Biomedical Engineering Reference
In-Depth Information
simplest synthetic bone-like grafts with a report in 1892 by Dreesman, as described by Peltier,
showing its use to fill bone cavities which later were found to be filled with solid bone
[46]
.
CS has been further demonstrated in many animal and clinical studies to be an effective osteoconduc-
tive scaffold that enhances bone regeneration
[47]
. In our laboratory, CS has been shown to adsorb
platelet-derived growth factor (PDGF-BB) and to support enhanced human osteoblastic cell prolifera-
tion in vitro when treated with the growth factor
[48]
. Although CS is a desirable osteoconductive
material and potential carrier of osteoinductive factors in its presently available state, it has some
deficiencies, including slow and variable degradation rate and weak mechanical properties
[49]
.In
an attempt to use nanotechnology to improve some of the properties of CS, our laboratory has been
working to fabricate a nanocalcium sulfate (nCS) scaffold material. We recently presented our stud-
ies on the use of a cryo-vacuum technique to process dihydrate CS into dihydrate nCS, which was
then subjected to oven drying to produce a hemihydrate nCS. The cryo-vacuum process for prepar-
ing CS dihydrate nanocrystals was based on that previously demonstrated by Salvadori et al.
[50]
.
The advantages of this cryo-vacuum technique are that it is simple and avoids the introduction of
any surfactants or other components beyond CS and water.
The nCS synthesized in this manner was sterilized by glow discharge treatment, a practical
method for most clinical situations. Electron microscopy showed that the nCS powder consists of
aggregates of closely arranged acicular crystals, approximately 30
80 nm in width, 400
600 nm
in length and approximately 80
100 nm in diameter, providing a surface area as determined by
Brunauer, Emmett, and Teller surface area analysis using a Micromeretics Model 2000 ASAP nitro-
gen physisorption apparatus, to be about 10 times that of conventional CS. Physicochemical charac-
terization confirmed the composition and phase of the material. Surface microhardness testing
showed that the nCS was stronger than conventional CS and may provide an additional advantage
to the scaffolding properties of the material. Cell viability/metabolic activity assays with human
osteoblastic and PDL cells verified the safety and biocompatibility of nCS and alkaline phosphatase
assays showed that the material supports the differentiation of osteoblastic cells
[49]
.
Studiesfromourlabaswellasmanyotherspoint to the potential use of scaffold materials
as carriers that can release and maintain levels of growth factors to aid in their ability to facili-
tate bone repair
[51]
. Release kinetics for adsorbed PDGF and bone morphogenetic protein-2
(BMP-2)
[49]
suggested that nCS may serve as an appropriate vehicle for slow release delivery
of these agents that have been approved for clinical use in a number of bone regenerative
procedures
[52,53]
.
Our laboratory has found that when human recombinant BMP-2 (rhBMP-2) was mixed with CS
(conventional size, medical-grade calcium sulfate) or nCS and allowed to dry into disks of equal
weight and proportion, there was a significantly greater amount of the BMP-2 released from the
nCS disks at 37
C over a 7-day period as measured with a specific immunoassay for the growth
factor. However, when a mixture of 10% alginate, a natural polysaccharide, and nCS was mixed
with the BMP-2, there was a much faster and significantly greater release of the BMP-2 compared
to nCS alone with a significant amount released after 2 h that did not change for up to 7 days. This
study suggests that the use of alginate can significantly improve the properties of an nCS scaffold
at least with respect to the release of growth factors (
Figure 19.5
).
However, although these data suggest that nCS has release characteristics for growth factors
different than conventional-sized CS and that they can be modified with the use of alginate, they
do not provide sufficient information to predict how this nCS material will function as a vehicle
