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Antibacterial sonothermal therapy (ASTT) is attractive for treating implant‐associated infection, which addresses the limitations of poor penetration of photothermal therapy. However, achieving implant surface‐specific ultrasound heating is incredibly challenging. Inspired by the porous acoustic metastructure in noise reduction, the acoustic metastructure would be a new strategy for attaining ASTT. Herein, an "acoustic confinement effect" is proposed to "trap" ultrasound for the metastructure TiO2 porous coating on titanium implants. The metastructure coating accomplishes specific acoustic absorption and efficient acoustic‐to‐thermal conversion, surpassing the non‐specific heating of conventional coatings. The theoretical calculation and experiment of metastructure porous coating prove the acoustic‐to‐thermal conversion mechanism, which is also validated in metastructure porous coatings on medical polyetheretherketone, indicating it is universal. Excitingly, this acoustic metastructure "trap" can capture bacteria and local sonothermal enhancement, exhibiting superior ASTT antibacterial rates (S. aureus, 99.69%; E. coil, 99.58%) at low‐power ultrasound. In addition, the metastructure TiO2 coating mimics human bone and demonstrates outstanding osseointegration. This study sheds substantial light on developing the acoustic responsive surface, broadening a new direction of acoustic metamaterials in medical applications. [ABSTRACT FROM AUTHOR]

The occurrence of bone diseases has been increasing rapidly, in line with the aging population. A representative spinal fusion material, polyetheretherketone (PEEK), is advantageous in this regard as it can work in close proximity to the elastic modulus of cancellous bone. However, if it is used without surface modification, the initial osseointegration will be low due to lack of bioactivity, resulting in limitations in surgical treatment. In this study, we aimed to modify the surface of PEEK cages to a hydrophilic surface by coating with polyethylene glycol (PEG), hyaluronic acid (HA), and polydopamine (PDA), and to analyze whether the coated surface exhibits improved bioactivity and changes in mechanical properties for orthopedic applications. Material properties of coated samples were characterized and compared with various PEEK groups, including PEEK, PEEK-PEG, PEEK-HA, and PEEK-PDA. In an in vitro study, cell proliferation was found to be enhanced on PDA-coated PEEK; it was approximately twice as high compared to the control group. In addition, mechanical properties, including static and torsion, were not affected by the presence of the coating. Thus, the results suggest that PEEK-PDA may have the potential for clinical application in fusion surgery for spinal diseases, as it may improve the rate of osseointegration. [ABSTRACT FROM AUTHOR]

Osseointegration is highly desirable for implants used for bone replacement. Polyetheretherketone (PEEK) is an attractive material due to its characteristics such as high biocompatibility and Young's modulus similar to human bones. However, PEEK is bioinert, meaning cells do not adhere and proliferate on its surface. This problem is addressed in this study, with the goal of enhancing osseointegration of additively manufactured PEEK. The influences of surface modifications and porous structures on cellular behavior were assessed by wettability and in vitro tests with subclone of the human osteosarcoma cell line‐2 osteoblasts. Overall, the combination of surface modification, type of plasma process used, atmospheric pressure versus vacuum‐based, and surface structuring, especially gyroid structures, improve the cellular proliferation on PEEK. Therefore, its ability to enhance osseointegration is highly promising. [ABSTRACT FROM AUTHOR]

Polyetheretherketone (PEEK) has been widely used as orthopedic implants, but the poor antimicrobial and osseointegration properties hinder its advanced clinical applications. Most of the modification strategies are difficult to temporally fulfill initial broad‐spectrum antimicrobial and later pro‐osteogenic requirements for a long‐term success of implantation. N‐halamine is a kind of biofriendly antimicrobial agent, and its functional N─Cl groups could be converted into N─H groups, potentially resulting in new bioactivities. Therefore, it is supposed that N‐halamine might provide a feasible design for the dynamical integration of antimicrobial and pro‐osteogenic abilities. Herein, a new class of surface‐porous PEEK implant with an N‐halamine polymeric coating (sp‐PEEK‐NCl) is constructed by successive pore‐making, polymer grafting, and chlorination. The as‐prepared sp‐PEEK‐NCl exhibits broad‐spectrum antibacterial, antifungal, anti‐inflammatory, and pro‐osteogenic effects. More importantly, with the consumption of oxidative chlorine, the N─Cl groups in sp‐PEEK‐NCl are transformed into N─H groups with enhanced pro‐osteogenic ability, endowing sp‐PEEK‐NCl with dynamically compatible bioactivities for osseointegration in different periods after implantation. Rat implant‐associated osteomyelitis model confirms that sp‐PEEK‐NCl obviously reduces infectious bone destruction and promotes osseointegration in vivo. This work may provide a promising strategy for intelligent integration of bioactivities and valuable insight into the design of orthopedic implants in bone tissue engineering. [ABSTRACT FROM AUTHOR]

Introduction: The success of implant therapy depends on a number of parameters, including bone volume implant shape, surface topography, the patient's overall health, and local factors. Despite the fact that polyetheretherketone (PEEK) implants have undergone a lot of alterations, only a small number of studies have examined the bioactivity and osseointegration of PEEK implants with titanium. Aim: To summarise and evaluate protein adsorption and osseointegration capacity of PEEK and titanium dental implants. Materials and Methods: Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines were used and PROSPERO (CRD42023415494) registration was done. Electronic databases were searched for studies assessing the outcome in terms of protein adsorption and osseointegration capacity of PEEK and titanium dental implants. Quality assessment of included studies was evaluated using the Newcastle-Ottawa Scale (NOS). Results: Depending on inclusion and exclusion criteria, seven studies fulfilled the eligibility criteria and were included in qualitative synthesis. Risk of bias assessment revealed that all the included studies were largely comparable in methodological quality. All the included studies had moderate to low-risk of bias with all the respective domains. All the included studies revealed that PEEK with optimal surface roughness might hold great potential for protein adsorption and osseointegration capacity. Conclusion: Within the limitations of the study, it was found that compared to titanium, PEEK is less osseoconductive and bioactive. PEEK is therefore unsuitable for use as a dental implant in its unmodified form. Implantitis and implant failure occurs from improper osseoconductivity and bioactivity of dental implants. [ABSTRACT FROM AUTHOR]

Orthopedic implants should have sufficient strength and promote bone tissue regeneration. However, most conventional implants are optimized for use either under high mechanical load or for active osseointegration. To achieve the dual target of mechanical durability and biocompatibility, polyether ether ketone (PEEK) filaments reinforced with internal titanium dioxide (TiO2) nanoparticles via dopamine‐induced polymerization are additively manufactured into an orthopedic implant through material extrusion (ME). The exterior of the PEEK/TiO2 composite is coated with hydroxyapatite (HA) using radiofrequency (RF) magnetron sputtering to increase both the strength and biocompatibility provided by homogeneous ceramic–ceramic interactions and the protuberant nanoscale topography between the internal TiO2 nanoparticle reinforcement and external HA coating. The hardness, tensile, and compression, and scratch test results demonstrate a considerable enhancement in the mechanical strength of the hierarchical PEEK/TiO2/HA hybrid composite structure compared to that of the conventional 3D‐printed PEEK. Furthermore, PEEK with internal TiO2 reinforcement improves the proliferation and differentiation of bone cells in vitro, whereas the external HA coating leads to a more prevalent osteoblast absorption. Micro‐computed tomography and histological analyses confirm new bone formation and a high bone‐to‐implant contact ratio on the HA‐coated PEEK structure reinforced with TiO2 nanoparticles. [ABSTRACT FROM AUTHOR]

