| Skin is the largest organ of the human body and the first barrier against external pathogens.Skin lesions may cause immune imbalance,and can be life-threatening in severe cases.In order to promote wound healing and reduce the incidence of lesions,it is necessary to create a moist local environment that can absorb excess exudate and inhibit the proliferation of bacteria at the wound site.In recent years,the research of hydrogel materials for wound repair has attracted wide attention.The high water content of hydrogels enables it to give a moist environment to the wound,and hydrogels can efficiently pack drugs and slower the release rate of drugs,which is also conducive to wound healing.Besides,hydrogels can be given specific functional properties,such as p H sensitivity,antibacterial properties and high adhesion,which makes it more targeted in different types of skin lesions.In this study,we prepared thiolated hyaluronic acid,silk fibroin and mesoporous bioglass nanoparticles as raw materials to prepare double network hydrogels with antibacterial properties and demonstrated their potential applications in skin repair.The specific research contents are as follows:Firstly,synthesis of related materials was completed.(1)Thiolated hyaluronic acid with different degree of substitution was synthesized through the reaction between amino group of cysteamine and carboxyl group of hyaluronic acid.The synthesized thiolated hyaluronic acid was characterized by ~1H-NMR and FTIR.It was proved that cysteamine was successfully modified on the backbone of hyaluronic acid.At the same time,the degree of substitution was determined by integrating the corresponding absorption peak on ~1H-NMR.(2)Mesoporous bioglass nanoparticles with different morphologies and structures were prepared by adjusting the ratio of ethanol to ether.The morphologies and structures were characterized by TEM,SEM,and dynamic light scattering.The results show that when the ratio of ethanol to ether is 1:1,the synthesized nanoparticles have better dispersion as well as relatively highest specific surface area and pore volume.Then,it was applied to the loading and release of gentamicin.The experimental results showed that the prepared mesoporous bioglass nanoparticles had a high loading efficiency on gentamicin,which could reach about 8%,but there was a significant burst effect in the process of drug release.(3)The solution of silk fibroin was obtained through steps of dissolving silk fibroin in lithium bromide solution,dialysis and concentration.Secondly,thiolated hyaluronic acid/silk fibroin double network hydrogels were prepared by mixing silk fibroin solution with thiolated hyaluronic acid,using horseradish peroxidase as catalyst.The gelation time and rheological properties of the hydrogels were characterized.By comparing two types of single network hydrogels with these double network hydrogels,it is proved that the formation of dual network greatly improves the mechanical strength of hydrogels.At the same time,by optimizing the concentration and proportion of thiolated hyaluronic acid and silk fibroin,a double network hydrogel with suitable gelation time and better mechanical strength was obtained.On this basis,mesoporous bioglass nanoparticles were introduced into the double network hydrogel system.The relevant experimental results showed that the introduction of nanoparticles to a certain extent prolonged the gelation time of the double network hydrogels,which made the hydrogels more suitable for clinical use,but at the same time,the mechanical strength of the hydrogels decreased.After that,the drug-loaded mesoporous bioglass nanoparticles were mixed with the double network hydrogel solution to prepare the drug-loaded hydrogels.The release experiment showed that the hydrogel system had good controlled release effect on gentamycin.Finally,Escherichia coli and Staphylococcus aureus were co-cultured with drug-loaded hydrogels,and the antibacterial properties were characterized by the plate counting method.The experimental results showed that the drug-loaded hydrogels had an obvious inhibitory effect on the growth of the two kinds of bacteria,which proved that these hydrogels had good antibacterial properties.On the other hand,L929 and HUVEC cells were also co-cultured with these hydrogels respectively,and the cell proliferation and cell viability were detected by cck-8 and live/dead staining method.The results showed that the two kinds of cells could proliferate normally on the surface of the hydrogel,indicating that hydrogels prepared in this study had good biocompatibility.Meanwhile,results of the proliferation experiment also showed that the composite hydrogels greatly promoted the proliferation of L929 cells.These results confirm the potential application of the composite hydrogels in the field of skin repair. |
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