Research progress in the application and modification of PEEK in implants

At present, dental implantation has become the preferred repair method for patients with dentition defects and missing teeth, which improves the quality of life of patients.

 

Polyether ether ketone (PEEK) is a major member of the polyaryletherketone (PAEK) family and a type of linear aromatic polymer compound.

 

PEEK has high chemical stability, which is beneficial for reducing its biological corrosion, avoiding the release of toxic by-products, and is insoluble in any solvent except concentrated sulfuric acid; Due to the unique aromatic chemical structure of PEEK, it exhibits excellent performance in disinfecting medical devices γ Strong resistance to radiation and electron beams; Due to the radiation transparency of PEEK, it does not produce artifacts on X-rays and can be compatible with magnetic resonance imaging; In addition, PEEK has thermal stability and can maintain high strength even at high temperatures.

 

In vivo studies have shown that PEEK has satisfactory biocompatibility, no mutagenicity to the human body, and its material surface bacterial adhesion is lower than Ti, indicating good biosafety. Due to its elastic modulus being close to that of human bone tissue, research on implants, repair abutments, fixed dentures, and other aspects is increasing. However, when PEEK is applied to oral implants, due to insufficient mechanical strength and weak stress resistance, the appearance of some strengthening materials effectively improves the mechanical strength of PEEK.

 

Lee et al. used three-dimensional finite element method to analyze the stress distribution of PEEK implants. The study showed that glass fiber reinforced polyether ether ketone (GFR-PEEK) implants with a diameter of 4mm can withstand the cyclic bite force of front teeth (140-170N).

 

Due to the static compressive strength of carbon fiber reinforced polyether ether ketone (CFR-PEEK) and 5mm diameter GFR-PEEK implants exceeding 450N, they are able to withstand the bite force between the anterior and posterior teeth (250-400N).

 

In addition, PEEK has poor surface biological activity, which neither allows protein adsorption nor promotes cell proliferation, limiting its practical application. Therefore, how to modify PEEK and optimize its biological activity has attracted close attention from researchers. This article provides a systematic review of the research progress on the application of polyether ether ketone modification in implants.

 

Recent research reports have shown that there are roughly two conventional methods for improving the surface biological activity of PEEK: surface modification, which activates PEEK biological activity through physical and chemical treatment of individual material surfaces or by combining with surface coatings; The second is to prepare bioactive PEEK composite materials by impregnating a material that can activate or enhance biological activity into PEEK.

 

1、 Surface modification

 

1. Physical methods:

 

(1) Sandblasting: Sandblasting is the process of cleaning and roughening the substrate surface using the impact of high-speed sand flow, which has a significant impact on the biological activity of polyether ether ketone. Cui Jingjing et al. studied the bone binding rate by sandblasting the surface of nano fluoroapatite/polyether ether ketone implants. The results showed that the surface BIC of the sandblasted nFA/PEEK implant was higher and the osteogenic effect was better.

 

Xu et al. developed a novel carbon fiber reinforced polyether ether ketone nano hydroxyapatite (PEEK/CF/n HA) ternary biological composite material with micro/nano morphology surface by combining oxygen plasma and sandblasting. In vitro experiments showed that PEEK/CF/n HA can improve osteoblast proliferation, differentiation, and promote bone bonding between implants and bone, indicating its promising application prospects in orthopedics.

 

(2) Plasma etching: Plasma etching mainly introduces different functional groups to the surface of PEEK, making it more hydrophilic. Oxygen and ammonia plasma activation of polyether ether ketone alters the surface nanostructure, contact angle, and electrochemical properties. The surface of PEEK treated with plasma generates nanostructured substrates, enhancing the proliferation and differentiation of mesenchymal stem cells, and allowing these elastic, MRI compatible, and X-ray transparent implants to undergo bone bonding in vivo.

 

(3) Physical vapor deposition: Physical vapor deposition is the process of separating materials under vacuum conditions using physical methods to deposit a thin film with special properties on the surface of the substrate, thereby tightly bonding with the substrate and improving surface performance.

 

Yu et al. used the PVD method to coat pure magnesium (Mg) on PEEK substrates, with the optimal deposition temperature of 230 ℃. The PEEK encapsulated in Mg has strong killing ability against Staphylococcus aureus, with a antibacterial rate of up to 99%, and can be maintained in Hanks solution for at least 14 days. Through PVD, biologically functional Mg can be coated on various inert medical materials to enhance their biological activity.

