Fabrication Of Supramolecular Hydrogels With Antibacterial Activities From Peptides And Polyphenols

Bacterial infection is a clinically common disease that seriously threatens human health and affects normal human life.The bacterial infections,whether introduced by surgery or implants,can result in slow wound healing and even life-threatening conditions in severe cases.Therefore,clinical used antibiotics or some antibacterial drugs to prevent bacterial infections.However,with the widespread use of antibiotics,drug-resistant microorganisms appear and are renewed as antibiotics are renewed.At the same time,traditional antibiotics cannot achieve the best therapeutic effect due to their poor solubility and toxicity due to excessive local drug dosage.Therefore,natural polyphenols with good biocompatibility,degradability,oxidation resistance,antiviral and antibacterial properties emerge as new candidates for antibacterial agents.Antibacterial hydrogels prepared by adding bacteriostatic agent within gel matrix can not only reduce the risk of bacterial resistance,but also regulate their antibacterial activities.Its special three-dimensional pore structure can be made by physical or chemical cross-linking to achieve slow control and controlled release of encapsulated drgs.In turn,the frequency of administration of drugs is lowered,and the compliance with organisms is improved.It is also possible to design environmentally sensitive hydrogels as needed to increase the porosity under specific environment and the outflow of the contents to achieve the purpose of targeted therapy.Among them,hydrogels with inherent antibacterial ability are also widely used in the field of biomedicine because of their almost non-toxic characteristics and excellent antibacterial properties.Therefore,the main research contents of this thesis include design and synthesis of hydrogels with tissue adhesion,antioxidation resistance and antibacterial properties by using cross-linking between natural polyphenols and regenerated natural modecules.Furthermore,we also explore the potential application of the hydrogel in promoting tissue healing in the field of tissue engineering.The first part of this paper describes a simple and easy-to-use method that promotes the gelation of silk fibroin(SF)and imparts its antibacterial and versatile properties.Tannic acid(TA)is simply added to the SF to accelerate the SF sol-gel transition under physiological conditions and increase the mechanical strength of the gel.Due to the multi-functionalitis of TA,the prepared SF-TA gel has good tissue adhesion and exhibits excellent radical scavenging efficiency in antioxidant experiments.Mouse fibroblasts(NIH-3T3)cultured on SF-TA gel adhered well to the gel surface and showed significant growth and proliferation.In vitro antibacterial experiments showed that the SF-TA gel showed significant inhibitory activity against both Gram-positive and Gram-negative bacteria.Because of its inherent antibacterial,antioxidant activity,injectable and good biocompatibility with mammalian cells,SF-TA gel can be used to treat wound of a full-thickness skin defect infected with bacteria in mice,exibiliting high potetials to accelerate the wound healing process and promote the formation of new tissue.The second part of this thesis is about the synthesis of two kinds of peptide-based gelators,which consisted of a naphthyl group,a tetrapeptide segment(Phe-Phe-Lys-Tyr(H2PO3))and a caffeic acid or a gallic acid moiety attachted to the side chain of Lys via amide linkage(e.g.,NapFFK(CA)Yp and NapFFK(GA)Yp).The introduction of gallic acid(GA)and caffeic acid(CA)endows gels with excellent antioxidant and antibacterial properties.The naphthyl moiety and Phe-Phe dipeptide segment acted as a rigid scaffold to promote supramolecular self-assembling of gelators via extended aromatic-aromatic interactions;the Lys group was exploited for site-specific caffeic acid or gallic acid modifications;and the tyrosine phosphate group(e.g.,Tyr(H2PO3))worked as an excellent substrate of alkaline phosphatase for catalytic supramolecular gelation.Because of good sensitivity toward alkaline phosphatase for dephosphorylation reaction,these two gelators can undergo supramolecular self-assembly under physiological conditions and form hydrogels with excellent mechanical properties.Due to the modification by caffeic acid and gallic acid,these two gelatorsexhibited good free radical scavenging properties,and antibacterial activities against E.coli.