Preparation Of All-small-molecule Dynamic Covalent Hydrogels With Multistimuli Responsiveness And Antibacterial Applications

Hydrogels have the characteristics of soft texture,porosity,biocompatibility,etc.,making them important applications in drug delivery,tissue engineering,antibacterial materials,biosensors and other fields.Hydrogels can be classified into polymer hydrogels and small molecule hydrogels depending on the composition of the hydrogel.Polymer hydrogels are a relatively large class of hydrogels whose polymer scaffolds can be synthetic hydrophilic polymers or natural biomacromolecules.These hydrogels have high mechanical properties and good biocompatibility,and thus have potential application prospects in the biomedical field.Small molecule hydrogels usually self-assemble to form fibrous supramolecular structures,which are then crosslinked by non-covalent forces between the fibrous structures,such as static electricity or hydrogen bonding.Such small molecule hydrogels have the advantages of ease of construction,stimulus responsiveness,ease of degradation,and low immunogenicity.On the other hand,however,the non-covalent forces that maintain the gel structure are relatively weak,which may result in low mechanical properties and poor stability of the supramolecular gel.Dynamic covalent bonds have the advantages of both covalent bond stabilization and non-covalent bond reversibility,therefore it is one of the effective methods to improve the above problems by introducing dynamic covalent bonds to construct small molecule hydrogels.Therefore,all-small-molecule hydrogels crosslinked by dynamic chemical bonds were designed and prepared.Compared with physically crosslinked supramolecular hydrogels,such all-small-molecule hydrogels crosslinked by dynamic chemical bonds have the advantages of high mechanical strength and good stability,and dynamic chemical bonds impart multi-stimulation responsiveness to the gel.The paper is divided into five chapters.The first chapter introduces the definition,classification and applications of hydrogel in the fields of drug delivery,tissue engineering,antibacterial materials,biosensors and so on.Polymer hydrogels and small molecule hydrogels are highlighted in the classification of hydrogels,and a class of stimuli-responsive hydrogels is described separately.Finally,the research ideas and research contents of this thesis are expounded.In the second chapter,all-small-molecule hydrogels with dynamic covalent bond cross-linking were prepared.The gelation mechanism and various properties of the hydrogel were studied.Further,the effects of gelatin concentration and pH on gelation and the effect of gelatin concentration on gelation time and gelation modulus were also explored.The all-small-molecule hydrogels were formed by a reversible Schiff base bond that formed by aldehyde group of the 3,4-dihydroxybenzaldehyde and the amino group of the aminoglycoside antibiotic,dynamic coordination bond that formed by the ortho-dihydroxy structure of 3,4-dihydroxybenzaldehyde and trivalent iron and hydrogen bond formed between sugar units in aminoglycoside antibiotic molecules.The elemental concentration affects the gelation and the gelation time and the gelation modulus by affecting the degree of crosslinking of the gel.The study found that when the final concentration of FeCl₃·6 H₂O was fixed,the final concentration of tobramycin changed from 105 mg/mL to 210 mg/mL,the time required for gelation was shortened by about 10 times,and the modulus had increased by about 6 times.The pH affects the gelation by affecting the dynamic Schiff base bond and the dynamic coordination bond.It has been found that a hydrogel cannot be formed at pH≤5.0.The third chapter explores the responsiveness of hydrogels.The prepared gels have multiple responsiveness such as temperature response,light responsiveness,redox responsiveness,acid responsiveness and electrical responsiveness.The reason for its temperature responsiveness is that the hydrogen bond utilized by crosslinking has thermal instability;The reason for photoresponsiveness is that the gel can absorb light energy and convert light energy into heat energy,thereby destroying hydrogen bonding interaction;The reason for redox responsiveness is that Fe（III）can be reduced to Fe（II）by a reducing agent,then the tricoordinated chelate is converted into a di-coordinated or mono-coordinated compound to destroy the crosslinked network;The reason for the acid response is that the dynamic Schiff base bond and the dynamic coordinate bond have acid instability;The reason for the electrical responsiveness is that when copper is used as an electrode,a reduction reaction occurs at one endof the negative electrode of the power source（cathode）,and Fe（III）is reduced to Fe（II）to destroy the crosslinked structure.When graphite is used as an electrode,Fe（III）is reduced to Fe（II）at the negative end of the power source（cathode）.At the same time,H₂O is oxidized at the positive end of the power source（anode）to form O₂ and H⁺,thus the resulting H⁺further destroys the crosslinked network formed by the dynamic Schiff base and the dynamic coordination bond.The fourth chapter studies the antibacterial properties of hydrogels.According to previous studies,the hydrogel has acid responsiveness and can release tobramycin and3.4-dihydroxybenzaldehyde by acid response in a weak acid environment in which E.coli grows,and thus has highly effective antibacterial properties in vitro.After the hydrogel is made into a film,it still has significant antibacterial activity in vitro,which indicates that the hydrogel film has potential application value as an antibacterial coating for medical devices.The hydrogel can be prepared by replacing tobramycin in the gel with other aminoglycoside antibiotics such as neomycin sulfate,and the prepared gel has high antibacterial properties in vitro.The fifth chapter summarizes and forecasts the full text,focusing on the innovation of this topic:（1）The materials used in this work are all natural small molecules,and there is no pre-synthesis work.The preparation method of the gel is simple,and no complicated preparation process is required.（2）The building blocks forming the hydrogel are derived from natural sources,so the products of hydrogel degradation are natural small molecules,and the use of the gel is environmentally friendly.（3）Dynamic covalent bond imparts multiple responsiveness to the gel,such as temperature、light、redox、pH、electricity,etc.The hydrogel degradation behavior can be adjusted by adjusting temperature,light,redox,pH,electricity and other factors.