| Similar to the extracellular matrix of natural tissues,hydrogels have attracted extensive attention because they could provide a moist environment at the wound interface,absorb excess tissue exudates,allow oxygen to permeate,and serve as carriers for various bioactive factors.Hydrogels with in situ forming ability can fill irregularly shaped wound and accelerate wound healing,which is a promising wound healing material.However,the poor adhesion on the tissue surface seriously hinders the close bonding of the hydrogel to the tissue surface,limiting the application of the hydrogel.It is necessary to design a hydrogel tissue adhesive with rapid forming,high adhesive strength,good biocompatibility,antibacterial and hemostatic properties.The research idea of this paper is to prepare a series of multifunctional hydrogels with tissue adhesion,antibacterial and hemostatic properties by using gelatin and sodium hyaluronate as the matrix and introducing dopamine and serotonin into the system through molecular structure design.The specific research contents are as follows:Firstly,the dynamic cross-linking hydrogels of gelatin and oxidized polysaccharide were studied.Oxidized sodium hyaluronate(OHA)with aldehyde groups was obtained by oxidizing sodium hyaluronate(HA)with sodium periodate.GHA,GOHA and GOHAL hydrogels loaded with antibacterial drug levofloxacin were prepared by compounding HA and OHA with gelatin,respectively.The effects of macromolecule crosslinking and oxidation on the gelation time,internal morphology,compression and adhesion properties of hydrogels were discussed.The blood compatibility and cell compatibility of hydrogels were studied.The results showed that compared with gelatin self-crosslinking hydrogel and GHA hydrogel,GOHA hydrogel had higher compression strength and adhesion strength due to the increase of crosslinking density,and the adhesion strength(15.03 k Pa)was better than that of commercial fibrin glue(1.09 k Pa).GOHAL hydrogel showed good antibacterial effect against Escherichia coli and Staphylococcus aureus.These four groups of hydrogels all are good in blood compatibility and cytocompatibility to human umbilical vein endothelial cells.Secondly,in order to improve the adhesion of hydrogels on wet tissue surfaces and the inherent antibacterial efficiency of hydrogels,dopamine-modified gelatinbased antibacterial tissue-adhesion hydrogels were prepared.The content of dopamine in the modified gelatin increased with the increase of the feed ratio.Dopaminemodified gelatin with different degrees of substitution were crosslinked with OHA to obtain composite hydrogels.The effects of dopamine content on swelling,internal morphology,antioxidant,adhesive and antibacterial properties of hydrogels were investigated,and in vitro coagulation tests of hydrogels were conducted.The results showed that with the increase of dopamine content,the adhesion strength,antibacterial efficiency and in vitro coagulation effect of hydrogels increased first and then decreased,which was related to the number of catechol group exposed on the surface of hydrogel.The dopamine-modified gelatin hydrogels showed good antibacterial effects against Escherichia coli and Staphylococcus aureus.The addition of dopamine promoted the hemostatic effect of hydrogels.Finally,for further improve the hemostatic properties of the hydrogels,serotoninmodified gelatin-based tissue-adhesive hydrogel with hemostatic and antibacterial properties was synthesized.In order to explore the effect of serotonin on the properties of hydrogel tissue adhesive,the GOHAS and GSOHA hydrogels were prepared by adding serotonin directly and grafting into hydrogels respectively.The effects of these two addition methods on the degradation performance,internal morphology,antioxidant,adhesive and antibacterial properties of the hydrogels were investigated.The serotonin release rate and in vitro coagulation effect of the two groups of hydrogels were compared.Cell experiments were performed to evaluate the cytocompatibility of hydrogels.The results show that,compared with GOHA hydrogel,the adhesive strength of the hydrogels were improved after the introduction of serotonin into the system,and the serotonin endowed the hydrogels with antioxidant and antibacterial properties.Compared with the direct addition of serotonin,the effect of grafted serotonin on the adhesion,antibacterial efficiency and in vitro coagulation performance to the hydrogel was more significant.Both groups of hydrogels showed good cytocompatibility to human umbilical vein endothelial cells. |
PDF Full Text Request