On the Future Design of Bio‐Inspired Polyetheretherketone Dental Implants

Polyetheretherketone (PEEK) is a promising implant material because of its excellent mechanical characteristics. Although this polymer is a standard material in spinal applications, PEEK is not in use in the manufacturing of dental implants, where titanium is still the most‐used material. This may be caused by its relative bio‐inertness. By the use of various surface modification techniques, efforts have been made to enhance its osseointegrative characteristics to enable the polymer to be used in dentistry. In this feature paper, the state‐of‐the‐art for dental implants is given and different surface modification techniques of PEEK are discussed. The focus will lie on a covalently attached surface layer mimicking natural bone. The usage of such covalently anchored biomimetic composite materials combines many advantageous properties: A biocompatible organic matrix and a mineral component provide the cells with a surrounding close to natural bone. Bone‐related cells may not recognize the implant as a foreign body and therefore, may heal and integrate faster and more firmly. Because neither metal‐based nor ceramics are ideal material candidates for a dental implant, the combination of PEEK and a covalently anchored mineralized biopolymer layer may be the start of the desired evolution in dental surgery.     

Surface Modification Strategies to Improve the Osseointegration of Poly(etheretherketone) and Its Composites

In the last 5 years, a wide variety of surface modification strategies are explored to improve the integration of poly(etheretherketone) (PEEK) implants with bone. Since PEEK does not support bone on‐growth, its surface properties need to be tailored to promote osteogenesis at the bone‐implant interface. Surface modifications applied to achieve this response range from simple surface morphology changes to the deposition of osteoconductive coatings. Of the many methods, titanium and/or hydroxyapatite coatings, extrusion to create surface pores, and an accelerated neutral atom beam treatment have been approved by the U.S. Food and Drug Administration to improve the integration of PEEK spinal cages. The success of these surface modifications brings hope for the clinical translation of other techniques in the future, but there are several limitations that may be preventing other treatments from reaching the clinic. This review describes numerous strategies that have been applied to PEEK‐based implants for improving their osseointegration and enhancing their antibacterial properties. The review concludes with a discussion about future directions for the field and provides suggestions for advancing clinical translation of surface‐modified PEEK implants to improve the lives of patients in need of these implants.     

Highly porous PEEK and PEEK/HA scaffolds with Escherichia coli-derived recombinant BMP-2 and erythropoietin for enhanced osteogenesis and angiogenesis

The present study reports the results of structural and mechanical analysis, as well as proteins release kinetics and osteointegration in mice craniotomy model of highly porous PEEK (PolyEther Ether Ketone) and PEEK/HA (PolyEther Ether Ketone/HydroxyApatite) biomimetic scaffolds loaded with Escherichia coli-derived recombinant Bone Morphogenetic Protein-2 (BMP-2) and ErythroPOietin (EPO). Porous scaffolds were obtained by thermopressing with NaCl as a pore-forming filler. Two fractions of pore-forming filler were used to imitate natural trabecular bone tissue by making a preferential porosity using large fraction and creating an extended surface and special microrelief using small fraction. Hydroxyapatite (HA) was added up to 20% to activate bioinert PEEK providing loading of recombinant growth factors and osteointegration as well as sufficient level of mechanical properties imitating human trabecular bone. Unexpectedly, the non-activated PEEK produced by our technology was also able to spontaneously bind both BMP-2 and EPO. Loading of both BMP-2 and EPO to both types of implants resulted in enhanced neoosteogenesis and angiogenesis in a critical-size cranial defect model in mice in 3–6 weeks. Considering good mechanical characteristics and excellent osteoinductive and angiogenic properties, both materials in combination with BMP-2 and EPO can find their application in regenerative medicine.     

聚醚醚酮表面的亲水改性和胶原蛋白固定化

采用紫外光接枝法对聚醚醚酮(PEEK)表面进行化学修饰和生物分子固定化.首先向PEEK表面引入亲水性的丙烯酰胺,并以此为反应位点通过戊二醛将胶原和胶原蛋白固定在PEEK表面.用接触角测定仪、扫描电镜、荧光标记和X射线光电子能谱等对改性薄膜进行了表征.结果表明,PEEK上丙烯酰胺的接枝密度高达50.9μg/cm~2;改性薄膜表面浸润性显著提高,水接触角最低降至(22±3)°.荧光标记胶原固定的PEEK薄膜荧光发射光谱强度最高,并在X射线光电子能谱中检测到N元素,表明胶原已固定化,固定胶原蛋白的浓度为10.2μg/cm~2.     

