Development and Application of Naturally Renewable Scaffold Materials for Bone Tissue Engineering - The Nanoscience and Technology of Renewable Biomaterials - page 305

the porous scaffold was higher in BMMSC-seeded scaffolds as compared to controls
(54.2% and 8.6%, respectively). Their investigation also tested the mechanical proper-
ties of seeded and unseeded scaffolds and found that cell-seeded specimens had a higher
stiffness compared with cell-free scaffolds. The success of using BMMSC-seeded scaf-
folds in animal models led to the first human clinical trial to repair critical-size bone
defects by Quarto et al . (134). Three patients were treated with bone grafts com-
prised of BMMSCs seeded on HA scaffolds, representative in size and shape to their
injury. Using radiographs and computed tomography scans, callus formation along the
implants and integration at the interfaces with native bone was observed 2 months after
surgery. By 13 months post surgery, all external fixations at the site of injury, origi-
nally supplied for mechanical stability, were removed and patients had not reported any
problems.
Coral scaffolds have many strikingly similar characteristics to trabecular bone. Appro-
priately coral has been used as a bond scaffold material for over 20 years. With its
interconnective 3D porous structure, coral has great osteoconductive activity. Hou et al .
examined the synergistic effects of BMP-2 with coral in a rabbit critical-sized (15 mm)
cranial defect (135). Radiopacity observations were made at 16 weeks showing pref-
erence for a MSC/BMP-2/coral system over BMP-2/coral or coral alone. Fluorescently
labeled MSCs were examined histologically and confirmed a faster rate for osteogenesis
compared to coral alone, and were able to conclude that this treatment was as effective
as an autologous bone graft. A study by Foo et al . used a coral matrix and studied
the gene expression of osteoblasts. The authors analyzed gene expression of RUNX2,
osteopontin, alkaline phosphatase, and osteocalcin. Their results showed similar expres-
sion levels to osteoblast controls signifying that coral matrix did not change the genetic
expression of osteoblasts. Hou et al . analyzed the synergistic effects of coral scaffolds
with MSCs and BMP-2 in a rabbit model (135). oral scaffolds without MSCs showed
inferior results compared to when MSCs were present, as integration into the cranium
was not complete after 16 weeks. Histological sections revealed densely organized tissue
compared to a void randomness seen in the coral/BMP-2 control. The authors specu-

late that in light of their study, a one-time dose of 200 g BMP-2 could be applied

by clinicians to initiate bone regeneration (135). When compared to Hofmann's work,
there seems to be a carrier specific effect (136). A recent study by Cui et al . analyzed
ASCs on coral in a cranial defect for a canine model (137). The authors analyzed cel-
lularity alkaline phosphatase activity, and osteocalcin. Cells were precultured in either
growth or osteogenic medium conditions. Cell density was similar for both conditions
yet osteocalcin and was highest for the osteogenically induced group. Opacity volume
was significant for cell-seeded coral scaffolds where neat coral scaffolds underwent rapid
degradation. The authors concluded that when coral is seeded with progenitor cells, it
has a major advantage of matching its degradation rate to the kinetics of new bone
growth (137).
Nacre is another inorganic material that has been experimented with as a scaffold
for bone tissue engineering. Rousseau et al . showed that nacre stimulated osteoblast
differentiation and mineralization after only 6 days in culture compared to the soluble
factors such as dexamethasone, which takes periods of up to 14 days in vitro to trigger
mineralization (138).

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