The complex bone regeneration microenvironment puts high demands on orthopedic implants. The implants are not only desired to satisfy the meeting of the biomechanical properties, but should also possess capabilities to promote osseointegration and bone immune regulation. PEEK is a promising polymeric material for bone implants due to its suitable mechanical properties that well match natural cortical bone tissue. However, its inert biological properties limit its application. As a newly-developed bioactive polysaccharides complex, strontium Eucommia ulmoides polysaccharides (EUP-Sr) has been proved to have capabilities including promoting osteogenesis and regulating bone immunity. In this study, in order to improve the bioactivities of PEEK, we introduce EUP-Sr to the PEEK surface via polydopamine-based coating and form a bioactive PEEK named DPEEK@EUP-Sr. The as-fabricated DPEEK@EUP-Sr was systematically investigated through scanning electron microscopy, X-ray photoelectron spectroscopy, water contact angle analysis to verify the successful introduction of EUP-Sr to PEEK, and in vitro biological experiments including cell proliferation and RT-PCR analysis suggested that the DPEEK@EUP-Sr can effectively promote the proliferation of preosteoblast MC3T3-E1, and exhibit significant anti-inflammation and osteogenesis effects, and so should be beneficial for osteointegration between bone and implants. [ABSTRACT FROM AUTHOR]

The work describes a polydopamine-wrapped zeolitic imidazolate framework-8 (ZIF-8) coating constructed on the sulfonated polyetheretherketone (PEEK). The coating is not only conducive to the controllable Zn2+ releases, but also exhibits excellent photothermal capacity under near-infrared (NIR) irradiation. in vitro antibacterial experiments indicate the coating possesses bactericidal efficiencies of 100% against Staphylococcus aureus and Escherichia coli under NIR. Without NIR, the ZIF-8/pDA-functionalized substrate shows favorable biocompatibility and enhanced osteogenic activities. We are convinced that this study may provide prospective opinions for developing the PEEK implants with photoinduced disinfection and osteogenesis for the repair of infected bone defects. [ABSTRACT FROM AUTHOR]

• PEEK biointerfaces were constructed by dopamine-triggered one-step polymerization of CBAA. • The PEEK biointerfaces possessed osteogenesis and antibacterial efficacy. • The in situ induced biomineralization improved osseointergration in vivo. Polyetheretherketone (PEEK) is increasingly recognized as a promising biomaterial for orthopedic implants due to its mechanical properties that are very similar to those of human bones. However, its inherent bioinertness still poses a challenge to effective osseointegration, and surface modification of PEEK implants often faces limitations such as multi-step complexity. In this study, we innovatively developed a dopamine-triggered one-step polymerization of 3-[(3-acrylamidopropyl)dimethylammonio] propanoate (PCBAA), which in situ induced biomineralization and constructed a functional PEEK biointerfaces, directly and effectively enhancing osseointegration and antibacterial effects. The successful immobilization of PCBAA on the surface of PEEK significantly enhanced osteogenic differentiation of bone mesenchymal stem cells, as evidenced by the significant improvement in alkaline phosphatase activity and mineral deposition. Moreover, the functional biointerfaces exhibited substantialantibacterial efficacy in vitro. Micro-computed tomography (micro-CT) and histological evaluation of rat tibia implantation showed that compared to uncoated screws, the PCBAA-functionalized PEEK screws significantly enhanced new bone formation and possessed superior pull-out strength. The findings of this study suggest that the one-step polymerization of PCBAA coatings on PEEK substrates is facile and can efficiently overcome the limitations of current surface modification. The resultant PCBAA-coated PEEK biointerfaces have shown great promise in promoting osseointegration and mitigating postoperative infections for clinical outcomes of PEEK-based orthopedic implants. [ABSTRACT FROM AUTHOR]

[Display omitted] • The controlled release of Li+ was successfully accomplished through the encapsulation of lithium-doped bioglass nanospheres on sulfonated polyetheretherketone. • Polyetheretherketone coated by lithium-doped bioglass nanospheres has anti-inflammatory properties, inducing macrophage polarization to M2 phenotype. • The biofunctionalized polyetheretherketone surface with lithium-doped bioglass nanospheres exhibited enhanced osteogenesis and immunomodulatory osteogenesis properties. Polyetheretherketone (PEEK) is a frequently utilized orthopedic implant material in clinical settings. However, the adverse inflammatory and immunological reactions due to the PEEK surface after implantation often cause poor osseointegration and thereby hinder its clinical utility. To improve osseointegration and enhance the success rate of PEEK implants, the surface can be biofunctionalized to be immunomodulatory. Consequently, in this study, lithium-doped bioglass nanospheres (Li/BGs) was coated on the sulfonated PEEK surface. Furthermore, we assessed the anti-inflammatory potential of the biofunctionalized PEEK implants and their impact on osteogenesis. In our study, it was observed that the in vitro biofunctionalized PEEK surface exhibited enhanced osteogenesis and immunomodulatory osteogenesis properties, while also effectively suppressing the acute inflammatory response initiated by macrophages. Furthermore, our in vivo experiments demonstrated that the biofunctionalized PEEK surface contributed to improved osteogenesis properties and mitigated the formation of fibrous capsules. Therefore, the in vitro and in vivo results demonstrated that PEEK surface modification with Li/BGs not only changed the disadvantage of being bioinert on the surface but also endowed it with osteoimmunomodulatory regulation and bone-promoting properties. Thus, the biofunctionalized PEEK may be a promising candidate for use as an orthopedic implant in clinical settings. [ABSTRACT FROM AUTHOR]

Polyetheretherketone (PEEK) is a kind of nontoxic high-performance thermoplastic widely used for medical applications. Compared with other special engineering plastics, PEEK has many excellent properties, such as high temperature resistance, chemical corrosion resistance, radiation resistance, hydrolysis resistance, excellent mechanical properties, good self-lubrication and easy processing. Although PEEK has been widely used as the replacements of metallic and ceramic implants in medical field, it is biologically inertia, which reduces the fusion with host bone tissue after implantation. In addition, the high friction coefficient and hydrophobicity of PEEK also seriously hinder its applications. In view of these, the studies of PEEK biomaterials have now focused on the improvement of biological activity by various material engineering strategies. In this paper, these recently developed strategies to improve PEEK bioactivity to address clinical orthopedic needs (e.g., anti-inflammation, anti-infection and osteointegration) are reviewed. The advantages and disadvantages of these methods are further analyzed. This review paper may provide more targeted direction for developing multifunctional PEEKbased implants in the future. [ABSTRACT FROM AUTHOR]

Existing biologically inert or unmodified implants to treat infectious bone defects or osteomyelitis still cannot effectively solve bacterial infection and osseointegration. In this work, a simple co-deposition strategy was developed to modify porous polyetheretherketone (PEEK) with improved antibacterial activity and controllable immunoregulatory ability. After PEEK was treated by H2SO4 to obtain porous PEEK (SPEEK), the self-polymerization of dopamine was operated on SPEEK in the solution of dopamine and gentamicin sulfate (GS) to prepare polydopamine (pDA) and GS layer-modified SPEEK (labeled as SPEEK-pDA-GS). The morphology, surface property, and molecular structure of SPEEK-pDA-GS were investigated. Besides the antibacterial property of SPEEK-pDA-GS ascribed to the successful immobilization of GS, SPEEK-pDA-GS exhibited promoted osseointegration through the results of mineralization, alkaline phosphatase (ALP) levels and osteogenic gene expression. Furthermore, the evaluation of the cell proliferation suggested that SPEEK-pDA-GS possessed the biocompatibility and the immunoregulatory ability that induced macrophages to anti-inflammatory M2 phenotype. Using rat as model, in vivo results containing X-ray, l-CT, immunohistochemistry, and pathological analysis showed the excellent healing effect of SPEEK-pDA-GS on bone defect with infection with biological safety. This work illustrates a new insight into the simple and effective modification of PEEK and other implants with antibacterial, immunoregulatory, and osseointegration abilities for clinical requirement. [ABSTRACT FROM AUTHOR]

