The Preparation Of Conductive Macroporous Nanocomposite Hydrogels Towards Skin Wound Healing

Polymer hydrogels applied widely in tissue repair and regenerative medicine due to its mimic extracellular matrix(ECM)functions.The interconnected porous structure with appropriate size in hydrogel is conducive to the transportation of nutrients and the discharge of cell metabolic waste.Hydrogels which have electrical conductivity could realize electrical signal transduction,simulate the extracellular matrix microenvironment to regulate cell proliferation,differentiation and migration,etc.,thereby promoting wound healing and tissue regeneration.In this dissertation,we use air-in-water emulsion template and the strategy of composite conductive active ingredients,develop conductive nanocomposite hydrogel with connected porous structure,and explore its effect on skin wound healing and tissue repair.The main research contents and results are as follows:The hybrid formed by the compound of methacrylic acid acylated gelatin(Gel MA)and carbon nanotubes(CNT)was used as stabilizer to prepare the air-in-water emulsion template.Through continuous phase free radical polymerization,we construct conductive macroporous nanocomposite hydrogel(MNH).Experimental results show that Gel MA can be adsorbed on the surface of CNTs and promote the uniform dispersion of CNTs,the CNT/Gel MA hybrid can effectively stabilize the air-in-water emulsion.The introduction of CNT significantly enhances the mechanical properties and electrical conductivity of the porous hydrogel.The results of the co-culture of cells and hydrogel shows that MNH hydrogel has good cell compatibility and could effectively promote the proliferation and differentiation of NE-4C neural stem cells.In addition,MNH hydrogel can load and release antimicrobial peptides(AMPs)to achieve long-lasting antibacterial effect.Animal model of skin wounds prove that MNH conductive porous hydrogel has good tissue compatibility and can effectively promote skin wound healing.In order to broaden the application of macroporous hydrogels,further developing conductive macroporous nanocomposite hydrogel with both hemostatic and tissue adhesion properties.Taking poly(3,4-ethylenedioxythiophene):poly(styrenesulfonate)(PEDOT:PSS),nano-clay hectorite(Laponite)and Gel MA as unit,conductive macroporous nanocomposite hydrogel GLP is prepared also by air-in-water emulsion template and free radical polymerization.The electrostatic interaction between three components effectively enhances the mechanical properties of the hydrogel network and reduces its degradation rate.PEDOT:PSS and Laponite nanosheets give the hydrogel good electrical conductivity and blood coagulation properties,respectively.GLP prepolymerization solution has the property of shear thinning which can be injected into the wound site for in-situ polymerize.In vitro and in vivo experiments show that GLP hydrogel has good hemostatic properties and tissue adhesion,can effectively seal wounds,reduce bleeding and significantly promote skin wound healing and tissue regeneration.