Investigation On Characteristics And Biomedical Functions Of Electrospun Ultrafine Fibers

Electrospinning is a novel processing technique for the production of polymer fibers with diameter of several nanometers and tens micrometers from electrically charged liquid jets of polymer solutions or melts under static electric field.Electrospun fibers show potential applications in reinforced composites,filtration,protective clothing, optical and electrical devices,and especially biomedical fields.However,due to the complexity of the electrospinning process and the diversity of the electrospinning parameters,one of the challenges is to control fiber morphology and diameters.Moreover, the applications of electrospun fibers as tissue engineering scaffolds,drug delivery carriers and composites matrices were developed only within last few years,and basic problems are still needed to be solved.In order to address above issues,the electrospinning process,the surface wettability and degradation patterns of poly(DL-lactide)(PDLLA) fibers was initially examined;the compsite fibers of hydroxyapatite and PDLLA was constructed through in situ growth,biomacromolecules and chemical groups induced mineralization,respectively;and finally,electrospun fibrous mats were invesitigated as drug carriers and tissue engineering scaffolds.Orthogonal experimental method was firstly used to investigate process parameters of the electrospinning system.Results of statistical analysis showed that significant influences were observed for polymer molecular weight and solution concentration on fiber diameters,and there were significant effects of polymer molecular weight,solution concentration,and solvent system on fiber morphologies.The regression analysis revealed quantitative relations of fiber diameters and beads percent with process parameters.Validation test showed that the experimental values of fiber size and beads percent were in good agreement with the calculated ones.Based on these results,optimal conditions could be obtained for predetermined diameters and morphologies for electrospun fibers.The effect of surface morphologies and chemical groups on surface wettability and degradation profiles were investigated using electrospun poly(D,L-lactide)(PDLLA) and poly(D,L-lactide)-poly(ethylene glycol)(PELA) fibers.The hydrophobic surface could be enhanced through increasing percents of beads and nano-holes of single fibers,decreasing the size of beads,diameter of fibers and aperture of fibrous mats.Chemical groups with lower binding energy were found to be enriched on the fiber surface due to the high voltage of the electrospinning process.Electrospun PDLLA and PELA fibrous mats showed the hydrophobic surface because of the surface chemical groups and special microstructures,resulting in surface erosion degradation pattern for electrospun fibers, while casting films of PDLLA and PELA indicated a bulk degradation pattern.The composite fibers of poly(ethylene glycol)(PEG) and PDLLA were prepared through blend electrospinning,and the surface wettability,dimensional stability, degradation and mechanical properties were investigated as potential scaffolds for skin tissue engineering.By increasing the PEG content,the surface hydrophilicity was improved,and tensile stress,modulus and stress were gradually decreased.PDLLA degradation patterns of PDLLA/PEG fibrous mats changed from surface erosion to bulk degradation with the increase in PEG contents.The dimensional shrinkage was alleviated because of the formation of crystal regions of PEG in the fibers matrix.Human dermal fibroblasts(HDFs) interacted and integrated well with the surrounding fibers containing 20 and 30%PEG,which provided significantly better environment for biological activities of HDFs than electrospun PDLLA mats.It indicated that electrospun mats containing 30%PEG exhibited the most balanced properties,including moderately hydrophilic surface,minimal dimensional changes,adaptable bulk biodegradation pattern and enhancement of cell penetration and growth within fibrous mats.A systematic investigation was carried out on the drug releasing mechanism, thermodynamics and degradations of electrospun PDLLA fibers with paracetanol incubation.The in vitro drug release study showed a pronounced burst release,which decreased with the increase in fiber diameters and decrease in drug contents.And the release profile fit well with Weibull pattern,indicating the initial drug diffusion followed by matrix erosion.Drug loaded electrospun fibers showed hydrophobic surface,and a surface erosion pattern of PDLLA matrix was determined.Development of nanocomposites of hydroxyapatite(HA) and polylactic acid(PLA) is attractive as advantageous properties of two types of materials can be combined to suit better the mechanical and biological demands for biomedical uses.To solve problematic issues of the agglomeration of HA crystallites in the PDLLA matrix,a novel method was introduced to use electrospun nanofibers as reaction confinement for composite fabrication.Poly(DL-lactide) ultrafine fibers with calcium nitrate entrapment were prepared by electrospinning,and then incubated into phosphate solution to form in situ calcium phosphate on the polymer matrix.The formation of non-stoichiometric nanostructured HA and well dispersion of HA particles on the electrospun fibers were observed.The formation of the calcium-phosphate phase was dependent upon the precipitation conditions,and the effects of the incubation time,temperature and the pH values of the incubation medium were investigated on the spontaneous precipitation and amorphous-crystalline transformation of HA.Compared to blend fibers of HA and PDLLA,the in situ grown fibrous mat achieved higher mechanic properties,and significantly promote cell attachment,proliferation and differentiation.Composite fibrous mats of HA/PDLLA were constructed by the use of electrospun PDLLA nanofibers with gelatin graft as the induction sites for HA nucleation and growth. The formation of nonstoichiometric nanostructured HA and a well dispersion on electrospun fibers were determined.In the aminolysis and gelatin grafting process,the amount of amino groups and gelatin could be modeled with quantitative equations as a function of the aminolysis time.Gelatin was demonstrated to control the nucleation and growth of crystals on fibrous templates,and kinetic equations of HA growth were drafted as a function of the incubation time for fibrous mats with different gelatin contents.The composite fibrous mats achieved higher mechanics properties and significantly promote cell attachment,proliferation and differentiation.Different functional groups and the combinations were introduced on PDLLA electrospun fibers to induce HA crystal nucleation and growth.Carboxyl group showed stronger inducing ability for HA formation compared to amine and hydroxyl groups.The combinations of amino,hydroxyl and carboxyl groups on the fibers surface with the mole ratio of 2/3/5 indicated a better inducing effect than other combinations.The combinations of hydroxyl and carboxyl groups on the fiber surface with the mole ratio of 3/7 achieved a better HA formation compared to others.Fibrous composites were obtained with smaller crystal size of HA,higher content of HA and higher mechanic properties.Carboxyl group should combine Ca²⁺ through electrostatic attraction for HA growth,while hydroxyl modulated the carboxyl group density on the fiber surface.The amino,hydroxyl and carboxyl should combine Ca²⁺ through the chelated ring.In conlcusion,this dissertation has clarified the mechanism and methodology to control the morphology and diameters of electrospun fibers,investigated the degradation pattern and surface wettability of electrospun fibrous mats,examined factors determining the drug release profile and degradation behavior of drug loaded fibers,evaluated PEG/PDLLA blend fibers as potential skin tissue engineering scaffold,and exploited novel methods to preprae HA/PDLLA composites fibers through in situ growth, biomacromolecule and functional groups induced mineraliztion.The obtained results will provide theoretic and experimental basis for further research and exploration the application of electrospun fibers and the composites in biomedical fields as drug carriers, tissue engineering scaffold and tissue repair substitutes.