BMP‑2
Derived Peptide and Dexamethasone Incorporated Mesoporous Silica Nanoparticles
for Enhanced Osteogenic Differentiation of Bone Mesenchymal Stem Cells
Bone morphogenetic protein-2 (BMP-2),
a growth factor that induces osteoblast differentiation and promotes
bone regeneration, has been extensively investigated in bone tissue
engineering. The peptides of bioactive domains, corresponding to residues
73–92 of BMP-2 become an alternative to reduce adverse side
effects caused by the use of high doses of BMP-2 protein. In this
study, BMP-2 peptide functionalized mesoporous silica nanoparticles
(MSNs-pep) were synthesized by covalently grafting BMP-2 peptide on
the surface of nanoparticles via an aminosilane linker, and dexamethasone
(DEX) was then loaded into the channel of MSNs to construct nanoparticulate
osteogenic delivery systems (DEX@MSNs-pep). The in vitro cell viability
of MSNs-pep was tested with bone mesenchymal stem cells (BMSCs) exposure
to different particle concentrations, revealing that the functionalized
MSNs had better cytocompatibility than their bare counterparts, and
the cellular uptake efficiency of MSNs-pep was remarkably larger than
that of bare MSNs. The in vitro results also show that the MSNs-pep
promoted osteogenic differentiation of BMSCs in terms of the levels
of alkaline phosphatase (ALP) activity, calcium deposition, and expression
of bone-related protein. Moreover, the osteogenic differentiation
of BMSCs can be further enhanced by incorporating of DEX into MSNs-pep.
After intramuscular implantation in rats for 3 weeks, the computed
tomography (CT) images and histological examination indicate that
this nanoparticulate osteogenic delivery system induces effective
osteoblast differentiation and bone regeneration in vivo. Collectively,
the BMP-2 peptide and DEX incorporated MSNs can act synergistically
to enhance osteogenic differentiation of BMSCs, which have potential
applications in bone tissue engineering