Preparation And Properties Of Modified Hyaluronic Acid Hydrogels Based On Schiff Base Reaction

Natural polymer hydrogels have become one of the research focuses of biomedical polymer materials because of their wide application in drug delivery,tissue engineering,and other fields.However,some hydrogels have weak mechanical strength or complex preparation methods.In this thesis,a series of hyaluronic acid-based hydrogels were prepared via Schiff base reaction,and the rheological properties,microstructure,swelling behavior,degradation behavior,and in vitro release behavior of bovine serum albumin(BSA)were investigated.1.Oxidized hyaluronic acid(oxi-HA)was carried out by partial oxidation of hyaluronic acid,and the oxidation rate was about 49%.2.The redox responsive oxidized hyaluronic acid/3,3’-dithiobis(propionohydrazide)(oxi-HA/DTP)hydrogels were prepared by crosslinking oxi-HA with DTP via Schiff base reaction at 37 oC,and characterized by FT-IR spectroscopy.The oxi-HA/DTP hydrogels showed good rheological properties,good stability,fast swelling rate and high equilibrium swelling ratio(SR > 16)in phosphate buffered saline(PBS)solution,and the comprehensive performance of oxi-HA5/DTP6 hydrogel was better than it of others.It showed that DL-1,4-dithiothreitol(DTT)could accelerate the degradation of hydrogels and the release of BSA,the degradation rate of hydrogels and the release rate of BSA were increased with increasing concentration of DTT.The cumulative release of BSA was about 68% in PBS solution after 180 h,while it was up to 95% in PBS with 1 mmol·L-1 DTT after 84 h and BSA was almost completely released in PBS with 10 mmol·L-1 DTT solution within 3 h.3.Oxi-HA was crosslinked with 3,3’,3’’-nitrilotris(propionohydrazide)(NTP)via Schiff base reaction to prepare oxidized hyaluronic acid/3,3’,3’’-nitrilotris(propionohydrazide)(oxi-HA/NTP)hydrogels at 37 oC,and the effects of concentrations of oxi-HA and NTP on the properties of hydrogels were discussed.Lyophilized oxi-HA/NTP samples showed a continuous porous structure.Oxi-HA/NTP hydrogels showed good rheological properties,fast swelling rate and great equilibrium swelling ratio and good stability.The oxi-HA6/NTP8 hydrogel showed the best comprehensive performance,and the complex shear modulus of oxi-HA6/NTP8 can reach 15.46 kPa,and the yield stress can reach 2963 Pa,the degradation percentage within 20 days was56.65 ± 3.22%,the equilibrium swelling ratio was 13.19 ± 0.63.The results showed that the cumulative release of BSA from oxi-HA6/NTP8 drug-loaded hydrogel was98% within 156 h in PBS solution at 37 oC.In conclusion,all hyaluronic acid-based hydrogels which prepared via Schiff base reaction showed good performance,and they could be potentially applied in the fields of short-and medium-term protein drugs controlled release.