Cell instructive
scaffolding platforms displaying synergistic effects
by virtue of their chemical and physical cues have tremendous scope
in modulating cell phenotype and thus improving the success of any
graft. In this regard, we report here the development of Si- and Zn-doped
brushite cement composited with silk scaffolding that hierarchically
emulated the cancellous bone. The composite scaffolds fabricated exhibited
an open porous network capable of enhanced osteoblast survival as
attested by increased alkaline phosphatase activity and also sustaining
osteoclast activity affirmed by tartrate resistant acid phosphatase
staining. Moreover, the chemical cues presented by dissolutions products
from the composite scaffold enabled the osteoblasts to secrete proangiogenic
factors which favored better endothelial cell survival, confirmed
through in vitro experiments. Moreover, the efficacy of these composite
biomimetic scaffolds was validated in vivo in volumetric femur defects
in rabbits, which revealed that these matrices influenced vascular
cell infiltration and favored the formation of matured bony plate.
Fluorochrome labeling studies and microtomography analysis revealed
that at the end of three months, the implanted composite scaffolds
had completely resorbed, leaving behind neo-osseous tissue and vouching
for clinical translation of these composite matrices as viable and
affordable bone-graft substitutes.
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