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Review article
2021
:14;
202103
doi:
10.1016/j.arabjc.2020.102977

PEEK (Polyether-ether-ketone) and its composite materials in orthopedic implantation

, , , , , , , , ,
a Department of Orthopedics, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710061, PR China
b Department of Orthopedics, Qinghai Provincial People's Hospital, Qinghai 810007, PR China
c State Key Laboratory for Manufacturing Systems Engineering, Xi'an Jiaotong University, Xi'an 710049, PR China

⁎Corresponding author. zyingang@mail.xjtu.edu.cn (Yin-gang Zhang)

Received: , Accepted: ,
© The Author(s) 2021
Disclaimer:
This article was originally published by Elsevier and was migrated to Scientific Scholar after the change of Publisher.

Abstract

Large bone defects caused by tumors and traumas are difficult clinical problems. For its treatment, autogenous bone transplantation is the “gold standard”. However, there are some shortcomings of this treatment, such as limited supply and extra trauma from bone removal. In recent years, orthopedic implants and bone tissue engineering materials have developed rapidly, adding impetus to the solution of this problem. At present, the main orthopedic implants include medical metal materials, medical polymer materials, bone cement, ceramic materials, artificial bone materials, etc. Among which medical polymer materials have become the research hotspot and achieved outstanding results in recent years, especially the in-depth study of polyether-ether-ketone (PEEK) materials has great promising to solve this medical problem. PEEK materials have the advantages of non-toxicity, high-temperature resistance, corrosion resistance, abrasion resistance, high strength, high toughness, X-ray radiolucency, and excellent sterilization performance. PEEK materials have been successfully applied in clinical practice and have achieved excellent clinical efficacy and wide recognition. This review overviews the research progress of the performance requirements, material development, and material surface modification of PEEK as an orthopedic implant, and discusses prospects for the advance of medical PEEK materials.

Keywords

Bone defects
PEEK
Orthopedic applications
Systematic review

Abbreviations

PEEK

polyether-ether-ketone

MRI

magnetic resonance imaging

CT

computed tomography

Tg

glass transition temperature

Tm

melting point

CF

carbon fiber

PTFE

graphite and polytetrafluoroethylene

UHMPE

ultra-high molecular weight polyethylene

PES

polyethersulfone

BGs

bioactive glass

HA

hydroxyapatite

β - TCP

β - tricalcium phosphate

NIS

Nationwide Inpatient Sample

ACL

Anterior cruciate ligament

ALP

alkaline phosphatase

SBF

simulation body fluid

CF/PEEK

Carbon fiber reinforced PEEK

CS

30CaO·70SiO2

g-C3N4

graphitized carbon nitride

h-CN

hydroxylated g-C3N4

AS-CN

addition of synthetic g-C3N4

CNTs

carbon nanotube nanoparticles

MWCNTS

multi-walled carbon nanotubes

TGA

thermogravimetric analysis

SEM

scanning electron microscope

PLLA

poly(l-lactide)

GF

glass fiber

IF-WS2

inorganic fullerene-like tungsten disulfide

NM

NanoMetalene

PAEK

poly(aryletherketone)

pDA

polydopamine

1

1 Introduction

Orthopedic implants are a general term for a large class of implants that replace, repair, supplement, and fill human bones. They are used to support, maintain, and repair human bones, and are commonly used orthopedic medical materials in clinical practice. Traditional orthopedic implants such as stainless steel and titanium alloy have high mechanical strength, good bio-compatibility and fatigue resistance, and have been widely used in the hard tissue repair and replacement in orthopedics (Chen and Thouas, 2015). However, the elastic modulus of these traditional metal implant materials is much higher than bone tissue, causing the stress stimulation value of the bone around the implant to be much lower than the stress stimulation value required for the bone tissue to maintain its regeneration. The bone tissue around the implant is absorbed and its strength is reduced, causing the implant to loosen and ultimately leading to the failure of the implant, which is the so-called “stress shielding” effect (Abdullah et al., 2015; Asgharzadeh Shirazi et al., 2017). Besides, metal implants may release harmful metal ions, resulting in osteolysis and allergenicity. Furthermore, they are incompatible with commonly used computed tomography (CT) and magnetic resonance imaging (MRI) techniques, which does not contribute to monitoring bone growth and healing.

Polyether-ether-ketone (PEEK) is a new type of special thermoplastic engineering plastic (Basgul et al., 2018). It has excellent biological, mechanical and chemical properties (Zhao et al., 2013). As an orthopedic implant in vivo is its most prominent biomedical application. PEEK has been shown to have bio-mechanical properties close to human bones, which can reduce the risk of bone resorption and osteolysis caused by the stress shielding effect of implants. PEEK polymer as a biological engineering material, its basic characteristics and advantages include: 1. High thermal stability. The melting point (Tm) of PEEK materials are 334–343 °C, and the glass transition temperature (Tg) is 143 °C. Its instantaneous use temperature can even reach 300 °C; 2. Toughness and rigidity. PEEK has extremely high toughness and rigidity, especially their excellent fatigue resistance, comparable with alloy material (Santing et al., 2012); 3. Creep resistance and excellent performance. PEEK is the best creep resistance material in thermoplastic polymer; 4. Easy to process. There are numerous processing methods such as compression molding, extrusion molding, injection molding, additive manufacturing, subtractive manufacturing can be used; 5. Self-lubricating and abrasion resistance. PEEK has excellent self-lubricating properties, the wear amount of carbon fiber (CF) reinforced PEEK is half of ultra-high molecular weight polyethylene (UHMWPE). PEEK modified with CF, graphite and polytetrafluoroethylene (PTFE) has excellent abrasion resistance; 6. The mechanical properties can be adjusted by adding different additives, including CF, glass fiber (GF) and barium sulfate (BaSO4), etc. to meet diverse specific application requirements; 7. Non-toxic. cell compatibility is close to titanium alloy, and the wear particles do not damage body cells (Stratton-Powell et al., 2016); 8. Lower elastic modulus. Elastic modulus is about 2–6 GPa, can effectively prevent the stress shielding effect (Lee et al., 2012); 9. It has X-ray radiolucency, which is not visible during CT and MRI scans (Sobieraj et al., 2009; Toth et al., 2006), and in some cases when the implant has to be seen, it can also be achieved by polymer modification; 10. Excellent sterilization performance. Even if it is exposed to hot high-pressure steam, radiation and ethylene oxide for a long time, it can still maintain its original properties (Godara et al., 2007). Table 1 summarizes the advantages and disadvantages of PEEK and its composites in orthopedic applications (see Table 1).

