Preparation And Properties Of Tea Polyphenol-Loaded Silk Fibroin/Cellulose/Poly-Acrylic Acid Composite Hydrogel Dressing

Wound healing has always been a hotspot in the bio-medical field.Drug-loaded hydrogels can keep wound moist,control the slow release of drugs,and promote wound healing.Natural polymers such as silk fibroin protein and cellulose have excellent biocompatibility and biodegradability,which are widely used in biomaterials.However,the single component hydrogel has disadvantages such as poor mechanical properties,poor swelling property and low drug loading rate.Synthetic polymer hydrogels often have poor biocompatibility and poor degradability.Therefore,the development of natural polymer and synthetic polymer composite hydrogel can make up for each other’s performance defects and enhance its application value.Tea polyphenols is a natural extract with good antibacterial,antioxidant and anti-inflammatory properties.It can play a role in multiple stages of wound healing and promote wound recovery.In this study,natural polymer silk fibroin protein and cellulose with good biocompatibility,gel performance better synthetic polymer polyacrylic acid was used as raw material,which were used to prepare composite hydrogels.Tea polyphenols with broad-spectrum antibacterial,antioxidant and anti-inflammatory properties were used as active substances.The polyphenols fibroin egg white/cellulose/polyacrylic acid composite hydrogel was prepared and its physicochemical and biological properties were evaluated.Objective to explore its role in wound healing.The main results are as follows:（1）Preparation of silk fibroin/cellulose/poly-acrylic acid composite hydrogel.After selective oxidation of cellulose through sodium periodate,silk fibroin and cellulose were crosslinked by Schiff base reaction,acrylic acid was introduced,and 9groups of hydrogel-1-9 with different component ratios were prepared through free radical polymerization.Silk fibroin/cellulose/polyacrylic acid composite hydrogel has a three-dimensional pore structure,showing a good gel behavior.SF-OC-PAA-9has the best mechanical properties,the compressive strength is 7 MPa,and the tensile strain of SF-OC-PAA-8 is up to 640%.The prepared hydrogel also has good hydrophilicity and excellent swelling property.The swelling rate in deionized water can reach 279.4 g/g,and has p H responsiveness.The swelling rate in different p H solutions is different.Silk fibroin/cellulose/polyacrylic acid composite hydrogel was degraded in vitro for 40 days.The degradation rate was up to 69.87%,and it also had good biodegradability and cytocompatibility.（2）Performance test of tea polyphenols aqueous solution.The antibacterial activity of tea polyphenols against Escherichia coli,Staphylococcus aureus,Streptococcus albicans,Salmonella,Bacillus cereus,the minimum inhibitory concentrations of which were 250 mg/L,31.25 mg/L,31.25 mg/L,125 mg/L and 62.5 mg/L,respectively;the antioxidant activity of tea polyphenols was tested by DPPH radical scavenging method,and the results showed that the IC₅₀was 26.14 mg/L;the anti-inflammatory activity of tea polyphenols showed that the NO inhibition rate of 100 mg/L tea polyphenols was 50%.Tea polyphenols can inhibit cancer cells.200 mg/L tea polyphenols aqueous solution can inhibit Hep G2 cells to a certain extent,with an inhibition rate of 50%,while 100 mg/L tea polyphenols aqueous solution can significantly inhibit SMMC7721 cells,with an inhibition rate of 60%.In addition,the cell test showed that tea polyphenols had good cytocompatibility.In conclusion,tea polyphenols have good antibacterial,antioxidant,anti-inflammatory and anti-cancer properties,which can be used in wound healing and cancer treatment.（3）Performance test of tea polyphenols hydrogel（SF-OC-PAA-TP）The aqueous solutions of tea polyphenols were loaded onto Silk Fibroin/cellulose/polyacrylic acid composite hydrogels through physical adsorption.After 48h release,the tea polyphenols hydrogel sustained release concentration up to 82.82 mg/L,which reached the antibacterial,antioxidant and inhibitory effects of the tea polyphenol aqueous solution.The test of 9 groups of hydrogels showed that the SF-OC-PAA-9hydrogel group had better mechanical properties and slow release properties.Therefore,the SF-OC-PAA-9-TP ratio group was used for subsequent tests.Antibacterial test showed that SF-OC-PAA-9-TP had good antibacterial activity against Escherichia coli,Salmonella,Staphylococcus aureus,Bacillus cereus and Streptococcus albicans.The DPPH radical scavenging rate of SF-OC-PAA-9-TP was 78.798%,showing good antioxidant activity.The hemolysis rate of SF-OC-PAA-9-TP was 4.9%,which was lower than the national standard.In cell test,the cell survival rate reached more than80%,which showed that SF-OC-PAA-9-TP had good blood compatibility and cell compatibility.The wound healing ability of SF-OC-PAA-9-TP was evaluated by animal full-thickness skin excision model,and the wound was covered by SF-OC-PAA-9 and SF-OC-PAA-9-TP hydrogel.After 15 days of treatment,the wound healing rate of SF-OC-PAA-9-TP group was 96.7%,which was higher than that of SF-OC-PAA-9 group and blank control group.Compared with blank group and SF-OC-PAA-9,SF-OC-PAA-9-TP group had fewer inflammatory cells,more capillaries and collagen tissue,more uniform epidermis and intact hair follicle tissue.RT-PCR results showed that SF-OC-PAA-9-TP could promote the expression of VEGF,EGF,b FGF and TGF-β,and regulate the expression of inflammatory factors TNF-α,IL-10 and IL-1βin different stages of wound healing,so as to promote wound healing.In this study,tea polyphenol fibroin/cellulose/polyacrylic acid composite hydrogel SF-OC-PAA-9-TP was prepared.It has good physical and chemical properties,antibacterial and anti-inflammatory properties.It can effectively promote wound healing and has a good application prospect in wound dressing field.