Study On Multifunctional Hydrogels Loaded With Histatin-1 For Wound Healing

The treatment of large-area acute burn wounds and chronic diabetic wounds is still a clinical problem.Hydrogels have high water content,soft properties,various types,and provide moist environment and similar structure with extracellular matrix,therefore have a wide range of applications in wound healing.In this paper,two different kinds of multifunctional hydrogels have been designed and prepared,which intended to be used as skin substitutes to accelerate the repair and regeneration of acute burn wounds and chronic diabetic wounds,respectively.1.Study of supramolecular hydrogel?HGM/Res/His-1?loaded with resveratrol?Res?and histatin-1?His-1?on burn woundsIn this study,the supramolecular hydrogel?HGM?based on gelatin was prepared using weak host-guest assembly and photo-crosslinking triggered by lithium phenyl-2,4,6-trimethylbenzoylphosphinate?LAP?,and then loaded with Res and His-1 for acute burn wound therapy.The cross-linked network of hydrogel was formed using acryl-modified cyclodextrin.Res has the ability of antioxidation and promoting vascularization.His-1 can promote the migration and adhesion of endothelial cells and vascularization,both of which are loaded into the HGM hydrogel to work together.The characterization of HGM in vitro was carried out.The rheological results showed that HGM had shear-thinning property.When the strain changed alternately between 1%and 600%,a gel-sol transition occurred and the modulus did not attenuate.The results from universal testing machine indicated that HGM had good tensile properties,viscoelasticity and fatigue resistance.Furthermore,HGM had good biocompatibility,and Res and His-1 can jointly promote the migration and tube formation of human umbilical vein endothelial cells?HUVECs?.The in vivo animal experiments of burn wound model in SD rats exhibited that HGM/Res/His-1 accelerated wound healing and showed comparable healing efficiency with commercial dressing of Tegaderm^TM.After 14 days of treatment,both of HGM/Res/His-1 and Tegaderm^TM groups healed completely.The analysis of wound tissue showed that the expression of IL-6 and IL-1?were down-regulated while TGF-?1,CD31 and?-SMA were up-regulated,which indicated that HGM/Res/His-1 has the ability of anti-inflammatory,promoting collagen deposition and vascularization.2.Study of conductive adhesive hydrogel of Gel-MA/Chi-C/G-PPy/His-1 loaded with His-1 on diabetic woundsThe application of conductive adhesive hydrogels on wound healing has been reported widely.In this study,the conductive adhesive hydrogel of Gel-MA/Chi-C/G-PPy was prepared by the polymerization of Gelatin-Methacrylamide?Gel-MA?,Catechol-conjugated chitosan?Chi-C?and Gelatin-Methacrylamide modified polypyrrole?G-PPy?triggered by ammonium persulfate?APS?and tetramethylethylenediamine?TEMED?,then loading His-1 for the repair of diabetic wounds.The characterization of hydrogel in vitro and in vivo was carried out respectively.The results of rheology and universal testing machine showed that the hydrogel had good stability,viscosity and compression performance.Due to the addition of G-PPy,not only the strength of hydrogel increased,but the conductivity also increased significantly which changed with concentration of G-PPy.Gel-MA/Chi-C/G-PPy showed comparable conductivity with skin tissue.The cell experiments indicated that His-1 promoted the migration and tube formation of HUVECs,and the hydrogel had good biocompatibility.Gel-MA/Chi-C/G-PPy/His-1 hydrogel with G-PPy of 1 mg/m L was used on the diabetic wound healing.The diabetic wounds of Gel-MA/Chi-C/G-PPy/His-1 group completely healed in 21days.The results of histochemical and WB of wound tissue indicated that Gel-MA/Chi-C/G-PPy/His-1 down-regulated the expression of TNF-?but up-regulated expression of TGF-?1,CD31 and?-SMA.Therefore,Gel-MA/Chi-C/G-PPy/His-1 is considered to have anti-inflammation,promote collagen formation and vascularization,and has certain application prospects in the repair of diabetic wounds.