As a chronic metabolic disease, diabetes mellitus (DM) creates a hyperglycemic micromilieu around implants, resulting inthe high complication and failure rate of implantation because of mitochondrial dysfunction in hyperglycemia. To address the daunting issue, the authors innovatively devised and developed mitochondria‐targeted orthopedic implants consisted of nutrient element coatings and polyetheretherketone (PEEK). Dual nutrient elements, in the modality of ZnO and Sr(OH)2, are assembled onto the sulfonated PEEK surface (Zn&Sr‐SPEEK). The results indicate the synergistic liberation of Zn2+ and Sr2+ from coating massacres pathogenic bacteria and dramatically facilitates cyto‐activity of osteoblasts upon the hyperglycemic niche. Intriguingly, Zn&Sr‐SPEEK implants are demonstrated to have a robust ability to recuperate hyperglycemia‐induced mitochondrial dynamic disequilibrium and dysfunction by means of Dynamin‐related protein 1 (Drp1) gene down‐regulation, mitochondrial membrane potential (MMP) resurgence, and reactive oxygen species (ROS) elimination, ultimately enhancing osteogenicity of osteoblasts. In vivo evaluations utilizing diabetic rat femoral/tibia defect model at 4 and 8 weeks further confirm that nutrient element coatings substantially augment bone remodeling and osseointegration. Altogether, this study not only reveals the importance of Zn2+ and Sr2+ modulation on mitochondrial dynamics that contributes to bone formation and osseointegration, but also provides a novel orthopedic implant for diabetic patients with mitochondrial modulation capability. [ABSTRACT FROM AUTHOR]

Sol–gel-derived TiO2 coatings have been confirmed to effectively promote bone-bonding behavior on polyetheretherketone (PEEK) surfaces; however, the optimal layer thickness to maximize the osseointegration and adhesive performance has not been yet determined. In this study, we applied sol–gel-derived TiO2 coatings with different layer thicknesses (40 and 120 nm) on PEEK implants to determine the effects of layer thickness on the surface characteristics, adhesive strength, and bone bonding capabilities (including histological osseointegration). The surface analysis results of both coated implants indicated no significant differences concerning the water contact angle, layer adhesion strength, and apatite formation ability in a simulated body fluid. Additionally, the in vivo biomechanical tests revealed a higher bone-bonding strength for both coated PEEK implants (compared with that of the uncoated sample). It was thus concluded that the factor of layer thickness marginally influences the bioactive advantages attained by sol–gel-derived TiO2 coatings on PEEK surfaces, highlighting the significant versatility and clinical availability of this coating technology. [ABSTRACT FROM AUTHOR]

The 3D printing of polyether ether ketone (PEEK) composite of lightweight, high strength, and relatively low-cost composite are rare. This is due to the high melting temperature and poor adhesion problems. This research carefully examines the computational characterization of the nanos-tructure and finite element analysis (FEA) of PEEK/hydroxyapatite (HAP)/-graphene oxide (GO) to solve the problems of high melting temperature and poor adhesion and makes it possible to achieve the lightweight characteristic. Based on the loading condition, a new principal stress trajectory is generated through FEA and used as the guidance for the placement path of PEEK/HAP/GO. The design of the hot extrusion head was implemented at the ambient temperature. Many essential factors were considered while printing PEEK/HAP/GO structures without distortion and degradation of the composite. Compression and traction tests were performed to investigate the mechanical properties of the new PEEK/HAP/GO structure. These were done using three-point flexure test techniques. The addition of physiologically active substances such as bioglass and the incorporation of porosity in PEEK/HAP/GO have been identified as an effective way to improve the osseointegration of bone-implant interfaces, produce a lightweight structure, and improve the biocompatibility of product. A 3000 mm/min printing speed was observed in the 3D-printed PEEK/HAP/GO, with a porosity of 1.2% of maximum increasing strength. This article will help researchers to strengthen their conceptual and computational knowledge of 3D printing tools and medical devices as well as explore future possibilities based on the use of PEEK/HAP/GO. [ABSTRACT FROM AUTHOR]

[Display omitted] • Bisphosphonate groups are introduced onto PEEK implant using mussel-inspired chemistry. • Surface bisphosphonation mitigates the early acute inflammatory immune response by modulating macrophages M2 polarization. • A favorable osteoimmune microenvironment is constructed by surface bisphosphonation to enhance osteogenesis and angiogenesis. • PEEK implant with surface bisphosphonation achieves ameliorative osseointegration. Polyetheretherketone (PEEK) is deemed to be a promising alternative to biomedical metals for orthopedic and dental implantation attributed to its bone-like elastic modulus and good biocompatibility. Nevertheless, the bioinert PEEK elicits an acute and irreducible inflammatory immune response after implantation, resulting in fibrous encapsulation and ultimately inferior osseointegration. Therefore, endowing the PEEK surface with immunomodulatory function is essential for advanced osseointegration. Herein, surface bisphosphonation of PEEK is achieved by using mussel-inspired chemistry together with alendronate, which can not only mitigate the early servious inflammatory immune response by promoting macrophages polarization toward the pro-healing M2 phenotype, but also construct a favorable osteoimmune microenvironment to promote the angiogenesis of human umbilical vein endothelial cells (HUVECs) and the osteogenesis of MC3T3-E1 osteoblasts. In vivo evaluation reveals an ameliorative osseointegration of PEEK implant after surface bisphosphonation, confirming the in vitro results. Our findings elucidate that the PEEK implant after surface bisphosphonation can positively regulate early immune reaction to facilitate subsequent angiogenesis and osteogenesis processes, which is desirable for orthopedic and dental implantation. [ABSTRACT FROM AUTHOR]

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]

Abstract Polyether-ether-ketone (PEEK) is one of the most common materials used for load-bearing orthopaedic devices due to its radiolucency and favorable mechanical properties. However, current smooth-surfaced PEEK implants can lead to fibrous encapsulation and poor osseointegration. This study compared the in vitro and in vivo bone response to two smooth PEEK alternatives: porous PEEK and plasma-sprayed titanium coatings on PEEK. MC3T3 cells were grown on smooth PEEK, porous PEEK, and Ti-coated PEEK for 14 days and assayed for calcium content, osteocalcin, VEGF and ALP activity. Osseointegration was investigated by implanting cylindrical implants into the proximal tibiae of male Sprague Dawley rats for 8 weeks. Bone-implant interfaces were evaluated using μCT, histology and pullout testing. Cells on porous PEEK surfaces produced more calcium, osteocalcin, and VEGF than smooth PEEK and Ti-coated PEEK groups. Bone ingrowth into porous PEEK surfaces was comparable to previously reported porous materials and correlated well between μCT and histology analysis. Porous PEEK implants exhibited greater pullout force, stiffness and energy-to-failure compared to smooth PEEK and Ti-coated PEEK, despite Ti-coated PEEK exhibiting a high degree of bone-implant contact. These results are attributed to increased mechanical interlocking of bone with the porous PEEK implant surface. Overall, porous PEEK was associated with improved osteogenic differentiation in vitro and greater implant fixation in vivo compared to smooth PEEK and Ti-coated PEEK. These results suggest that not all PEEK implants inherently generate a fibrous response and that topography has a central role in determining implant osseointegration. [ABSTRACT FROM AUTHOR]

