Preparation Of Cationic Polymer Containing Hydrogel Dressing And Integrated Treatment Of MRSA Infection Wound

Bacterial infections of the wound surface are common chronic wound complications that,in addition to causing pain and discomfort to the patient,may cause toxemia and infectious shock,and can even be severe enough to cause death.Bacterial infections have become the second leading cause of death worldwide in 2020,after ischemic heart disease.According to statistics,8 million deaths in 2020 are associated with 33 common bacterial infections.In recent years,antimicrobial hydrogel dressings containing cationic polymers have received increasing attention due to their high antibacterial efficiency,low induction of drug resistance and good biocompatibility.However,due to the stage and complexity of wound healing mechanisms,the antimicrobial effect of cationic polymer hydrogels alone in mediating infected wound healing can hardly meet the actual clinical needs.In recent years,with the concept of multifunctional dressings,the development of dressings with functions such as hemostasis,synergistic effects of multiple antimicrobial mechanisms,regulation of inflammation,and promotion of revascularization is expected to realize the needs of integrated infected wound treatment.Therefore,based on the current research status and development trend in this field,two multifunctional antimicrobial hydrogel dressings were designed and synthesized in this thesis:（1）PAA-MBAA@h-PAMAM hydrogel with anti-drug-resistant bacteria and mediating wound hydration;（2）HEA-HAMA-h-PAMAM multifunctional hydrogel with hemostasis,anti-drug-resistant bacteria,inflammation modulating effect and promoting vascular neovascularization dressing,which is expected to achieve the integrated treatment of MRSA-infected wounds by regulating the function of different stages of wound healing.The specific research contents and results are as follows:（1）First,to solve the problem of inherent biotoxicity of high generation cationic dendritic macromolecules applied alone,we constructed a cationic polymeric drug delivery system PAA-MBAA@h-PAMAM by encapsulating a synthetic cationic dendritic polymeric antimicrobial agent（h-PAMAM）in PAA-MBAA hydrogel,and the study showed that this system could effectively reduce In vivo experiments have shown that this system can effectively reduce the inflammation of wounds and promote wound healing.（2）The existing hydrogel dressings that have been commercialized and widely used have a single function,and most of them can only regulate one or two specific stages of wound healing,but cannot play a regulatory role in all stages of wound healing.To solve this problem,we prepared a new multifunctional dressing HEA-HAMA-h-PAMAM containing cationic polymer hydrogel by an enzymatic oxidative coupling reaction that generates-OH in large quantities within a short time as an initiator and methacrylate-modified h-PAMAM as a macromolecular cross-linker,copolymerized with HEA on the basis of the previous chapter.H₂O₂and-OH can produce H₂O₂and-OH in a short period of time,which can act as a barrier to achieve good hemostasis through rapid in situ polymerization and molding of trauma.H₂O₂and-OH can also act synergistically with h-PAMAM through multiple antibacterial mechanisms to efficiently kill drug-resistant bacteria and avoid the production of drug-resistant bacteria,and at the same time play a role in relieving trauma inflammation and promoting vascular renewal.The prepared HEA-HAMA-h-PAMAM is able to modulate the effect at different stages of wound healing to achieve integrated treatment of MRSA infected wounds and promote wound healing comprehensively.Based on the interdisciplinary research of polymer chemistry and physics,pathophysiology and life science,this thesis provides a new idea of new multifunctional antibacterial hydrogel dressing for chronic wound treatment through the design and synthesis of cationic dendritic macromolecular hydrogel materials to achieve multipathway management of drug-resistant bacterial infected wounds.