Fabrication and In vitro Bioactivity of Robust Hydroxyapatite Coating on Porous Titanium Implant

Compared witli the traditional dental implant, TixOs■ manufactured by direct laser metal forming(DLMF) technology exhibits improved capability for bone osteointegration due to its porous surface structure, and has achieved remarkable clinical effect. However, like the traditional titanium and other alloyed implants, the porous titanium implant TixOsR also has relatively weak bioactivity. To address this issue, a proper surface modification method may be needed. Hydroxyapatite(HA) has been widely used in implant surface coating for its similar chemical composition to bone tissue and its osteoconductive properties. Thus, combining TixOs■ implants with hydroxyapatite can be an efficient way to enhance their bioactivity. We herewith reported a competent pulsed laser deposition(PLD) method of coating nano-sized HA thin film onto the porous TixOs■ implant. The HA coatings were characterized by means of scanning electron microscopy(SEM), energy dispersive X-ray spectroscopy(EDS), X-ray photoelectron spectroscopy(XPS) and focused ion beam(FIB) method, and nanocrystal sized thin HA films were identified on the surface of TixOs■ implants. The low cytotoxicity and improved cell proliferation ability of HA coated implants were further tested and verified using MC 3T3 E1 cells with the consideration of the controlling group. Our results show that a stable and bioactive HA tliin film is able to form on the surtace of the porous titanium implant by PLD method.This may benefit the fiirther clinical application of TixOs■ implants.     

Graphene‐Oxide‐Decorated Microporous Polyetheretherketone with Superior Antibacterial Capability and In Vitro Osteogenesis for Orthopedic Implant

Due to its similar elastic modulus of human bones, polyetheretherketone (PEEK) has been considered as an excellent cytocompatible material. However, the bioinertness, poor osteoconduction, and weak antibacterial activity of PEEK limit its wide applications in clinics. In this study, a facile strategy is developed to prepare graphene oxide (GO) modified sulfonated polyetheretherketone (SPEEK) (GO‐SPEEK) through a simple dip‐coating method. After detailed characterization, it is found that the GO closely deposits on the surface of PEEK, which is attributed to the π–π stacking interaction between PEEK and GO. Antibacterial tests reveal that the GO‐SPEEK exhibits excellent suppression toward Escherichia coli. In vitro cell attachment, growth, differentiation, alkaline phosphatase activity, quantitative real‐time polymerase chain reaction analyses, and calcium mineral deposition all illustrate that the GO‐SPEEK substrate can significantly accelerate the proliferation and osteogenic differentiation of osteoblast‐like MG‐63 cells compared with those on PEEK and SPEEK groups. These results suggest that the GO‐SPEEK has an improved antibacterial activity and cytocompatibility in vitro, showing that the developed GO‐SPEEK has a great potential as the bioactive implant material in bone tissue engineering.     

Applications of Polydopamine in Implant Surface Modification

There is great clinical demand for orthopedic and dental implant surface modification methods to prevent osseointegration failure and improve implant biological functions. Notably, dopamine (DA) can be polymerized to form polydopamine (PDA), which is similar to the adhesive proteins secreted by mussels, to form a stable bond between the bone surface and implants. Therefore, PDA has the potential to be used as an implant surface modification material with good hydrophilicity, roughness, morphology, mechanical strength, biocompatibility, antibacterial activity, cellular adhesion, and osteogenesis. In addition, PDA degradation releases DA into the surrounding microenvironment, which is found to play an important role in regulating DA receptors on both osteoblasts and osteoclasts during the bone remodeling process. Furthermore, the adhesion properties of PDA suggest its use as an intermediate layer in assisting other functional bone remodeling materials, such as nanoparticles, growth factors, peptides, and hydrogels, to form “dual modifications.” The purpose of this review is to summarize the recent progress in research on PDA and its derivatives as orthopedic and dental implant surface modification materials and to analyze the multiple functions of PDA.     