Adjusting the topography of implant surfaces on a micro‐scale allows improvement of osseointegration. Titanium surface modification like sand blasting is one of the known methods to alter the topography of the surface. Polyetheretherketone as a biomaterial is a suitable alternative to titanium but exhibits an inert surface character. The aim of this study was to combine the positive bulk properties of polyetheretherketone with the positive surface properties of sand blasted titanium. For the creation of particle free structured polyetheretherketone surface, four different sand blasted die were pressed on counter die polyetheretherketone to transfer the structure. Furthermore, a titanium layer was applied on the surface using physical vapor deposition. The transfer process of the four different topographies was investigated with roughness measurements and scanning electron microscope. One topography, created with aluminum oxide particles on copper, was found with the required Ra value of 1 μm and Rz value of 9.2 μm for improved osseointegration. [ABSTRACT FROM AUTHOR]

Poly(ether ether ketone) (PEEK) has emerged as a candidate to replace metal implants because of its satisfactory mechanical properties, radiolucency, and lack of metal allergy. However, PEEK lacks osseointegration ability limiting its clinical applications. To overcome this problem, we prepared PEEK with a micro-rough surface using the sandblast method to modulate its osseointegration property; the sandblast method is simple, cost-effective, and is already applied to clinical metal implants. The surface roughness of the sandblasted PEEK was about 2.3 µm, whereas that of mirror-polished PEEK was 0.06 µm. Rat bone marrow-derived mesenchymal stem cells (RMSCs) showed higher proliferation, osteocalcin (OC) expression and bone-like nodule formation on micro-roughened PEEK compared with those cultured on mirror-polished PEEK, suggesting that micro-roughening facilitated RMSCs proliferation and differentiation. The micro-roughened surface slightly mitigated secretion of inflammatory C-C motif chemokine 2 (CCL-2) from lipopolysaccharide (LPS)-stimulated macrophages, but not of tumor necrosis factor a (TNFa) and interleukin-6 (IL-6). Finally, to compare osseointegration, specimens were implanted in rat femur bone marrow cavities, and then the pull-out force was measured. The pull-out force of micro-roughened PEEK was about four times higher than that of the mirror-polished PEEK. These results showed that micro-roughening of PEEK using the sandblast method was able to improve osseointegration, partly through elevating proliferation and differentiation of RMSCs. [ABSTRACT FROM AUTHOR]

Background Context: Increasing bone ongrowth and ingrowth of polyether ether ketone (PEEK) interbody fusion devices has the potential to improve clinical outcomes.Purpose: This study evaluated the in vivo response of promoting new bone growth and bone apposition with NanoMetalene (NM) compared with PEEK alone in a cancellous implantation site with an empty aperture.Study Design: This is a randomized control animal study.Methods: Implants and funding for this study were provided by SeaSpine (60,000 USD). Cylindrical dowels with two apertures were prepared as PEEK with a sub-micron layer of the titanium (NM). The titanium coating was applied over the entire implant (Group 1) or just the apertures (Group 2). Polyether ether ketone implants with no coating served as controls (Group 3). Implants were placed in the cancellous bone of the distal femur or proximal tibia with no graft material placed in the apertures in eight adult sheep. Bone ongrowth to the surface of the implant and ingrowth into the apertures was assessed at 4 and 8 weeks after surgery with micro-computed tomography (CT) and undecalcified histology.Results: The apertures in the implants were notably empty in the PEEK group at 4 and 8 weeks. In contrast, new bone formation into the apertures was found in samples coated with NM even though no graft material was placed into the defect. The bone growing into the aperture tracked along the titanium layer. Apertures with the titanium coating demonstrated significantly more bone by micro-CT qualitative grading compared with PEEK with average bone coverage scores of Group 1 (NM) 1.62±0.89, Group 2 (NM apertures only) 1.62±0.77, and Group 3 (PEEK) 0.43±0.51, respectively, at 4 weeks (p<.01) and Group 1 (NM) 1.79±1.19, Group 2 (NM apertures only) 1.98±1.18, and Group 3 (PEEK) 0.69±0.87, respectively, at 8 weeks (p<.05). The amount of bone in the apertures (ingrowth) quantified using the volumetric data from the micro-CT supported an overall increase in bone volume inside the apertures with the titanium coating compared with PEEK. Histology showed newly formed woven bone tracked along the surface of the titanium in the apertures. The PEEK interface presented the typical nonreactive fibrous tissue inside the apertures at 4 weeks and some focal contact with bone on the outside at 4 weeks and 8 weeks.Conclusions: Micro-CT and histology demonstrated bone ongrowth to the surfaces coated with NM where the newly formed bone tracked along the thin titanium-coated surfaces. Polyether ether ketone surfaces presented the nonreactive fibrous tissue at the interface as previously reported in preclinical scenarios. [ABSTRACT FROM AUTHOR]

Background Context: Various surface modifications, often incorporating roughened or porous surfaces, have recently been introduced to enhance osseointegration of interbody fusion devices. However, these topographical features can be vulnerable to damage during clinical impaction. Despite the potential negative impact of surface damage on clinical outcomes, current testing standards do not replicate clinically relevant impaction loading conditions.Purpose: The purpose of this study was to compare the impaction durability of conventional smooth polyether-ether-ketone (PEEK) cervical interbody fusion devices with two surface-modified PEEK devices that feature either a porous structure or plasma-sprayed titanium coating.Study Design/setting: A recently developed biomechanical test method was adapted to simulate clinically relevant impaction loading conditions during cervical interbody fusion procedures.Methods: Three cervical interbody fusion devices were used in this study: smooth PEEK, plasma-sprayed titanium-coated PEEK, and porous PEEK (n=6). Following Kienle et al., devices were impacted between two polyurethane blocks mimicking vertebral bodies under a constant 200 N preload. The posterior tip of the device was placed at the entrance between the polyurethane blocks, and a guided 1-lb weight was impacted upon the anterior face with a maximum speed of 2.6 m/s to represent the strike force of a surgical mallet. Impacts were repeated until the device was fully impacted. Porous PEEK durability was assessed using micro-computed tomography (µCT) pre- and postimpaction. Titanium-coating coverage pre- and postimpaction was assessed using scanning electron microscopy (SEM) and energy dispersive X-ray spectroscopy. Changes to the surface roughness of smooth and titanium-coated devices were also evaluated.Results: Porous PEEK and smooth PEEK devices showed minimal macroscopic signs of surface damage, whereas the titanium-coated devices exhibited substantial visible coating loss. Quantification of the porous PEEK deformation demonstrated that the porous structure maintained a high porosity (>65%) following impaction that would be available for bone ingrowth, and exhibited minimal changes to pore size and depth. SEM and energy dispersive X-ray spectroscopy analysis of titanium-coated devices demonstrated substantial titanium coating loss after impaction that was corroborated with a decrease in surface roughness. Smooth PEEK showed minimal signs of damage using SEM, but demonstrated a decrease in surface roughness.Conclusion: Although recent surface modifications to interbody fusion devices are beneficial for osseointegration, they may be susceptible to damage and wear during impaction. The current study found porous PEEK devices to show minimal damage during simulated cervical impaction, whereas titanium-coated PEEK devices lost substantial titanium coverage. [ABSTRACT FROM AUTHOR]