Table 1 The advantages and disadvantages of PEEK and its binary and ternary composite materials.
Advantages Disadvantages Citations
Pure PEEK materials Bio-compatibility Bioinertia (Li et al., 2017)
Elastic modulus close to bone (Kersten et al., 2015); (Panayotov et al., 2016b)
Excellent corrosion resistance (Kurtz and Devine, 2007); (Monich et al., 2016)
Non-toxic (Stratton-Powell et al., 2016); (Katzer et al., 2002)
High toughness and rigidity (Santing et al., 2012)
X-ray radiolucency (Sobieraj et al., 2009)
Binary PEEK composite
HA/PEEK Bio-active General mechanical properties (Zhao et al., 2016); (Ma and Guo, 2019); (Zhong et al., 2019)
TCP/PEEK Bio-active and biodegradability General mechanical properties (Mao et al., 2019)
BaSO4/PEEK X-ray imaging General mechanical properties (Ponnappan et al., 2009); (Schwitalla et al., 2017)
CF/PEEK Excellent mechanical properties and disinfection performance Bioinertia (Qin et al., 2019); (Nakahara et al., 2013); (Godara et al., 2007)
CS/PEEK Bio-active Bioinertia and General mechanical properties (Kim et al., 2009); (Ma et al., 2014)
Ternary PEEK composite
CF(CNT)/HA/PEEK Bio-active and excellent mechanical properties (Xu et al., 2015a); (Deng et al., 2015); (Uddin et al., 2019)
CNTs/BG/PEEK Bio-active, excellent mechanical properties and thermal stability (Cao et al., 2019); (Han et al., 2013)
TCP/PLLA /PEEK Bio-active and biodegradability General mechanical properties (Feng et al., 2018)
GF/mica/PEKK Excellent wear resistance and economical Bioinertia (Gan et al., 2001)
IF-WS2@C/PEEK Excellent mechanical properties and thermal stability Bioinertia (Wang et al., 2017)

PEEK was first used in the study of orthopedic trauma internal fixation devices and femoral stems in the late 1980s (Panayotov et al., 2016a). In the mid-to-late 1990s, various manufacturers began to implement it to spinal interbody fusion cages. At present, PEEK materials have been widely used in trauma and spinal fixation (Kurtz and Devine, 2007). Spinal fusion cage is its main application. PEEK biomaterials are currently used in hundreds of thousands of spinal fusion patients around the world every year (Kurtz, 2019b). In 2014, an estimated 332, 000 thoracolumbar fusions and 176, 000 cervical fusions were performed in the United States based on the data from the Nationwide Inpatient Sample (NIS). By 2017, PEEK cages accounted for 68% of interbody devices (Kurtz, 2019a). There are over 250, 000 anterior cruciate ligament (ACL) repairs and 875, 000 meniscal repairs performed annually in the United States, representing the two most common arthroscopic procedures (Berg-Johansen et al., 2019). PEEK arthroscopic anchors have many potential advantages over metal anchors and bioabsorbable anchors, and therefore has become the main clinical application of arthroscopic anchors. For more than a decade, the material has been recognized by many medical device manufacturers and surgeons because of its excellent performance and quality.

PEEK materials as membrane-related applications are an important research direction, including battery ion exchange membranes (Rico-Zavala et al., 2020; Sun et al., 2019), fruit and vegetable fresh-keeping equilibrium-modified atmosphere packaging, brine ion recovery, etc. In recent years, the application of PEEK membrane in biomedicine has attracted a large number of researchers and has bright prospects. Kalambettu and Dharmalingam studied the preparation of SPEEK film incorporating hydroxyapatite (HA) (Kalambettu and Dharmalingam, 2014). In their further study, they prepared a mixture of SPEEK and polyethersulfone (PES), and then manufactured SPEEK/PES/nHAP composite membrane materials using solvent casting technique. The composite membrane shows better protein adsorption than the bare PES membrane, and also shows good cell adhesion. These composite membrane materials have great potential for filling bone defects in non-weight bearing areas (Kalambettu and Dharmalingam, 2015). Montero et al. studied the biofilm prepared by SPEEK (Montero et al., 2017). Moreover, Kaya and colleagues prepared l-arginine conjugated MWCNT/SPEEK nanocomposite films. Cell culture studies have shown that l-arginine modification enhances the proliferation ability of osteoblasts on MWCNT/SPEEK membranes (Kaya et al., 2018). Pimentel et al. made sulfonated polyether/hydroxyapatite (SPEEK/HA) membrane biomaterials through sulfonation and addition of HA to increase its wettability, cell adhesion, and viability (Pimentel et al., 2019). In addition to the PEEK membrane, Pokorny and colleagues summarized the application of PEEK materials in joint replacement, recommending the use of CFR-PEEK as a joint liner (Pokorny et al., 2010). Schwitalla et al. analyzed the application of PEEK, titanium and zirconia implants in oral implants, and believed that PEEK needs to be chemically modified to improve its biological and mechanical properties (Schwitalla and Muller, 2013). Almasi et al. introduced the progress of preparation methods to improve the biological activity of PEEK, and discussed the advantages and disadvantages of existing methods (Almasi et al., 2016). Haleem et al. reviewed the medical applications of PEEK materials and their 3D printed implants. They believe that 3D printing PEEK can realize economical, personalized, and sophisticated implant design and development, and has a promising medical application prospect (Haleem and Javaid, 2019). Mishra believed that PEEK could replace titanium implants in the future (Mishra and Chowdhary, 2019). In short, PEEK is a very promising orthopedic implant material.

Common PEEK implants in clinical practice include trauma implants, spinal implants, artificial joint implants, bone defect repair implants, and so on. However, the mechanical strength of PEEK is not as good as that of metal materials, and it does not possess the ability of secondary processing. Besides, it does not have biological activity and cannot form osseointegration with bone tissue, which has limited its application in bone tissue repair and reconstruction to a certain extent. In response to these deficiencies, researchers have added CF (Li et al., 2015), bioactive glass (BGs), HA and other materials to PEEK matrix to prepare composite materials and improve their performance. In addition, orthopedic implants come in contact with bone tissue through its surface. Surface modification is an approach that only changes the physicochemical properties of the material or near the surface, which can improve the biological activity of PEEK while maintaining its excellent properties. At present, surface modification methods of PEEK mainly include preparing a microporous structure on the surface, preparing a modified coating, or directly modifying the surface by plasma, laser, and wet treatment. Our article reviews the research progress of performance requirements, material development and material surface modification of PEEK materials implanted in orthopedics.

2

2 Performance requirements of medical PEEK materials

As the implant material in vivo is the most important biomedical application of PEEK and its composites. In addition to the basic performance requirements of medical PEEK implants, it also needs to meet special requirements based on the function.

2.1

2.1 Biological performance

The biological properties of PEEK implants for medical use include bio-compatibility (Katzer et al., 2002), bio-activity, and biostability. Good bio-compatibility is a basic requirement for implant materials in vivo. Bio-compatibility refers to the interaction between the material and the host body after the material enters the body. It mainly includes the host's biological body response caused by the material and the physicochemical reactions of materials. The ideal orthopedic implant material should have excellent bio-compatibility, on the one hand, it will not cause an obvious clinical response of the host body. And on the other hand, it should have appropriate physical and chemical stability that meets the expected use effect, so that the material can be stable and lasting in the expected use cycle.

