Preparation And Properties Of Injectable Polysaccharide Nanocomposite Hydrogels

Polyhedral oligomeric silsesquioxane?POSS?is a unique nano-scale cubic hybrid molecule consisting of a core inorganic silica cage and an organic group at the apex.The molecule is highly configurable,good compatibility with the polymer system,and can enhance its mechanical properties and thermal stability.More importantly,POSS has the advantages of good biocompatibility and non-toxicity,and is considered to be a new generation of biomedical materials with great application potential.Natural polysaccharides have attracted widespread attention due to their good biocompatibility,biodegradability,low cost and abundant quantity,and have become one of the ideal choices for the construction of injectable hydrogels.However,the mechanical properties of natural polysaccharide hydrogels are poor and their functions are single,which severely limits their further application.In this paper,natural polysaccharides were used as research objects,and two kinds of cage-type polysilsesquioxanes with amino functional groups:cage-like octakis??-chloroaminopropyl?silsesquioxane?OCAPS?and Octachloroamine phenyl silsesquioxane?OAPS?were introduced into the polysaccharide system through dynamic covalent bonds,and three injectable hydrogel systems based on Schiff base bond were prepared,and the structure,properties and applications of the three hydrogel systems were studied.The research contents are as follows:1.First,hydroxypropyl cellulose?HPC?is introduced into the aldehyde group by sodium periodate?NaIO₄?oxidation,followed by HPC of containing aldehyde groups and chitosan?CS?as reactants,and OCAPS is a multifunctional crosslinker and nano-enhancer.A Schiff base-based CS/HPC/OCAPS hydrogel was constructed by solution blending under physiological conditions.It was found that the CS/HPC/OCAPS hydrogels of gelation time was suitable under the conditions of 5.0 wt%CS and pH 5.9,and the gelation time was regularly reduced from 80s to 49 s with the increase of OCAPS content in the gel system,and have good injectability.Due to the presence of dynamic Schiff base bonds in the hydrogel,it has good pH responsiveness and self-healing properties.FTIR,XRD,SEM and EDX analysis showed that the introduction of OCAPS affected the hydrogen bonding between CS and HPC molecules,interfered with the ordered arrangement of molecules and reduced the crystallinity of CS.As the OCAPS content increases,the pore diameter of the hydrogel gradually decreases,and the pore structure becomes denser and denser.At the same time,OCAPS has good dispersibility in hydrogels.Mechanical properties studies show that the introduction of OCAPS can improve the elastic modulus,viscous modulus,compressive strength and compressive modulus of CS/HPC/OCAPS hydrogels.The BSA release behavior and in vitro degradation performance test of CS/HPC/OCAPS hydrogels showed that the introduction of OCAPS can increase the cumulative release rate of CS/HPC/OCAPS hydrogel and reduce the degradation rate of CS/HPC/OCAPS hydrogels.The release mechanism of BSA is the result of a synergistic effect of the major Fickian diffusion and minor dissolution release.Biocompatibility test results show that CS/HPC/OCAPS hydrogels have good biocompatibility and anti-hemolytic properties.Conductivity tests show that CS/HPC/OCAPS hydrogels have good electrical conductivity.2.A water-soluble acylated chitosan?NCS?was prepared by acylation of chitosan with succinic anhydride.Sodium alginate is oxidized by sodium periodate to prepare oxidized sodium alginate?OSA?containing aldehyde functional groups.NCS/OSA/OCAPS hydrogels based on Schiff base bond were prepared by aldehyde amine condensation reaction of OSA,NCS and OCAPS.In this study,with the introduction of OCAPS in the system and the increase of the content,the color of the hydrogels gradually deepened,the transparency gradually decreased,the gelation time decreased from 220 s to 40 s,and good injectability.FTIR and XRD analysis showed that the imine bond?-C=N-?was present in the hydrogel network and destroyed the ordered structure of OCAPS and NCS/OSA,resulted the crystallinity decreased.SEM and EDS observations show that the higher the OCAPS content in the hydrogels,the smaller the pore size,the thinner the wall thickness,the denser the network structure,and the better the dispersion of OCAPS in the hydrogels.Rheological and compression properties studies have shown that the introduction of OCAPS can improve the elastic modulus,viscous modulus,loss factor,compressive strength and compressive modulus of NCS/OSA/OCAPS hydrogels.Drug release behavior and in vitro degradation performance tests showed that compared with NCS/OSA hydrogel,the drug loading rate and cumulative release rate of NCS/OSA/OCAPS increased,and the degradation rate decreased.Biocompatibility studies have shown that NCS/OSA/OCAPS hydrogels have good biocompatibility and resistance to hemolysis.Conductivity studies have shown that NCS/OSA/OCAPS hydrogels have good electrical conductivity.3.A water-soluble octaaminoamine phenyl cage silsesquioxane?OAPS?was synthesized by using phenyltrichlorosilane as raw material and benzyltrimethylammonium hydroxide as catalyst.The OAPS was introduced into the CS/HPC system to prepare a CS/HPC/OAPS nanocomposite hydrogel based on Schiff base bond of aromatic amine and fatty aldehyde.The CS/HPC/OAPS hydrogels have excellent injectability.With the increase of OAPS content,the hydrogels are easier to form,and the gelation time is reduced from 80 s to 62 s.At the same time,the pore size of the hydrogels are reduced and the wall thickness are thinned.Although the yield strain of CS/HPC/OAPS hydrogel ranges from 7.1 to 33.2%,which is lower than the yield strain of CS/HPC hydrogel by 314.6%,However,its modulus of elasticity,viscous modulus,compressive strength and compressive modulus are all improved.The presence of OAPS in the hydrogel increases the loading rate and cumulative release rate of the gel,and reduces the degradation performance of CS/HPC/OAPS,indicating that its have potential application value in the field of drug carriers.Conductivity studies have shown that NCS/OSA/OCAPS hydrogels have good electrical conductivity.