| Stem cells are a kind of multifunctional cells with the potential of self-renewal and differentiation,among which Mesenchymal stem cells(MSCs)commonly exist in a variety of tissues and have a huge potential of self-renewal and differentiation into osteoblasts,adipocytes,chondrocytes,muscle cells and other cell types.In many diseases,MSCs can provide functional replacement and nutritional support for worn or defunct cells and tissues.Therefore,MSCs have attracted extensive attention in tissue regeneration and disease treatment.At present,stem cell technology based on stem cells is used in a variety of diseases such as bone repair.In the application of stem cell technology,targeted regulation of stem cell fate is the key to stem cell treatment of diseases.There are many factors that regulate stem cell differentiation such as intracellular proteins,growth factors,extracellular matrix,and nanomaterials.Nanoparticle can not only induce stem cell differentiation by itself,but also act as a carrier carrying drugs to regulate the fate of stem cells.Metal-organic framework(MOF)is a crystalline material composed of metal ions and an organic framework.It has the characteristics of diverse structure,large specific surface area,uniform cavity and so on.MOF materials have been widely used in catalysis,sensing,gas storage and separation,drug delivery and other fields.ZIF-8,as one of the MOFs,constructed by zinc ions and 2-methylimidazole,which has a large specific surface area and pore volume,and is an ideal drug carrier.Moreover,zinc ions in ZIF-8 can be used to regulate the osteogenic differentiation of stem cells.However,due to the immune response caused by the nanoparticles entering the body,the nanoparticles are quickly expelled from the body,reducing their efficacy.The modification of cell membrane enables the nanoparticles to have the characteristics of immune escape and long circulation,thus enhancing the effects of nanoparticles on stem cells.In this paper,the effect of membrane-encased metal-organic framework on stem cell differentiation and bone injury was studied.The main research contents are as follows:1.Stem Cell Membrane-Encapsuled Metal-Organic Frameworks for Enhanced OsteogenesisBased on the inductive effect of zinc ions on osteogenic differentiation of cells and the immune escape and long cycling properties of nanoparticles given by cell membrane,we constructed nanoparticles coated with ZIF-8(ZIF-8-SCM).The results showed that ZIF-8-SCM was successfully constructed by SEM,TEM,XRD and FTIR,and the release of zinc ions in ZIF-8 was detected by ICP-OES.Biological TEM revealed a higher uptake of ZIF-8-SCM than ZIF-8 against cells.Live/dead staining and CCK-8 revealed good biocompatibility of ZIF-8-SCM.In addition,alkaline phosphatase assay,immunofluorescence staining,Q-PCR,and calcium nodules demonstrated the ability of ZIF-8-SCM to induce osteogenic differentiation in vitro.The construction of bone defect model in vivo and its micro-CT,HE staining and immunofluorescence staining indicated that ZIF-8-SCM had the potential to repair bone defect in vivo.Therefore,ZIF-8-SCM can enhance osteogenic differentiation based on the release of zinc ions and the encapsulation of the cell membrane.2.Stem Cell Membrane-Encapsuled Metal-Organic Frameworks as Targeted Vehicles of Dexamethasone for Enhanced OsteogenesisDue to its large specific surface area and pore size,ZIF-8 is an ideal candidate for drug delivery system.In this chapter,we constructed a drug delivery system with ZIF-8encapsulated in cell membrane and loaded with DEX(DEX@ZIF-8-SCM).First,the successful construction of DEX@ZIF-8-SCM was detected by SEM,TEM,XRD,FTIR and other characterization methods,while the slow release of DEX was detected by UV-vis.The biological TEM shows that the encapsulation of cell membrane is more conducive to the uptake of nanoparticles by cells.Live/dead staining and CCK-8 revealed good biocompatibility of DEX@ZIF-8-SCM.In addition,alkaline phosphatase assay,immunofluorescence staining,Q-PCR,and calcium nodules suggest that DEX@ZIF-8-SCM has the ability to induce osteogenic differentiation in vitro.RNA sequencing results showed that PI3K-Akt and NF-κB signaling pathways were closely related to osteogenic differentiation induced by DEX@ZIF-8-SCM composite and its anti-inflammatory effects on DEX receptor and biological stress response.The construction of a rat model of bone defect in vivo and its micro-CT,HE staining and immunofluorescence staining indicated that DEX@ZIF-8-SCM has the potential to repair bone defect in vivo.Therefore,osteogenic differentiation can be enhanced based on the synergistic effect of zinc ion and DEX,as well as the encapsulation of cell membrane DEX@ZIF-8-SCM. |
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