An Experimental Study Of PDA-modified PCL Composite Scaffold Loaded With Vancomycin PLGA Sustained-release Microspheres In The Treatment Of Bone Infections

Objective The aim of this study was to design and test a novel composite scaffold using a three-dimensional(3D)printed poly(e-caprolactone)(PCL)scaffold coated with polydo-pamine(PDA)for the adsorption of polylactic acid-glycolic acid(PLGA)microspheres loaded with vancomycin.Methods Vancomycin-loaded PLGA microspheres were produced by the double-emulsion method,and microsphere morphology,drug-loading dosage,encapsulation efficiency,average diameter,and release characteristics were examined.Composite scaffolds were prepared by adsorption of the microspheres on PDA-coated,3D-printed PCL scaffolds,and scaffold morphology,biocompatibility,vancomycin release,antibacterial efficacy and osteogenic performance were evaluated in vitro.Then the scaffolds were implanted in an animal model of infectious bone defects to detect antibacterial and osteogenesis effects in vivo.Results The vancomycin-loaded microspheres were smooth,round,uniform in size,and had no adhesion phenomenon,and exhibited sustained release of vancomycin from the microspheres for more than 4 weeks.Upon modification with PDA,the PCL scaffold changed from white to black,and after microsphere adsorption,dot-like white particles were seen.On scanning electron microscopy,PDA particles were observed on the PCL/PDA composite scaffolds,and PLGA microspheres were evenly dispersed over the PDA coating on the PCL/PDA/PLGA composite scaffolds.In vitro cell viability assays showed that the adhesion and proliferation of rabbit bone mesenchymal stem cells were greater on the PCL/PDA scaffolds than on unmodified PCL scaffolds.Microsphere adsorption had no significant effect on cell proliferation.In vitro release of vancomycin from the composite scaffolds was observed for more than 4weeks,and observation of the inhibition zone on agar plates of Staphylococcus aureus showed that the scaffolds maintained their antibacterial effect for more than 4 weeks.The composite scaffolds of rabbit mesenchymal stem cells in osteogenic induction co-culture showed that the alkaline phosphatase activity of the PDA-coated PCL group was higher than that of the blank group and the PCL group at 7 days and 14 days,while the PDA-coated PCL group adhered to the microspheres was not significantly different from that of the PDA-coated PCL group.In vivo experiment: Rabbit tibia with chronic infectious bone defect was successfully implanted with the scaffolds.After three months,X-ray film,micro CT examination and histological HE staining were performed.It was found that the composite scaffold we developed has a good antibacterial effect in the body,and the long-term bone-promoting effect is also significant.Conclusions The 3D-printed,PDA-coated PCL scaffold carrying vancomycin-loaded PLGA microspheres exhibited good biocompatibility,a sustained antibacterial effect and osteogenesis effect in vitro and vivo.So it is an ideal scaffold material for the treatment of infected bone defects.