Bone‐guided regeneration: from inert biomaterials to bioactive polymer (nano)composites

Natural bone is a unique nanostructured material made of collagen fibre matrix and hydroxyapatite (HA) nanocrystals, providing mechanical support and protection from the vertebrate skeleton. However, in severe cases like bone‐deficiencies, bone needs to be “externally” repaired. Initially, different biological solutions were developed in bone‐guided regeneration. However, due to the limitations with the existing biological grafts, a lot of researches have been devoted toward biomaterials including metals, ceramics, and polymers. On the basis of the interface reactions between the implant and the surrounding tissues, these biomaterials may be classified as “nearly inert” or bioactive. Interestingly, the bioactive materials exhibit a specific biological response, leading to the formation of a natural bonding junction between the bone and the implant during bone regeneration. Recently, a special attention has been paid to a new generation of bioactive materials, i.e. (nano)structured biomaterials composed of a bioresorbable polymer matrix reinforced with bioactive inorganic compounds. While (bio)ceramic component provides the bioactivity, these materials can be readily engineered in such a way that their resorption rate in the body match the formation rate of the new tissue. This review hence reports the different biological and non‐biological solutions developed in bone‐guided regeneration, with a special emphasis on polymer‐based materials, and our recent results obtained in osseointegration The bone physiology, and its natural regeneration are also described. Copyright © 2011 John Wiley & Sons, Ltd.     

In vivo degradation behavior of Ca-deficient hydroxyapatite coated Mg-Zn-Ca alloy for bone implant application

In present paper, an in vivo study was carried out on uncoated and calcium-deficient hydroxyapatite (Ca-def HA) coated Mg-Zn-Ca alloy to investigate the effect of Ca-def HA coating on the degradation behavior and bone response of magnesium substrate. Magnesium alloy rods were implanted into rabbit femora and evaluated during 24 weeks implantation. The characterization of both implants indicates that in vivo degradation of the Ca-def HA coating and magnesium substrate occurs almost simultaneously, and in vivo valid life of the coating is about 8 weeks, after that the degradation rate of the coated implants increases obviously. The main reasons for the Ca-def HA coating degradation can be attributed to its reaction with body fluid and the substitution of Mg²⁺ ions in Ca-def HA. Histopathological examinations show that the Ca-def HA coating has good osteoconductivity and is in favor of the formation of more new bone on the surface of magnesium alloy. So the Ca-def HA coating could not only slow down in vivo degradation of magnesium alloy but also improve its bone response.     

Study on the Friction and Wear Properties of PEEK against Cortical Bone Tissue Under Different Lubricating Conditions

The tribological behavior between orthopedic implants and cortical bone is important but usually neglected. Poly(ether-ether-ketone) (PEEK) is a promising material for orthopedic applications. To further understand and improve the interfacial tribological properties between PEEK implant and host bone tissue, a PEEK-cortical bone tribo-pair is designed and fabricated. The frictional and wear performance of such tribo-pair is investigated under different lubricants, i.e., simulated body fluid (SBF), calf serum (CS), hyaluronic acid (HA), and mucin (MUC). The results suggest that MUC solution can be utilized as an artificial natural synovial fluid to improve the tribological properties of PEEK-based implants.     

The Role of Epigenetic Functionalization of Implants and Biomaterials in Osseointegration and Bone Regeneration—A Review

The contribution of epigenetic mechanisms as a potential treatment model has been observed in cancer and autoimmune/inflammatory diseases. This review aims to put forward the epigenetic mechanisms as a promising strategy in implant surface functionalization and modification of biomaterials, to promote better osseointegration and bone regeneration, and could be applicable for alveolar bone regeneration and osseointegration in the future. Materials and Methods: Electronic and manual searches of the literature in PubMed, MEDLINE, and EMBASE were conducted, using a specific search strategy limited to publications in the last 5 years to identify preclinical studies in order to address the following focused questions: (i) Which, if any, are the epigenetic mechanisms used to functionalize implant surfaces to achieve better osseointegration? (ii) Which, if any, are the epigenetic mechanisms used to functionalize biomaterials to achieve better bone regeneration? Results: Findings from several studies have emphasized the role of miRNAs in functionalizing implants surfaces and biomaterials to promote osseointegration and bone regeneration, respectively. However, there are scarce data on the role of DNA methylation and histone modifications for these specific applications, despite being commonly applied in cancer research. Conclusions: Studies over the past few years have demonstrated that biomaterials are immunomodulatory rather than inert materials. In this context, epigenetics can act as next generation of advanced treatment tools for future regenerative techniques. Yet, there is a need to evaluate the efficacy/cost effectiveness of these techniques in comparison to current standards of care.     

