Physical treatments constitute plasma treatment, accelerated neutron atom beam (ANAB), photodynamic therapy, sandblasting, and laser irradiation.

Plasma treatments primarily aim to decrease the contact angle of the PEEK surface by increasing the surface energy. Secondarily, the plasma treatments incorporate the element constituting the plasma onto the surface of a PEEK (Plasma Immersion Ion Implantation). This improves its response to human osteoblasts. Several elements have been successfully tested for the plasma treatment of PEEK (Table 1).

As evident from the studies, plasma treatments are utilized as a pre-treatment for several other surface treatments. Oxygen plasma was tested with various forms of radiation, whereas Argon plasma was combined with various chemical treatments. However, the rationale for the preference for such combinations could not be deciphered. Considering the decrease in contact angle and increase in the bioactivity of PEEK, nitrogen plasma was found to be most suited for implant applications of PEEK. Plasma treatments and sulphonation are the most common surface treatments used to increase the surface energy of PEEK to receive a bioactive coating. The two treatments are also used extensively together. In addition to increasing the surface energy and hydrophilicity of the surface, plasma immersion ion implantation also increases the hardness of the surface [38]. This property may decrease the tribological wear of orthopaedic implants due to gliding surfaces but is not important for dental implants [39]. However, due to the nature of electromagnetic radiation, plasma treatments are restricted by line-of-sight limitations. Therefore, it is difficult to utilize plasma for modifying implants with complex geometry [40].

Accelerated Neutral Atom Beam (ANAB) is a technique for employing an intensely directed beam of neutral gas atoms that improves the bioactivity of PEEK without altering its chemical or mechanical properties. Studies have demonstrated a decreased contact angle and increased bioactivity of osteogenic cells in response to ANAB-treated PEEK in-vitro [41,42,43,44] and an increased bond strength to bone in-vivo [42], as shown in Table 2. An in-vitro decrease in the bacterial colonization of Methicillin-resistant Staphylococcus aureus (MRSA), Staphylococcus epidermidis (S. epidermidis), and Escherichia coli (E.coli) have been demonstrated following treatment of PEEK with ANAB [43]. Though ANAB has exhibited significant improvement when used as a solitary treatment, its synergy with other treatments is yet to be tested. ANAB-treated PEEK surfaces are capable of osteoblast differentiation following osteoinduction in an osteogenic medium. However, ANAB-treated PEEK surfaces have not demonstrated independent osteoinduction ability [44].

Photodynamic treatment is primarily a therapeutic approach to decrease the microbial load on the surface. It involves the introduction of a drug on the surface of the biomaterial, followed by irradiation with a laser beam. It has been proven to decrease the microbial load and can be used in cases of inflammation around PEEK implants [45,46] (as given in Table 3). However, any potential role of photodynamic treatment in improving osseointegration in the absence of a periodontal pathology is yet to be investigated. However, significant improvements are required in light sources, absorption rates, and penetrating abilities of photosensitizers to decrease the exposure time required to modify PEEK surfaces with photodynamic treatment [46].

Sandblasting is a widely used procedure in the surface treatment of titanium implants. It was broadly used when the surface roughening of implants was first advocated to enhance osseointegration. It is a process of physically roughening the surface by subjecting it to a stream of abrasive particles. This method has been shown to increase the proliferation and differentiation of mesenchymal stem cells and also to mitigate inflammatory mediators around the implant [47] (Table 3). As observed in titanium implants, blasting is one of the most widely used surface treatments but is insufficient to improve tissue response and bone-implant contact. [38] Due to the advent of newer physical methods to treat PEEK surfaces, sandblasting has been restricted as a pre-treatment before the application of a bioactive coating.

A femtosecond laser can be employed to induce periodic grooves on the surface of the PEEK implant, which improves the surface characteristics. Xie et al. confirmed that the PEEK surface after exposure to a femtosecond laser showed increased adhesion, proliferation, and differentiation of mouse bone marrow mesenchymal stem cells (mBMSC) cells and increased expression and activity of alkaline phosphatase [48] (Table 3). However, these findings will require substantiation with in vivo studies.

One of the most common surface treatments employed for PEEK, sulphonation, involves the exposure of the surface to concentrated sulphuric acid. (H₂SO₄). The term ‘sulphonation’ refers to the exposure to H₂SO₄ as well as its removal from the surface by an alkali, although in some studies it has been used exclusively for the exposure to the acid.

Studies demonstrating the exposure time of H₂SO₄ have yielded conflicting results; however, most studies have employed an exposure time of 3–5 min. Ma et al. proved that an exposure time of 5 min to 98% sulphuric acid yielded optimal surface topography [49]. Cheng et al. demonstrated that a 3 min sulphonation decreased the contact angle and increased pre-osteoblastic activity [51]. On the other hand, Wang et al. found that a short exposure time of 30 s was optimal for decreasing the contact angle of PEEK; however, the longest time of exposure in the study was only 90 s [50]. If an additive coating will be applied after sulphonation, the time of exposure is determined by the other treatments used in the combination, as well as the nature of the coating. The time of exposure is a critical factor as the chemical composition of PEEK, which imparts superior mechanical properties to PEEK, gets altered as a function of time.