Bio-active materials can induce a special physiological response at the biointerface of the material, which can enable effective mutual communication and combination between the material and the tissue. Since the 1980s, bio-active materials have been rapidly developed and successfully used in clinical applications. Traditional bioactive materials, such as HA, β - tricalcium phosphate (β - TCP) and BGs, all have good bio-activity and bio-compatibility, which can form an effective bond with living tissue. Biological stability refers to the ability to maintain long-term stability of bio-compatibility, biological activity, and physicochemical properties under physiological environment after the material enters the host body. It is a consideration of the performance of biomaterials in the time dimension. There are a series of physicochemical changes in the human body that damage the properties of the material, such as aging, degradation, fracture or re-crosslinking. Therefore, it is necessary to consider the long-term performance of implant materials in vivo and pay attention to the changes in the surrounding environment when designing implants. PEEK has excellent bio-compatibility and biological stability, and is a very promising implant material. Stratton-Powell et al. review the biological response of PEEK-based wear particles from total joint replacement. They found that the wear particles produced by PEEK-based bearings are within the phagocytic capacity range (0.1-10 μm) and the cytotoxicity of PEEK-based particles is within acceptable limits relative to the control of UHMWPE. But when considering the release of inflammatory factors, PEEK and UHMWPE wear particles are inconsistent (Stratton-Powell et al., 2016). Trindade and colleagues compared the bone immune response of PEEK, titanium and copper implanted in rabbits and found that all materials showed immune activation and bone resorption inhibition. Compared with PEEK and copper, titanium shows clearer M2 anti-inflammatory / reparative regulation. All groups showed up-regulation of CD4, suggesting that the bone immune response of these materials was driven by CD4 phenotype lymphocytes (Trindade et al., 2018).

2.2

2.2 Mechanical performance

Elastic modulus is a general property of materials and generally refers to the stress divided by the strain in that direction under unidirectional stress state. The stress state of the bone-implant system is closely related to the overall stiffness of the implant. Because the elastic modulus and the rigidity of metal material is much higher than that of the human skeleton, resulting in the stress shielding effect at the implantation site, which leads to a series of negative effects. The range of cortical bone elastic modulus is about 7–30 GPa (Kizuki et al., 2015), and Poisson's ratio is about 0.2–0.5. The elastic modulus of cancellous bone varies from 0.01 to 10 GPa and Poisson's ratio is about 0.01–0.35. The search for implant materials that are close to the elastic modulus of human bone is always the research and development direction in this field.

Static and fatigue strengths are two important indicators of material mechanical strength. Orthopedic implants replace some or all of the functions of human bones after they are implanted in the body. First, they must meet the mechanical and kinematic requirements of the human body to avoid mechanical failure such as fracture. With the movement of the human body, the orthopedic implants will be subjected to a cyclic load. Although this cyclic load may be far less than the static strength of the material, fatigue fracture may also occur if the fatigue strength of the material is exceeded. Therefore, the implant material must have both sufficient static and fatigue strength. As an engineering plastic, PEEK has sufficient static, fatigue strength and good mechanical compatibility to reduce stress shielding effects. It is an excellent biological internal fixation material.

Mechanical stability is the ability of the implanted material to maintain the original mechanical properties without degradation for a certain period of time. Metal materials have strong stability in mechanical properties, but attention should be paid to the material's wear resistance and corrosion resistance to avoid degradation of mechanical properties. During the development of the joint prosthesis, it was discovered that PEEK polymer cracking of composite hip joints exposed to lipid-containing in vivo environments (Kurtz, 2019b). In the design of artificial joint implants, the excellent friction and wear properties of the prosthesis must be considered. The friction coefficient between articular cartilage in natural joints under joint fluid lubrication is even less than 0.01. In addition, the current evaluation of joint wear performance includes not only mechanical size wear, but also the toxicity of abrasive particles. Therefore, a good joint implant should have excellent friction and anti-wear properties, sufficient bio-compatibility, and reduce damage to the body by abrasive particles. PEEK materials, especially CF reinforced PEEK composite materials, have excellent friction and wear properties (Li et al., 2015). Moreover, it has good bio-compatibility, and its abrasive particles have no obvious toxicity to the body (Kurtz, 2019b).

2.3

2.3 Chemical performance

The human body is a harsh corrosive environment. There are a large number of electrolyte ions and various complex organic compounds in body fluids. After metal materials are implanted in the body, they need to be immersed in body fluids for a long time, and chemical erosion is inevitable. Therefore, orthopedic implants should have good corrosion resistance. The nature of most corrosion processes is electrochemical. The pitting corrosion process of metal orthopedic implants in the human environment is the process of electrochemical changes. In the medical device industry standard, the principle of “different metal materials must not be used in the same part of the human body” is to avoid that different of the materials form a two-stage microbattery in the human body fluid environment, causing electrochemical corrosion. The PEEK implant has excellent corrosion resistance, which is one of its major advantages over metal implants.

2.4

2.4 Sterilization performance

Sterilization is the process of killing all microorganisms in items. There are three commonly used sterilization methods: heat sterilization, chemical sterilization and radiation sterilization. Since the implant will stay in the human body for a long time after implantation, it needs to be thoroughly disinfected to avoid infection and affect human health. The main sterilization methods for current implants are ethylene oxide, radiation sterilization, high-frequency polarization, low-temperature plasma, ultraviolet light, high-pressure humid heat, high-temperature dry heat, and membrane filtration. Different implant materials should be sterilized in different ways. Besides, the design of the implant should also consider the sterilizable of the implant material. PEEK materials have good stability and radiation resistance, and they are very mature as a sterile orthopedic implant. They can be sterilized using a variety of means including hot steam, ethylene oxide, and gamma rays (Godara et al., 2007).

3

3 Applications of PEEK materials in bio-medicine

PEEK was first used in the study of orthopedic trauma internal fixation devices and femoral stems in the late 1980s (Kurtz and Devine, 2007). In the mid-to-late 1990s, various manufacturers began to apply it to spinal interbody fusion cages (Toth et al., 2006). At present, PEEK materials have been widely used in trauma and spinal internal fixation. For more than a decade, the material has been recognized by many medical device manufacturers and surgeons for its excellent performance and quality.

3.1

3.1 Pure PEEK materials

PEEK materials are currently widely used as internal implants in spine surgery, joint surgery, and trauma surgery (As shown in Fig. 1). In the 1990s, the American company AcroMed first applied PEEK to the interbody fusion cage. The PEEK interbody fusion cage is compatible with X-ray photography and MRI. In addition, it has low elastic modulus, and has been rapidly promoted. In 2005, the US FDA approved the PEEK lumbar transpedicular screw dynamic fixation system for single-segment lumbar intervertebral fusion, which includes titanium-alloy pedicle screw and PEEK elastic rod. The device is designed to unload the pressure load on adjacent segments’ intervertebral discs and articular processes, while retaining proper mobility. It can reduce the stress between the pedicle screw and bone interface, and thereby reducing the risk of screw extraction and screw breakage. The PEEK materials are also used in artificial intervertebral discs.