[Display omitted] • It was first time to attempt to cross link polydopamine and epigallocatechin-3-gallate together to enhance osteointegration for polyetheretherketone. • It showed that the cross-linked coatings provided phenolic hydroxyl and amino groups and enhanced hydrophilicity of the polyetheretherketone. • It may lay the foundation for the further deployment of the cross-linked polydopamine and epigallocatechin-3-gallate coating in clinical practice. The increasing demand for enhanced osteointegration calls for next-generation polyetheretherketone (PEEK) that can offer fast bone integration. Whether polydopamine (PDA) and epigallocatechin-3-gallate (EGCG) cross-linked coatings could improve osteointegration of PEEK remains unclear. Here, we fabricated a series of PDA and EGCG cross-linked coatings (PE coatings: P2E0.1, P2E0.5, P2E1, and P2E2 coatings) to enhance osteointegration of PEEK. The material characteristics of coatings were studied using scanning electron microscopy, X-ray photoelectron spectroscopy, micro-BCA tests, and static water contact angle tests. We evaluated the cytotoxicity, cell adhesion, and osteogenic effects of the coatings in vitro. Furthermore, the P2E0.5 coating was selected to coat porous PEEK scaffold to observe osteointegration using micro-computed tomography and histology in a rabbit. The results show that the PE coatings provide phenolic hydroxyl and amino groups and enhanced hydrophilicity of PEEK, especially in the P2E0.5 coating. Several lines of cellular evidence suggest that P2E0.5 coatings exhibit a noncytotoxic and excellent osteogenic effect. Compared with PEEK, the P2E0.5-coated PEEK shows higher values of bone volume, trabecular number, and trabecular thickness. This study suggests that the PE coating is a promising candidate for surface modification of PEEK and may lay the foundation for further application of PE coatings in clinical practice. [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]

[Display omitted] Polyetheretherketone (PEEK) is increasingly popular for use in dental applications because of its excellent chemical stability, biocompatibility, and mechanical qualities. However, its surface inertness hinders the osseointegration of the implant and limits the bonding strength of prostheses, significantly limiting its clinical application overall. During recent decades, there has been more and more attention to improve surface inertness of PEEK via various modification methods. Here, our work is aimed to review and discuss recent progress on the application of treatment strategies proposed to enhance the bonding strength and bioactivity of PEEK materials, including surface modification and blending modification. Surface modification was divided into physical modification, chemical modification and surface coating, according to the surface treatment approaches. Despite the challenges, modified PEEK, in our perspective, will be a viable material for dental applications. [ABSTRACT FROM AUTHOR]

[Display omitted] • LCFRPEEK with a MOF hydrogel surface is prepared for enhancing anti-inflammatory and angiogenesis and osteogenesis. • The MOF hydrogel is composed of HAP@Mg-GA MOF nanoparticles with core–shell structure and pH-sensitive methacryloyl chitosan. • This implant has excellent pH-sensitive biomolecule release capabilities. • The multifunctional implant displays excellent anti-inflammatory and angiogenesis and osteogenesis in vitro and in vivo. The ideal orthopedic implant has sufficient biomechanical strength and physiological activity to coordinate with the intricate physiological healing process of the tissue. Herein, multifunctional stimuli-responsive metal–organic framework (MOF) hydrogels on the surface of the sulfonated long carbon fiber reinforced polyetheretherketone (LCFRPEEK) implant using the UV-grafting method is constructed to coordinate with the osseointegration process. The hydrogels are composed of nano-hydroxyapatite cored magnesium-gallic acid (HAP@Mg-GA) MOF nanoparticles and methacryloyl chitosan. The stimuli-responsive MOF hydrogels exhibit outstanding pH-sensitive biomolecule release capabilities. The outcomes of in vitro cell experiments demonstrate that the multifunctional sulfonated LCFRPEEK could actively and precisely perform immunomodulation, timely scavenge excess ROS and reduce NO production under the immune environment (low pH), as well as promote angiogenesis and osteogenic differentiation benefiting from the cooperation of GA, Mg2+ and Ca2+. Furthermore, the in vivo SD rat subcutaneous implantation and rabbit tibia defect models further demonstrate that the implant has superior in vivo immunomodulation, angiogenesis, osteogenic differentiation, and osseointegration abilities. Therefore, the study provides a new multifunctional orthopedic implant that can achieve osseointegration, which broadens the effective application of LCFRPEEK biomaterials in orthopedics. [ABSTRACT FROM AUTHOR]

[Display omitted] • Porous polyether ether ketone (PEEK) scaffolds coated with hydroxyapatite (HA) layer were prepared using a bionic manufacturing strategy. • The bionic sacrificial porogen was inspired by the Chinese food Matuan, which is glutinous rice ball stuck with sesames. • The PEEK@HA scaffolds presented favorable environment for in vitro biomineralization and in vivo osseointegration. • It provides a unique perspective for integratedly fabricating PEEK@HA scaffolds and further creating multifunctional PEEK-based implants. Porous polyether ether ketone (PEEK) scaffolds with hydroxyapatite (HA) layer coated on the pore wall surface were prepared using sacrificial porogen of HA-coated sodium chloride (NaCl) microspheres. The manufacture of bionic porogen was structurally inspired by the Chinese traditional food Matuan, which is a glutinous rice ball stuck with sesames. Spherical-shaped NaCl@HA microspheres with a uniform size facilitated the generation of an interconnected porous PEEK@HA scaffold with a HA coating layer on the pore surface. And the mechanical properties of PEEK@HA scaffolds were not affected by the coating layer of HA compared with PEEK porous scaffolds. After immersing in simulated body fluid and transplanting in rat proximal tibia, the PEEK@HA porous implants possessed superior in vitro biomineralization and in vivo osseointegration due to the favorable environment of the HA layer for bone ingrowth. This facile manufacturing strategy provides a unique perspective to integratedly fabricate bionic porous PEEK scaffolds with a mineralized coating layer enhancing the osseointegration of PEEK materials with bony tissue interfaces in orthopedics and stomatology. It also presents a general platform for further creating multifunctional porous PEEK implants, such as antibacterial, immunomodulatory, and photothermal therapy, by coating various inorganic nanoparticles with desired characteristics on the pore wall surface. [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]

• FP-engineered orthopedic PEEK implants are constructed in this study. • Engineering of fusion peptides promotes angiogenesis and bone differentiation. • pDA/Ag NPs bio-HJs empower PEEK with robust sterilization ability under NIR. • FP-engineered PEEK exhibits superior osteogenesis ability in vivo and in vitro. Owing to its superior mechanical and physicochemical characteristics, polyetheretherketone (PEEK) is considered a potent orthopedic material. Yet, poor bactericidal, osseointegrative and angiogenic properties of bioinert PEEK collectively hamper its clinical adoption. Herein, we present a strategy for developing multifunctional hierarchical coatings bearing a synthetic fusion peptide and polydopamine/silver nanoparticles (pDA/AgNPs) bio-heterojunctions (bio-HJs), in an attempt to empower PEEK with triple-modal abilities, which prevents bacterial infection, enhances ossification and promotes re-vascularization for physiological osseointegrative fixation. By harnessing the adhesion of bioinspired pDA, AgNPs are facilely immobilized onto peripheral surface and incorporated into interior cavity of micro/nano-porous sulfonated PEEK (SP) to form hierarchical pDA/AgNPs heterostructures. The bio-HJs coatings exhibit robust and repeatable bacteria-eradicating ability, assisted by near-infrared illumination, due to the synergistic effects of the metal ion/photothermal therapy. The fusion peptide-engineered PEEK exhibits osteogenesis activity in terms of promoting osteoblast proliferation, spreading, boosting the synthesis and secretion of osteogenesis-related genes. Besides, the fusion peptide-engineered PEEK also has the ability to promote HUVECs growth, reproduction, and tube formation, facilitating the synthesis and secretion of angiogenesis-associated genes. Moreover, the results of the in vivo experiments further corroborate the in vivo osteointegration and angiogenic abilities of materials. Expectantly, the multifunctional coatings with the presented triple-therapeutic effects represent a prospective clinical solution to address the current clinical challenges associated with the use of PEEK implants. [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]

