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Preparation And Properties Of PLGA/Gelatin Electrospun Tissue Engineering Scaffold And Drug Carrier

Posted on:2012-09-19Degree:DoctorType:Dissertation
Country:ChinaCandidate:Z X MengFull Text:PDF
GTID:1221330377459396Subject:Materials science
Abstract/Summary:PDF Full Text Request
Electrospining is an effective method to yield continues fiber of nanometer tomicrometer scale. The fibrous membrane with large surface to volume ratio, interconnectedpores and high porosity, is similar to extracellular matrix and can carry drugs, thus has broadapplication in biomedical fields. In this paper, the electrospun nanofibers consisted ofsynthetic polymer poly(D,L-lactide-co-glycolide)(PLGA) and natural polymer gelatin areinvestigated systematically in tissue engineering, surface mineralization, surface entrapmentand drug release. The main contents are as followed:Firstly, randomly-oriented and aligned nanofibers with different ratios of PLGA/gelatinare produced through electrospinning. The surface morphology, chemical structure,hydrophilicity and mechanical property of PLGA/gelatin nanofibers before and aftercrosslinking are revealed by scanning electron microscope (SEM), attenuated total reflectionFourier transform infrared (ATR-FT-IR), swelling ratio and tensile test. It is found that thefiber diameter first increases and then decreases with broader fiber diameter distribution whenthe gelatin content increases. The hydrophilicity of fibrous scaffolds increases with increasingof gelatin content. The increasing of gelatin makes the elastic modulus and tensile stress offibrous scaffolds first increase and then decrease sharply. The crosslinking by glutaraldehydedecreases the hydrophilicity, but improves the elastic modulus and tensile stress of fibrousscaffolds. Compared with randomly-oriented PLGA/gelatin nanofibrous scaffolds, the fiberdiameter, porosity and swelling ratio of aligned nanofibrous scaffolds are lower, but theelastic modulus and tensile stress are higher than that of randomly-oriented nanofibrousscaffolds. Moreover, the addition of gelatin improves the biocompatibility of the nanofibrousscaffold, and aligned nanofibrous scaffold reveals better performance for cell adhesion andproliferation.Secondly, calcium phosphate apatite mineralization on the PLGA and PLGA/gelatin9/1nanofibrous scaffolds is prepared by three methods: concentrated simulated body fluid(10SBF), supersaturated calcification solution and alternate soaking. The carboxyl groups ofgelatin could lead to the enrichment of Ca2+ion, which could induce the nucleation ofcrystallites and result in the higher weight increase of mineralized PLGA/gelatin9/1nanofibers than PLGA nanofibers. The results of EDS, FT-IR and XRD depicts the apatiteyielded by three methods all contains DCPD, OCP and HA. The main component in10SBF isDCPD, and HA content is increasing in the other two methods. The efficiency of mineralization is higher, and large apatite coats on the nanofibers. It is also found that themineralized nanofibers show positive influence on adhesion, proliferation and differentiationof cells, which has a potential application in bone tissue engineering.Thirdly, the entrapment technology is used for surface modification of PLGA electrospunnanofibers with natural polymers. The influence of concentration of2,2,2-thifluoroethanolaqueous solution, swelling time and concentration of entrapment polymer on entrapment areinvestigated to confirm the best conditions and obtain the gelatin entrapment PLGAnanofibers and sodium alginate/gelatin entrapment-graft PLGA nanofibers. The results ofSEM and FT-IR shows the natural polymer is entrapping on the surface of PLGA nanofibers.The water contact angle test shows the higher hydrophilicity of modified PLGA nanofibers,and the hydrophilicity of sodium alginate/gelatin entrapment-graft PLGA nanofibers is betterthan that of gelatin entrapment PLGA nanofibers. The mechanical property of PLGAnanofibers is improved through entrapment. The MTT results shows that the entrapmentenhances the biocompatibility of the PLGA elecrospun nanofibers, and the biocompatibility ofsodium alginate/gelatin entrapment-graft PLGA nanofibers is better than that of gelatinentrapment PLGA nanofibers. The entrapment not only improves the hydrophilicity but alsoenhances the mechanical property, thus broader the application as tissue engineeringscaffolds.Fourthly, fenbufen (FBF)-loaded electrospun PLGA and PLGA/gelatin nanofibrousscaffolds as well as FBF-loaded solvent-cast films are produced and their drug releasecharacteristics are further investigated. It is found that FBF is in amorphous condition withinthe electrospun nanofibers but form crystal within the films, which lead to the higher drugrelease rate of nanofibers than that of films. The increasing of gelatin in the drug carrierenhances the swelling ratio, resulting in the large drug release. But after crosslinking, the drugrelease decreases with the increasing of crosslinking time. The structure of alignednanofibrous membrane is more compact than that of randomly-oriented nanofibrousmembrane, which leads to the lower drug release. In addition, the pH value of the buffersolution could change the Tgof the polymer, which affects the drug release rate. The furtherinvestigation finds that multi-layer structure is suitable as the two drug carrier ofmetronidazole/fenbufen, and the drug content depends on the thickness of the layer. Finally,the outer protected PLGA nanofibrous layer of the drug-loaded nanofibrous membrane couldinhibit the burst release of the drug effectively.
Keywords/Search Tags:Electrospinning, PLGA, Gelatin, Tissue engineering, Drug release
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