| Diabetes mellitus is one of the most prevalent diseases worldwide,and diabetic skin injury is a common form of diabetic complications.At present,in terms of clinical treatment,the technical methods for the repair of diabetic skin injuries include surgical debridement,hyperbaric oxygen therapy and plantar pressure relief.With the deepening and improvement of hydrogel dressing research,the preparation of hydrogel dressing with good biocompatibility and wound repair ability has become a research hotspot.Hydrogel has a three-dimensional network structure,the water content is greater than90%,with the characteristics of keeping the wound moist and absorbing excess wound exudate,and can encapsulate drugs or bioactive factors,becoming a good wound repair material.In the early stage of diabetic skin injury,compared with clinical treatment of diabetic skin injury,hydrogel dressing has the advantages of reduced treatment cost,self-dressing change without professional help,accelerated wound healing and reduced patient’s pain.Therefore,this topic intends to prepare drug-loaded hyaluronic acid/carboxymethyl chitosan hydrogel,characterize and analyze the physical properties,and biological properties of the hydrogel,and verify the healing effect through wound repair experiments in diabetic rats.Through the determination of swelling performance and water retention performance,optimize the partition ratio of hyaluronic acid and carboxymethyl chitosan hydrogel substrates,and prepare hyaluronic acid/carboxymethyl chitosan hydrogel and hyaluronic acid hydrogel as dressing substrate materials by chemical cross-linking and physical freezing and thawing,respectively.The physical properties of hydrogel dressing were characterized by testing the swelling rate,water content and drug release.The morphology and structure of hydrogel materials were characterized by scanning electron microscopy and Fourier infrared scanning.The effects of hydrogel dressing on mouse fibroblasts were studied,and the cytotoxicity,hemocompatibility,anti-oxidation and properties of hydrogel materials were evaluated,respectively.The skin injury model of diabetic rats was established.The tissues of experimental rats after wound repair and repair were observed by HE staining,immunohistochemistry and Masson staining.The venous blood of rats was taken to detect the expression of inflammatory factors in rats.The experimental results showed that the optimal ratio of hyaluronic acid/carboxymethyl chitosan hydrogel base was 1%(w/v)for hyaluronic acid and 5%(w/v)for carboxymethyl chitosan.The hyaluronic acid content in hyaluronic acid hydrogels prepared by physical method was 1%(w/v).Hyaluronic acid/carboxymethyl chitosan hydrogel chemically crosslinked by EDC/NHS can absorb 29 times of its own weight of water,and the gel fraction above 60% had good stability.The moisture content of the composite hydrogel of physical freeze-thaw hyaluronic acid hydrogel and chemical cross-linking was more than 99%,and the moisture content of the two hydrogels was more than 9%.Fourier transform infrared scanning analysis of chemically cross-linked composite hydrogels was mainly amide bonding,while physical freeze-thaw hyaluronic acid hydrogels was mainly hydrogen bonding.The pore diameter of chemically cross-linked composite hydrogels is larger than that of physical freeze-thawed hydrogels.The release rate of panax notoginseng saponins in simulated body fluids of the two hydrogels was higher than that in PBS buffer at the same p H,in which the composite hydrogel could be released continuously for 24 h,reaching a release rate of 76%,which was higher than 23.6% of hyaluronic acid hydrogels prepared by physical methods.Both drug-loaded hydrogels can inhibit NO secretion by macrophages and have the efficacy of inhibiting inflammatory responses.And the drug-loaded hyaluronic acid/carboxymethyl chitosan hydrogel has better free radical scavenging ability than the drug-loaded hyaluronic acid hydrogel prepared by physical method.The good biocompatibility and hemocompatibility of loaded hyaluronic acid/carboxymethyl chitosan hydrogel were shown by cytotoxicity experiments and hemocompatibility experiments.However,the hyaluronic acid hydrogel prepared by physical method did not have the biological properties in line with clinical medical use.In wound repair experiments in diabetic rats,drug-loaded dressings upregulated IL-10,b FGF and VEGF expression and inhibited the expression of TNF-α and IL-6 in serum.At 16 days,the wound healing rate of the experimental group reached 97.04%,which healed 4 days earlier than that of the blank control group.In summary,this topic compares various properties of drug-loaded hyaluronic acid/carboxymethyl chitosan hydrogels prepared by chemical cross-linking method and drug-loaded hyaluronic acid hydrogels prepared by physical method,i.e.The base material of hyaluronic acid/carboxymethyl chitosan hydrogel dressing prepared by chemical cross-linking method has good swelling properties,water retention and threedimensional spatial structure,i.e.Hyaluronic acid/carboxymethyl chitosan hydrogel dressing loaded with panax notoginseng saponins has antioxidant and antiinflammatory properties.After loading panax notoginseng saponins into the dressing base material,the drug could be continuously released in 24 h,with a release rate of76%.The biocompatibility and hemocompatibility of drug-loaded composite hydrogels meet the clinical medical requirements.The results of animal experiments showed that the hydrogel dressing could accelerate the healing of diabetic skin wound,providing a new method for the treatment of diabetic skin injury. |
PDF Full Text Request