Polyetheretherketone (PEEK) is an alternative to biomedical metals for fabricating bone implants, which possesses many advantages but its clinical applications are still impeded by the considerable release of worn debris and inferior osseointegration after long-term implantation. To circumvent these problems, in this study, diamond-like carbon (DLC) coating is initially fabricated on PEEK using C 2 H 2 + Ar plasma immersion ion implantation (PIII), and then the targeted biomolecules including osteoprotegerin (OPG) and alendronate (ALN) are simultaneously grafted onto the outer surface of DLC-coated sample by a two-step treatment consisting of N 2 PIII activation and solution immersion. On one hand, DLC coating can improve the wear resistance of PEEK substrate by surface hardening. On the other hand, the introduced OPG and ALN tune the biological performances in vitro and in vivo from many aspects such as immunomodulation, anti -osteoclastogenesis and pro-osteogenesis. Collectively, our study presents a feasible one-stop solution as "deposition-activation-incubation" for the surface multi-functionalization of PEEK implants, which has a broad application prospect also due to the clean approach and excellent versatility. [ABSTRACT FROM AUTHOR]

Carbon-fibre-reinforced polyether ether ketone (CFR-PEEK) exhibits excellent biomechanical properties as it has an elastic modulus similar to bone. However, CFR-PEEK displays inferior biocompatibility compared with titanium alloy and coating techniques are therefore of interest in order to improve integration. In this paper, the early biological response to CFR-PEEK implants, with and without hydroxyapatite coating, was investigated. Furthermore, a hydroxyapatite-coated titanium alloy reference served as a clinically relevant control. The study was conducted in a rabbit model, both in femur trabecular bone as well as in tibia cortical bone. The results demonstrated that an hydroxyapatite coating significantly enhances the bone response to PEEK implants in vivo. Moreover, in cortical bone, hydroxyapatite-coated PEEK implants induced superior bone response compared with hydroxyapatite-coated Ti ones. These results suggest that hydroxyapatite-coated CFR-PEEK is a suitable material for in vivo implantation. [ABSTRACT FROM AUTHOR]

Because of the good heat stability and similar mechanical properties to natural bone, polyetheretherketone (PEEK) was widely used in preparation of prosthesis. While the chemical inertness limited its osseointegration with the adjacent host bone. In this work, PEEK/HA scaffolds with hydroxyapatite (HA) contents of 0, 20%wt and 40%wt were fabricated by fused filament fabrication (FFF) process to improve osteointegration with the host bone. The cell experiment showed that the adhesion, proliferation, osteogenic differentiation and mineralization ability of BMSCs on the PEEK/HA scaffolds were significantly improved. Micro-CT results showed that PEEK/HA scaffold exhibited a higher bone ingrowth volume than those of pure PEEK scaffold. Specially, the ingrowth volume (24.3%) of 40%HA/PEEK scaffold after implantation for 12 weeks was comparable to the bone ingrowth reported for metallic or ceramic scaffolds. A smaller clearance between the PEEK/HA scaffolds and bone was found by histological staining, demonstrating a better osteointegration effect of PEEK/HA scaffold. The push-out tests result showed that PEEK/HA composites scaffolds exhibited higher bonding strength than that of the pure PEEK scaffold. In conclusion, the increased bioactivity and higher surface roughness of PEEK/HA scaffolds by introducing HA, achieved high level of bone ingrowth volume and mechanical interlocking between the scaffolds and bone. • Bioactive PEEK/HA composites scaffolds with interconnected microporous structure were printed by FFF process. • The bone formation within the PEEK/HA scaffold was promoted and gap between host bone and PEEK/HA scaffolds was reduced. • The bonding strength between the PEEK/HA scaffold and host bone was greatly improved. [ABSTRACT FROM AUTHOR]

As an attractive biomaterial for orthopedic implants, polyetheretherketone (PEEK) has many prominent characteristics such as good biocompatibility and biomechanical properties, as well as natural radiolucency. However, the potential clinical application is limited due to its biologically inert surface and poor osseointegration. To solve this problem, we fabricate a macroporous PEEK scaffold modified with methacrylated chitosan/polyhedral oligomeric silsesquioxane (CSMA/POSS) nanocomposite through 3D printing, sulfonation and UV-induced graft polymerization. The water contact angle, protein adsorption ability and biomineralization study of the sulfonation-treated PEEK (SPEEK)-CSMA/POSS scaffolds were measured in order to evaluate the surface properties. The results indicated that CSMA/POSS as a bioactive microporous surface integrated with nanoparticles promoted the protein adsorption and apatite formation. For the in vitro and in vivo evaluation of the osteogenicity, rat bone marrow mesenchymal stem cells (rBMSCs) and rat calvaria defect repair model were used. Biological results showed that the 3D porous structure and bioactive surface of modified PEEK scaffolds provided a suitable condition for cell adhesion and proliferation, enhanced the osteogenic differentiation of rBMSCs and promoted osteogenesis in vivo compared to the untreated PEEK scaffold. Therefore, 3D-printed macroporous PEEK scaffold modified with CSMA/POSS bioactive microporous surface represents a promising modification strategy for enhancing osseointegration of PEEK implants. [ABSTRACT FROM AUTHOR]

[Display omitted] • Sulfonate-bearing PEEK surface is successfully developed by ultraviolet-initiated graft polymerization. • Improved antibacterial activity for sulfonate-bearing PEEK. • Enhanced anti-inflammatory properties for sulfonate-bearing PEEK. • Ameliorative cytocompatibility and osteogenic activity for sulfonate-bearing PEEK. Polyetheretherketone (PEEK) has a similar elastic modulus to that of human bone and is considered a promising alternative for biomedical metallic implants. However, the poor antibacterial, anti-inflammatory, and osteogenic activity of bioinert PEEK impedes its clinical use for orthopedic and dental implants. Furthermore, using a single functional strategy to achieve all three biological functions simultaneously is challenging. Previous studies have demonstrated that sulfonate-bearing surfaces have antibacterial activity as well as decreased secretion of pro-inflammatory cytokine TNF-α. Therefore, in this study, sulfonate groups were introduced onto the PEEK surface by a one-step ultraviolet-initiated graft polymerization method. In vitro studies revealed enhanced adhesion, spreading, proliferation, and osteo-differentiation of MC3T3-E1 osteoblasts. Furthermore, the sulfonate-bearing PEEK had anti-inflammatory properties, and antibacterial activity to Escherichia coli and Staphylococcus aureus. Collectively, our findings indicate that PEEK implants bearing sulfonate groups with ameliorative antibacterial, anti-inflammatory, and osteogenic activity have potential clinical applications as orthopedic and dental implants. [ABSTRACT FROM AUTHOR]