Schematic illustrating the applications of PEEK implants in orthopedics.
Fig. 1
Schematic illustrating the applications of PEEK implants in orthopedics.

With the development of arthroscopic technology, especially shoulder arthroscopy, arthroscopic suture anchors have been widely used for the treatment of rotator cuff tears or other intra-articular injury diseases, and have been reported to have good clinical efficacy. PEEK applied to suture anchors has its own advantages: higher strength than other bioabsorbable materials (such as poly-L-lactic acid); X-ray radiolucency; elastic modulus closer to the bone; If the initial implantation position is not good, there is no need to remove the anchor, only need to re-drill and implant a new anchor in situ, which greatly reduces the difficulty of revision surgery; Its unique “knot-free” design makes arthroscopic suture fixation safer.

However, due to its biological inertness and its lipophilicity on the immune mechanism, the bone integration of the pure PEEK materials are significantly reduced, and their application in orthopedics is limited in clinical practice (Trindade et al., 2019).

3.2

3.2 Binary PEEK composite

Although pure PEEK has good mechanical compatibility as an orthopedic implant material, it still needs a long way to go to replace alloy material as a mature implant material. In addition to good mechanical compatibility, mature implant materials also need to have good osseointegration, sufficient mechanical strength, imaging and histological compatibility, and so on.

Osseointegration is a structural response of living bone tissue to inanimate implant (Albrektsson and Johansson, 2001). The concept of osseointegration was first proposed by Branemark et al (Brånemark et al., 1977). It refers to the direct contact of the fiber-free connective tissue interface layer between the internal implant and the bone tissue under an optical microscope. Clinically, osteointegration is defined as the process of achieving and maintaining asymptomatic fixation of allogeneic bone material under physiological load. Good osseointegration implants can transfer physiological load to surrounding bone or soft tissue without causing long-term complications such as loosening. In addition to osseointegration, other factors including the medical imaging properties of the implant, the effective stiffness associated with stress shielding, and durability may also contribute to the clinical success of the implant. The above performance largely depends on the material structure and composition of orthopedic weight-bearing implants (Yuan et al., 2018). In order to achieve the osseointegration of PEEK materials, researchers have tried to use bioceramics and other materials to improve their performance. To further improve the mechanical properties, CF and ceramic materials have been added for research. To achieve the X-ray development of the PEEK materials, BaSO4 was added to construct the binary composite material, which demonstrated excellent effects. PEEK binary composites have become a research hotspot, achieving different biomedical functions and expanding the field of biomedical applications of PEEK implant materials.

3.2.1

3.2.1 HA/PEEK

HA is the most important inorganic mineral component in biological bones. It can release harmless ions to the body and participate in metabolism in the body. It can stimulate or induce bone hyperplasia, promote the repair of defective tissues, and show biological activity. Zhao et al. have studied the regulation of human osteoblast function and metabolism by PEEK-HA through proteomics. The HA component can increase alkaline phosphatase (ALP) activity. The intracellular Ca2+ concentration in the HA/PEEK group was higher than that in the pure PEEK group. Quantitative proteomics analysis shows that calcium ion pathways are associated with most up-regulated proteins, while RNA processes are associated with most down-regulated proteins. This finding may account for the molecular biological mechanism of HA/PEEK enhancing osteoblast adhesion, differentiation and inhibiting proliferation. (Zhao et al., 2016).

Ma and colleagues prepared HA/PEEK bio-composites with different content of HA (10%, 20%, 30%, 40%) by using injection molding technology. Through measuring the elastic modulus and tensile properties of HA/PEEK composites, it is concluded that the material with an HA content of 30% has the best mechanical properties. In vitro co-culture of Mc3t3-e1 cells showed that the composite had good cell adhesion, proliferation and diffusion ability. In addition, HA/PEEK composites can effectively induce apatite formation after soaking in simulation body fluid (SBF). The results of in vivo experiments showed that compared with UHMWPE and pure PEEK materials, the osteointegration efficiency of HA/PEEK composites is significantly higher. These results confirm that adding HA can significantly improve the biological activity and osteogenic ability of PEEK materials. (Ma and Guo, 2019). However, it is difficult to achieve precise control of the biomechanical properties and pore structure of the scaffold through traditional processing technology. Zhong et al. used 3D printing and compression molding processes to achieve adequate control of the biomechanical properties of HA/PEEK bioactive scaffolds. On the basis of accurately characterizing the extrusion pressure, they established an optimization model by using response surface method, optimized the extrusion process parameters, and studied the effect of filament/pore size on the penetration depth of PEEK in the HA scaffold. As we can see from Fig. 2, the biomechanical performance test results verified that the HA/PEEK composite has good biomechanical compatibility, good compressive strength and yield strength within the range of human cortical bone mechanical (Zhong et al., 2019).

A) Schematically illustrates the preparation method of the porous PEEK and biologically active PEEK/HA composite. B) Typical microscopic morphology of hydroxyapatite and PEEK/HA composites: (a, b) scanning electron microscope (SEM) images of sintered hydroxyapatite scaffolds, (c, d) CT images of PEEK/HA composites. C) Characterization of biological and mechanical properties: SEM imaging of cultured cells on HA scaffold (a) in 1 day, (b) after 1 day, (c) at 7 days, (d) cell adhesion and cell surface interaction at PEEK/HA composite after 7 days, (e) stress-strain curves and (f) compressive strength of different materials (Zhong et al., 2019).
Fig. 2
A) Schematically illustrates the preparation method of the porous PEEK and biologically active PEEK/HA composite. B) Typical microscopic morphology of hydroxyapatite and PEEK/HA composites: (a, b) scanning electron microscope (SEM) images of sintered hydroxyapatite scaffolds, (c, d) CT images of PEEK/HA composites. C) Characterization of biological and mechanical properties: SEM imaging of cultured cells on HA scaffold (a) in 1 day, (b) after 1 day, (c) at 7 days, (d) cell adhesion and cell surface interaction at PEEK/HA composite after 7 days, (e) stress-strain curves and (f) compressive strength of different materials (Zhong et al., 2019).

3.2.2

3.2.2 TCP/PEEK

Like HA, β-TCP also belongs to calcium phosphate ceramics. β-TCP ceramics are a kind of degradable bioceramics. After being implanted in the human body, they will be gradually dissolved by body fluids and absorbed by tissues. At the same time, new bones will gradually grow and replace the implants, making it a good bone repair material. The TCP/PEEK composite material can take advantage of the dual components to make it have excellent mechanical properties, biological activity and degradability, and become an excellent orthopedic implant material. Mao and his colleagues developed a bionic TCP/PEEK anchoring device for anterior cruciate ligament reconstruction, and verified its effectiveness and safety on a canine model. Histological observations at 3 and 6 months postoperatively showed that the cartilage layer can be seen within the tendon-bone interface. And new bone trabecular tissue can be observed at 6 months postoperatively, indicating that the anchor was directly connected to bone tissue (Mao et al., 2019).

