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Graphical abstract Highlights • Phosphate-modified PEEK is successfully prepared. • Phosphate-modified PEEK enhances bone marrow stromal cells responses. • Phosphate-modified PEEK mitigates inflammatory responses by macrophage. • Phosphate modification can significantly improve implant-bone bonding strength in vivo. Abstract Poly(ether ether ketone) (PEEK) has emerged as an alternative endosseous material to metal implants mainly because of its lack of allergic sensitivity and radiolucency, while maintaining similar mechanical properties with bone. However, a disadvantage of PEEK is its weak osseointegration ability compared with metal implants. To overcome this, we prepared a phosphate group-modified PEEK by plasma treatment and subsequent phosphorylation reaction. Plasma treatment and phosphate modification of PEEK changed its hydrophobic surface to a hydrophilic surface while maintaining the original surface topography and roughness. Phosphate modification increased the bioactivity of rat bone marrow stromal cells (BMSCs), including proliferation, alkaline phosphatase activity, and bone-like nodule formation; however, this effect was negligible in plasma-treated PEEK. In addition, phosphate modification attenuated the phenotypic polarization of lipopolysaccharide-primed RAW264.7 macrophages to an inflammatory phenotype, based on the finding that macrophages on phosphate-modified PEEK produced decreased levels of the inflammatory cytokine and increased levels of the anti-inflammatory cytokine. Finally, in an animal study, phosphate-modified PEEK exhibited a doubled pullout force from the femur bone cavity compared with bare PEEK. Thus, we conclude that phosphate modification can significantly improves the implant-bone bonding strength of PEEK by enhancing BMSCs activity and reducing excessive inflammation. [ABSTRACT FROM AUTHOR]

Polyether ether ketone (PEEK) is an appropriate biomaterial for orthopedic implant applications due to its superior mechanical properties, chemical resistance, nontoxicity, and Magnetic resonance imaging (MRI) compatibility. Unfortunately, the inherent bio-inertness of PEEK restricted its application and required some modification to provide better bioactivity. Besides it, the generated electrical signals in the bone due to its piezoelectricity features have a vital role in regulating bone repair and regeneration. We aimed to modify the surface of PEEK with a dual-functionality nanocomposite that provides surface bioactivity and simulates the piezoelectricity of bone. So, we introduced a novel piezoelectric-bioactive nanocomposite of dispersed poly (vinylidene fluoride) (PVDF) in a sulfonated PEEK (SPEEK) matrix containing Nanohydroxyapatite (nHA) and Carbon nanofiber (CNF) fillers for coating on PEEK substrate to improve its biological activity and simulate the electrical microenvironment for bone tissue. Furthermore, sulfonation of the PEEK surface was conducted as an intermediate layer to prepare better adhesion between the coating nanocomposite and the PEEK sublayer. Surface and cross-section morphology, apatite formation, and cell attachment were investigated on the different treated PEEK surfaces using field-emission scanning electron microscopy (FESEM) and energy dispersive X-ray analysis (EDX). Also, piezoelectric performance, electrical conductivity, contact angle, and mechanical properties were examined on the prepared samples. Moreover, cell viability and cell morphology were investigated for biological evaluation with human osteoblast-like MG-63 cells. Collectively, the hydrophilicity of modified PEEK (mPEEK) coated with nanocomposite was improved due to the synergistic effects of SPEEK functional groups and nHA. Also, comprehensive investigation on the mPEEK treated with nanocomposite indicated a noticeably better bone-like apatite formation, cell proliferation, and cell attachments in the presence of nHA. The transfer of induced piezoelectric charges from dispersed PVDF in the matrix to the surface of nanocomposite containing 2 wt% of CNF increased output voltage to 1893 mV. On the other hand, the presence of CNF in nanocomposites enhanced tensile strength and Young's modulus by 92% and 117%, respectively. [Display omitted] • SPHC nanocomposite coated on the PEEK substrate in the presence of an intermediate sulfonated layer. • The effect of the intermediate sulfonated layer on surface morphology and roughness was investigated. • Coated mPEEK with SPHC nanocomposite showed a dual function of bioactivity and piezoelectric. • The modified PEEK with nanocomposites containing nHA exhibited superior cell compatibility than bare PEEK. [ABSTRACT FROM AUTHOR]

