Biomedical Engineering Reference
In-Depth Information
is differentiated into three time periods: (i) \24 h, intra-operative contact, (ii) 24 h
to 30 days, defined as short term implantation, and (iii) [30 days, which is called
permanent or chronic implantation.
The classification of the end-use of a medical device product requires a more
distinct approach. The first class is called external devices, and includes wound
dressings, monitors, and splints. Here, intact and injured (breached) body surfaces
are distinguished. The ISO standard suggests the addition of a third subclass, i.e. for
devices coming in contact with mucous membranes. The second class is termed
externally communicating devices, which include any devices that are applied and
inserted via natural channels or trans-cutaneously. Examples include contact lenses,
tracheal tubes, all types of catheters and hypodermic needles. While ISO 10993-1
differentiates only between indirect blood path, tissue/bone/dentin, and circulating
blood, ASTM F748 makes a more pronounced differentiation between devices
communicating with intact natural channels, communicating with body tissues and
fluids, indirect blood path, and direct blood path. The third and last class is
implantable devices. Again, ASTM and ISO standards diverge in their subcatego-
rization. ISO has tissue/bone and blood as subcategories while ASTM differentiates
between their contacting tissues, especially ''devices principally contacting
bones, devices principally residing in the subcutaneous space, devices principally
contacting soft tissue and tissue fluids, and devices principally contacting blood''.
All the standards require specific tests to be performed, dependent on the classi-
fication, subcategories and contact duration. The cytotoxicity, sensibilization and
irritation/intracutaneous reactivity tests are required and common to all products and
materials. Additional requirements depend on the subcategories and contact duration.
Details should be sought in the respective ISO 10993-1 or ASTM F748 standards
since requirements may change over time. It is important to realize that standards are
not irrevocable documents, but undergo revisions and changes that allowing for
incorporation of new insights or novel techniques. The committee F04 on Medical and
Surgical Materials and Devices of ASTM international actively follows the needs of
industry for new and refined standard test methods and guides; in particular, the
subcommittees F04.42/43/44/46 on different aspects of Tissue Engineered Medical
Products and F04.16 on biocompatibility are very active and consolidate very recent
findings (see for details see [
5
]). In all the discussion on biocompatibility one has to
keep in mind that it is just a rated definition without hard limits.
2 Cytotoxicity
2.1 Factors Influencing Toxicity
The appearance of cellular responses (summarized in Fig.
1
) depends on the kind
of compound and its concentration, and can be classified as toxic, cytoeffective,
and no visible effects. Each of the responses can be assessed in vitro by a specific
test regimen and evaluating the corresponding key parameter(s). The varieties of
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