Biomedical Engineering Reference
In-Depth Information
bone-related protein expression. Constructs consisting of cell sheets and
scaffolds were assessed in vivo with and without 8 weeks pre-culture in
osteogenic media. The constructs were then subcutaneously implanted into
nude rats, which allowed assessment of the osteogenic capabilities of the
scaffold-cell sheet constructs by assessing the ability to form bone in an
ectopic site, away from bone tissue. Both groups indicated the formation of
neo-cortical and well-vascularised cancellous bone within the constructs
with up to a 40% bone volume. Histological and immunohistochemical
analyses revealed that new bone formation followed predominantly an
endochondral pathway, whereby chondrocytes proliferated, underwent
hypertrophy and apoptosis whilst the ECM space was invaded by blood
vessels, osteoclasts, bone marrow cells and osteoblasts. The osteoblasts
deposited bone matrix into the ECM space and gradually the woven bone
matrix matured into fully mineralised compact bone, exhibiting the histo-
logical markers of native bone. 36
Abbah et al. 37 employed the same approach as Zhou et al. 36 whereby dif-
ferentiated autogenous porcine bone marrow stromal cell sheets were
wrapped around PCL-TCP (80 : 20 wt%) scaffolds. These scaffolds were then
implanted into a pig model to assess spinal interbody fusion. Scaffolds
without bone marrow stromal cell sheets served as a control. New bone
formation was evident at 3 months in the cell group. At 6 months, bone
fusion was observed in five out of eight scaffolds in the cell groups but no
bone as observed in the control groups. Biomechanical analysis revealed that
segmental stability was significantly increased in the cell group compared to
the control group at 6 months post-implantation. 37 These two studies have
shown that combining PCL-TCP scaffolds with cell sheet technology can
contribute towards extensive in vivo bone formation thus have great poten-
tial in the field of bone tissue engineering.
It can be deduced from the aforementioned studies that effective cell
delivery and distribution within scaffolds is essential in ensuring cell pro-
liferation, differentiation and relevant extracellular matrix production; im-
portant prerequisites to enable new bone formation. Fibrin glue has been
shown to improve the stability and cell attachment properties of scaffolds
and hence enhance cell seeding eciency as well as subsequent cell pro-
liferation. 38 Investigations into the potential of fibrin glue and lyophilised
collagen as cell-delivery matrices within PCL scaffolds were undertaken by
Leong et al. 39 Adipose tissue-derived stem cells were seeded onto PCL-TCP
scaffolds with either fibrin glue or lyophilised collagen. Results from in vitro
studies showed that both fibrin and collagen were effective matrices for cell
delivery into scaffolds, with adipose tissue-derived stem cells showing good
adherence to the PCL-TCP scaffold surfaces and formation of bridging and
overlapping cell sheets, as well as substantial ECM deposition within both
types of scaffold matrix systems. 39
Collagen was also used by Lee and Kim 40 to improve cell attachment onto
PCL-TCP (60 : 40 wt%) scaffolds. It was shown that collagen coated PCL-TCP
scaffolds exhibited improved surface hydrophilicity, enhanced initial cell
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