An Effective Osteogenesis Porous CaP/Collagen Interface Compatible with Various Substrates Fabricated by Controlled Mineralization in a Delicately Adjustable Organic Matrix

Increasing bone formation on the surfaces of implants such as screws, plates, or shims holds great significance for clinical medicine. However, osteogenesis implant coatings that mimic natural bone in terms of both their components and structural features are still lacking. Here we report the biomimetic interface of calcium phosphate (CaP) in a collagen matrix fabricated by controlled mineralization that presents biomimetic porous features. The porous CaP/collagen interface, with a thickness of about 1 μm, significantly enhances osteogenesis, as verified at both the gene and protein levels as well as by in vivo experiments. Taking advantage of the generality of the method, the biomimetic interface was prepared on a variety of substrates, including conductive substrates, 3D metal meshes, plastic or elastic substrates, and even on filter papers. The adjustability and generality of the method have enabled new characterization tests to be developed during experiments on cells and thus should greatly facilitate clinical medicine and tissue engineering.     

Oriented nucleation of hydroxylapatite crystals on spider dragline silks

Spider dragline silk as a protein fiber can be pictured as the oriented organization of protein nanocrystals along the long axis with their spacing filled by amorphous protein domains. We used the surface of the spider dragline silk as a biological template to nucleate bone mineral hydroxylapatite (HAP) site-specifically from a HAP-supersaturated solution. HAP crystals were found to be nucleated on the surface of silks with their c axis preferentially oriented at an average angle of 72.9 degrees with respect to the long axis of the silks. The preferred orientation is nearly identical among the different mineralized silks that we studied. Other materials such as Au and CdS could be nucleated on the silks but did not show any preferred orientation. We believe that the oriented nucleation of HAP is directly related to the structures of silks and HAP. The mineralized silks will combine the good mechanical properties of the spider silks and the biocompatibility of HAP and may be assembled into ideal biomaterials as bone implants.     

羟基磷灰石/胶原矿化机理的研究进展

仿生合成的羟基磷灰石(HAp)/胶原复合材料的结构和成分与天然骨相似,具有很好的生物相容性、生物活性和生物可降解性,有望成为新一代的骨替代材料。羟基磷灰石/胶原矿化过程其实质是晶体在自组装的胶原纤维上形成的过程,但这一过程在体内是如何进行的至今仍然不清楚。对胶原矿化机理的研究能为制备具有更优越结构和功能的新型骨替代材料提供理论参考。本文概述了羟基磷灰石/胶原矿化机理的研究进展。     

Mechanical performance and in vivo bioactivity of functionally graded PEEK–HA biocomposite materials

A functionally graded material (FGM) of polyetheretherketone (PEEK)–hydroxyapatite (HA) with a symmetrical three-layer structure containing 8.7, 2.6 and 8.7 vol% HA, respectively, is successfully fabricated by hot pressing and evaluated by scanning electron microscopy and tensile testing. A good bonding between the HA particles and the PEEK matrix is achieved by virtue of an in situ method in fabricating each PEEK–HA composite layer. There are no apparent microcracks and microscopic interfaces within each layer of the FGM. The symmetrical PEEK–HA FGM does not fall apart or delaminate during loading with a tensile strength of 86.2 MPa, and its fracture energy is 56.5 kJ/m². Furthermore, in vivo bioactivity of the FGM sample is also evaluated, showing that it has sound biocompability and bioactivity. Accordingly, the FGM in the future may be a promising biomaterial to be used as replacement implant of human bone through a proper design to balance mechanical properties and bioactivity.     

