Study Of Polyetheretherketone And Its Composites In The Repair Of Oral And Maxillofacial Bone Defects

Oral and maxillofacial bone tissue is the basis of supporting facial structure,and trauma,tumor,and congenital malformation are the main causes of bone defects.How to restore the facial shape and function of patients urgently needs to be solved in oral and maxillofacial surgery.In recent years,with the development of surgical techniques and the wide application of biomaterials,the treatment for repairing bone defects has also been developed.The advantages of autologous bone grafting are non-immunogenicity and good osseointegration,which is the "gold standard" for the repair of bone defects,but there are problems of insufficient donors and causing new trauma.For bone replacement materials,titanium and its alloys have suitable mechanical properties and good biocompatibility and can form a more solid integration with bone tissue.However,the elastic modulus of titanium and its alloys is higher than that of human bone tissues,resulting in the load not being well transferred and dispersed from the implant to the adjacent bone tissues,which is called the phenomenon of "stress shielding".Thus,bone resorption around the implant and loosening or fracture of the host bone tissues happened,ultimately leading to the failure of the graft surgery.The search for a new bone replacement material with a low modulus of elasticity has become a major goal.Polyetheretherketone(PEEK),a semi-crystalline synthetic polymer,has good biocompatibility,chemical stability,and more suitable mechanical properties than conventional bone replacement materials,but the biological inertness of PEEK limits its use in clinical applications.Various modification methods have been extensively investigated to effectively increase the bioactivity of PEEK.In summary,we prepared a porous PEEK matrix with connected pores by thermophilic phase separation and then fabricated nanoscale hydroxyapatite(n HA)in situ inside the pores by hydrothermal synthesis.We also delivered antimicrobial drugs into the porous PEEK material by the temperature-sensitive hydrogel.We aim to investigate the effects of the modification methods on osteogenesis and antimicrobial function in vitro and in vivo.This study is divided into three experimental parts:Experiment 1: Synthesis characterization of porous PEEKPorous PEEK materials with high porosity and interconnected pores were prepared using a thermally induced phase separation method combined with a porogenic agent addition technique.Mechanical property tests and porosity measurements showed that the mechanical strength of the porous material decreased with increasing porosity,indicating that the porous structure reduced some of the mechanical strength.With field emission scanning electron microscopy,we observed that the surface and internal pore sizes of porous materials were of different levels,i.e.,smaller level pores would appear on the walls of large pores,and the pores can be connected.The results of water contact angle tests confirmed that the prepared porous PEEK material could effectively improve the hydrophilicity of pure PEEK.Experiment 2: Preparation of in situ n HA/PEEK porous composite and study of its osteogenic properties in vitro and in vivoBased on the prepared porous PEEK material,in situ n HA deposition inside the pores was treated by hydrothermal synthesis to enhance the osteogenic and osteointegration activities of the porous material.Nano hydroxyapatite nucleation reactions as well as nanostructures were confirmed by X-ray diffraction mapping techniques and field emission scanning electron microscopy.Water contact angle measurements showed further improvement in the water wettability of the n HA-loaded porous PEEK material compared to the porous PEEK group.Mouse preosteogenic stem cells(MC3T3-E1)were used as the testing cell line to investigate the in vitro bone osteogenic properties of each group.Cell viability and cell proliferation tests showed good cytocompatibility of the materials in all groups.The results of cell adhesion analysis confirmed that both the porous PEEK materials as well as the n HA-loaded porous PEEK materials contributed to the cell adhesion behavior.The results of in vitro differentiation experiments showed that both porous materials and n HA-loaded porous materials could promote osteogenic differentiation of cells to different degrees,but the promotion effect was more significant in the n HA group.An animal model of cylindrical bone defect in rat tibia was established,and the results indicated that both porous materials and n HA-loaded porous materials could improve the osseointegration performance of the materials in vivo,but the osseointegration effect of the n HA group was more superior.Experiment 3: Preparation of PLGA-PEG-PLGA temperaturesensitive hydrogel/minocycline/PEEK porous composite and study of its antibacterial properties in vitro and in vivoThe results of the previous chapters showed that the porous structure can effectively improve the osteogenic properties of PEEK.In view of the severe infection situation after transplantation,it is necessary to prepare and develop an osteogenic composite with significant antibacterial properties.A PLGA-PEG-PLGA temperaturesensitive hydrogel was prepared as a drug carrier by a ring-opening polymerization technique,and then a highly effective antibacterial drug(minocycline)was selected and mixed with the temperature-sensitive hydrogel,delivered and immobilized inside the porous material to prepare a porous PEEK antibacterial-osteoblast composite loaded with minocycline.The degradation and drug release curves of the hydrogel showed that the drug release of the composite could be up to about 20 days or more.The results of water contact angle tests showed that the drug-loaded hydrogel could effectively improve the water wettability of the material.In vitro cell testes showed that the composites of each group had good cytocompatibility and cell adhesion promoting properties.In vitro antibacterial(Staphylococcus aureus and Escherichia coli)experiments showed that the minocycline-loaded composites had significant antibacterial effects and could sustain the proliferation of transplanted bacteria.In vivo tests,a rat subcutaneous antibacterial experimental model was used,and the different materials were implanted into subcutaneous pockets on the back of rats.The materials were collected after a period of time to observe the bacterial content on the surface of the materials as well as the inflammation of the surrounding tissues,and the results showed that the composites still had good antibacterial and anti-inflammatory properties in vivo.Through the research in this graduation study,it is hoped that the prepared composites can provide new methods and ideas for the fields of bone tissue regeneration as well as bone replacement biomaterials.