3.2.3

3.2.3 BaSO4/PEEK

Ponnappan et al. designed and studied the dynamic and static mechanical properties of BaSo4/PEEK rods. Another significant feature of PEEK bio-materials in spinal applications is its radiolucency. The radiation clarity of PEEK greatly promotes the radiological evaluation of in vivo fusion, thereby improving the accuracy of clinical evaluation. The addition of BaSO4 enables the PEEK materials to be clearly developed without X-ray artifacts, and is MRI compatible. This feature makes the fusion assessment more complete and makes them widely used in the spine (Ponnappan et al., 2009).

In view of PEEK materials have good mechanical properties and bio-compatibility, its application in orthopedics and stomatology is more and more widely. Schwitalla and colleagues evaluated the compressive properties, elastic properties and other parameters of 11 PEEK composite materials (including two BaSo4/PEEK materials). They concluded that based on bite force testing, all materials seem to have the potential to be used in oral implants (Schwitalla et al., 2016). The convergence of material elastic modulus and bone modulus around the implant ensures the elastic transition of mechanics, thereby reducing the occurrence of complications. In order to ensure lasting reliability, further research, such as fatigue loading test, is necessary. Therefore, in their follow-up research, they studied the cyclic loading of these 11 composite materials, and the results showed that all materials can resist the pressure caused by the maximum chewing force (Schwitalla et al., 2017).

3.2.4

3.2.4 CF/PEEK

Carbon fiber reinforced PEEK (CF/PEEK) with low elastic modulus and high strength has been used in femoral stem prostheses since the 1990s. The elastic modulus of CF/PEEK is higher than that of pure PEEK and lower than that of metal materials, generally around 8 GPa. Since the mechanical properties of the CF/PEEK composite prosthesis are identical to those of bone tissue, the strain variables of the two during loading are consistent, which can produce good mechanical compatibility. This greatly increases the bonding strength of the interface, reduces shear stress, fretting and vertical displacement, and further ensures that bone tissue grows into the prosthesis to achieve biological fixation. CF/PEEK materials, especially short-chain CF reinforced PEEK, have excellent abrasion resistance and low elastic modulus, which makes it a substitute for joint friction interfaces.

For decades, CF reinforced composites have attracted widespread attention in the academic and industrial circles for their excellent mechanical properties (Li et al., 2015). The composition, design and manufacturing process of CF reinforced composite materials were improved, and a lightweight load-bearing structure was developed. In this sense, PEEK is considered to be the most attractive base material because of its special properties, such as light weight, stable performance, and easy molding. In general, functional composite materials usually combine the strength of carbon fiber with the ductility of the matrix material to enhance its application performance (Chung, 2017). These composite materials are widely used in automotive, aviation, construction and other industries. In recent years, CF/PEEK composites have also been extensively investigated in the biomedical field (Miyazaki et al., 2017). At present, they have been successfully promoted and applied to the development of medical implants such as hip joints, fixators, anchors, etc. (Lindeque et al., 2014; Nakahara et al., 2013). In addition, the FDA's approved CF/PEEK composites are the most suitable load-bearing implanting materials. However, the biological inactivity of the CF/PEEK complex has limited its clinical application because the formation of fibrous sacs around the implant limits its binding to the host bone (Xu et al., 2015b). Therefore, the biological activity of CF/PEEK composites needs to be improved. Nakahara et al. prepared CF/PEEK hip joints, and prepared HA-containing cementless implants as an experimental group by plasma spraying, and uncoated CF/PEEK bone cement implants as a control group. After 52 weeks of implantation in sheep, the stability and osseointegration of implanted prosthesis were evaluated by imaging and histology. Good bone tissue growth and osseous fixation were observed in the HA-coated cementless CF/PEEK hip joint prosthesis. And HA-coated CF/PEEK bone prosthesis has great potential for cementless fixation (Nakahara et al., 2013).

3.2.5

3.2.5 Other binary PEEK composite

The combination of bioactive ceramic filler and organic high molecular polymer can obtain bioactive bone repair material with similar mechanical properties as natural bone. Kim and colleagues made a bioactive composite material in which PEEK was reinforced with 0–50 vol% 30CaO·70SiO2 (CS) microspheres (CaO-SiO2-PEEK) (Kim et al., 2009). In SBF, the HA is formed on the surface of the CaO-SiO2-PEEK. The induction period of HA formation decreases with the increase of CS particle content. The mechanical properties of the composite materials were evaluated by the three-point bending test. Their research on bioactive CaO-SiO2-PEEK showed that the composites reinforced with 20 vol% CS particles are the most promising implant material.

3.3

3.3 Ternary PEEK composite

Although some binary composite structures have been able to achieve improvements in biological properties, mechanical properties, or developmental performance, real biomimetic materials in orthopedic implants have complex structures and often need to be compatible with multiple biological properties in order to achieve the best biological function substitution. Therefore, researchers have started to develop a series of PEEK ternary composite materials, among which CF/HA/PEEK is the most representative.

3.3.1

3.3.1 CF(CNT)/HA/PEEK

Since PEEK has been approved by the US FDA for medical use, great efforts have been conducted into the study of PEEK as a spine, trauma, and dental implantable material. However, the biological inertia of PEEK hinders osseointegration after implantation and seriously hampers its clinical application (Khonsari et al., 2014; Liu et al., 2018; Zhenjie et al., 2018). Because PEEK is a bio-inert material, after implantation in the human body, a fibrous tissue encapsulation forms and isolates the implant from surrounding tissues. Long-term clinical observations indicate that the main reason for the failure of bio-inert implants is the fixation of bone tissue by unstable implants (Meyers et al., 2009). Therefore, the main obstacle is that PEEK is a biologically inert substance, that reduces the efficiency of osseointegration.

HA has good biological activity and osteoinductivity, and it can effectively promote bone growth and biological tissue adhesion. To this end, Xu et al. introduced HA into PEEK-CF composite materials to develop osseointegrative implants. (Xu et al., 2015a). Similarly, Deng and colleagues also reported CF/HA/PEEK ternary composites as bioactive bone grafts (Deng et al., 2015). In these studies, CF-reinforced polymer-HA composites were synthesized by composite molding process. However, this processing method has the disadvantages of fiber abrasion, uneven fiber dispersion, and interface non-interaction, which reduces the application value of the composite material.

