Construction Of Porous Tantalum Loaded Double Antibiotic Microsphere Scaffolds And Evaluation Of Osteogenic And Antibacterial Activity

Purpose : The 3D-printed porous tantalum composite scaffold containing vancomycin/rifampicin PLGA/PLLA core-shell microsphere was prepared with gelatin coating,and its effect on osteogenic ability and antibacterial activity were investigated.Methods:Chapter 1: 3D printing porous tantalum scaffolds were prepared by SLM technology.The study was divided into porous tantalum group and dense tantalum group.Various characterization and biomechanical tests were conducted on the scaffolds,and whether the scaffolds would affect the adhesion,proliferation and differentiation of osteoblasts was studied through in vitro experiments.Chapter 2: PLGA/PLLA core-shell microspheres containing vancomycin and rifampicin were prepared by coaxial electrostatic spray technique,and their appearance,core-shell structure and particle size were observed.Different drug-carrying microspheres were prepared by distributing drugs in nuclei or shells.The experiment was divided into four groups: Vancomycin/rifampicin microspheres group,rifampicin/vancomycin microspheres group,blank/blank microsphere groups and control group.Encapsulation rate and in vitro drug release of drug-loaded microspheres were determined,and their biocompatibility and antibacterial properties were estimated.Chapter 3: By using gelatin coating,the core-shell microspheres loaded with double antibiotics were fixed on the 3D printed porous tantalum scaffold for surface modification,and the porous tantalum composite scaffold loaded with antibiotic microspheres was prepared and characterized.The experiment was divided into three groups: gelatin coated porous tantalum antibiotic carrying microspheres,gelatin coated porous tantalum and porous tantalum.In vitro and in vivo experiments were conducted to evaluate the biocompatibility,antibacterial ability and the effect on the bone defect repair ability of each group of scaffolds.Results:Chapter 1: The elastic modulus of 3D porous tantalum was close to human cortical bone,and has good biocompatibility.Compared with compact tantalum,porous tantalum can promote osteoblast adhesion,proliferation and differentiation better.Chapter 2: The drug-carrying core-shell microspheres with obvious structure,smooth surface,good dispersion and uniformity can be successfully prepared by selecting appropriate parameters,and synchronous sequential release of vancomycin and rifampicin can be achieved.Each group of microspheres has no cytotoxicity and has no effect on the adhesion,proliferation,etc.of osteoblasts.Drug loaded microspheres have good antibacterial activity,the antibacterial rate of S.aureus in vitro reaches more than 95%,and can prevent the formation of biofilms.In animal subcutaneous infection,drug loaded microspheres showed strong ability to clear bacteria and control inflammation.Chapter 3: The 3D porous tantalum composite scaffold loaded with dual antibiotic microspheres can achieve simultaneous sequential release of the two drugs,and has no effect on the adhesion,proliferation and differentiation of osteoblasts,showing good biocompatibility.Porous tantalum scaffolds carrying antibiotic microspheres have good bacteriostatic rate and anti-bacterial adhesion ability in vitro,and can prevent bacteria from forming biofilms.Animal experiments showed that there was no significant difference in the amount of new bone tissue generated by each group of scaffolds at the same time point,suggesting that local implantation of composite scaffolds did not affect bone defect repair,in addition,it could release drugs for a long time after implantation in vivo.Conclusion:The 3D printed porous tantalum loaded dual antibiotic microsphere composite scaffold can achieve synchronous sequential drug release,and has good biocompatibility and antibacterial activity.68 figures,5 tables,164 references...