Preparation Of Metal-Organic Frameworks/Hydrogels-Based Composite Dressings And Their Application In Wounds Healing

As the first line of defense between the body and the external environment,the skin is susceptible to damage from the external environment and produce wounds,so rapid wound healing is an important process for the repair of skin and other tissues.During the wound healing process,bacteria in the environment can easily invade the wound,which can then become infected and lead to slow wound healing or even more serious tissue damage.Metal-organic frameworks(MOFs)show great potential for antimicrobial therapy by releasing metal ions or organic ligands with antimicrobial activity,and secondly by interacting with bacterial membranes,or by generating reactive oxygen species through stimulation by external light sources and assembling with other antimicrobial materials.In recent years,with the increasing demand for personalized medicine and multi-scenario applications,patients are increasingly demanding multifunctional clinical dressings.Combining MOFs materials with hydrogel materials can build a new class of wound dressings that address the shortcomings of traditional dressings in the treatment of wound healing.In addition,the high moisturizing property and good biocompatibility of hydrogels can be perfectly combined with the multifunctionality of MOFs to give full play to their respective advantages,and based on the synergistic effect can achieving rapid healing of multiple types of wounds.The research in this thesis focuses on the challenges of bacterial infection,slow healing and excessive inflammation at the wound site.Three MOFs-hydrogel composite wound dressings were constructed and their application in the treatment of infected wounds was explored,as follows:1.Designing multifunctional hydrogels with dual-mode synergistic antimicrobial activity for accelerating wound healing in bacterial infections is of critical importance in clinical applications.Therefore,a bandage-type double-layer hydrogel dressing system was developed.which has excellent skin adaptability and photothermal-ionic synergistic antimicrobial activity that has the potential for safe and effective treatment of bacterial infected wounds.The inner layer of the dressing was prepared by cross-linking gelatin and oxidized dextran via Schiff base reaction,and was combined with ZIF@CNT nanocomposites(referred to ZNT)with synergistic photothermal-ionic antimicrobial properties.The outer layer of the dressing is made of quaternary chitosan-gelatin-propolis reaction cross-linked with flexible mechanical strength and strong adhesion properties,which can adapt to dynamic wound skin with high-intensity exercise.More importantly,this bandage structure solves the problem of secondary fixation of traditional dressings.In addition,this bandage-type double-layer hydrogel dressing also exhibits good biocompatibility,which can promote the proliferation and migration of fibroblasts and vascular endothelial cells.Particularly,the dual-mode antimicrobial therapy is expected to further accelerate wound healing and has potential to be applied in clinical treatment in the future.2.To address the challenges of bacterial infection and oxidative stress during the healing process of diabetic wounds,a synergistic visible light catalyzed-MOFshydrogel-based platform(Met/MOF(Ti)@gel)was developed to achieve effective treatment of diabetic infected wounds.The Ti-based metal organic framework(MOF(Ti))with visible photocatalytic properties can efficiently catalyze the decomposition of H2O2 to generate-OH,which confers the excellent antibacterial ability to the hydrogel dressing.In addition,the high porosity and large specific surface area of MOF(Ti)realized the efficient loading of metformin.The hydrogels cross-linked with polyvinyl alcohol(PVA)and sodium alginate(SA)via dynamic phenyl borate have good adhesive,self-healing and shape adaptation properties.Hydrogel dressings can accelerate degradation in the weakly acidic microenvironment of diabetic wounds,thus facilitating rapid release of nanomaterials.The release of metformin can achieve local and even systemic regulation of blood glucose concentration in wounds.Meanwhile,metformin also significantly promoted the polarization of macrophages from M1 phenotype to M2 phenotype,thus accelerating the transformation of wounds from the inflammatory phase to the remodeling phase.In vivo experimental results showed that the hydrogel dressing could significantly promote the healing and collagen production of infected wounds in diabetic mice under visible light activation,providing a promising platform and strategy for the treatment of diabetic wounds.3.To address the problems of antibiotic resistance and persistent inflammation in the treatment of bacterially infected wounds,a multifunctional wound dressing(MOF(Fe-Cu)/GOx-PAM gel)consisting of bimetallic MOFs loaded with glucose oxidase(GOx)further integrated with hydrogel was constructed.The dressing provides an effective cascade catalytic system to accelerate the healing of bacterial infected wounds through synergistic antimicrobial and inflammatory modulation.Importantly,the catalytic performance of the bimetallic MOF(Fe-Cu)is approximately five times higher than that of the monometallic MOF(Fe).Based on this cascade catalytic system,glucose decomposition by GOx can continuously generate abundant gluconic acid and H2O2.Gluconic acid can effectively enhance the peroxidase performance of MOF(Fe-Cu),which further accelerates H2O2 decomposition and achieves efficient antibacterial activity.MOF(Fe-Cu)/GOxPAM gel dressing not only promotes efficient migration of fibroblasts,but also induces macrophage transformation to M2 phenotype,accelerates the transition of wound microenvironment to a remodeled state,and accelerates vascular and nerve regeneration.This topic provides a multifunctional bioactive wound dressing with great potential for clinical application to promote bacterial infection wound healing.In summary,this paper constructed a bandage-type double-layer hydrogel dressing based on NIR photothermal and ionic dual-mode sterilization,which can solve the problem of secondary fixation of the dressing and has the potential to be used for accelerating wound healing in bacterial infections.Further,based on visible light activation and drug molecule synergy,a microenvironmental dual-responsive hydrogel dressing was constructed to achieve inflammatory factor modulation at the cellular level,which can be used to accelerate wound healing in diabetic bacterial infections.Finally,based on the self-activation mode of wound microenvironment,bimetallic MOFs were combined with GOx to construct an efficient cascade catalytic system,which was further combined with hydrogel to prepare a bioactive wound dressing for accelerating wound healing of bacterial infection and modulation of inflammatory factors,and could promote the regeneration of blood vessels and nerves.The above research opens up new ideas for the development and application of MOFs-hydrogel-based composite wound dressings.