Preparation And Properties Of Injectable Composite Hydrogels Based On Modified Hyaluronic Acid And Sodium Alginate

Injectable hydrogels have attracted much attention for their high plasticity,minimally invasiveness,simple and effective packaging of cells and drugs.But there are still problems,such as the poor compatibility of different crosslinking pattern,poor toughness,and low mechanical strength,etc.Due to easy operation and mild reaction conditions of hydrazide bonds and/or disulfide-bonds crosslinking hydrogels,in this thesis,a series of injectable modified hyaluronic acid/alginate composite hydrogels were prepared via hydrazone bonds and/or disulfide bonds crosslinking.The gelling time,rheological properties,swelling,degradation,and drug release behavior in vitro were investigated in detail.1.Hydrazide-modified hyaluronic acid(HA-CDH)was synthesized by amide coupling reaction,and a series of injectable hydrogels(HA-CDH/oxi-ALG)were prepared via Schiff base reaction of HA-CDH and oxidized sodium alginate(oxi-ALG).The gelling time,rheological properties,morphologies,swelling ratio,degradation percentage and drug release behavior of hydrogels were investigated.The results showed that the gelling time,swelling ratio,degradation percentage and rheological properties of HA-CDH/oxi-ALG hydrogels can be adjusted and controlled by changing the concentration of precursor solution.For HA-CDH/oxi-ALG2,HA-CDH/oxi-ALG3,and HA-CDH/oxi-ALG4 hydrogels,the gelling time were 3729,1020,and 360 s,the values of yield stress were 1941,3395,and 4863 Pa,the composite shear modulus were 833,2103,and 3823 Pa,the swelling ratio were 34.49±0.42,25.99±0.52,and 24.06±1.05 after incubating 10 hours,the degradation percentage were 68.24±1.14%,59.36±2.91%,and 50.05±1.52% after incubating 26 days,respectively.Bovine serum albumin(BSA)was used as a model drug to investigate the release properties,and the in vitro cumulative release percentage of BSA from drug-loaded HA-CDH/oxi-ALG2,HA-CDH/oxi-ALG3,and HA-CDH/oxi-ALG4 hydrogels were 83.09±4.26%,76.66±0.97%,and 70.11±5.41% after incubating 10 days,respectively.2.A series of injectable in situ dual-crosslingking hydrogels(HA/ALG)based on oxidized sodium alginate(oxi-ALG)and hyaluronic acid modified with thiol and hydrazide(HA-SH/CDH)were prepared via hydrazone and disulfide bonds crosslinking.The gelling time,rheological properties,morphologies,swelling ratio,degradation percentage and drug release behavior of hydrogels were investigated.HA/ALG hydrogels exhibited tunable gelling time,rheological properties,swelling ratio,and degradation percentage with varying precursor solution concentrations.For HA/ALG2,HA/ALG3,and HA/ALG4 hydrogels,the gelling time were 955,307,and 157 s,the values of yield stress were 1724,4349,and 5306 Pa,the composite shear modulus were 825,2822,and 4662 Pa,the degradation percentage were 63.64±2.74%,51.42 ±5.08%,and 41.61±2.82% after incubating 35 days,respectively.The in vitro cumulative release percentage of BSA from drug-loaded HA/ALG2,HA/ALG3 and HA/ALG4 hydrogels were 78.64±7.66%,72.00±6.19%,and 69.11±2.78% after incubating 20 days,respectively.3.TEOS and BTES were used as precursors,and CTAC was used as a structure-directing agent,hollow mesoporous organosilicon nanoparticles(HMON)were prepared by sol-gel method.HMON were further modified to prepare the thiol-functionalized hollow mesoporous organosilicon nanoparticles(HMON-SH).A series of HMON-SH@HA/ALG composite hydrogels were prepared by combining HMON-SH with HA/ALG hydrogels.The morphologies,swelling and degradation behavior of composite hydrogels were investigated.The results showed that the swelling ratio of HMON-SH@HA/ALG composite hydrogels were lower than those of the series of HA/ALG hydrogels.For HMON-SH@HA/ALG2?HMON-SH@HA/ALG3 and HMON-SH@HA/ALG4 composite hydrogels,the swelling ratio were 27.11±3.10,21.25±2.29,and 20.71±0.35 after incubating 10 hours,and the degradation percentage of were 46.34±4.88%,44.45±1.92% and 39.34±2.78% after incubating 35 days,respectively,which were less than those of the series of HA/ALG hydrogels from same concentration of precursor solution.Therefore,HMON-SH@HA/ALG hydrogels exhibited better stability than HA/ALG hydrogels.In summary,the series of injectable hydrogels based on modified hyaluronic acid and sodium alginate have good comprehensive properties and could be potentially applied in the fields of drug delivery,tissue engineering,and regenerative medicine.