Preparation And Application Of Double-network Antibacterial Hydrogel With High Adhesion

Skin—the largest organ of the human body,as the first line of defense for human immunity,can block the invasion of most pathogenic microorganisms.Since the skin contains a variety of complex cell networks,they carry out a variety of cell communication to maintain the immune response in the body to maintain the dynamic balance of the human body environment,thereby actively protecting the individual from external threats.While the integrity of the skin is destroyed,the dynamic balance will be terminated,causing the human body to be infected with pathogenic microorganisms rapidly and serious infections may even bring the risk of death.As the most commonly used medical material for skin wound treatment,medical dressings are mainly used to cover and protect wounds and provide a favorable environment for wound healing.At present,as a new type of wound dressing,hydrogel has received extensive attention due to its content high water and high biocompatibility.On the basis of extensive literatures,the work of this thesis uses chemical cross-linking method to synthesize two kinds of hydrogels with high adhesion,high biocompatibility and excellent antibacterial activity,named Fc-PAAM hydrogel and ICG/EDTA@GTGL hydrogel,respectively.Their physicochemical properties,in vitro antibacterial properties and in vivo antibacterial activity had been characterized.The main research work is as follows:（1）Acrylamide（AM）,methylene bisacrylamide（Bis）and polyacrylic acid（PAA）are the raw materials for hydrogels,which form PAAM double-network hydrogel under the initiation and catalysis of Ammonium persulphate（APS）and Tetramethylethylenediamine（TEMED）.Subsequently,1-（3-Dimethylaminopropyl）-3-ethylcarbodiimide hydrochloride and N-Hdroxysuccinimide（EDC/NHS）was used to activate the carboxyl group（-COOH）of the PAAM hydrogel,and the aminoferrocene（Fc-NH₂）was modified to the PAAM hydrogel to form a Fc-PAAM hydrogel.The scanning electron microscope（SEM）,Fourier infrared spectrometer（FT-IR）,universal testing machine,hydrogel’s swelling experiment was used to perform the physical and chemical characterization of the PAAM hydrogel.TA fluorescent color reaction,3,3’,5,5’-Tetramethylbenzidine（TMB）and 2,2’-azino-bis（3-ethylbenzothiazoline-6-sulfonic acid）（ABTS）color reaction were characterized the peroxidase-like activity of the Fc-PAAM hydrogel.The in vitro antibacterial and antibacterial biofilm activity of the Fc-PAAM hydrogel was verified by the inhibition zone and crystal violet staining.The cytotoxicity test and mice wound model were proved the high biocompatibility and antibacterial activity of the Fc-PAAM hydrogel.The results exhibited that the Fc-PAAM hydrogel not only had excellent swelling performance,but also had good skin adhesion performance and anti-pressure performance.In addition,the hydrogel had excellent peroxidase-like activity,which could catalyze lower concentration H₂O₂ to produces a large amount of hydroxyl radical（·OH）,showing excellent broad-spectrum antibacterial properties against S.aureus and P.aeruginosa and effectively inhibiting the formation of bacterial biofilms.Fluorescence staining imaging and SEM images further proved that the Fc-PAAM+H₂O₂ system could destroy bacterial cell membrane.Most importantly,the Fc-PAAM as a wound dressing showed good bactericidal activity under the stimulation of low concentration of exogenous H₂O₂ in mice in vivo experiments,and at the same time promoted wound healing.（2）Gelatin and gellan gum were used as raw materials for the hydrogel.The gelatin molecules were chemically cross-linked through EDC/NHS,and then the photosensitizers indocyanine green（ICG）and ethylenediaminetetraacetic acid（EDTA）were mixed with the hydrogel precursor to form the ICG/EDTA@GTGL double-network hydrogel.The scanning electron microscope（SEM）,mechanical performance test,swelling performance were used to perform physical and chemical characterization of the ICG/EDTA@GTGL hydrogel.The 1,3-Diphenylisobenzofuran（DPBF）color reaction was applied to analyze the activity of the ICG/EDTA@GTGL hydrogel to produce ¹O₂.The bacteria plate coating proved in vitro antibacterial activity of the ICG/EDTA@GTGL hydrogel.The result of the cytotoxicity and mice wound model proved the high biocompatibility and in vivo antibacterial activity of the ICG/EDTA@GTGL hydrogel.The results indicated that the ICG/EDTA@GTGL hydrogel had good skin adhesion properties and moderate compression resistance.At the same time,the singlet oxygen（¹O₂）produced by the hydrogel under near-infrared light irradiation at 808 nm expressed excellent antibacterial activity against S.aureus.Finally,the ICG/EDTA@GTGL hydrogel showed good antibacterial activity in vivo and could promote wound healing.In summary,Fc-PAAM hydrogel and ICG/EDTA@GTGL hydrogel are expected to provide new application prospects in the treatment of wound inflammation and ulceration caused by pathogen infection.