PEEK is used to make bio-nanocomposite foam materials with high-porosity for new bone formation. In Uddin's research, PEEK foam containing HA, CF, and carbon nanotubes (CNTs) was prepared by casting smelting and salt-induced pore leaching technology. (Uddin et al., 2019). As shown in the Fig. 3, after adding 0.5 wt% of CNTs to HA/PEEK, its mechanical properties are superior to all other components in this study. It was also observed in the compression test that under the condition of 75% porosity, the compression modulus of the prepared bio-nanocomposites was 252.91 MPa, the yield strength was 4.51 MPa, and the neat PEEK was 66.45 MPa, and the yield strength was 1.98 MPa. In contrast, adding more carbon particles to PEEK will reduce its mechanical properties. The reason may be the accumulation of carbon particles, which increases local stress. Micro-CT shows that the pore structure and connectivity of the composite foam material are in accordance with the design dimensions. All test results prove that PEEK nanocomposite foams containing HA, CF and CNTs are promising for use in bone scaffolds and other biomedical applications.

A) Schematically illustrates the synthesis process of MWCNTs/HA/PEEK bio-nanocomposite. B) Compressive modulus and yield strength of bio-nanocomposites (75% porosity) containing CF and CNTs (Uddin et al., 2019).
Fig. 3
A) Schematically illustrates the synthesis process of MWCNTs/HA/PEEK bio-nanocomposite. B) Compressive modulus and yield strength of bio-nanocomposites (75% porosity) containing CF and CNTs (Uddin et al., 2019).

3.3.2

3.3.2 CNTs/BG/PEEK

Cao and colleagues designed multi-walled carbon nanotubes (MWCNTS), which were combined with BG/PEEK, and successfully prepared a bio-compatible ternary composite material of MWCNTS/BG/PEEK by composite injection molding process. The thermogravimetric analysis (TGA) measurement results show that the MWCNTS in the PEEK matrix increase the thermal stability of the composite. After immersion in SBF, a bone-like apatite layer was formed on the surface of the composite material, showing good apatite forming ability. The mechanical properties of ternary MWCNTS/BG/PEEK composites are significantly better than BG/PEEK composites. Importantly, cell culture experiments show that the MWCNTS/BG/PEEK composite material significantly enhances the metabolic activity and osteogenic differentiation ability of osteoblasts. The results of MTT and ALP show that MWCNTS in composite materials is the main influencing factor. Therefore, MWCNTS/BG/PEEK biomaterial is a very potential bone graft scaffold material, which is expected to be used in orthopedic clinics (Cao et al., 2019).

Han et al. prepared CNTs/BG/PEEK ternary composites by injection molding. Among them, CNTs and BG nanoparticles are uniformly dispersed in the PEEK matrix by co-precipitation and adsorption. The microstructure of the composites was studied by SEM. Moreover, the addition of CNTs significantly improved the mechanical properties of the composites. The highest content of CNTs in the composite was 6%. The composites containing 6 wt% CNTs and 4 wt% BG have the same mechanical strength as neat PEEK. By adding BG to the composite, the biological activity of PEEK in SBF was improved. These new ternary composites have good mechanical properties and high biological activity, and and are very promising bone graft scaffold material (Han et al., 2013).

3.3.3

3.3.3 TCP/PLLA/PEEK

Biodegradation has always been the pursuit of implant research in orthopedics. It can solve the shortcomings of metal implant fixation requires a second surgery to remove the implant. How to achieve the synchronization of bone regeneration and internal fixation degradation without affecting the mechanical properties has been a challenge in this field. As shown in Fig. 4, Feng and colleagues used poly(l-lactide) (PLLA) as the biodegradable polymer to prepare TCP/PLLA/PEEK scaffolds. With the degradation of PLLA, the scaffold has good biodegradability and a large number of holes are formed in the membrane. The encapsulated β-TCP is released to promote new bone formation. In bone defect repair experiments, they found that new bone tissue grew from the edge of the scaffold to the center of the scaffold, and the bone defect area was completely connected to the host bone end after 8 weeks of implantation (Feng et al., 2018).

A) The H&E staining pictures of the bone defect sections in the TCP/PLLA/PEEK scaffolds with 0 wt% PLLA (0PLLA group) and 30 wt% PLLA (30PLLA group) at different times after surgery B) Quantitative analysis of new bone area. C) The optical graphs of scaffolds (Note: SM = scaffold material; NB = new bone; MB = mature bone; *P < 0.05, **P < 0.01) (Feng et al., 2018).
Fig. 4
A) The H&E staining pictures of the bone defect sections in the TCP/PLLA/PEEK scaffolds with 0 wt% PLLA (0PLLA group) and 30 wt% PLLA (30PLLA group) at different times after surgery B) Quantitative analysis of new bone area. C) The optical graphs of scaffolds (Note: SM = scaffold material; NB = new bone; MB = mature bone; *P < 0.05, **P < 0.01) (Feng et al., 2018).

3.3.4

3.3.4 Other ternary PEEK composite

Wang et al. prepared a unique high-performance thermoplastic PEEK ternary composite material (IF-WS2@C/PEEK) by using IF-WS2 (inorganic fullerene-like tungsten disulfide) coated with nanographene. The structure was characterized by electron microscope imaging, electron dispersion elemental analysis and X-ray diffraction. The mechanical and thermal properties of the composites were significantly improved. The ultimate tensile strength at 2 wt% was increased by 54%, and the thermal conductivity at 8 wt% was increased by nearly 235%. In addition, its decomposition temperature is raised (>50 °C) with the increase of IF-WS2@C content. Further research found that the Kissinger method estimates the activation energy of pure PEEK and IF-WS2@C/PEEK to be 61 and 97 kJ mol−1, respectively. These performance improvements will undoubtedly expand the application of PEEK composite materials (Wang et al., 2017).

4

4 PEEK implants surface modification and coating treatment

Orthopedic implants are increasingly used worldwide, with hundreds of thousands of orthopedic surgeries being performed every day. However, most of the reasons for surgical failure are mainly due to poor osseointegration. In order to handle this problem, many modified approaches have been explored, especially those to improve the bio-compatibility of orthopedic equipment by changing the biological response of the implant surface. The bionic functionalization of the surface of orthopedic implants can be achieved by fixing functional proteins and other biological signal molecules. This method can promote osteogenic differentiation and new bone formation at the implant-bone interface, resulting in the osseointegration. Stewart et al. reviewed the recent research progress in biomolecule functionalization of orthopedic surfaces through adsorption, chemical covalent immobilization and physical covalent immobilization. The immobilization mechanism of each method was examined, and the strategy was evaluated based on its complexity, effectiveness, reproducibility, and scalability (Stewart et al., 2019). They also explain and discuss how the surface morphology and chemical properties regulate the mechanism of interaction between implants and tissue proteins.

Bionic surface functionalization is an effective way to improve the osseointegration of orthopedic implants. In this regard, research on PEEK has already been in full swing, and a great number of researches have revealed some new application areas, including blend modification, coating, physicochemical surface modification, porous and fibrous structures (as shown in Fig. 5).

Schematic diagram illustrating the mainstream methods of PEEK implant modification.
Fig. 5
Schematic diagram illustrating the mainstream methods of PEEK implant modification.

