Construction And Application Of Hemicellulose-based Self-assembled Micelles And Its Composite Hydogels

The conversion of waste biomass raw materials into environmentally friendly,high value-added bio-based materials through biorefining technology is the current research hotspot and important development direction,which meet the major strategic needs of the country.It is important for replacing fossil resources,developing circular economy,and building a resource-conserving and environment-friendly society.In this work,hemicellulose by-products produced during the production of dissolving pulp by the pre-hydrolysis kraft pulping were used as raw materials,analyzed the chemical structure of hemicellulose and polymer chain conformation,amphiphilic modification of hemicellulose and its self-assembly behavior were studied,the enhancement mechanism of self-assembly micelles as macro-crosslinkers for micelle hydrogel composites was studied,and preliminary studied the micelle hydrogel composites in sustained release applications.The main research contents and conclusions can be summerized as follows:(1)Using a variety of analysis and characterization methods for structural characterization,it was found that the hemicelluloses were mainly composed of linear?-(1-4)glycosidic bonds connected D-xylose units.This xylan-based hemicellulose can be completely dissolved in a good solvent of dimethyl sulfoxide as a single molecule chain,and its molecular mass(M_w)was 57400 g/mol.Static light scattering data analysis showed its square radius of rotation(R_g)was 150 nm,and its the chain conformation was a flexible linear chain.Using various hydrophobic chain fatty acids for homogeneous hydrophobic esterification,a series of amphiphilic hemicellulose grafted fatty acid polymers with similar degree of substitution of hemicellulose were synthesized.After modification,the crystalline structure of hemicellulose was destroyed and the thermal stability was reduced,too.The flexible linear chain conformation of hemicellulose was transformed into a hard sphere of hemicellulose-graft-fatty acid micelles through hydrophobic interaction.The results showed that hemicellulose-graft-fatty acid can self-assembled in aqueous solution,forming compact core-shell structured micelles with hydrodynamic radius(R_h)varied from 34?57 nm and radius of gyration(R_g)varied from 30?44 nm.It was also found that,with the increased of the hydrophobic chain length,the R_h,R_g,zeta potential and critical micelle concentration(CMC)of the micelles gradually decreased.The aggregation number of micelles can be controlled by adjusting alkyl chain lengths.In addition,the curcumin(Cur)-loaded micelles exhibited a chain length-controlled drug release.(2)Prepared amphiphilic hemicellulose-graft-lauric acid(H-LA)polymers by alkylation modification,and then self-assembled through hydrophobic association interaction in aqueous solution to form spherical nanomicelles with certain hydrophobic domains.Its molecular chain conformation was hard sphere conformation.Then,H-LA nanomicelles were used as macro-crosslinkers to polymerize with acrylamide monomer to form micelle hydrogel composites.This kind of hydrogel composites based on the physical interaction of hydrogen bonds and hydrophobically associated micelles caused corresponding slippage through intermolecular hydrogen bonding,micellar deformation and intertwined chains inside the micelles when deformed under loading.Dissipate energy by removing and unwinding,thereby improving the mechanical properties and fatigue resistance of the hydrogel.The results showed that as the concentration of H-LA micelles increased,the network density of the non-covalent physical crosslinking of the hydrogel increased,and the mechanical properties of the hydrogel were improved.When the micelle concentration was 1%,the tensile strength and elongation at break of the micelle hydrogel composites were 0.175 MPa and 1140%,respectively,which were increased by 3.2 times and 1.87 times compared with the blank PAM hydrogel.(3)By further functionalizing the alkylated modified H-LA polymer,an amphiphilic polymer(H-LA-GMA)with unsaturated double bonds(DS=0.5)and long carbon chains(DS=0.5)was obtained,and then self-assembled through hydrophobic association interaction in aqueous solution to form spherical nanomicelles with double bonds.The H-LA or H-LA-GMA micelles were then introduced as non-covalent and covalent macro-crosslinkers to in situ copolymerize with polyacrylic acid-co-dimethylaminoethyl methacrylate P(AA-co-DMAEMA)/sodium alginate double network hydrogel to form a pH-responsive,glutathione/ethylenediaminetetraacetic acid(GSH/EDTA)synergistic responsive micelle hydrogel composites.The results showed that the elongation at break,tensile stress and compressive stress were increased after the addition of micelles.The curcumin encapsulated micelles cross-linked into the hydrogel network to achieve sustained and responsive drug release.At low pH,the equilibrium swelling ratio of the hydrogel increased,while the mechanical properties decreased,and the diffusion and release rate of micelles and drugs were increased.The double-bond functionalized hydrogels formed a denser network structure,so that the diffusion and release rate of micelles and curcumin were slower,and they had a long-term drug release effect.The EDTA/GSH stimulus response results of the hydrogel showed that after adding a certain concentration of EDTA or GSH,the compressive stress of the hydrogel was significantly reduced,and the release rate of micelles and drugs was accelerated.When the concentration of EDTA and GSH was 20 m M and 60 m M,respectively,the physically cross-linked micelle hydrogel composites were completely degraded into a viscous solution,and the diffusion and release of micelles and curcumin were significantly enhanced.The hydrogel composites with curcumin encapsulated in micelles had good antibacterial and antioxidant properties.The cytotoxicity experiment showed that these micelle hydrogel composites had good biocompatibility with NIH3T3 cells.(4)Preparation of hemicellulose graft polymers with hydrophobic long chain and amino functionalization through transesterification reaction and thiol-ene click reaction,and then self-assembled to form nanomicelles.After curcumin was encapsulated,Cur-loaded micelles with hydrodynamic diameters of 56 nm and 71 nm were formed.The functionalized Cur-loaded micelles were introduced into the aldehyde-based nanocellulose(CNF-DA)and carboxymethyl chitosan(CCS)system to construct a dynamic imine bond-based antibacterial,antioxidant and biocompatible all-biomass-based injectable micelle hydrogel composites for drug delivery system.The results showed that the gelation time was shortened as the concentration of the monomer solution increased under neutral conditions.The amino-functionalized micelles were cross-linked into the three-dimensional hydrogel network through dynamic imine bonds,which improved the cross-linking density and mechanical properties of the hydrogels,moereover,gelation time was accelerated.This micelle hydrogel composites showed a pH-responsive sol-gel transition behavior and a controlled release of curcumin.The Cur-loaded micelle hydrogel composites had good antibacterial properties,antioxidant ability and biocompatibility.In summary,the multifunctional injectable pH-responsive drug-loaded micelle hydrogel composite materials have potential applications in the field of intelligent drug delivery system.