title: BMP-2 Derived Peptide and Dexamethasone Incorporated Mesoporous Silica Nanoparticles for Enhanced Osteogenic Differentiation of Bone Mesenchymal Stem Cells.
abstract: 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.
authors.affiliation: †College of Chemistry, Chemical Engineering and Biotechnology; State Key Laboratory for Modification of Chemical Fibers and Polymer Materials, Donghua University, Shanghai 201620, China.|‡College of Materials Science and Engineering, Donghua University, Shanghai 201620, China.
authors.forename: Xiaojun
authors.initials: X
authors.lastname: Zhou
authors.affiliation: ‡College of Materials Science and Engineering, Donghua University, Shanghai 201620, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Feng
authors.affiliation: †College of Chemistry, Chemical Engineering and Biotechnology; State Key Laboratory for Modification of Chemical Fibers and Polymer Materials, Donghua University, Shanghai 201620, China.|‡College of Materials Science and Engineering, Donghua University, Shanghai 201620, China.
authors.forename: Kexin
authors.initials: K
authors.lastname: Qiu
authors.affiliation: ‡College of Materials Science and Engineering, Donghua University, Shanghai 201620, China.
authors.forename: Liang
authors.initials: L
authors.lastname: Chen
authors.affiliation: ‡College of Materials Science and Engineering, Donghua University, Shanghai 201620, China.
authors.forename: Weizhong
authors.initials: W
authors.lastname: Wang
authors.affiliation: ‡College of Materials Science and Engineering, Donghua University, Shanghai 201620, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Nie
authors.affiliation: †College of Chemistry, Chemical Engineering and Biotechnology; State Key Laboratory for Modification of Chemical Fibers and Polymer Materials, Donghua University, Shanghai 201620, China.|‡College of Materials Science and Engineering, Donghua University, Shanghai 201620, China.
authors.forename: Xiumei
authors.initials: X
authors.lastname: Mo
authors.affiliation: †College of Chemistry, Chemical Engineering and Biotechnology; State Key Laboratory for Modification of Chemical Fibers and Polymer Materials, Donghua University, Shanghai 201620, China.|‡College of Materials Science and Engineering, Donghua University, Shanghai 201620, China.
authors.forename: Chuanglong
authors.initials: C
authors.lastname: He
mesh_terms: D065966:Absorption, Physicochemical; D000818:Animals; D055396:Bone Morphogenetic Protein 2 / Q000008:administration & dosage* / Q000737:chemistry; D002454:Cell Differentiation / Q000187:drug effects / Q000502:physiology; D049109:Cell Proliferation / Q000187:drug effects / Q000502:physiology; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology; D002478:Cells, Cultured; D003907:Dexamethasone / Q000008:administration & dosage* / Q000737:chemistry; D004058:Diffusion; D004338:Drug Combinations; D005260:Female; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000187:drug effects / Q000502:physiology; D053769:Nanocapsules / Q000737:chemistry* / Q000648:ultrastructure; D058608:Nanopores / Q000648:ultrastructure; D010006:Osteoblasts / Q000166:cytology* / Q000187:drug effects / Q000502:physiology; D010012:Osteogenesis / Q000187:drug effects / Q000502:physiology*; D016062:Porosity; D051381:Rats; D017207:Rats, Sprague-Dawley; D012822:Silicon Dioxide / Q000737:chemistry
chemical_list: C525718:BMP2 protein, human; D055396:Bone Morphogenetic Protein 2; D004338:Drug Combinations; D053769:Nanocapsules; D012822:Silicon Dioxide; D003907:Dexamethasone
keywords: bone morphogenetic peptide; cellular uptake; dexamethasone; mesoporous silica nanoparticles; osteogenic differentiation