Design,Preparation And Application Of Poly(Aryl Ether Ketone) For 3D Printing Orthopedic Implants

Poly ether ether ketone(PEEK)is a commonly used material for artificial bone,with excellent biocompatibility and matching mechanical properties with bone tissue.In particular,PEEK can be made into personalized implants by fused deposition molding(FDM)process,which have been applied in orthopedics.However,3D-printed PEEK orthopedic implants still exist some problems,such as poor interlaminar fused effect,smooth and biologically inert surface,insufficient osteogenic activity and antibacterial activity.Starting from the design and preparation of novel poly(aryl ether ketone)implants,this paper mainly focuses on two research lines including mechanical properties and biological properties of materials.Firstly,the intermolecular interaction is regulated by molecular chains entanglement and intermolecular force,in order to improve the mechanical properties of poly(aryl ether ketone)implants.Secondly,the interaction between materials and cells is regulated by the surface and interface of materials,for purpose of enhancing the biological activities of poly(aryl ether ketone)implants.In this paper,a series of poly(aryl ether ketone)implants are designed and prepared based on intermolecular interaction,surface topology,surface osteogenic activity and surface antibacterial activity.The performances and applications of materials are explored.The main contents are as follows:Part Ⅰ:Design,preparation and application of poly(aryl ether ketone)based on intermolecular interaction.Thermoplastic PEEK materials are usually printed by FDM process.However,due to the different cooling rates between crystalline region and amorphous region,the dimensional shrinkage of different regions is uneven caused by cooling,leading to the unsatisfactory dimensional stability of 3D-printed PEEK.In addition,the diffusion and entanglement of molecular chains in the crystal region are constrained due to the limitation of lattice,having a bad influence on the interlayer fused effect.Based on the molecular structure design,amorphous poly(aryl ether nitrile ketone)containing nitrile groups(PEK-CN)was synthesized by nucleophilic polycondensation,in order to improve the interlaminar fused effect and mechanical properties of orthopedic implants through the interaction of polar groups and intermolecular chains entanglement.A series of polymers with adjustable viscosity were synthesized by adjusting the monomer ratio and capping dose,making their fluidity matching the 3D-printing process.3D-printed PEK-CN shows excellent dimensional stability,mechanical properties and cellular compatibility,which meets the biosafety standards of orthopedic implants.Part Ⅱ:Design,preparation and application of poly(aryl ether ketone)orthopedic implants with multi-stage pores.In the above work,the surface of the poly(aryl ether ketone)orthopedic implant printed by FDM process is smooth and hydrophobic,which is not conducive to cellular adhesion and presents biologically inert.In this work,for improving biological activity by surface topology,an amorphous poly(aryl ether ketone)with carboxyl groups(PEK-COOH)was designed and synthesized.Then a series of PEK-COOH inks with adjustable concentration were prepared,and the porous scaffold with multi-stage pores was formed by low-temperature printing at the optimal concentration.The mechanical properties of the scaffold are matched with cancellous bone.And the scaffold presents 100 nm～10 μm micro-pores and 200μm-500 μm macro-pores.The micro-pores are beneficial to promote the adhesion and migration of cells,and the macro-pores are beneficial to the growth of new bone tissue.A rabbit tibia defect model was established,and the results show that the PEK-COOH scaffold with multi-stage pores presents better bone integration effect than PEEK scaffold by imaging,histological and biomechanical analysis.Part Ⅲ:Design,preparation and application of poly(aryl ether ketone)-nano-hydroxyapatite composite scaffolds.As a chemically synthesized polymer,poly(aryl ether ketone)has limited osteogenic activity.Therefore,in this work,nano-hydroxyapatite(nHA)is introduced into the poly(aryl ether ketone)to make composite scaffolds for further improving osteogenic activity.nHA particles present high surface energy and are easily agglomerate,leading to uneven dispersion in polymer,may affect the implanted effect.In this work,poly(aryl ether ketone)-nano-hydroxyapatite(PEK-COOH-nHA)composites were prepared by partial surface chemical bonding without affecting the properties of nHA crystals,and porous composite scaffolds with different nHA contents were prepared by low-temperature printing.The results show that nHA particles are evenly distributed on the surface of PEK-COOH-nHA composite scaffolds,and the mechanical properties of composite scaffolds match the cancellous bone.In vitro cell experiments prove that nHA can promote cellular proliferation and osteogenic differentiation.Part Ⅳ:Design,preparation and application of anti-infective poly(aryl ether ketone)orthopedic implants.As an orthopedic implant,poly(aryl ether ketone)is susceptible to infection,especially the porous surface is conducive to bacteria adhesion,which increases the possibility of implant infection.Therefore,in this work,under the premise of not affecting the mechanical properties of the matrix material,poly(aryl ether ketone)-ant antibacterial peptide(LP-AMP)composite scaffold with anti-infection function was prepared,via combining ant antibacterial peptide(AMP)to the surface of poly(aryl ether ketone)scaffold by chemical and physical loading.The results show that the LP-AMP composite scaffold presents high antibacterial activity against S.aureus and E.coli(bactericidal rate higher than 98%).And the LP-AMP composite scaffold has excellent hydrophilicity and cellular compatibility.Therefore,the LP-AMP composite scaffold not only has ideal biocompatibility,but also presents broad-spectrum and efficient antibacterial activity,which has potential application value in bone repair.