| Currently,there are few wound dressings that are suitable for both hemostasis and wound healing in minimally invasive surgery,so it is urgent to develop effective hemostasis and wound dressings.Hydrogel is porous 3D polymer network with a structure similar to extracellular matrix(ECM),which could be ideal hemostasis and wound dressing.However,traditional hydrogels lack injectable and self-healing properties,which limit their application in minimally invasive surgery.Chitosan(CS)and hyaluronic acid(HA)are ideal raw materials for hemostasis and wound dressing,but they cannot form injectable self-healing hydrogels rapidly under physiological conditions.Therefore,in this study,CS and HA were modified,and nine kinds of N-succinyl chitosan-oxidized hyaluronic acid(NSC-OHA)based hydrogels with rapid formation,injectable and self-healing properties were designed at room temperature.Besides,the effects of these hydrogels and their powders on hemostasis and wound healing were further explored.The main research contents were as follows:Firstly,water-soluble N-succinyl chitosan(NSC)and oxidized hyaluronic acid(OHA)with aldehyde groups were prepared by chemical modification of chitosan and hyaluronic acid,and characterized by nuclear magnetic resonance spectroscopy(1H NMR)and infrared spectroscopy(FTIR).Subsequently,a series of NSC-OHA-based hydrogels were prepared at room temperature by taking NSC and OHA as the main raw materials,introducing one or two of the following substances:calcium ions(Ca2+),four-armed amine-terminated polyethylene glycol,carboxyl-terminated polyethylene glycol amine,EDC/NHS.The chemical structure and microstructure of hydrogels were analyzed by FTIR,thermogravimetric analysis(TGA)and scanning electron microscope(SEM).These hydrogels showed loose and porous internal structure.These hydrogels could be injected successfully through a 23G needle(outer diameter 0.6 mm).Through tensile tests,it was found that the tensile properties of the NSC-OHA hydrogel was poor,but the addition of Ca2+ can significantly increased its ductility,and PEG derivatives increased its flexibility and ductility,and EDC/NHS significantly increased the tensile properties,but the ductility reduced,which suggested these hydrogels had adjustable mechanical properties.Rheological tests showed that these hydrogels kept rapid self-healing properties after repeated cycles at room temperature.The cytotoxicity of hydrogels was detected by CCK-8 method and live-dead cells staining method,which showed that the NSC-OHA hydrogel had certain cytotoxicity,but the hydrogels containing Ca2 and/or PEG derivatives could promote the growth of fibroblastsNSC-OHA-based hydrogels and raw powder showed good in vitro coagulation and in vivo hemostasis properties by calculating the coagulation index and using the mouse liver bleeding model.Among them,the calcium-containing hydrogels and the hydrogel raw powder exhibited excellent hemostasis effects similar to that of Arista hemostatic powder used in clinicThe NSC-OHA-based hydrogels and their raw powder could promote wound healing of full-thickness skin defects on the back of mice,and the hydrogels containing Ca2 showed the best effect on promoting wound healing.Through immunofluorescence staining and tissue analysis,it was found that hydrogels could promote the secretion of vascular endothelial growth factor(VEGF),the migration of fibroblasts and the deposition of collagen,and could reduce the proinflammatory factors and inflammatory reactions,indicating their good biocompatibility.In addition,the NSC-OHA hydrogels added with Ca2 could accelerate the regeneration of blood vessels,hair follicles and sebaceous glandsThe above studies indicated that NSC-OHA-based hydrogels prepared in this study,especially those containing Ca2,had injectable self-healing properties and good application prospects in hemostasis and wound healing. |
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