Long carbon fiber reinforced polyether ether ketone (LCFRPEEK) is fabricated using a three-dimensional (3D) needle-punched method in our previous work, which is considered as a potential orthopedic implant due to its high mechanical strength and isotropic properties, as well as having an elastic modulus similar to human cortical bone. However, the LCFRPEEK has inferior integration with bone tissue, limiting its clinical application. Thus, a facile surface modification method, using gelatin methacrylate/polyacrylamide composite hydrogel coating (GelMA/PAAM) loading with dexamethasone (Dex) on our newly-developed LCFRPEEK composite via concentrated sulfuric acid sulfonating and ultraviolet (UV) irradiation grafting methods, has been developed to tackle the problem. The results demonstrate that the GelMA/PAAM/Dex coating modified sulfonated LCFRPEEK (SCP/GP/Dex) has a hydrophilicity surface, a long-term Dex release capability and forms more bone-like apatite nodules in SBF. The SCP/GP/Dex also displays enhanced cytocompatibility and osteogenic differentiation in terms of rat bone marrow mesenchymal stem cells (rBMSCs) responses in vitro assay. The in vivo rat cranial defect assay confirms that SCP/GP/Dex boosts bone regeneration/osseointegration, which significantly improves osteogenic fixation between the implant and bone tissue. Therefore, the newly-developed LCFRPEEK modified via GelMA/PAAM/Dex bioactive coating exhibits improved biocompatibility and osteogenic integration capability, which has the basis for an orthopedic implant for clinical application. [Display omitted] • Long carbon fiber reinforced polyether ether ketone (LCFRPEEK) with a matched modulus to the cortical bone. • GelMA/PAAM/Dex composite hydrogel grafting on LCFRPEEK surface by sulfonating and UV irradiation. • Composite hydrogels on LCFRPEEK surface improved osteogenic differentiation in vitro. • Composite hydrogels on LCFRPEEK surface enhanced the in vivo osseointegration. [ABSTRACT FROM AUTHOR]

[Display omitted] • Moxifloxacin hydrochloride and osteogenic growth peptide were co-loaded onto PEEK surface under sulfonated porous adsorption and polydopamine molecular adhesion. • Dual-functional PEEK surface exhibited excellent antibacterial capability in vitro. • Dual-functional PEEK surface remarkable enhanced the adhesion, proliferation and osteogenic differentiation of MC3T3-E1 cells. • Dual-functional PEEK implant displayed superior bacteriostasis and osseointegration in vivo. The overall aim of the current study is to develop a dual-functional PEEK implant to simultaneously fight off bacterial contamination and promote osseointegration by sustained release of moxifloxacin hydrochloride (MOX) and osteogenic growth peptide (OGP) from mussel-inspired polydopamine (PDA)-coated porous sulfonated PEEK (SPK) surface. Our study revealed that the MOX/OGP PDA-modified SPK (SPD-MOX/OGP) surface exhibited a durable and excellent antibacterial effect against planktonic/adherent Staphylococcus aureus and Escherichia coli in vitro. A remarkable enhancement in specific cell adhesion, proliferation and osteogenicity were observed on the SPD-MOX/OGP substrate due to the presence of OGP and PDA molecules compared to all other groups. More significantly, using the infected and non-infected rat tibia models confirmed the in vivo antimicrobial and osteogenesis abilities of SPD-MOX/OGP. Therefore, we are confident that such dual-functional PEEK surface with both antibacterial and osseointegrative capacities in this study would give a positive answer to periprosthetic joint infection-related issues. [ABSTRACT FROM AUTHOR]

Implant surface design has evolved to meet oral rehabilitation challenges in both healthy and compromised bone. For example, to conquer the most common dental implant-related complications, peri-implantitis, and subsequent implant loss, implant surfaces have been modified to introduce desired properties to a dental implant and thus increase the implant success rate and expand their indications. Until now, a diversity of implant surface modifications, including different physical, chemical, and biological techniques, have been applied to a broad range of materials, such as titanium, zirconia, and polyether ether ketone, to achieve these goals. Ideal modifications enhance the interaction between the implant's surface and its surrounding bone which will facilitate osseointegration while minimizing the bacterial colonization to reduce the risk of biofilm formation. This review article aims to comprehensively discuss currently available implant surface modifications commonly used in implantology in terms of their impact on osseointegration and biofilm formation, which is critical for clinicians to choose the most suitable materials to improve the success and survival of implantation. [ABSTRACT FROM AUTHOR]

The primary stability and final osseointegration of endosseous implants may be hindered by certain abnormal bone-metabolism conditions, such as osteoporosis. Polyetheretherketone (PEEK), which shows similar adjustable elastic modulus with cortical bone, is considered to be an ideal candidate to replace metallic implants, especially for osteoporotic bone. However, the bioinertness and poor osteogenic properties of PEEK fail to pave the way for clinical application. Here, a novel coating (EBE-SrSi) with bioactive elements on PEEK implants was generated via electron beam evaporation (EBE) to enhance the rapid osseointegration by inducing osteogenesis, as well as angiogenesis. In vitro, the dual Sr/Si ion modified surface exihibits a better osteo-inductive effect on the BMSCs derived from ovariectomized rats (rBMSCs-OVX). Furthermore, the modified samples also stimulated human umbilical vein endothelial cells (HUVECs) migration and angiogenesis. Finally, in the OVX rat bonedefect model, the EBE-SrSi group exhibited faster bone formation which might be attributed to the impact of the transformation of endogenous MSC accompanied by promotion of the angiogenic activity of endothelial cells. Our results unveiled the potential of dual Sr/Si modified PEEK in promoting osseointegration under osteoporotic conditions and will further broaden the adoption of PEEK materials in dental fields. [Display omitted] • A novel bioactive coating on polyetheretherketone was generated via electron beam evaporation. • A strong adherent film was constructed without altering the beneficial features of polyetheretherketone. • The incorporation of Sr ions can significantly enhance angiogenesis effect • Unveiled the potential of dual Sr/Si modified PEEK in promoting angiogenesis/osteogenesis under osteoporois. [ABSTRACT FROM AUTHOR]

In this article, recent advances in the development, preparation, biocompatibility and mechanical properties of polyetheretherketone (PEEK) and its composites for hard and soft tissue engineering are reviewed. PEEK has been widely employed for fabricating spinal fusions due to its radiolucency, chemical stability and superior sterilization resistance at high temperatures. PEEK can also be tailored into patient-specific implants for treating orbital and craniofacial defects in combination with additive manufacturing process. However, PEEK is bioinert, lacking osseointegration after implantation. Accordingly, several approaches including surface roughening, thin film coating technology, and addition of bioactive hydroxyapatite (HA) micro-/nanofillers have been adopted to improve osseointegration performance. The elastic modulus of PEEK is 3.7–4.0 GPa, being considerably lower than that of human cortical bone ranging from 7–30 GPa. Thus, PEEK is not stiff enough to sustain applied stress in load-bearing orthopedic implants. Therefore, HA micro-/nanofillers, continuous and discontinuous carbon fibers are incorporated into PEEK for enhancing its stiffness for load-bearing applications. Among these, carbon fibers are more effective than HA micro-/nanofillers in providing additional stiffness and load-bearing capabilities. In particular, the tensile properties of PEEK composite with 30wt% short carbon fibers resemble those of cortical bone. Hydrophobic PEEK shows no degradation behavior, thus hampering its use for making porous bone scaffolds. PEEK can be blended with hydrophilic polymers such as polyglycolic acid and polyvinyl alcohol to produce biodegradable scaffolds for bone tissue engineering applications. [ABSTRACT FROM AUTHOR]

