Biomedical Engineering Reference
In-Depth Information
1 Introduction
Cell culture test conditions are comparatively quick, well defined and reproducible.
Cell morphology and number can be used to evaluate cell compatibility of the mate-
rial surface [
1
-
3
]. However, in vitro results cannot reliably be extrapolated to the in
vivo situation. An important difference is for example, the presence of the immune
system in vivo. Therefore, it is essential to test novel implant materials in vivo before
clinical applications can be envisioned. This includes the evaluation of the tissue
compatibility of the materials per se, the processing and surface structures and more
recently, potential coatings that may be used for drug release purposes to improve
the implant performance [
4
]. Mainly, such tests characterize the effects on the tis-
sue surrounding the implant and the potential to induce immune reactions. For the
detailed analysis of the tissue response to novel implant materials, histology can be
used. Simple staining procedures can be used to visualize tissue damage, identify
immune cells and the extent of granulation tissue is an indication for the degree of
inflammation. Subsequently, the progress of the wound-healing reaction and the for-
mation of fibrous capsule around implants can be evaluated. Staining with antibodies
can be used for the highly specific detection of cells, including their differentiation
and activation status. The major disadvantage of histological analysis is that solely
a single predetermined time point can be analyzed for each implant and each ani-
mal. Alternatively, gene expression analysis has become a routine tool for obtaining
detailed information about molecular events of the implant tissue interaction. This
may serve to identify specific biological mechanisms and find ways to enhance this
interaction or to improve the healing process. On the other hand, gene expression
analysis generally gives only an average summary over processes in the tissue from
many diverse cell types and complex interactions that take place between them. Gene
expression analysis is an intensive method and similar to histological analysis, al-
lows a single time point per implant or per animal [
5
].These methods preclude the
monitoring of tissue responses to individual implants over time. Alternatively, in vivo
imaging can be used advantageously to quantify and monitor tissue responses over an
extended period of time in individual animals [
6
-
12
]. In this study, various clinically
established implant materials were used for comparison. As biocompatible standard
materials titanium and glass-ceramic implants were used. These are clinically used
as dental, orthopedic or middle ear implants respectively [
13
-
16
]. In addition, inac-
tivated bacteria were used as highly inflammatory and immune-stimulatory agents
that could reflect implant infections.
As soon as an implant material comes into contact with body liquids such as
blood or interstitial fluid, proteins are adsorbed on the implant surface [
17
]. It is
however not clear to what extend this protein layer affects the subsequent interac-
tions. In addition, inflammatory molecules are released by stressed or damaged cells
and by reactions taking place during blood coagulation [
18
]. These molecules form
a concentration gradient that recruits inflammatory cells from the blood circulation.
In response, endothelial cells that line nearby blood vessels express adhesion mole-
cules on the cell surface that allow the adhesion of circulating granulocytes and
