| Electrospun nanofibers, with controllable diameters, high specific surface area and porosity, andthree dimensional network structures, which closely mimic the structure of natural extracellular matrix,are widely used in the fields of drug delivery systems and tissue engineering. Poly(lactide-co-glycolideacid)(PLGA) is a copolymer with excellent biocompatibility and biodegradability. It has been widelyused in the fields of electrospun nanofiber-based drug delivery systems and tissue engineering.attapulgite (ATT) nanorods, a naturally occurring clay material, a kind of magnesium aluminiumphyllosilicate with a formula (Mg, Al)2Si4O10(OH)4(H2O), is a good inorganic carrier material havinghigh surface activity and strong mechanical property.The second chapter of the thesis reports the preparation electrospun ATT-doped PLGA nanofibersfor osteogenic differentiation of hMSCs. The formed ATT-incorporated electrospun PLGA hybridnanofibers were characterized via different techniques. Scanning electron microscopy (SEM), tensiletests, and water contact angle measurements were used to investigate the influence of the incorporatedATT on the morphology, mechanical properties, and surface hydrophilicity of the hybrid fibers,respectively. The cytocompatibility of the hybrid nanofibers was evaluated by cell viability assay (MTT)and SEM morphology observation of hMSCs cultured onto the prepared fibrous scaffolds. Thehemocompatibility of the ATT-doped PLGA nanofibers was evaluated via hemolytic and anticoagulantassays. Finally, the osteogenic differentiation of hMSCs cultured onto ATT-doped PLGA nanofibers wasquantitatively investigated by measuring the alkaline phosphatase (ALP) activity, osteocalcin secretion,and cellular calcium content, and qualitatively evaluated by von Kossa staining of calcium phosphatecrystals produced in culture.The results show that the incorporation of ATT nanorods does notsignificantly change the uniform morphology and the hemocompatibility of the PLGA nanofibers;instead the surface hydrophilicity, mechanical durability and cytocompatibility of the hybrid nanofibersare slightly improved after doping with ATT. Alkaline phosphatase activity, osteocalcin secretion,calcium content, and von Kossa staining assays reveal that the doped ATT within the PLGA nanofibers is able to induce the osteoblastic differentiation of hMSCs in growth medium without the inducing factorof dexamethasone. The fabricated organic/inorganic hybrid ATT-doped PLGA nanofibers may find manyapplications in the field of tissue engineering and regenerative medicine.In the third chapter, we attempted to first encapsulate the anticancer drug doxorubicin (DOX) usingthe inorganic rod-like attpulgite (ATT) as a carrier. Then, the DOX-loaded ATT particles were mixedwith poly(lactic-co-glycolic acid)(PLGA) solution to fabricate electrospun hybrid nanofibers. Theformation of drug-ATT complexes and the drug-loaded composite nanofibers were characterized usingdifferent techniques. In vitro DOX release behavior was examined using UV-vis spectroscopy underboth neutral (pH=7.4) and acidic conditions (pH=5.4). The anticancer activity of the drug-loadedcomposite nanofibers was evaluated via the resazurin reduction assay and microscopic morphologyobservation of a human osteosarcoma cell line (CAL72). We show that DOX can be successfully loadedonto the ATT and the formed composite fibers have a uniform and continuous fibrous morphology.Importantly, the loaded DOX shows a sustained release profile, and the released DOX from thenanofibers displays strong antitumor activity towards the growth inhibition of CAL72cells. With thesignificantly reduced burst release profile and the improved mechanical durability of the compositenanofiber system compared with ATT-free PLGA nanofibers, the designed organic-inorganic hybridnanofibers could be used as a versatile drug delivery system for encapsulation and sustained release ofdifferent drugs with prolonged therapeutic efficacy for different biomedical applications. |
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