Biomedical Engineering Reference
In-Depth Information
4.4.10 BCP Granules for Drug Delivery
Calcium phosphate bioceramics have frequently been proposed for the adsorp-
tion of bioactive factors and Drug Delivery Systems. However recently, Smucker
et al. [108] reported for the fi rst time a study demonstrating enhanced posterolat-
eral spinal fusion rates in rabbits using a synthetic peptide (B2A2-K-NS) coated
on to microporous granules of BCP with a 60/40 HA/TCP ratio. Different concen-
trations of the peptide (a synthetic receptor-targeted peptide that appears to am-
plify the biological response to rh BMP-2) were tested. This study provided more
evidence of mature/immature bone ingrowth across the inter-transverse process
spaces than did the controls. Microporous macroporous biphasic calcium phos-
phate granule bioceramics for peptide adsorption and local delivery seem to be a
good compromise for future associations of osteoconductive/osteogenic pro-
perties for such bioceramics and the osteoinductive properties of peptides and
growth factors.
Other kinds of drug which can be delivered are antibiotics. It is common
practice for surgeons to mix antibiotics with bone grafts when treating infected
bone defects or for preventing infection after surgery [109]. Local delivery of
antibiotics is both pharmacologically more effective and safe. Bioactive cements
have been shown to be an ideal carrier for antibiotics for local delivery if prop-
erly formulated [110,111]. New calcium phosphate cement has been specifi cally
engineered to have micro-porosity, macro-porosity and resorbability for optimal
cell adhesion, cell migration, and bone formation. Recently, the MCPC® reported
in this paper was associated with gentamycin [112].
The gentamycin release profi les from the cement samples with different set-
ting times were quite similar. Both cement groups showed an initial burst of
gentamycin release in the fi rst 24-hours. After the initial burst, the release rate
slowed signifi cantly, and stayed relatively constant after day seven up to the day
28 endpoint. The amount and rate of the initial burst release was affected by the
cement setting time. The release of gentamycin from the cement set for one hour
showed greater variation than the cement allowed to set for 24 hours. Within the
fi rst 24 hours, approximately 72% of the gentamycin was released from the
cement with a one hour set time, compared to slower release of approximately
51% of the gentamycin from the cement with a 24 hour set time. By 28 days,
around 87% and 76% of the gentamycin had been released from the cements that
had set for either one hour or 24 hours, respectively. The gentamycin release rates
from both the one hour and 24 hour set-time samples were almost constant after
day seven, averaging 59
g/
day for the 24 hour set time. In our release system, therefore, these constructs are
capable of producing gentamycin concentrations of 12
μ
g/day for the cement with a one hour set time, and 87
μ
g/ml on a
daily basis for the one hour and 24 set-time cement samples, respectively. This is
more than one order of magnitude greater than the Minimum Inhibitory Concen-
tration (MIC) for reference strains of S. aureus, which is in the range of 0.12-
0.25
μ
g/ml and 17
μ
μ
g/ml [113] .
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