Biomedical Engineering Reference
In-Depth Information
Besides nHA composite materials, nHA-coated scaffolds have also been
studied. nHA coated onto collagen beads did not alter the proliferation
of MG63 cells but increased ALP activity and expression of osteocalcin (a
component of the ECM) compared with noncoated collagen beads. Thus,
nHA seemed to switch the MG63 cells from the proliferation stage to the
differentiation stage.
6
Other studies, comparing nHA coatings with conven-
tional microsized HA coatings, showed an increased osteoblast adhesion.
The underlying mechanism was supposed to be an increase in specific pro-
tein absorption, thus increasing osteoblast adhesion.
8,9
However, a study
contradicting these positive findings on nHA was reported by Zhu et al.
111
who observed that cell attachment and spreading was decreased when
smooth titanium implants were coated with nHA compared with noncoated
implants. In addition to the Zhu study, Ostim was also shown to have a nega-
tive effect on cells
in vitro
, as primary osteoblasts were not able to grow on
the material. This, however, was hypothesized to be primarily due to the
high amount of free water in the product and not to the presence of nHA.
112
Although there is no complete uniformity between all studies, the data show
that in an
in vitro
situation, the addition of nHA into, or onto, bone tissue engi-
neering constructs, mostly provides the construct with an increased cytocom-
patibility, as confirmed by increased adhesion and differentiation of the cells.
4.4.1.2
In Vivo
Studies on Nanohydroxyapatite
In an
in vivo
situation, nHA was reported to improve the performance of
bone tissue engineering constructs as well. PA/nHA constructs, produced
by Wang et al.
29
showed adequate bone ingrowth in rabbit mandibles, with
a bone density almost equal to the host bone. Enriching the construct with
rabbit mesenchymal cells before implantation resulted in even more and
earlier bone formation. The commercial product Ostim also proved to be
biocompatible in most
in vivo
studies, in contrast to disappointing results
from
in vitro
studies. After injecting Ostim in the dorsal skin chambers of
hamsters, biocompatibility was shown by the absence of leukocyte activa-
tion, a more pronounced angiogenic response and an increased microvessel
density, when compared with a synthetic hydroxyapatite bone substitute.
113
Injecting Ostim in a critical-sized defect in the calvaria of minipigs resulted
in bone formation in the defects, which also indicates the biocompatibility
of the material.
114
On the other hand, a study with Ostim injected in fresh
extraction sockets in dogs revealed a remaining gap up to 0.2 mm in the
graft surrounding tissue, which indicated that the use of this material does
not always lead to positive results.
112,115
Also, in a study of Meirelles et al.
116
in which titanium nHA-coated implants were compared with noncoated
implants, no obvious positive effect of nHA was observed. The implants
were implanted in a gap healing model in rabbit tibia, and for both implants
there was no difference in gap closure. This proves that not all results from
in vitro
studies can be extrapolated to an
in vivo
situation.
