Construction Of Low Molecular Weight Hydrogels Using Dynamic Covalent Linkage

Small molecule gelators mediated low molecular weight hydrogels,are usually formed by physical interactions,such as hydrophobic interaction,hydrogen bonding or ?-? stacking.Compared with traditional polymeric hydrogels,these low molecular weight hydrogels possessed several advantages,including facile construction,availability for bio-responsiveness,predictable degradation,and reduced immunogenicity.However,previous low molecular weight hydrogels are generally formed by weak physical interactions,which result in defects,such as low mechanical strength and poor stability.Introducing reversible covalent cross-links into the gel's network may be helpful in the improvement of the hydrogel's properties.To solve this problem,this dissertation developed a series of all-small-molecule dynamic covalent hydrogels through reversible covalent crosslink.Compared with physical interaction mediated supramolecular hydrogel,the hydrogels proposed in this work exhibited improved mechanical strength and stability.In addition,these new hydrogels also exhibit multiple responsiveness and antibacterial ability.This dissertation is comprised of four chapters.Chapter 1 systematically introduced the definition,development,classification and application of hydrogels.Firstly,we focused on polymer hydrogels and small molecule hydrogels.Next,we introduced the application of hydrogels,such as drug delivery,antibacterial medical materials,tissue engineering.Finally,the main concept and content of this dissertation were given.In chapter 2,a class of all-small-molecule dynamic covalent hydrogel were synthesized using aminoglycoside and formaldehyde,and the gelation mechanism and responsiveness properties were investigated.The reaction of formaldehyde with aminoglycosides generates hemiaminal dynamic covalent network which connects aminoglycoside molecules.The abundant hydroxyl groups on the aminoglycosides form hydrogen bonding interactions.Both the interactions contribute to the formation of dynamic covalent hydrogels.The thermal instability feature of hydrogen bonds endows the hydrogel temperature responsiveness,while acid-labile hemiaminal dynamic covalent network leads to the pH-sensitive behavior of the hydrogels.Moreover,the gel stiffness can be easily modulated by the introduction of alkali cations and halogen anions during gel formation.The alkali metal ion enhances the hydrogel's rheological property by coordinating with oxygen atom in hydroxyl group or ether bond that on the aminoglycosides structure.On the other hand,the halogen ion binds with the alkali metal ion,further regulates the performance of hydrogels.Our study suggested that a 65.5-fold increase in gel storage modulus can be achieved in the presence of 20 mM lithium iodide.In chapter 3,to overcome shortcomings of traditional Guanine-quartet(G4)-based supramolecular hydrogels,which are instability and can't be loaded with biologically active molecules,a class of all-small-molecule dynamic covalent hydrogel were prepared using o-aldehyde phenylboronic acid,G4 and aminoglycoside.The oaldehyde phenylboronic acid works as an aptamer to connect G4 and aminoglycoside.The boronic acid group on the molecule can form a boron ester bond with G4,while the aldehyde group forms a Schiff base with the aminoglycoside.As a result,a drugloaded G4 hydrogel constructed by small molecules through dynamic chemical bonds was obtained.The hydrogel shows improved stiffness and stability compared to the pure G4 hydrogel.It exhibits multi-stimuli responsiveness,such as temperature,acidity,glucose and oxidation.The hydrogel also shows good biocompatibility in vitro and in vivo.Finally,the antibacterial experiment suggests that the hydrogels can efficiently kill various bacteria in vitro and in vivo.The fourth chapter summarized the full dissertation and looked forward to the application prospect of all-small-molecule dynamic covalent hydrogel in biomedical field.With the clarification of new responsive mechanism,the introduction of new interactions and the continuous development of new materials,the properties of all-small-molecule hydrogels will be more finely regulated.It is believed that more and more all-small-molecule hydrogels with good mechanical properties,biocompatibility and responsiveness will be developed to meet the different needs of clinical treatment in biomedical fields.