Constraction Of MOF Mimic Enzymes On The Surface Of Nanofibers And Its Combat To Drug-Resistant Bacteria

Diabetes is known as the"silent killer"because of its insidious symptoms and high rate of disability and even death.As a typical complication,diabetic chronic wounds implicate several organs and seriously impair the health of patients.Under normal circumstances,wounds heal gradually through the hemostasis,inflammation,repair,and remodeling phases.However,the prolonged inflammatory response has arrested the wound-healing process,and high blood glucose level provides the energy supply for bacterial colonization and growth,resulting in delayed wound healing in diabetic patients.Conventional clinical interventions,such as surgical debridement and antibiotic dressings,are becoming increasingly ineffective due to the global bacterial resistance crisis,and effective management of chronic diabetic wound infections remains the focus of current research and challenges.Benefiting from the development of nanotechnology,Metal-Organic Frameworks（MOFs）,which are porous nanomaterials with tunable structural properties and high specific surface area,have gained prominence in the field of antimicrobial activity.MOFs can kill bacteria by releasing metal ions,generating thermal effects,and releasing reactive oxygen species（ROS）,and are thus promising as an alternative to antibiotics.However,powder-style MOFs loaded on conventional dressings can hinder the release of their antimicrobial active substances.Meanwhile,the unique microenvironment in diabetic wounds can disrupt the effectiveness of MOFs.Therefore,further research is needed to develop novel wound dressings to effectively integrate MOFs to address chronic diabetic wound infections.Based on this,our study relies on electrospinning technology to fabricate nanofibers as carriers and choose MOF mimetic enzymes,which can generate ROS,as the alternative for antibiotics,together with simultaneous electrospray technology to build MOFs on the surface of nanofibers.Then,based on the"starvation therapy",the microenvironment which is not conducive to diabetic wound healing is changed into a beneficial environment that can activate the MOFs to release ROS,thus performing a self-activating cascade of antimicrobial activity in response to the diabetic wound microenvironment.Meanwhile,gas foaming technology is introduced to enhance the wound exudate management ability of dressings.The main contents are as follows:（1）The MOF mimetic enzyme（MIL-88B-NH₂ NPs）was successfully synthesized by solvothermal methods.The as-synthesized MOFs showed a homogeneous octahedral morphology with uniform distribution of elements and porous structure.The 3,3,5,5-Tetramethylbenzidine colorimetric reaction confirmed its peroxidase-like activity and the optimal catalytic p H was 4.Besides,the enzymatic kinetic results showed good affinity to the substrate and high catalytic capacity,which made it possible to be used as a mimetic enzyme in the antibacterial field.（2）A one-step electrospinning combined with the electrospray technique was used to load MOF mimetic enzymes onto the surface of polycaprolactone（PCL）electrospun nanomembranes（ENMs）.The patterns of morphology,thermal stability,mechanical properties,and moisture permeability of the as-prepared ENMs were investigated.Moreover,the catalytic activity,antibacterial activity,and biocompatibility were evaluated.The results showed that the morphology and thermal stability of ENMs were not significantly affected by the loading of MOFs,and the hydrophilicity and water vapor transmittance rate were improved due to the presence of amino groups on the surfaces of MOFs.Besides,PCL/MOF-8 ENMs obtained with MOF mimetic enzyme’dispersion at a concentration of 8 mg/m L showed good peroxidase-like activity and achieved 94.53%and 99.99%inhibition of Staphylococcus aureus（S.aureus）and Escherichia coli（E.coli）in an acid environment,respectively.In addition,the ENMs have good biocompatibility for their feasibility as wound dressings.（3）On this basis,GOx was loaded onto PCL/MOF-8 ENMs through the coordination interaction between groups such as-NH₂ and-COOH on the surface of GOx and metal nodes on the surface of MOFs,and a three-dimensional nanofibrous composite sponge was designed in combination with gas foaming technology.Therefore,the as-prepared GOx@（PCL/MOF-8）ENMs can achieve a cascade antimicrobial response to the diabetic wound microenvironment through the following ways.Firstly,synergetic starvation therapy of GOx by consuming glucose blocked the energy supply to bacteria.Secondly,MOFs’enzymatic activity was activated through gluconic acid and hydrogen peroxide generated by the catalytic reaction of GOx.Besides,enhanced wound fluid management was realized through the three-dimensional structure.The results showed that in synergy with starvation therapy and self-activated cascade antimicrobial strategy,the GOx@（PCL/MOF-8）ENMs obtained with GOx’s loading concentration of 0.8 mg/m L achieved 99.99%and 99.78%bacterial inhibition against S.aureus and E.coli,respectively.In addition,the nanofibrous composite sponge showed reinforced wound fluid management and achieved efficient killing of methicillin-resistant Staphylococcus aureus（MRSA）,along with good biocompatibility.Based on these beneficial effects,the nanofibrous composite sponge wound dressing has the potential to cope with chronic diabetic wound infections.