Biomedical Engineering Reference
In-Depth Information
Ongoing investigations aim to explain the negative effect of the hydroxyapatite
carrier on cartilage formation. For calcium phosphate ceramics in cell culture
media, several processes with effects on cell behavior can occur, like dissolution
from the ceramic, precipitation from the solution onto the ceramic and diffusion
into the ceramic or ion exchange at the ceramic-tissue interface [ 41 ]. To inves-
tigate if the material itself or some dissolution products of hydroxyapatite into cell
culture media cause this negative influence on tissue formation, cartilage without a
carrier was cultivated next to a carrier (Figs. 3 , 4 , notation:with carrier). No
significant effects could be observed between cultivation of cartilage cultivated
without and next to a carrier in the cell culture liquid, which is expected as
hydroxyapatite is known to have a low dissolution rate [ 42 ]. However, the pos-
sibility cannot be ruled out that high local concentrations of dissolution products or
a change in the pH near the tissue-biomaterial interface affect cartilage formation
when cultivated on top of the carrier.
Although no influence of dissolution products of hydroxyapatite in the culture
media could be observed in this study, surface properties of the carrier may still affect
cell reactions. Curran et al. [ 43 ] found that -NH 2 and -SH modified surfaces promote
osteogenesis of mesenchymal stem cells, that -OH and -COOH modified surfaces
support chondrogenesis and that mesenchymal stem cells grown on -CH 3 surfaces
maintained their phenotype. These surface groups were found to modulate focal
adhesion assembly, particularly selective integrin binding, and thereby regulate
cellular response [ 44 ]. As expected for hydroxyapatite, determination of surface
groups of the Sponceram HA carrier by Fourier transform infrared spectroscopy
(FTIR spectroscopy) showed, besides PO 4 , predominantly OH functional groups.
In addition, hydroxyl groups are hydrophilic and this facilitates wetting of the bio-
material with cell culture liquid and initial adherence of cells. Altogether, regarding
chemical properties, it is assumed that the hydroxyapatite material of the carriers
Sponceram HA has no harmful effect during the formation of in vitro cartilage and
that no disturbing impurities affect cartilage development.
When examining the influence of substrate properties on cartilage formation,
further parameters should be kept in mind, such as the surface topography. This is
discussed in the next section. In parallel to the chemical aspect of surface groups,
an enhanced surface energy can be measured for surfaces modified with hydroxyl
groups compared to the other functional groups mentioned [ 43 ]. Again, high
surface energy indicates advanced adhesion strength of cells [ 28 ]. Furthermore,
surface charge may be an additional factor which induces cell attachment and
differentiation [ 13 , 45 ]. It is assumed that negative charges which occur due to
COOH groups interact strongly with serum proteins, but that OH groups offer a
rather neutral surface charge. Surface charges may alter the membrane potential of
cells and with it cause signaling inside the cell [ 13 ]. In addition, certain
mechanical parameters of the biomaterial such as the elastic modulus support cell
differentiation via focal adhesion complexes which act as mechano-transducers at
the cellular level [ 15 , 46 - 48 ]. With nanoindentation measurements, a Young's
modulus of 1.7 ± 0.4 GPa for the Sponceram HA carrier was measured, which on
comparison to the Young's modulus for bovine native cartilage of 0.08-2.1 MPa
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