Biomedical Engineering Reference
In-Depth Information
al. 2001; Kartsogiannis and Ng 2004). High levels of bone ALP are usually detected in both
preosteoblasts (osteoblastic cells) and osteoblasts
in vivo
and in differentiating osteoblastic
cells
in vitro
. Along with ALP, OC, known as a late marker of cell differentiation, is a small
molecular weight protein (5.7 kDa) produced by osteoblasts and has the ability to chelate
Ca
2+
to form bone minerals (Stein and Lian 1993; Gerstenfeld et al. 1987). For this reason, it
is a particularly effective marker of a well-differentiated osteoblastic cell. Generally, once
mineralization is initiated, ALP will decrease, whereas osteocalcin accumulation contin-
ues, reflecting an expression related to deposition of mineral for the latter.
As one of calcium phosphate ceramics, sintered HA has been well established as a bioac-
tive material that enhances osteoblastic cell viability and osteointegration with host bone
(Hench 1991; Greenspan 1999). Those valuable biological properties are well maintained
when HA is used as coatings on metallic implants. In comparison with those bioinert
metallic implants, many studies reported that the fabricated HA coatings on their surface
not only can help to stimulate cell growth and DNA synthesis, but also can enhance the
ALP and OC activities and the mineralization of extracellular matrix (Massaro et al. 2001;
Yang, Kim, and Ong 2005; Li et al. 2005). However, these desired biological properties of
HA coatings are highly dependent on coating surface roughness. Lee et al. (2002) investi-
gated the cell responses to HA coatings with different roughness values (
R
a
), 0.67 and 10.37
μ
m, and concluded that the smoother surface was more favorable for cell attachment than
the rougher one. Moreover, Kim et al. (2005) reported that the higher surface roughness
(
R
a
= 0.84
μ
m) could significantly enhance the number of attached cells compared with the
lower surface roughness (
R
a
= 0.22
μ
m), but there was no significant difference regarding
cell proliferation and differentiation. An enhanced effect on cell differentiation activities
and the formation of bone nodules was observed in other researchers' studies (Li et al.
2005; Perizzolo et al. 2001; Borsari et al. 2005).
On the other hand, several other studies also indicated that the behavior of cultured
osteoblastic cells are affected by the crystallinity and phase composition of the prepared
HA coatings (Yang, Kim, and Ong 2005). Kim et al. (2005) claimed that on the coatings with
higher crystallinity (>76%), the cells attached and proliferated well and expressed ALP and
OC to a higher degree as compared to the poorly crystallized coatings (~43% crystallin-
ity). Chou, Marek, and Wagner (1999) reported that the lower crystalline coatings with
some other impure phases (CaO, TCP, etc.) were favorable to cell attachment but exerted
inhibiting effects on cell proliferation due to the elevated medium pH value caused by
the dissolution of the impure phase. However, other studies illustrated insignificant influ-
ences on cell attachment, proliferation, and differentiation or mineralization with respect
to different crystallinity and/or phase compositions (Siebers et al. 2006).
Although it is commonly accepted that the HA coatings could improve the
in vitro
bio-
logical properties for those metallic implants, there still exist some inconsistent or even
conflicting viewpoints regarding the influences of coating properties on cell responses.
Considering those differences in coating preparation, experimental setup, testing meth-
ods, etc., it is hard to judge which one is more acceptable.
In Vivo
Animal Trial
Practically speaking, the goal of
in vivo
animal trial of implants or devices is to deter-
mine and predict whether such implants/devices possess potential harm to the human
body by evaluations under conditions simulating clinical end-use applications (Anderson
2001).
In vivo
models allow the direct evaluation of toxicity of a biomaterial and the effi-
cacy of a biomaterial as implant/device within a therapeutic application. Therefore, those
