Preparation And Application Of Cyclodextrin-based Metal-Organic Framework And Its Composite Fibers

The cage-like porous structure metal-organic frameworks(MOFs)are emerging as crystalline porous carriers.The development of MOF-based carrier materials with good biocompatibility is of great significance in the field of biomedicine.In response to the needs of the biomedicine field,this study developed cyclodextrin(CD)-MOF-based materials with good biocompatibility and studied its application in tissue repair and drug delivery.The main contents are listed as follows:1.Synthesis and loading performance of CD-MOF.Cyclodextrin(CD)was chosen as the organic ligand for its biocompatibility,and take K~+as the ion center.CD-MOF was synthesized via the hydrothermal method combined with the vapor diffusion method.The effects of reaction time,solvent ratio of the reaction and diffusion system on the CD-MOF were studied.Besides,the morphology was observed by SEM and the single crystal structure was analyzed by XRD.Naringin(NAR)and Catalase(CAT)were loaded with the synthesized CD-MOF via the impregnation method.Their loading conditions were to explored and the loading performance were evaluated.2.Preparation and properties study of CD-MOF-based composite fibers.NAR/CD-MOF@polycaprolactone(PCL)fiber was prepared by electrospinning.Dual-drug-loaded multifunction CD-MOF@coaxial fiber composite also was developed by co-electrospinning.We determined optimized parameters and study the drug-loaded properties and biological functions of both CD-MOF-based composite fibers.The conclusions are listed as below:1.CD-MOF particle shows a oblique column shape.Particles with sizes of 5?m?100 nm can be prepared through regulating parameters.It has a 3D multi-level cage structure with obvious double-channel characteristics.2.For NAR/CD-MOF system,the entrapment efficiency of over 80%was obtained,while the drug release with a zero-order kinetic rule was observed over 32 days.The results show that the multi-level complex 3D pores structure of CD-MOF help prolong the release of NAR.The cell test indicated that NAR/CD-MOF has excellent biocompatibility.3.The optimized parameters of preparing CAT/CD-MOF were:CAT:CD-MOF=8:1(mmol),1 w/v%PVP,stirred at 4?for 24 hours.The specific activity of CAT was increased at least twice by CD-MOF,and catalytic activity was maintained after repeated for six times.4.The optimized parameters of preparing NAR/CD-MOF@PCL composite fiber were obtained.The morphology of the composite was in continuous fibrous shape without beads-on-a-string.The diameter was 1.7?2.5?m with some granular protrusion.And NAR/CD-MOF remained intact and evenly distributed in the fiber.The tensile strength of the NAR/CD-MOF@PCL fiber was 3.2±0.2 MPa and the breaking elongation was 1300±100%,which can meet the mechanical requirements of an absorbable guided bone remodeling membrane.The release profile of loaded-NAR indicated a sustained release with approximately a zero-order kinetic rule for 35 days.And the cells exhibited well osteogenesis under the sustained stimulation of NAR by Alkaline phosphatase(ALP)tests and alizarin red staining.5.The optimized parameters of preparing dual-drug-loaded MOF@coaxial fiber composite were obtained.Metronidazole(MNA)/PCL@NAR/CD-MOF@PLGA-PDLLA coaxial composite fiber was prepared.The composite fiber with good fiber-forming properties,smooth surface,uniform nodules,and an average diameter of less than 1?m was obtained.The tensile strength of the composite was 2.0±0.2 MPa under dry condition and 1.5±0.3 MPa under wet condition,and the breaking elongation were 59±2%and 32±3%under dry and wet conditions,respectively.Which can meet the mechanical requirements of an absorbable guided bone remodeling membrane.The release profile of loaded-NAR indicated a sustained release with approximately a zero-order kinetic rule over 36 days,which kept the controlled release advantage of NAR/CD-MOF.The loaded-MNA was completed released from the shell layer of the coaxial fiber in 4 days.The MC3T3-E1 cell test and hemolysis test indicated that the composite has excellent biocompatibility.ALP and alizarin red staining experiments indicated that the cells exhibited well osteogenesis.And the antibacterial test indicated a good antibacterial performance of the composite against escherichia coli within five days.The novelties of this study are as follows:(1)CD-MOF with high entrapment efficiency and long-term zero-order release and its composite fiber are prepared.(2)The composite of electrospun coaxial fiber and drug loading MOF was realized.Moreover,the sequential release of MNA and NAR was realized,and the function of inducing osteogenic differentiation while inhibiting bacteria was realized.