 

(4) Electron beam induced deposition: Electron beam induced deposition is a low-temperature coating process that decomposes and deposits non volatile fragments on the substrate. Deposition of a thin Ti coating on polyether ether ketone using EBID method can increase its wettability without affecting the characteristics of the implant. Cell viability assay (MTS) and alkaline phosphatase assay (ALP) were used to measure the proliferation and differentiation levels of MC3T3-E1 cells, respectively. The results showed that the implant with titanium coating had a higher bone binding rate.

 

Han et al. formed a titanium dioxide (TiO2) layer with uniform pore size by anodizing the Ti film formed on the surface of PEEK. The nano porous and hydrophilic TiO2 surface can effectively immobilize bone morphogenetic protein-2 (BMP-2), thereby improving in vitro biocompatibility, promoting cell differentiation, and improving bone conduction.

 

2. Chemical methods:

 

(1) Sulfonation: Sulfonation is an electrophilic substitution reaction that uses sulfuric acid to introduce charged groups into polymer chains for ion exchange, which helps in the transport of cations and increases the hydrophilicity of PEEK materials. Yuan et al. used 3D printing to construct a PEEK porous model, and the surface was etched with concentrated sulfuric acid for 15, 30, and 60 seconds before being implanted into the bone defects of the rabbit model to evaluate the repair effect of sulfonated polyether ether ketone.

 

In vivo animal experiments have shown that SPPEK is beneficial for the growth and binding of new tissues, inhibits the secretion of inflammatory cytokines, and promotes bone resorption. Especially, SPEEK-15, SPEEK-60, and SPEEK-30 have good nanostructures and biological properties.

 

(2) Load growth factor: The organic components of bone tissue include a large number of growth factors and proteins, which can stimulate cell activity and play an important role in osteogenesis and angiogenesis. BMP-2 is one of the strongest bone inducing factors that can induce mesenchymal stem cells to differentiate into osteoblasts.

 

Functionalized cell interfaces and cell regulatory proteins can also improve the biological characteristics of implants. Adiponectin (APN) is a factor secreted by adipocytes and has been proven to achieve satisfactory modification effects. Yu Hedong et al. selected a polyether ether ketone composite material wrapped in vascular endothelial growth factor to evaluate the clinical effect of repairing bone defects. Animal experiments showed that this material can stimulate the activity of growth factors and promote bone regeneration.

 

(3) Amination: Amination involves the introduction of amino groups, followed by the diazotization of amino groups into other active groups. The modification of PEEK was studied using a mixture of concentrated sulfuric acid and nitric acid in different ratios. The results showed that the mixture of acids in different ratios could produce multi-layer and porous structures on the surface of PEEK, improve the hydrophilicity and biological activity of the material, and endow it with good antibacterial activity.

 

Hassan et al. used chemical treatment to graft aminated polyether ether ketone onto the surface of carbon fibers. Scanning electron microscopy found that the interlayer shear strength of the material interface was enhanced, which improved the interfacial adhesion. However, the adhesion was limited by the sensitivity of amino groups to high temperatures.

 

3. Surface coating:

 

(1) Calcium phosphate coating: Calcium phosphate (CaP) is the main inorganic component of human bones, with good biocompatibility, bone bonding, bone conduction, and bone induction. CaP can adsorb extracellular matrix (ECM) proteins and activate osteoblast differentiation through Cell ECM interactions. In recent years, studies have shown that CaP coated PEEK surface can significantly improve its compatibility with osteoblasts MC3T3-E1.

 

In addition, the CaP coated PEEK material can form a dense hydroxyapatite (HA) coating on its surface after laser assisted biomimetic processing in simulated body fluids. In order to improve the activity of PEEK, studies have used ozone and chemical treatment methods to prepare phosphate and/or calcium functionalized PEEK to study bone binding. In vitro experimental studies have shown that modified PEEK significantly increases the mutual contact between rat bone marrow mesenchymal stem cells.

 

Surface functionalization not only improves hydrophilicity, but also does not change its surface roughness or morphology, which is expected to become a new application method in dentistry.

 

(2) Graphene: Graphene is a simple carbon structure with good physical and chemical properties, high hardness, good toughness, ductility, and permeability. Recently, a simple strategy has been developed to prepare sulfonated polyether ether ketone (GO SPEEK) modified with graphene oxide (GO) using a dip coating method. It has been observed that GO closely adheres to PEEK.

 

Antibacterial experiments have found that GO SPEEK has an inhibitory effect on Escherichia coli; In vitro experiments have shown that it has an accelerating effect on the proliferation and differentiation of osteoblast like cells. Yan et al. established a bone defect model in animals to study the osteogenic effect. At 4, 8, and 12 weeks after surgery, Micro-CT analysis and histological observation showed that graphene modified carbon fibers could enhance the microstructure parameters of polyetheretherketone, and the average mineral deposition rate was significantly better than that of carbon fiber reinforced polyetheretherketone (CFR/PEEK) implants (P<0.05).