Research and Application of Medical Polyetheretherketone as Bone Repair Material

Polyetheretherketone (PEEK) can potentially be used for bone repair because its elastic modulus is similar to that of human natural bone and good biocompatibility and chemical stability. However, its hydrophobicity and biological inertness limit its application in the biomedical field. Inspired by the composition, structure, and function of bone tissue, many strategies are proposed to change the structure and functionality of the PEEK surface. In this review, the applications of PEEK in bone repair and the optimization strategy for PEEK's biological activity are reviewed, which provides a direction for the development of multifunctional bone repair materials in the future.     

Enhanced effects of nano-scale topography on the bioactivity and osteoblast behaviors of micron rough ZrO2 coatings

Implant surface topography is one of the most important factors affecting the rate and extent of osseointegration. Randomly micron-roughened surfaces have been documented to support osteoblast adhesion, differentiation, and mineralized phenotype, and thus favoring bone fixation of implants to host tissues. However, few studies have been done yet to investigate whether their effects on osteoblast behaviors can be enhanced by incorporation of nano-scale topographic cues. To validate this hypothesis, zirconia coatings with micron roughness (about 6.6 μm) superimposed by nano-sized grains (<50 nm) were fabricated by plasma spraying. To validate the impact of nano-sized grains, post-treatments of surface polishing (SP) and heat treatment (HT) were performed on the as-sprayed (AS) coatings to change the surface topographies but keep the chemical and phase composition similar. Results of in vitro bioactivity test showed that apatite was formed only on coating surfaces with nano-sized grains (AS coatings), indicating the significance of nano-topographic cues on the in vitro bioactivity. Enhanced osteoblast adhesion and higher cell proliferation rate were observed on coatings with both micron-roughness and nano-sized grains (AS-coatings), compared to coatings with smooth surfaces (SP-coatings) and coatings with only micron-scale roughness (heat-treated coatings), indicating the significant effects of nano-size grains on osteoblast responses. As the micron rough surfaces have been well-documented to enhance bone fixation, results of this work suggest that a combination of surface modifications at both micron and nano-scale is required for enhanced osseointegration of orthopedic implants.     

Interfacial studies on the ozone and air‐oxidation‐modified carbon fiber reinforced PEEK composites

In this work, ozone modification method and air‐oxidationwere used for the surface treatment of polyacrylonitrile(PAN)‐based carbon fiber. The surface characteristics of carbon fibers were characterized by XPS. The interfacial properties of carbon fiber‐reinforced (polyetheretherketone) PEEK (CF/PEEK) composites were investigated by means of the single fiber pull‐out tests. As a result, it was found that IFSS (interfacial shear strength) values of the composites with ozone‐treated carbon fiber are increased by 60% compared to that without treatment. XPS results show that ozone treatment increases the amount of carboxyl groups on carbon fiber surface, thus the interfacial adhesion between carbon fiber and PEEK matrix is effectively promoted. The effect of surface treatment of carbon fibers on the tribological properties of CF/PEEKcomposites was comparativelyinvestigated. Experimental results revealed that surface treatment can effectively improve the interfacial adhesion between carbon fiber and PEEK matrix. Thus the wear resistance was significantly improved. Copyright © 2009 John Wiley & Sons, Ltd.     

Ultra-Hydrophilic Transition Metals as Histophilic Biomaterials

Extremely hydrophilic surfaces have been prepared on titanium, stainless steel and cobalt chromium alloys after treatment by a chromosulfuric acid method at 200-240 °C. In spite of a ca. 300-500-fold higher surface roughness (Ra ∼ 880-1100 nm) in comparison to the quartz glass controls (Ra ∼ 2-3 nm), surfaces with contact angles close to 0° in the absence of contact angle hysteresis (ultra-hydrophilic surfaces) were obtained. We have called this phenomenon “Inverse Lotus Effect” . Metal surface layers exhibiting such properties form excellent priming coats with bioadhesive properties (histophilic surfaces) for the attachment of biocoats consisting of BMP-2 with bioactive properties in bone. Direct immobilization of BMP-2 on implant surfaces eliminates the need for a separate BMP-2 carrier or delivery system such as collagen, as is widely employed by others. A fundamental problem in such surfaces is that it is not at all certain that a protein immobilized in such a manner will retain its biological activity. In the case of BMP-2 it can be shown in vitro that the novel surfaces are biologically active. Similarly in vivo studies indicate an accelerated and improved osseointegration.