Preparation And Biomedical Applications Of Water Resistant Polysaccharide Nanofibers

Polysaccharide nanofibers combine the material advantages of polysaccharides such as biocompatibility,biodegradability and hydrophilicity and the structural advantages of nanofibers such as high specific surface area and high porosity,which are promising for biomedical applications.Poor water resistance is the key issue limiting the biomedical applications of polysaccharide nanofibers.The existing crosslinking methods can improve the water resistance of nanofiber membranes to a certain extent,but they suffer from high toxicity and low efficiency.The aim of this thesis is to develop safer and more effective methods to improve the water resistance of polysaccharide nanofibers,so as to develop more polysaccharide nanofiber materials with better performances and lay a foundation for their applications in biomedical fields.The main research content and results of this thesis include the following four aspects:In the first part,for neutral polysaccharides,a cross-linking method of periodate oxidation-dihydrazide was developed,and the differences in biomedically relevant properties between nanofibers prepared using this cross-linking method and the conventional glutaraldehyde cross-linking method were investigated.Using konjac glucomannan as a representative neutral polysaccharide and adipic dihydrazide as a representative dihydrazide,the periodate oxidation-dihydrazide crosslinked nanofibers showed better nanofiber morphology,significantly better water resistance(wet Young’s modulus up to 13.1 MPa,weight loss not more than 20% after 4 weeks of incubation in simulated body fluids)and better biocompatibility(weight loss not more than 20% after 4 weeks of incubation in simulated body fluids)than the glutaraldehyde crosslinked nanofibers,and better biocompatibility(no cytotoxicity),which can meet the needs of some biomedical applications.In the second part,based on the work in the first part,the versatility of the periodate oxidation-dihydrazide crosslinking strategy to various polysaccharides and various dihydrazide crosslinkers was investigated.The effect of the chemical structure of the dihydrazide crosslinker on the water resistance of the crosslinked fibers was investigated in detail.Other neutral polysaccharides such as starch and pullulan could also be fabricated into biocompatible and water-resistant nanofiber materials with the periodate oxidation-dihydrazide crosslinking strategy.Four dihydrazide crosslinkers with different alkyl sizes were used to crosslink the electrospun nanofibers of periodate oxidized konjac glucomannan.It was found that either too small or too large alkyl group would lead to the decreased solubility of the dihydrazide in ethanol/water mixed solvents,and that intermediate alkyl sizes favored the solubility.At the same crosslinker concentration,as the size of the alkyl group increased,the wet strength of the fiber membranes first decreased and then increased,and the degradation rate slowed down.For the same crosslinker,as its concentration increased,the wet-state tensile strength of the crosslinked fiber membranes increased and the degradation rate slowed down.All dihydrazide-crosslinked fibers had good cytocompatibility.The wet strength of nanofiber membranes with different dihydrazide crosslinks was in the range of 4 ～ 6 MPa,and the degradation rate was adjustable in the range of 20% ～ 50% after 4 weeks of incubation in simulated body fluids.In the third part,the application of periodate oxidation-diacylhydrazine cross-linking method in the preparation of water-resistant cellulose nanofibrous materials was expanded,and the biomedical properties of the related materials were investigated.The non-water-soluble cellulose micropowder is soluble in water by periodate oxidation and can be further electrostatically spun in pure water solvent to form nanofibers.The wet strength of oxidized cellulose nanofiber membrane after adipic dihydrazide crosslinking can reach about1 MPa,and it can absorb 10 ～ 30 times of its own weight of simulated wound exudate,with a mass loss of no more than 30% after four weeks of incubation in simulated body fluids,with good cytocompatibility,and it may be used as a wound dressing for the treatment of heavily exuding wounds.In the fourth part,for chitosan,an alkaline polysaccharide,a direct preparation of water-resistant nanofibers by electrostatic spinning of acetate precursors was developed and the fibers were applied for drug loading and development of functional medical materials.The chitosan acetate precursor was first prepared,and the chitosan acetate could be directly decomposed during the electrospinning process,to form water-resistant chitosan nanofibers.Compared with the chitosan nanofibers prepared by the conventional acid-soluble electrospinning,the chitosan nanofibers prepared by electrostatic spinning of the acetate precursor have smaller size,higher crystallinity and slower degradation.Chitosan nanofiber membranes containing small molecule antimicrobial drugs such as rifampicin and minocycline were further developed by co-spinning,achieving a long-lasting antimicrobial performance of 7 days,which may be used for the treatment of infected wounds.Bovine serum albumin as a model protein can also co-spun into the chitosan nanofibers,achieving a controlled and sustained release over 2 weeks.In summary,this thesis developped new methods to improve the water resistance of polysaccharide nanofibers,obtained a series of polysaccharide nanofiber materials with good biocompatibility,excellent water resistance,tunable properties,and possibility to be further functionalized,and laid the foundation for their applications in biomedical fields such as wound healing and drug delivery.