Hydrogels Based On The Hyaluronic Acid And Poly(?-Glutamic Acid) For Biomedicine Application

Hydrogels are three-dimensional networks with high water content,which are prepared by physical or chemical crosslinking and have a high permeability for oxygen,drugs and other water-soluble nutrients and metabolites.Besides,hydrogels prepared by natural polymers also have excellent biocompatibility.Therefore,hydrogels have been extensively used as delivery vehicles for therapeutic agents or as cell scaffold materials for tissue engineering.In this thesis,inspired by nature extracellular matrix(ECM),we chose hyaluronic acid(HA)as a backbone of the polymer network because it is an important glycosaminoglycan found in ECM.Collagen is also an important component of ECM,but due to the complexity and diversify of collagen,synthesized ECM often have a batch-to-batch variability.So we use poly(?-glutamic acid)(?-PGA)with a single structure as a substitute for collagen.Literature research found that both HA hydrogel and y-PGA hydrogel have good biocompatibility and biodegradability,but their mechanical properties are often weak.Due to their high hydrophilicity and enzymatic degradation,HA hydrogel and y-PGA hydrogel were easy to be corroded and degraded in vivo.In addition,the single component hydrogels are not conducive to be further functionalized due to the lack of active sites.These disadvantages impede their biomedical application.Previous work indicated that HA or y-PGA hydrogels prepared with other polymers,due to the diversity of composition and cross-linking,showed good mechanical properties and more active sites.Moreover,the swelling behavior,degradation behavior and mechanical properties as well as other important properties could be modulated conveniently.For the above reasons,hydrogels based on HA and y-PGA were prepared via different crosslinking methods(Photopolymerization,Schiff base reaction,Host-Guest complexation,etc.).The gelation time,swelling behavior,degradation behavior,thermal stability,mechanical properties and cell compatibility were investigated.Then the applications in drug carrier and cell 3D culture were evaluated.It was found that the prepared HA/?-PGA hydrogels had fast swelling rate,good thermal stability and enzymatic degradation.Rheological measurement and unconfined compression test found that hydrogels prepared by photopolymerization had excellent anti-compressive properties,while hydrogels prepared by Schiff base reaction had outstanding elastic properties.Combining the advantages of photopolymerization and Schiff base reaction,we prepared interpenetrating network hydrogels with better mechanical properties and hydrogels with graded controllable crosslinking degree.In vitro drug release behavior indicated that the drug-loaded hydrogels showed a weak burst release and sustained release behavior due to the rapid swelling of hydrogels in the early stage.In addition,MTT assay and live/dead assay confirmed that the functionalized polymers held excellent biocompatibility.Cell 3D culture found that the encapsulated NIH 3T3 cells showed a high viability,which indicated that HA/?-PGA hydrogels had great potential applications in 3D cell culture for tissue engineering.Finally,inspired by the ability of autonomously healing of biological tissues,combining the advantages of host-guest complexation and covalent crosslinking,we prepared a double-network hydrogel with stable structures and rapid self-healing properties.