The poor bacteriostasis and osseointegration properties of bioinert polyetheretherketone (PEEK) hinder its clinical application. This work reports a simple and versatile strategy for fabricating dual-functional coating with programmed sequential drug release properties on porous PEEK surfaces. The dual-drug-loaded composite coating composed of drug-loaded poly(lactic- co -glycolic acid) (PLGA) nanoparticles and drug-loaded polyvinyl alcohol (PVA) gel can be immobilized on the surface of sulfonated PEEK by a cyclic freeze-thaw method. Based on the swelling of PVA and the slow degradation of PLGA, the composite coating can realize rapid release of antibacterial drugs and sustained release of osteogenic drugs. The in vitro antibacterial evaluations show that the porous PEEK modified with drug-loaded composite gel coating exhibits an early effective fight against Staphylococcus aureus (S.aureus). The results of in vitro cell experiments show that the PEEK materials modified by the composite gel coating can well support the normal growth, adhesion and proliferation of cells. In addition, the PEEK material coated with the drug-loaded composite gel is found to have positive effects on the osteogenic differentiation of cells in detections of alkaline phosphatase (ALP) activity of cells and the amount of calcium deposition on the surface of the material. The results demonstrate that the proposed porous PEEK modified with dual-drug-loaded composite gel coating simultaneously exhibits excellent osseointegration and exerts early effective antibacterial activity. This dual-functional PEEK material has great application potential in clinical bone tissue repair. [Display omitted] • A dual-drug-loaded composite gel coating is constructed on the PEEK surface. • The composite coating can realize programmed sequential drug release. • Antibacterial drug is rapidly released and osteogenic drug is sustainedly released. • The coating is composed of drug-loaded PLGA nanoparticles and drug-loaded PVA gel. • The modified PEEK exhibits excellent osseointegration and antibacterial activity. [ABSTRACT FROM AUTHOR]

Due to its favorable chemical stability, biocompatibility, and mechanical properties, Poly(etheretherketone) (PEEK) is a promising material for repairing bone and dental hard tissue defects. However, there are critical disadvantages: PEEK is biologically and chemically inert, which influences osseointegration of implants and bonding strength of prostheses, and its mechanical properties still cannot meet the requirements for some medical applications. Furthermore, bacterial infections and inflammatory reactions often accompany bone defects caused by trauma or inflammation or teeth loss caused by periodontitis. Previous studies mainly focused on enhancing PEEK's bioactivity and mechanical performance, but PEEK also lacks effective anti-infection ability. Thus, it is necessary to improve its anti-infection ability, and this is considered in this paper from two aspects. The first is to inhibit the attachment and growth of bacteria on the material, and the second is to endow the material with immunoregulatory ability, which means mobilizing the host immune system to protect tissue from inflammation. In this review, we analyze and discuss the existing treatment methods to improve the antibacterial and immunomodulatory abilities of PEEK addressing their limitations, relevant future challenges, and required research efforts. [Display omitted] • Polyetheretherketone is a potential biomaterial for hard tissue repair. • Antibacterial and immunoregulatory ability of Polyetheretherketone needs improvement. • Antibacterial ability can be enhanced by surface treatments and filling modification. • Macrophages can be a target to improve the immunoregulation of Polyetheretherketone. [ABSTRACT FROM AUTHOR]

Polyetheretherketone (PEEK) has been widely applied for orthopedic and oral implants due to its excellent mechanical properties, biocompatibility, and radiolucency. However, its bioinert and the lack of anti-microbial activity limit its application. We modified the PEEK surface with Ta/Cu co-implantation using plasma immersion ion-implantation technology. After implantation of Ta/Cu ions, the morphology and roughness of the PEEK surface were not significantly changed at micron level. We estimated the cytocompatibility, anti-microbial ability, and osteogenic differentiation of rat bone mesenchymal stem cells (BMSCs) of the modified surfaces in vitro. Compared to the untreated surfaces, the Ta ion-treated surface showed improved adhesion, proliferation, ALP activity, ECM mineralization, and osteogenic gene expression of BMSCs. Further, the Cu ion-treated surface showed reduced initial adhesion and proliferation of Escherichia coli and Staphylococcus aureus in vitro and proliferation of Staphylococcus aureus in the mouse subcutaneous implant-associated infection model. According to a rat bone repair model, all Ta ion-implanted groups demonstrated improved new bone formation. In summary, Ta/Cu ion co-impanation improved anti-microbial activity and promoted osseointegration of the PEEK surface. • Cu and Ta nanoparticles were incorporated on PEEK surface by ion implantation. • Ta/Cu co-impanted PEEK showed improved anti-microbial activity in vitro and in vivo. • Ta/Cu co-impanted PEEK exhibited enhanced cytocompatibility and osseointegration. [ABSTRACT FROM AUTHOR]