Biomedical Engineering Reference
In-Depth Information
5 weeks post-implantation and cranial defects that were filled with the tissue engineered
bone appeared to be completely integrated into the skull when compared to (1) hMSC
seeded scaffolds that did not undergo differentiation prior to implantation, (2) scaffold
material alone, and (3) unfilled defects (120). The expression of osteocalcin was only
observed in the center of the defect when cellular scaffolds were used, reflecting that
the contribution of host cells to the defect was negligible with this scaffolding. Follow
up work by Meinel demonstrated that silk based scaffolds could be used in loadbearing
defects with those results displaying a similar trend in that only bone tissue engineered
in vitro a priori
to implantation created significantly greater bone volumes compared
to the control groups (119). Mechanical testing of the implanted grafts displayed a
significant maximal load, torque, and torsional stiffness for the tissue engineered bone
constructs compared to undifferentiated hMSC/silk scaffolds and silk scaffolds alone,
clearly displaying its functionality in its ability for skeletal restoration (119). However,
very recent work by Kirker-Head
et al
. gave controversial evidence that with the sim-
ple induction of a bioactive molecule such as BMP-2, similar results can be obtained
between implanted scaffolding materials with or without a progenitor cell population
(118). These findings signify that in their case, a differentiation period was not needed
to warrant skeletal integration as determined by microcomputed tomography (118). The
work by Kirker-Head
et al
. exemplifies how the appropriate matrix (silk) and bioactive
molecules (BMP-2) can act as effective osteoinductive mediators of local pluripotent
osteoprogenitor and osteoblastic cell populations.
Studies have slowly been moving towards keratin-based scaffolds for bone tissue engi-
neering. Keratins are fibrous proteins derived from wool, hair, and nail materials. These
materials contain protein sequences including RGD that are known to facilitate cell adhe-
sion via distinct integrin binding sites. Tachibana
et al
. began modifying keratin sponges
with calcium-phosphate absorption versus hydroxyapatite loading (125). Osteoblast dif-
ferentiation was assessed for hydroxyapatite, calcium phosphate, and control keratin
sponges and all materials maintained similar cell densities throughout the six day exper-
iment. Alkaline phosphatase activity was measured with the highest activity occurring in
the following order: Hydroxyapatite
>
Calcium phosphate
>
unmodified keratin sponge
(125). Tachibana
et al
. followed up their initial work by binding the bioactive protein
BMP-2 to carboxymethylated keratin sponges (126). The authors were able to show good
retention of BMP-2 and demonstrated confined differentiation to areas of the scaffold
that had bound BMP-2. Alkaline phosphatase activity for osteoblasts increased 2-fold
throughout the seven day culture period for BMP-2 modified keratin sponges, whereas
control keratin sponges displayed no change in ALP activity (126).
In addition to these materials some work has focused on the use of fibrin as a scaf-
fold and carrier of BMP-2. Gurevich
et al
. encapsulated bone marrow-derived MSCs
in fibrin microbeads and examined cell proliferation and ectopic bone formation with
rodent models (127). Karp
et al
. investigated whether fibrin sealants with different
thrombin concentrations would provide an adequate scaffold for bony wound healing
in rat models. Histological analysis revealed a significant decrease in bone infiltration
for both high and low concentrations of thrombin compared to defect controls (128).
Xu
et al
. experienced similar results with a mouse model when fibrin was investigated
at a delivery vehicle for BMP-2 (129). The fibrin scaffold combined with BMP-2 was
injected subcutaneously and compared to collagen, alginate, hyaluronan, agarose, and
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