Preparation And Properties Of Amino Acid Based Poly(Ester Urea)s Electrospun Composite Nanofiber Dressing

It takes a long time to repair the full-thickness wounds,and the wounds are more susceptible to infection.The bacterial infection keeps wounds in a state of pathological inflammation,resulting in excess cell damage and delayed wound repair,which makes the wound form a chronic wound.According to the American National Institutes of Health,bacterial biofilms account for nearly 80%of infected wounds.The bacteria in the biofilm will get together,and their resistance to antibiotics and the human immune defense system is 100-1000 times higher than that of bacteria in the floating state.A variety of wound dressings have been developed for wound treatment,among which amino acid based polymer nanofibers are a new type of material.These nanofibers are degradable and biocompatible,which will not cause tissue damage when they are used in the wound.Simultaneously,the dressings have a three-dimensional network structure that can mimic the natural extracellular matrix,which provides an ideal microenvironment for cell adhesion,proliferation,migration,and differentiation.What's more,combining nanofiber dressings with antibacterial drugs is an effective strategy to accelerate the healing of infected wounds.Nitric oxide has a broad-spectrum antibacterial and antibiofilm ability and bacteria will not develop resistance to it.Furthermore,nitric oxide can also promote the migration and proliferation of fibroblasts,regulate the level of inflammatory factors,and accelerate the deposition of collagen.Therefore,amino acid based polymer nanofibers can be used to deliver nitric oxide locally into the wound milieu to control infection and promote wound healing.The research mainly includes the following aspects:In this study,phenylalanine-based poly(ester urea)s(PBP,PHP,POP)were synthesized and the polymers were coelectrospun with polyacrylonitrile to prepare phenylalanine based poly(ester urea)s composites mats(PBP/PAN,PHP/PAN,POP/PAN).The nitrosoglutathione(GSNO)was grafted or loaded on the PHP/PAN mats to endow the mats with antibacterial activity(PHP/PAN-G,PHP/PAN/G).The diameters of PHP/PAN-G and PHP/PAN/G mats were found to be between 300-400 nm,and the porosity was about 54%.The PHP/PAN-G and PHP/PAN/G mats could continuously and stably release nitric oxide within 2 weeks,and the total release concentration of nitric oxide of PHP/PAN-G and PHP/PAN/G mats was 0.95?mol/L and 1.15?mol/L,respectively.The antibacterial effect of the PHP/PAN-G mat was better than that of the PHP/PAN/G mat.The antibacterial rate of PHP/PAN-G mat against E.coli and S.aureus was 94.5±4.2%and 96.0±2.1%.The cells grew well on the mats and the mats had no toxicity to the cells.When the PHP/PAN-G mat was used in the infected wounds of mice,it was found that the PHP/PAN-G mat could accelerate wound healing.In the process of wound tissue repair,the degradation of the material should match the time required for tissue remodeling.Therefore,it is important to adjust the degradation rate of the dressing to adapt to the repair rate.In order to achieve this goal,this chapter developed a class of tryptophan based poly(ester urea)s(TBP,THP,TOP)with adjustable degradation rates.The analysis of the degradation performance of the polymers showed that in the 0.05 M alkaline solution,the degradation rates of TBP,THP,and TOP within 29 days were 92.9%,88.1%,and86.6%,respectively.The cell survival rates of t TBP,THP,and TOP were all above 80%,which showed that the polymer was a biological material with good cell compatibility.The polymers and carboxyl-terminated polycaprolactone were electrospun to tryptophan based poly(ester urea)s composite mats(TBP/PCL,THP/PCL,and TOP/PCL).The GSNO was then grafted onto the nanofibers to give the mats the function of releasing nitric oxide(TBP/PCL-G,THP/PCL-G,TOP/PCL-G).The fiber arrangement of the mat was loose and straight,with a diameter of about 300-350 nm,and a porosity of 58%.Degradation experiments showed that in the 0.05 M alkaline solution,the weight-loss rates of TBP/PCL-G,THP/PCL-G,and TOP/PCL-G mats were 31.5%,32.1%,and 28.4 in 29 days,respectively.Within 14 days,the total concentration of nitric oxide released by TBP/PCL-G,THP/PCL-G,and TOP/PCL-G mats was 1.03?mol/L,1.12?mol/L,and 1.09?mol/L,respectively.Antibacterial experiments showed that THP/PCL-G mat had a significant inhibitory effect on the growth of E.coli and S.aureus,and the inhibitory rate against E.coli and S.aureus was 93.5±2.3%and 95.7±3.1%,respectively.Biological experiments showed that the mats had good cell compatibility and blood compatibility.In the process of wound repair of bacterial infection in mice,THP/PCL-G fiber mat significantly reduced the level of inflammatory factors in the blood of mice,regulated the inflammatory response,promoted collagen deposition,and accelerated wound healing.Bacteria encapsulated by bacterial biofilm have strong resistance to drugs,making it difficult to kill the bacteria.This keeps the wound in the inflammatory phase and it will be difficult for the wound to heal.To remove the bacterial biofilm in the infected wound and improve the degradation rate and compatibility of the mat,two natural amino acids,phenylalanine and tryptophan,were employed to synthesize the phenylalanine and tryptophan based poly(ester urea)s(TBPBP1,TBPBP2,and TBPBP3).Degradation tests and cell experiments showed that the TBPBP1,TBPBP2,and TBPBP3 could be completely degraded within 21 days and these polymers were not toxic to cells.The polymer and carboxyl-terminated polycaprolactone were blended to obtain phenylalanine and tryptophan based poly(ester urea)s electrospun composite mats(TBPBP/PCL).GSNO was then grafted onto the TBPBP/PCL mat to make the mats have antibacterial and antibiofilm properties.The degradation test showed that the weight loss rate of TBPBP/PCL-G fiber membrane was 35%within 21 days.TBPBP/PCL-G mat could release nitric oxide(the highest concentration can reach 0.9?mol/L).Experiments demonstrated that TBPBP/PCL-G mat had a good inhibitory effect against E.coli and S.aureus,and remove the biofilm.The biofilm inhibition rate of TBPBP/PCL-G mat was85.7±3.4%.The mats revealed good blood compatibility and cell compatibility.During the co-cultivation of cells and mats for 3 days,the diffusion area of L929 cells on the TBPBP/PCL-G mat was higher than that of cells on the TBPBP/PCL mat,and the diffusion area of cells on TBPBP/PCL-G was up to 732?m~2.The mouse infected wound model displayed that the prepared phenylalanine and tryptophan based poly(ester urea)s electrospun composite mats could reduce the level of inflammatory factors,regulate the inflammatory response and improve the deposition of wound collagen,and it is an ideal dressing for treating infected wounds.In this paper,three kinds of nitric oxide-releasing amino acid based poly(ester urea)s electrospun composite nanofiber dressings were prepared by electrospinning technology.Such dressings exhibited good antibacterial properties,antibiofilm properties,cytocompatibility,and hemocompatibility,and they could effectively promote the repair of infected wounds.This study provides new methods and ideas for the development of novel amino acid based wound repair materials.