests was slowly broadened and the umbrella
document F748 defining the requirements of biocompatibility testing was issued
[ 8 ]. These documents were adopted by the International Organization for Stan-
dards (ISO) which issued their first standard on biocompatibility series ISO 10993-
1[ 70 ]. Ever since, many new standards on biocompatibility have been issued and
revised by several organizations (see Table 1 ). Today, each new material that is
considered for use in medical devices has to pass a whole battery of standard tests
before it can be used in a product and put onto the market. As discussed above,
biocompatibility depends largely on the end-use application. Therefore, the stan-
dards differentiate and classify not the material itself but the end-use applications.
Typically, the material-tissue interaction is addressed regarding duration of con-
tact and end-use, i.e. contacting tissue type. In addition, the ratio of contact area to
host size may also matter and might have to be considered. At this point it is
important to point out that the test outcome should be an intrinsic property of the
material. This means that if a material of a given quality is tested for biocom-
patibility, taking the same exposure time and with the same material contact area
to host ratio, the same result should always be obtained—independent of the