| Polyetheretherketone(PEEK)has various advantages including closer elastic modulus to cortical bone,stable chemical resistance,good biocompatibility,thermal stability,and radiolucency.However,its bioinertness,inferior osteoconduction and poor bactericidal ability pose great challenges for clinical application.This thesis focuses on modifying PEEK with optimal surface structure and chemical composition to improve its antibacterial and osteointegration properties.Sulfonation was used to construct microstructure on PEEK surface,and the sulfonated PEEK was employed as metal ions or drug delivery platform to investigate the effect of surface structure and chemical composition on biological properties.The antibacterial and osteogenesis properties were evaluated by cell proliferation,cell differentiation,bacteria response and in vivo models.The osteoimmunomudulation effect was investigated by macrophages phnotype,cytokines secretion,and in vivo subcutaneous air pounch model.The main research contents are described as follows: 1.PEEK is sulfonated by concentrated sulfuric acid to fabricate three-dimensional (3D)network.A hydrothermal treatment is subsequently conducted to remove the residues and the temperature is adjusted to obtain different sulfur concentrations.In vitro results disclose enhanced proliferation and osteogenic differentiation of rat bone mesenchymal stem cells(rBMSCs)on the samples with small sulfur concentrations.In vitro antibacterial evaluation reveals that all the sulfonated samples possess excellent resistance against S.aureus and E.coli.In vivo rat femur implantation model indicates that new bone forms around the samples with small sulfur concentrations.2.Pravastatin(Pra)was loaded onto 3D network surface of sulfonated PEEK(SP)to achieve superior local drug effects.The SP loaded with Pra(SP-Pra)promoted angiogenesis and mitigated FBR via miR-29 dependent SLIT3 upregulation in wild-type(WT)mice.miR-29 a and miR-29b1 were significantly downregulated in SP-Pra capsule compared to the levels in SP capsule,while SLIT3 and neovascularization were substantially upregulated in WT mice.The above effects presented in the WT mice were not detected in miR-29ab1 knockout mice which was generated by CRISPR/Cas9 approach.Overall,the results suggest that miR-29 plays a critical role in reducing FBR to these implants by targeting SLIT3.3.Strontium was loaded into 3D-network structure of sulfonated PEEK via hydrothermal treatment and Sr content can be regulated by adjusting hydrothermal temperature.In vitro results show that Sr loading sulfonated PEEK can enhance the proliferation,ALP activity,ECM deposition,and osteogenesis related genes expression.In vivo results show that Sr loading sulfonated PEEK can enhance the new bone formation and improve the microstructure of femur.4.Mouse beta-defensin-14(MBD-14)was immobilized on PEEK surface with three-dimensional(3D)porous structure to improve its antibacterial activity and osseointegration.In vitro showed that the porous PEEK loaded with MBD-14 wages a durable and effective fight against both S.aureus and P.aeruginosa.Besides,the enhanced proliferation and osteogenic differentiation of bone mesenchymal stem cells were verified through various in vitro analyses.In vivo results show that the enhanced osseointegration of MBD-14-loaded samples was found in infection and non-infection models.No bacteria survived on the surfaces of samples with a relatively high MBD-14 concentration in the infection model.5.A nanowire-like composite material,named P@C,was fabricated by combining chitosan and puerarin via solid-phase reaction.P@C possesses good antibacterial property and osteoimmunomodulation.In vivo results show that P@C can inhibit the LPS induced bone destruction and sustaining fever post-surgery in the E.coli infected rat.P@C exhibits superior bone regeneration in E.coli infected rat due to the comprehensive functions of its superior antibacterial property,and its ability of LPS elimination and immunomodulation. |
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