Biomedical Engineering Reference
In-Depth Information
1.5 EXPERIMENTAL EVALUATION OF BIOCOMPATIBILITY
Any research program of assessment on biomaterials must include a range of
in vitro
and
in vivo
tests, as stated by various standard agencies (for example,
International Organization for Standardization [ISO]). ISO guidelines are also
available and such guidelines are followed to select the tests for the biological
evaluation of materials and medical as well as dental devices. It may be worth-
while to remember the difference between
in vitro
and
in vivo
tests.
In vitro
tests
are lab scale simulated experiments, which are rapid and are a must as initial
screening tests. From the results of the
in vitro
tests, one cannot obtain any infor-
mation of infl ammation and immune response of the materials. Also, most of the
in vitro
experiments use single cell lines, which do not refl ect the actual tissue in-
teraction (involving multiple cell types)
in vivo
. Although the
in vitro
experiments
are inexpensive, such tests do not provide appropriate representation of physio-
logical conditions. These tests, nevertheless, are effective as the fi rst step of
biocompatibility evaluations. On the other hand,
in vivo
experiments produce a
better approximation to the human environment. Here, the material comes in
contact with different cell types and the effect of hormonal factors can be ana-
lyzed. Also,
in vivo
tests provide interactions with extracellular matrix, blood-
borne cells, protein and molecules. These experiments can be regarded as the
second step prior to clinical use.
1.5.1
In Vitro
Tests
In order to harmonize the existing guidelines, ISO has prepared the guideline
document 'Biological testing of Medical Devices—Part 1: Guidance on Selection
of Test' (ISO 10933-1), which incorporates all the national and international doc-
uments. ISO 10993 requirements for long-lasting tissue/bone implants require
various biological tests and the following are the major
in vitro
tests:
•
Cytotoxicity:
This is an
in vitro
test of cell toxicity. The cytotoxicity experi-
ments determine whether the material is toxic in contact with some particu-
lar cell lines. The test is generally done in a laboratory using some standard/
relevant cell lines and the cells are seeded on the materials. As far as the
experimental evaluation of biocompatibility is concerned, the cytotoxicity
tests are widely cited as the primary assessment of biocompatibility and
therefore are discussed in more detail below.
As a fi rst step, the sterilization of the samples is carried out in order to
remove other micro-organisms, if present on the surface. Depending on
type of implant materials (i.e., chemistry and chemical composition), the
sterilization is either carried out in steam autoclave (15 psi, 121 ° C, 20 min-
utes) or using
-ray irradiation. The culture medium used for cell culture
testing is DMEM (Dulbecco's modifi ed Eagles' medium), containing 10%
serum, 1% antibiotic cocktail. The samples are incubated in the culture
γ
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