Biomedical Engineering Reference
In-Depth Information
their bioavailability. In tissue engineering strategies, there have been several attempts to incorporate
growth factor carriers on scaffolds to increase osteoinductivity and enhance the effectiveness of the
construct (
Yilgor et al., 2009, 2012
;
Young et al., 2009
;
Vo et al., 2012
).
Various growth factors have been used within 3D or injectable carrier structures to achieve en-
hanced bone regeneration in the craniofacial region. For example, in a multicentric clinical study, 160
patients were followed up for 5 years in a total of 21 US centers. Patients received 1.50 mg/ml BMP-2
within collagen sponges for maxillary sinus floor augmentation (
Triplett et al., 2009
). Patients revealed
proper tissue integration and functional recovery starting from 6 months after application. TGF-
b
3
(
Ripamonti et al., 2009
) and BMP-7 (
Abu-Serriah et al., 2006
) were used in preclinical animal models,
while TGF-
b
3 (1.5
m
g/application) was especially reported to be a strong mediator of mandibular de-
fect regeneration in primates.
Combined delivery of multiple growth factors was studied recently in order to recapitulate the natu-
ral timing of growth factor bioavailability. The coadministration of BMP-2/BMP-7 with a total BMP
amount of 50 ng/ml was shown to be effective in the cementoblastic differentiation of dental follicle
cells
in vitro
(
Kemoun et al., 2007
). Other growth factor cocktails have also been shown to be effec-
tive: the cocktail of IGF-1/PDGF (total: 5
m
g/ml) within methylcellulose gel carriers showed that bone/
implant contact and ossification could be enhanced when implanted into extraction sockets in a canine
model (
Stefani et al., 2000
).
10.5
SUMMARY
Osseous defects in the craniofacial skeleton are a large clinical and economic burden. Current repair
strategies rely on a limited source of donor tissue and cannot address the special requirements of
craniofacial bone geometry, which affects both facial features and mechanical function of mastica-
tion. A TE approach—building a bone graft
de novo
from cells seeded within scaffolds and signaled
with appropriate bioactive factors—may overcome these drawbacks. For use in craniofacial repair, the
scaffold must be porous enough to allow cell and tissue growth on the microscale and capture precise
craniofacial geometry on the macroscale. To guide cell fate, scaffolds must also possess appropriate
nanoscale features.
One major advance in meeting these demands is the advent of 3DP technology, which allows the
construction of any shape in a layer-by-layer fashion. While there are several different methods of 3DP,
all methods feature the ability to construct the complex geometries of the craniofacial skeleton while
controlling the scaffold's microarchitecture. To functionalize the scaffold, several nanotechnologies
including the use of nanoscale components in the scaffolding material, the construction of nanosize
features within the scaffold, and the release of bioactive compounds from nanoparticles. Both 3DP and
nanoscale technologies have been applied to craniofacial TE and hold promise for the future.
REFERENCES
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