4.1

4.1 Surface activation treatment and related coating materials

Biological activity, an important indicator of implant materials, refers to the ability of the implant materials to form chemical bonds with biological tissues, maintain or promote the characteristics of osteoblast differentiation, proliferation, and promote the growth of bone tissue. It is currently believed that the biological activity of orthopedic implant materials lies in the formation of bone-like apatite, or carbonated hydroxyapatite (HA) (Hench and Wilson, 1984; Kokubo and Takadama, 2006). Regardless of whether the implant material contains HA, as long as it can form HA on the surface under physiological conditions, it can show biological activity. The released HA crystals can promote bone cell differentiation and proliferation. The organic-inorganic matrix formed by HA and organic matter has the function of stabilizing cell metabolism and adsorbing growth factors.

Bioceramic coating can significantly improve the biological activity of bio-inert materials. Currently the most widely used is HA bioactive ceramic. Methods for preparing bioceramic coatings include thermal spraying, physical vapor deposition, chemical vapor deposition, sol-gel method, electrochemistry, hydrothermal reaction, glass adhesion sintering, and so on. Mahjoubi et al. introduced a phosphate group on the surface of PEEK implants through a diazo chemical method. They found that compared with unmodified PEEK, this approach increased the metabolic activity and cell viability of MC3T3-E1 cells. When implanted in a skull defect model of rat, phosphate coating successfully prevented the formation of fibrous sacs and promoted the deposition of minerals around the implant, thereby enhancing the osteointegration of PEEK (Mahjoubi et al., 2017). In addition, Bastan et al. used electrophoretic deposition to prepare HA coating on the surface of PEEK implants. The results show that the adhesion and biological activity of the coating are related to the relative content of PEEK and HA. Among them, increasing the content of HA components can enhance its biological activity and reduce the adhesion strength of the coating. After three days of SBF culture, the formation of a bone-like apatite layer on the high HA content coating can be observed (Bastan et al., 2018). Walsh et al. prepared a perforated PEEK implant with a submicron titanium coating and implanted it into the femoral distal femur and proximal tibia cancellous bone of eight adult sheep. As shown in Fig. 6, the experiment was divided into a fully-coated PEEK group, aperture-coated PEEK group and uncoated PEEK group. Micro-CT and histological staining were performed at 4 and 8 weeks after implantation. Micro-CT showed that the bone volume in the coating group increased overall. Histology showed that the newly woven bone in the coating group grew along the titanium coating surface, while the uncoated PEEK group showed typical non-reactive fibrous tissue proliferation (Walsh et al., 2018).

A) Simulation model of three groups of implants. B) Sagittal micro-CT images of each group at the 4th and 8th week. New bone formation can be seen on the surface of NanoMetalene (NM) coating. C) Polymethylmethacrylate (PMMA) histology in the sagittal plane at 4th and 8th week. (Walsh et al., 2018).
Fig. 6
A) Simulation model of three groups of implants. B) Sagittal micro-CT images of each group at the 4th and 8th week. New bone formation can be seen on the surface of NanoMetalene (NM) coating. C) Polymethylmethacrylate (PMMA) histology in the sagittal plane at 4th and 8th week. (Walsh et al., 2018).

Tantalum can also be coated on the surface of some non-metallic materials, such as the carbon cage for spinal fusion. Tantalum coating improves the strength and toughness of the cage, so as to fit the spinal load and better meet requirements of the surgical process (Li et al., 2007). The preparation of tantalum coating is mainly divided into physical and chemical vapor deposition. Although the film quality of physical vapor deposition is high, the coverage of materials with complex topography is not good. Due to this situation, the application of chemical vapor deposition technology is more extensive.

Although the coating material has greatly improved the biological activity of the implant material, due to the problem of poor interfacial strength of the coating, other methods except plasma spraying cannot meet the requirements of implant in clinical practice. Nakahara and co-workers used the model of rabbit femoral condyle defect to investigate the effect of HA coating on the osseointegration interfacial stress of CF/PEEK and titanium alloy implants. Except for uncoated CF/PEEK, the other groups showed good interfacial shear stress strength at the twelfth week pull-out experiment, indicating that the interfacial shear strength of the HA-coated CF/cPEEK implant reached the same level as that of HA sandblasted titanium alloy (Nakahara et al., 2012).

4.2

4.2 Surface physical and chemical modification

The physicochemical properties of surface of biomaterial determine the interaction between cell and material or/and the final osseointegration between bone tissue and implant. At present, the physical modification methods for PEEK materials mainly include plasma modification, accelerated neutral atom beam modification, sandblasting modification and plasma injection.

PEEK molecular chain has a regular structure and few chemical treatment methods can be used on its surface. Most of the means are to modify the ketone group in its molecular chain by wet chemical method. In addition, the sulfonation treatment on the benzene ring is another effective chemical treatment method. Through sulfonation treatment, not only the hydrophilic sulfonic group can be introduced into the PEEK molecular chain, but also the microporous network structure can be constructed on its surface. As we can see from Fig. 7, Yuan et al. prepared porous PEEK and PEKK implant materials and sulfonated them. The rat femoral condyle model was used to evaluate the in vivo osseointegration effect of the two physicochemically modified materials. The results suggested that PEKK has the best osteogenesis ability because it has more ketone groups. The overall osteogenesis trend was porous sulfonation group > porous group > pure material group (PEKK-D ≈ PEEK-D < PEKK-P ≈ PEEK-P < PEEK-BSP < PEKK-BSP) (Yuan et al., 2018). Hughes and colleagues used a covalent bonding method to prepare PEEK-L-HA polymer to improve the biomechanical properties of HA/PEEK composites. This method reduces the debonding of HA particles, inhibits the development of micro-cracks, and improves the stiffness transfer under load between HA and PEEK (Hughes et al., 2018). The covalent bonding between HA and PEEK effectively improves the applicability of such composites in orthopedics.

A) Micro-CT reconstruction image 12 weeks after PAEK samples implantation. B) H&E stained images of PAEK specimens 12 weeks after surgery. Quantitative analysis of new bone in the interface area C) and the inner pores D) after the implantation of the PAEK samples in the body (Note: # = New bone; ★ = Fibrous tissue; Arrow = The gap between the implant and host bone; *p < 0.05) (Yuan et al., 2018).
Fig. 7
A) Micro-CT reconstruction image 12 weeks after PAEK samples implantation. B) H&E stained images of PAEK specimens 12 weeks after surgery. Quantitative analysis of new bone in the interface area C) and the inner pores D) after the implantation of the PAEK samples in the body (Note: # = New bone; ★ = Fibrous tissue; Arrow = The gap between the implant and host bone; *p < 0.05) (Yuan et al., 2018).

Wan et al. fixed the double growth factors (IGF-1 and BMP-2) with a polydopamine (pDA) coating on the porous surface of the PEEK materials to construct a biologically active interface. The results of co-culture of Mc3t3-e1 cells in vitro showed that PEEK immobilized with double growth factors could significantly improve cell adhesion, diffusion, proliferation, extracellular matrix secretion, ALP activity and mineralization which indicates it has great potential for biological applications (Wan et al., 2019).

