Preparation And Properties Of Multi-Functional Macromolecule Hydrogels For Wound Dressings

The wound healing process is a complex process,involving multiple factors to restore the barrier function of the wound.Traditional wound dressings,such as gauze,sponges,and bandages,have been widely used in clinical practice.However,they usually do not adequately meet the multifaceted requirements of complex wound healing process(e.g.,providing a moist environment,good wound shape adaptation,etc.).Therefore,wound dressings with multifunctionality are essential to provide a stable healing environment.Hydrogels are a kind of soft materials formed by hydrophilic macromolecules or polymers with a three-dimensional network structure,which could mimic the three-dimensional microenvironment of extracellular matrix,and have a wide application prospect in the biomedical field.Compared to conventional wound dressings,hydrogels are easy to use,reduce the risk of infection and promote wound healing.The ideal hydrogel wound dressings must possess the following conditions: 1)biocompatibility.No cytotoxicity during use,does not cause tissuespecific immunogenicity,and has appropriate host responsiveness;2)shape adaptability.In real life,the shape of the wound will not always be regular,which requires the hydrogel to have a good shape adaptability,and be able to completely cover the wound;3)antibacterial and antioxidant properties.The antibacterial and antioxidant properties of hydrogels help to protect wounds from invasion by external microorganisms and scavenge free radicals produced on the wound surface.Therefore,the development of hydrogels with the ability to fulfil the above requirements is crucial in the field of biomedicine.Therefore,in response to these needs,in this thesis,a series of multifunctional hydrogel-based wound dressings were designed to promote wound healing.The results achieved are as follows:1.Inspired by the adhesion mechanism of mussels,the hydrogel wound dressing with high adhesion,self-healing and antimicrobial and antioxidant properties was prepared.Chitosan was modified using lysine to obtain lysine-modified chitosan(CL)polymer.On this basis,CLD polymer was prepared by grafting 3,4-dihydroxyphenylacetic acid onto the CL polymer chain.The presence of phenolic hydroxyl groups endowed the hydrogel excellent adhesion properties to various wet tissue surfaces.In addition,the hydrogel had excellent self-healing properties,antibacterial and antioxidant.Adhesion to wound surface could kill bacteria and effectively scavenge free radicals from the wound surface,reducing the inflammatory response.In the mouse skin defect model,the wound shrinkage rate after CLD hydrogel treatment was much greater than the control group,demonstrated CLD hydrogel could accelerate the wound healing.2.The hydrogel with enhanced antioxidant property was fabricated by cysteinemodified chitosan(CC)with gallic acid(GA).CCG hydrogel could rapidly adhere to various wet tissue surfaces,and the adhesion strength of the hydrogel on pig skin was measured to be up to 10.20 k Pa by tensile test.The hydrogel adhere to the wound surface and could rapid hemostasis of the wound.In addition,the presence of sulfhydryl and phenolic hydroxyl groups endowed the CCG hydrogel with higher antioxidant rate,and its scavenging efficiency of 1,1-diphenyl-2-picrylhydrazyl(DPPH)reached95.83%,which could effectively scavenge the free radicals generated by wound surface and promote the healing of wound.3.The ability to form gels in situ is an important property of wound dressing hydrogels to accommodate irregular deep wounds.A temperature responsive hydrogel(PFLD)was prepared using poloxamer(PF127),lysine(Lys)with antimicrobial activity and 3,4-dihydroxyphenylacetic acid(DOPAC).PFLD hydrogels exhibited excellent antibacterial and antioxidant properties,biocompatibility and efficient hemostatic capacity compared with previously reported thermo-sensitive hydrogels.The in vivo therapeutic efficacy of the PFLD hydrogel dressing was evaluated by wound contraction area,histopathological and immunohistochemistry,indicated that the PFLD hydrogel wound dressings have great potential for skin wound therapy.4.Thermo-sensitive hydrogel(PFNOCMC)was constructed by Schiff base reaction of oxidized carboxymethyl cellulose(OCMC)and aminated poloxamer 407(PF127-Lys).The sol-gel transition could occur at physiological temperature.In addition,the hydrogel has high transmittance(90.1%),excellent mechanical properties and good biocompatibility.Bone morphogenetic protein 4(BMP4)was loaded into PFNOCMC hydrogel could achieve sustained release.In the rat choroidal neovascularization(CNV)model,hydrogel loaded with BMP4 could achieve the sustained release of BMP4,thus inhibiting the formation of CNV.