| Bone loss caused by tumor, trauma or periodontitis, which is one of themost common clinical problems in dentistry, not only affects mastication andvocalization, but also causes physical and mental problems, and thereby qualityof life. However, traditional therapy for bone defect is still baffled by itslimitations, such as poor shaping of autologous bone or allograft, secondaryinjury or immunological rejection; difficulties in the popularization of distractionosteogenesis technology resulting from its limited indications, complexedoperation technology and high price. Based on the foregoing background, theapproach of exploiting the cogent growth factor to promote bone regenerationand reconstruction becomes in demand as a novel alternative therapy for boneinjury. In this paper, the prospect of SNs in bone regeneration study, and theresults of aspirin and BMP-2gene combination in bone regeneration will bediscussed in depth. In addition, we aim to prepare aspirin-based carbon dots(ACDs) which can be employed for bioimaging and anti-inflammation both, andopen up a novel approach to prepare CDs with multifunction.In the second chapter, three sizes of SNs were fabricated by controlling theratio of reactants and reaction time using St ber approach. Scanning electron microscope images demonstrated that all three sizes of SNs were spherical with auniform size and good dispersion. Hydrodynamic diameters of three SNs inaqueous solution were121.8±8.4nm,310.8±7.5nm and646.1±3.3nm,which were determined by dynamic light scattering analysis. All theFITC-labeled SNs of three different size had similar cellular uptake (>90%),determined by fluorescence activated cell sorting analysis, suggesting that allthree SNs usually had good cellular affinity. Fluorescence spectrophotometryresults, however, indicated that cellular uptake increased with a decrease in thesize of the SNs. Interestingly, the smaller SNs could induce more MC3T3-E1cellapoptosis than larger SNs in a dose-dependent manner. MTT assaysdemonstrated that all these three SNs were capable to decrease cell proliferationat a higher concentration (100mg/mL), indicating their size andconcentration-dependent cytotoxicity. Importantly, all three SNs could directlystimulate mineralized nodule formation, which was also size-dependent. Theseresults suggest that SNs are potentially applicable in bone regeneration, and it ispossible to decrease unwanted side effects by controlling dose and size of SNs.In the third chapter, dendrimer-like silica nanoparticles with porousstructure (PSNs) were synthesized by an ethyl ether emulsion approach whichcovalently grafted PEI onto the surface. The size of PSNs observed bytransmission electron microscopy (TEM) was80~180nm with porous structure,and there were no obvious changes when PEI modification applied. Drug loadingefficiency of PEI modified PSNs (PPSNs) could reach21.08%. Agarose gelelectrophoresis results indicated that PPSNs and EGFP plasmid could integratecompletely when the weight ratio reached10, and the complex couldsuccessfully express green fluorescent protein. Furthermore, we demonstrated that bone formation area of PPSNs encapsulating aspirin/BMP-2plasmid(pBMP-2) group could reach69.8±3.5%, which was significantly higher thanthat of the control group (26.4±1.6%)(P<0.01), PPSNs/aspirin group (36.9±1.4%)(P<0.01) and PPSNs/pBMP-2group (50.9±1.7%)(P<0.01). Our resultsdemonstrate that PPSNs encapsulating aspirin/pBMP-2could efficiently deliverthe drug aspirin, functionally express BMP-2plasmid in vivo, and effectivelypossess bone regeneration ability compared to PPSNs encapsulating BMP-2plasmid only.In the fourth chapter, fluorescent aspirin-based carbon dots (ACDs) weresynthesized by condensing aspirin and hydrazine through “one-step”microwave-assisted method. Images observed by TEM indicated that ACDspossessed diameters of ca.2-6nm with obvious crystalline structure. Functionalgroups of anti-inflammation were determined to be reserved by chemicalmethods of X-ray photoelectron spectroscopy and fourier transform infraredanalysis. Imaging data demonstrated that ACDs efficiently entered into mousemonocyte macrophage (RAW264.7) cells in vitro with low cytotoxicity. Resultsobtained from quantitative polymerase chain reaction and histological analysisindicated that ACDs possessed efficacious anti-inflammatory effects both in vitroand in vivo compared to aspirin or photoluminescent carbon-based nanomaterialsonly. Hematology, serum biochemistry and histology results suggested ACDsalso had no-significant toxicity in vivo. Our results demonstrate that the ACDsindeed have double functions, cellular imaging/bioimaging andanti-inflammation, and suggest that the ACDs have a great potential in futureclinical application. |
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