There is a statistically significant influence of sulphonation on the contact angle of PEEK. This phenomenon makes sulphonation acceptable as a pre-treatment before the application of a surface coating on PEEK. Furthermore, sulphonation has been extensively used in combination with plasma treatment for activation of the PEEK surface to receive organic and inorganic coatings and continues to be the most studied chemical treatment for the PEEK surface.

Phosphonation is the introduction of a phosphate group on the surface of a biomaterial. Various methods, such as diazonium chemistry and polymerization of Vinyl phosphonic acid, have been used to graft the functional group on the surface of PEEK, which has increased cell adhesion, spreading, proliferation, and differentiation in vitro and the bone–implant contact ratio in vivo [66,67,68], as shown in Table 5. It serves as an optimal surface treatment, but the compatibility of phosphonation with other treatments will have to be assessed.

Silanization is the introduction of a silane group to an object or surface. Silanization is utilized to improve the surface characteristics of materials like glass and metal oxides. It has been proven to increase the cell adhesion, spreading, proliferation, and differentiation of pre-osteoblasts in vitro, but in vivo studies confirming the same are not available.

Hydroxyapatite (HA) is the main inorganic component of the human bone; hence, it is intuitive to incorporate HA on the surface of PEEK to increase its bioactivity. HA has regularly been employed as a surface treatment to increase the bioactivity of metallic implants. However, the temperature required to incorporate HA is higher than the temperature range at which PEEK is chemically stable. Hence, in most studies, an intermediate layer of Titanium or Yttria Stabilized Zirconia (YSZ) was used to shield PEEK from thermal insult [70,71,72] (Figure 3). The thickness of the intermediate layer has been found to influence the coating’s bond strength to PEEK. [72] HA coating is thermally treated to transform it into a crystalline state from an amorphous bioinert state. This finding is consistent with the fact that HA found in the human bone occurs in a crystalline state. In terms of bioactivity and bone strength to PEEK, heat-treated crystalline HA outperformed untreated amorphous HA [70,71,72,73] (Table 6).

Titanium is the most widely used implant biomaterial due to its biocompatibility and osseointegration potential. The phenomenon of osseointegration was also accidentally discovered using titanium when titanium chambers that were used for studying the circulation of a healing fibula in a rabbit could not be removed due to their fusion with the bone [74]. A stable layer of titanium dioxide is formed on the surface of titanium on exposure to air [75,76]. This oxide layer has a high dielectric constant, which leads to the adsorption of proteins from blood on the surface, which is the first step in the cascade of events leading to osseointegration. Therefore, a coating of titanium or titanium oxide on the surface of PEEK would give the implant the favorable mechanical properties of PEEK and the higher bond strength of titanium with bone. In vitro studies have shown an increase in adhesion, proliferation, and differentiation of pre-osteoblasts in reaction to a titanium coating. In vivo studies have also inferred that the coating increases osseointegration and bond strength with bone (Table 7). 

Anti-microbial coatings like gentamycin and selenium have been used in vitro [83,84] as well as in vivo [83] in combination with a carrier agent. These coatings have also been shown to increase the bioactivity of PEEK in addition to its antimicrobial activity against microbes, such as S. aureus and Pseudomonas aeruginosa (P. aeruginosa), as shown in Table 8. However, the sustainability of the release of these agents will have to be titrated against the complexity of the surface treatments to determine their feasibility. Additional studies quantifying antimicrobial action as a function of time are required to establish the durability of these coatings in an in vivo environment.

Anti-inflammatory agents such as dexamethasone have been used to combat acute and chronic inflammatory responses of the body to noxious stimuli. Combinations of dexamethasone with other anti-inflammatory agents like interleukin-6 (IL-6) or metal-organic frameworks like Zn-Mg-MOF-74 have been proven to increase the anti-inflammatory response and antimicrobial activity of PEEK, respectively [86,87] (Table 9). Dexamethasone can be used as an implant coating in cases where the prognosis is compromised due to decreased local host immunity to infections, as supported by the current evidence.

A coating of polymers like 2-methacryloyloxyethyl phosphorylcholine (MPC) on PEEK surfaces has been studied and shown to decrease the contact angle of PEEK, increase its wettability, and facilitate osseointegration [88] (Table 9). However, in vivo demonstration of the increase in hydrophilicity has not been documented.

Composites of PEEK with various metals, oxides, inorganic fibers, and polymers have been used for improving the clinical performance of individual constituent biomaterials. The selection of material to be used with PEEK and the method of fabrication depend on the intended use of the implant. However, the main purpose of combining PEEK with other biomaterials is to improve the mechanical properties, with the improved surface characteristics being a by-product of the combination. Moreover, most composites of PEEK require an additional surface treatment for osseointegration. An exception in the following studies is a composite of HA and PEEK that did not require additional surface treatment and increased the adhesion, proliferation, and differentiation of pre-osteoblasts (Table 10), though in vivo studies are missing to substantiate the same. Most composites of PEEK are carbon-fiber reinforced PEEK (CFR PEEK) composites, which always require additional additive treatments for osseointegration.