Polyetheretherketone (PEEK) is an ideal implant material for orthopedic and dental application due to its high biocompatibility and mechanical property. However, biological inertness of PEEK hinders the effective clinical applications in treating bone defect, especially in the situation accompanied by bacterial infection. In this study, a layer-by-layer (LBL) deposition method with controlled cycles was developed to rapidly construct brushite (CaHPO 4 ·2H 2 O) (CaP) layers containing gentamicin sulfate (GS) on PEEK to obtain CaP-and-GS modified PEEK, named as PEEK/CaP-GS. Different PEEK/CaP-GS, like PEEK/CaP-GS*3, PEEK/CaP-GS*6 and PEEK/CaP-GS*9 were conveniently prepared by repeating the LBL cycles to 3, 6 and 9 times, respectively. The morphology, structure and surface property of the fabricated PEEK/CaP-GS were carefully characterized. In vitro antibacterial experiments illustrated that all of the PEEK/CaP-GS samples had excellent and sustained antibacterial property. Cell proliferation experiments revealed the acceptable biocompatibility and cell osteogenic differentiation of PEEK/CaP-GS, especially in PEEK/CaP-GS*6. X-ray, μ-CT, and histological analysis showed that PEEK/CaP-GS exhibited in vivo antibacterial activity and osseointegration ability in the treatment of bone defect with infection. In both the in vitro and the in vivo experiments, PEEK/CaP-GS*6 prepared from the 6 LBL cycles exhibited the best antibacterial and osseointegration ability for bone healing. This work opens new avenue of the facile and effective modification of PEEK with special biological functions for clinical application, especially for the implants requiring excellent antibacterial and osseointegration ability. In this work, a layer-by-layer (LBL) method with controlled cycles was designed to rapidly construct brushite (CaHPO 4 ·2H 2 O) (CaP) layers containing gentamicin sulfate (GS) on PEEK to obtain CaP-and-GS modified PEEK (PEEK/CaP-GS). In vitro and in vivo experiments were carried out to evaluate the excellent performance of antibacterial and osseointegration ability of designed PEEK/CaP-GS for bone healing. Unlabelled Image • A layer-by-layer (LBL) deposition method with controlled cycles was developed to modify PEEK • Brushite (CaP) and gentamicin (GS) modified PEEK (PEEK/CaP-GS) by LBL exhibited antibacterial and osseointegration ability • PEEK/CaP-GS exhibited in vivo antibacterial and osseointegration ability for bone defect with infection treatment • PEEK/CaP-GS*6 obtained from 6 LBL layers revealed the best antibacterial and osseointegration ability for bone healing • This work opens new avenue of PEEK modification with biological functions for implant application [ABSTRACT FROM AUTHOR]

• Assessment of cellular response on 3-D printed macroporous PEEK scaffolds. • Macropores with uniform sizes and reproducibility were successfully fabricated. • Effects of the scaffolds' macropores on osteoblast cellular functions were analyzed. • 800 µm pore sizes provided greater surface area and enhanced cell-cell connection. • Highlights importance of additive manufacturing in fabricating bio-scaffolds. This article reports on the fabrication and evaluation of 3-D printed polyetheretherketone (PEEK) scaffolds with controlled macroporosity. Specifically, uniform macropore sizes ranging from 800 to 1800 µm by design were generated by varying processing parameters. It is expected that the 3-D printing ability to obtain customized macropores can help arriving at the optimum pore size in scaffolds to encourage bone regeneration. This study conclusively showed optimal cell adhesion and proliferation in scaffolds containing uniform pores of an average size of 800 μm. A construct containing a wide distribution of pores cannot come to this conclusion. In this context, the precision and reproducibility of additive manufacturing in scaffold fabrication play an important role. [ABSTRACT FROM AUTHOR]

Osseointegration is likely the result of an immunologically driven bone reaction to materials such as titanium. Osseointegration has resulted in the clinical possibility to anchor oral implants in jaw bone tissue. However, the mechanisms behind bony anchorage are not fully understood and complications over a longer period of time have been reported. The current study aims at exploring possible differences between copper (Cu) and polyetheretherketone (PEEK) materials that do not osseointegrate, with osseointegrating cp titanium as control. The implants were placed in rabbit tibia and selected immune markers were evaluated at 10 and 28 days of follow-up. Cu and PEEK demonstrated at both time points a higher immune activation than cp titanium. Cu demonstrated distance osteogenesis due to a maintained proinflammatory environment over time, and PEEK failed to osseointegrate due to an immunologically defined preferential adipose tissue formation on its surface. The here presented results suggest the description of two different mechanisms for failed osseointegration, both of which are correlated to the immune system. [ABSTRACT FROM AUTHOR]

BACKGROUND CONTEXT Nearly 500,000 spinal fusion surgeries are performed each year in the U.S. Interbody fusion devices have been used for decades to facilitate fusion across the disc space, yet debate continues over the optimal material and structure used for these devices. Current cages are primarily made from PEEK due to its radiolucency and bone-like stiffness. However, current smooth PEEK cages are often associated with fibrous encapsulation and implant migration. This poor response is often attributed to inherent material properties of PEEK. However, the smooth surface of conventional PEEK surfaces may equally impede osseointegration, particularly when considering that rough and porous surfaces of various non-PEEK materials elicit more favorable osseointegration compared to smooth surfaces. PURPOSE The current study aimed to assess the relative influence of surface topography and chemistry on PEEK osseointegration by investigating the osseous response to smooth, rough, and porous surface topographies possessing a PEEK or titanium surface chemistry. STUDY DESIGN/SETTING Preclinical implant osseointegration model in the proximal tibial metaphysis of the rat. OUTCOME MEASURES Osseointegration was assessed by calculating bone ingrowth percentage, histological tissue evaluation, and biomechanical pullout testing. METHODS Porous PEEK implants were created as described previously. Rough surfaces were created by soda-blasting PEEK surfaces and smooth surfaces maintained an as-machined surface finish. Half of each group was coated with a ∼30nm thick layer of TiO 2 using atomic layer deposition (ALD) while the other half maintained their native PEEK chemistry. Sterile implants were implanted into the proximal tibial metaphyses of skeletally mature male Sprague Dawley rats. At 8 weeks, animals were euthanized and bone-implant interfaces were subjected to µCT analysis (n=12), histology (n=4), and biomechanical pullout testing (n=8). All data were reported as mean±SE. Comparisons between groups were calculated using a 2-way ANOVA followed by a Tukey multiple comparisons test. RESULTS Quantitative µCT analysis demonstrated that mineralized tissue ingrowth was 38.9±2.8% for porous PEEK and 30.7±3.3% for porous titanium (p=0.07). µCT tomograms and matching histological sections showed bone ingrowth in porous titanium surfaces primarily consisted of thin bone shells that conformed to the pore walls, leaving the center of pores devoid of bone. In contrast, bone ingrowth within porous PEEK was greater in the center of pores with periodic contact with pore walls. Greater bone-implant contact was observed for titanium compared to PEEK surfaces. Histological and µCT observations were corroborated by biomechanics outcomes. Across all groups both surface chemistry and topography had a significant overall effect on pullout force (p<0.05), but topography accounted for 65.3% of the total variance for pullout force (ω2=0.653), whereas surface chemistry accounted for 5.9% (ω2=0.059). Porous PEEK and porous titanium exhibited increases in pullout force compared to smooth and rough implants regardless of surface chemistry (p<0.05). CONCLUSIONS The poor osseointegration of conventional PEEK implants may be linked more to their smooth surface topography rather than their material composition. The effect of surface topography (specifically porosity) dominated the effect of surface chemistry in this study and could lead to further improvements in orthopaedic device design. [ABSTRACT FROM AUTHOR]