 

Experiments have shown that graphene modified CFR/PEEK exhibits satisfactory cell compatibility and bone binding ability.

 

(3) Ti coating: A thin protective oxide layer formed on the surface of titanium and titanium alloys, which plays an undeniable role in improving the surface activity of polymers. Boyle et al. used simulated osteoblast culture experiments in vitro and observations of implants in sheep to demonstrate the effect of Ti coated PEEK (Ti PEEK) on the biomechanical and histological properties of bone implant interfaces.

 

Both in vitro cell culture experiments and in vivo animal experiments have shown that Ti-PEEK significantly improves new bone formation and osteoblast attachment compared to pure PEEK at different stages.

 

(4) Plasma immersion ion implantation: Plasma immersion ion implantation involves wrapping a substrate with a thin film of different particles, placing the substrate in the plasma of the particles, repeatedly pulsing with high negative voltage, causing the plasma ions to accelerate, and then implanting them on the surface of the substrate.

 

Using the PIII method to treat the surface of PEEK (PIII PEEK), a free radical reaction is generated to covalently immobilize proelastin on the surface of PIII PEEK. The cells on the surface of PEEK treated with PIII showed improvements in attachment, diffusion, and proliferation, and compared with untreated PEEK surface cells, bone nodule formation was observed. Wang et al. treated the surface of PEEK with water plasma and observed the formation of hydroxyl groups and "groove structure" on the surface of PIII-PEEK through SEM, which is more conducive to cell diffusion and adhesion.

 

2、 Filled composite materials

 

1. Nano titanium dioxide filled PEEK composite material:

 

Titanium and titanium alloys are widely used as dental implants, and their excellent corrosion resistance and biocompatibility are due to the rapid formation of a protective oxide layer (mainly TiO2) on the surface of Ti when exposed to the atmosphere. A layer of micrometer sized TiO2 thin film was deposited on the surface of PEEK at low temperature using arc ion plating technology.

 

Research has shown that the deposited TiO2 has a dense columnar structure, exhibits good biocompatibility, and has the highest level in adhesion experiments. Thanigachalam et al. prepared nano TiO2 filled PEEK composite materials (n-TiO2/PEEK) based on plastic injection molding technology. MG-63 series cells were used for cell research on the material surface, and good cell adhesion and proliferation were observed by SEM.

 

2. Hydroxyapatite/polyether ether ketone composite material:

 

HA is the main inorganic component of human bones, with good biological activity and can promote the proliferation of osteoblasts. Ma et al. added hydroxyapatite to PEEK and manufactured hydroxyapatite/polyether ether ketone composite materials (HA/PEEK) using composite and injection molding techniques. In vitro cell experiments showed that the biological activity of PEEK filled with hydroxyapatite material was significantly increased, and cell proliferation, adhesion, and alkaline phosphatase activity were significantly improved.

 

3. Polyether ether ketone/gelatin composite material:

 

Gelatin (GEL) is a peptide with extracellular matrix like properties that, when combined with polyether ether ketone, forms a polyelectrolyte complex with excellent mechanical strength. When the concentration of GEL increased, the metal substrate coated with GEL improved the adhesion and proliferation of MG-63 osteoblasts.

 

Jiang et al. prepared porous PEEK/GEL/AgNPs nanocomposite hydrogel by blending PEEK/GEL with silver nanoparticles (AgNPs), and studied its antibacterial and biocompatibility in vitro. Transmission electron microscope analysis showed that AgNPs pores were well distributed on the surface of PEEK/GEL hydrogel, which improved the mechanical properties of the composite. Antibacterial activity testing shows that it can significantly inhibit the growth of Staphylococcus aureus and Escherichia coli.

 

3、 Summary and Conclusion

 

This article reviews several common methods of PEEK modification in recent years. Surface modification of PEEK significantly improves the hydrophilicity and biocompatibility of materials, and improves the interaction with bone tissue; PEEK composite materials have an elastic modulus closer to that of human bone tissue, further enhancing their mechanical properties and reducing material costs.

 

However, each modification method has its shortcomings, including how to maintain the mechanical properties of PEEK while improving its biological activity, whether the degradation products of the surface coating are harmful to the human body, and whether they affect the final bone bonding of the implant. We need to further improve animal experiments and clinical research to provide scientific basis for the clinical application of PEEK.