4.3

4.3 Surface roughening or porous treatment technology

Adjusting the topography of the implant surface at the microscale can improve osseointegration. Surface modification using titanium, such as sandblasting, is one of the methods known to change the surface topography. Martin et al. used four different shapes of sandblasted molds for structural transfer, and then used physical vapor deposition coatings to create micro-roughness on PEEK to promote osteointegration (Martin et al., 2018). Torstrick et al. studied the osteogenic properties of porous PEEK materials. Compared with smooth PEEK and plasma-sprayed titanium coatings, porous PEEK can improve cell osteogenic differentiation and increase implant osseointegration. A rat tibial defect model was used to verify the osseointegration of porous PEEK implants. After eight weeks, the Micro-CT, histology, and pull-out experiments was used to evaluate the mechanical riveting effect of the bone-body interface. The results show that the mechanical properties of bone growth on the implant surface are mainly regulated by the interlocking mechanism. The size and direction of the surface features are closely related to it. The larger surface features contribute to greater bone ingrowth and increase the load resistance of the bone-implant interface (Torstrick et al., 2018b). In addition, they also studied the impact resistance of porous PEEK and titanium-coated PEEK cervical cages (Torstrick et al., 2018a). Although the titanium-coated PEEK interbody fusion cage shows good osseointegration, it may be damaged and worn during the inserting process. Their study found that the porous PEEK intervertebral fusion device had the least damage during cervical impaction, while the Ti-coated PEEK intervertebral fusion device had considerable damage and loss of the titanium coating after implantation.

Carpenter et al. used a finite element model to analyze the effects of materials and porous structure on the stress loading distribution at the bone ingrowth interface. It was found that, regardless of the pore structure or bone ingrowth level of PEEK and titanium materials, porous PEEK can increase the load sharing of adjacent bone tissues (As shown in Fig. 8) However, most of the load of porous titanium is shared by the implant, and the tissue strain generated by it can increase the risk of bone resorption. Their results indicate that compared to existing 3D printed porous titanium, the lower elastic modulus of the porous PEEK structure may contribute to bone formation (Carpenter et al., 2018).

A) Finite element models of porous PEEK and porous titanium. (a, d) porous structure-bone model, (b, e) isometric view of porous PEEK and porous Ti. (c, f) bone ingrowth simulation model. B) Load sharing of bones and implants under compression, traction and shearing in different material models at 4th and 28th weeks. Regardless of the loading direction, the level of ingrowth, or the pore structure, most of the load is carried by the bone with PEEK implant, while the implant with Ti bears most of the load (Carpenter et al., 2018).
Fig. 8
A) Finite element models of porous PEEK and porous titanium. (a, d) porous structure-bone model, (b, e) isometric view of porous PEEK and porous Ti. (c, f) bone ingrowth simulation model. B) Load sharing of bones and implants under compression, traction and shearing in different material models at 4th and 28th weeks. Regardless of the loading direction, the level of ingrowth, or the pore structure, most of the load is carried by the bone with PEEK implant, while the implant with Ti bears most of the load (Carpenter et al., 2018).

5

5 Conclusions and perspectives

PEEK is a well-known polymer biomaterial. Due to its excellent biomechanical properties, it is often used as a substitute for metal implants in orthopedic applications. As the performance requirements of biomedical implants, additive manufacturing and other processing techniques, and surface modification techniques continue to update and develop, this part of the information needs to be updated in time. This article reviews the research progress in the preparation and surface modification of PEEK implant materials in recent years. Different from other reviews, our new review puts forward the performance requirements of PEEK as an internal implant, including biological properties, mechanical properties, chemical properties and sterilization properties. It should be noted that the past PEEK review studies have two limitations. First, PEEK implant materials, especially some emerging composite materials and modified materials, have a short clinical application time. And there is a lack of long-term clinical research follow-up data. Therefore, previous review studies failed to collect and clarify detailed data on the physical and chemical properties of PEEK materials after long-term implantation in the human body. Second, PEEK as an internal implant is its most important medical application, and previous review studies did not discuss the performance requirements of PEEK as an internal implant. Our review study addresses similar limitations, summarizes the progress of preclinical studies on the short-term changes in physical and chemical properties of PEEK materials after implantation, and focuses on the performance requirements of PEEK as an implant application.

The research of PEEK has been fully carried out, and more and more research fields have been developed, including interaction with cells, coatings, surface modification, and the relationship between porous, fiber structure and its mechanical properties. As an emerging medical application of PEEK materials, PEEK membrane has broad prospects. It increases the biological activity of PEEK materials such as release, antibacterial, and osseointegration, which has very important research value and significance. An evaluation in 2007 compared the response of osteoblasts in vitro to PEEK with that of commercial pure titanium materials and found that the osteoblasts' response to PEEK was comparable to that of titanium. Like other biomaterials, improving surface smoothness through processes such as injection molding or machining has little effect on cell behavior. The application of PEEK in the field of orthopedic implants has attracted more and more attention. The research results of multiple experiments, such as in vitro, in vivo and clinical research, have further proved this point. Its excellent low friction performance has expanded the choice of joint friction materials. Although encouraging mid-term clinical follow-up results have been obtained for its application to femoral stem prostheses, long-term follow-up is also important to evaluate its long-term effects. PEEK's radiolucency is very popular, but it is not a key function in the field of fracture internal fixation and joint replacement prostheses. More clinical researches are expected in the future to support its application in the field of orthopedic implants.

In recent years, with the collaborative development of material science, engineering, medicine, imaging and other disciplines, orthopedic implants have developed rapidly. And the researchers have overcome various technical difficulties and achieved multi-dimensional improvements in the physical, chemical, mechanical, biological, absorbability and anti-infective properties of the materials. This lays the foundation for solving clinical problems such as large bone defects, infectious defects, and internal fixation failure. However, Orthopedic implant science is still a multidisciplinary and interdisciplinary subject that requires long-term investigation of clinical problems. It is still a great challenge to develop implants that can meet the requirements of human tissues in many aspects and replace human functional structures. In the future, more scientific researchers will be engaged in this area of research. It is believed that implant science will develop with the continuous development of tissue engineering, material chemistry, medicine and other disciplines, and more and more fruits will be born.

Acknowledgements

Hongyun Ma retrieved the literature and wrote the first draft, Qiling Yuan, Chuncheng Yang and Xiaoming Zhao provided language help, Jingyuan Zhou, Liang Liu and Xiaoxiao Lou provided writing assistance and Prof. Yin-gang Zhang, Prof. Di-chen Li and Prof. Angxiu Suonan proofread the article. This work was supported by National Key R&D Program of China (2018YFE0207900) and the Program of the National Natural Science Foundation of China (81371987 and 51835010).

Declaration of Competing Interest

The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

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