Biomedical Engineering Reference
In-Depth Information
as is generally seen, as long as it is limited to this initial period. (It even may be
argued that a rapid initial toxic release of constituents at levels that are able to
kill these bacteria without systemic effects is desirable for most types of
implants, since the introduction of bacteria into the wound during implantation
is unavoidable). As a result, materials which in vivo could perform well may be
seen as unacceptable based on the ISO 10993-5 test.
3. Cell-type specificity. A suboptimal selection of cell type with which to perform
the tests may result in false positive and false negative results. In the standard
ISO 10993-5 guideline, cell lines are used whose sensitivity may differ greatly.
Such variations are not only seen between primary cells and cell lines but also
between cell lines (e.g. after a treatment period of six days 7.5 ppm of Fe
2
O
3
nanoparticles was lethal for MSTO-211H pleural cells, whereas 30 ppm of
these particles was almost ineffective for 3T3-NIH fibroblast cells [
40
].
In order to improve the prognostic value of in vitro tests, on the one hand several
specific in vitro parameters must be analysed and this data should be combined with
the known chemical information and biokinetic data (e.g. [
88
,
115
]), and on the
other hand the cytotoxicity of untreated and washed samples (e.g. after 24 h in
medium or even longer) should be compared. In addition, the in vitro models
should be improved to mimic more precisely the in vivo situation at the site of
implantation.
3 Bioactivity
Early tissue reaction to a biomaterial that does not release cytotoxic components
ranges between normal inflammatory reaction and subsequent wound healing, to
strong foreign body reaction, expressed in prolonged inflammatory reaction,
accumulation of multinucleated macrophages and formation of a thick fibrous
capsule at the tissue implant interface. In normal wound healing, different
sequential phases can be discriminated, starting with (a) stopping bleeding by
producing a temporary blood cloth, followed by (b) an inflammatory phase
characterized by swelling, debridement (removal of debris, foreign bodies and
bacteria mainly by phagocytosis by inflammatory cells), (c) closing the wound
with new tissue (proliferative phase) and finally (d) a remodelling phase (Fig.
5
).
If a foreign body reaction develops against the biomaterial, the inflammatory phase
of the healing process is greatly prolonged. Since the foreign body, i.e. the bio-
material, cannot be removed, the acute inflammation turns into a chronic type of
inflammation characterized by the formation of foreign body giant cells and a thick
fibrotic, generally avascular, capsule around the biomaterial, isolating it from the
host. The capsule is typically not tight around the biomaterial and the void is filled
with wound liquid.
The influences of a biomaterial on cell functionality can be divided into the
general groups of (i) chemical and spatial influences, (ii) mechanical influences,
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