**2. Bone graft substitutes as intervertebral spacers in ACDF**

Structural bone allografts have been used successfully in a broad range of clinical applications including ACDF procedures [11–13]. Although lacking direct osteogenic potential, structural allografts have similar osteoconductive properties to autograft while avoiding complications such as donor site morbidity [14]. Furthermore, studies have shown similar clinical outcomes when comparing the use of allograft to autograft in ACDF procedures [15, 16]. Other commonly used implants include interbody cages made of various materials, including metals, ceramics, and polymers. Metal implants have been widely used as spinal cages for ACDF procedures. In particular, titanium implants offer mechanical strength, maintenance of vertebral disc height, and are available in various forms including mesh and box implants [4]. However, there are concerns regarding the use of titanium implants due to their mismatched mechanical properties compared to native bone. The difference in elastic modulus between bone and titanium can cause stress shielding, weakening the surrounding bone and increasing risk of peri-prosthetic fractures [17]. Bioactive ceramics serve as an attractive alternative due to their demonstrated biocompatibility, osteoconductive potential, and availability [9]. Despite these advantages, varying porosity of ceramics can lead to brittleness, thus making them less ideal implants for load-bearing applications [18]. Finally, various polymers are used in biomedical applications due to their biocompatibility, chemical and mechanical stability, and wide ranging compositions. However, some polymers are not ideal for orthopedic implants due to their malleable nature and weak mechanical properties [19]. One polymer with desirable mechanical properties is polyetheretherketone (PEEK). Compared to autograft, PEEK cages offer shorter operating time and reduced donor site morbidity [4]. This chapter will focus on the properties of structural allograft bone compared to conventional PEEK implants due to their similar mechanical properties and common use. Pre-clinical studies examining mechanical properties, osteoconduction and osseointegration, and clinical fusion rates in the cervical spine will be presented.

### **2.1 Structural allograft**

Allograft bone, sourced from deceased human donors, is readily available and commonly used [20]. Allogenic bone grafts come in various forms, shapes, and

**65**

*Allograft Structural Interbody Spacers Compared to PEEK Cages in Cervical Fusion…*

sizes, based on clinical need, and can be either structural or non-structural. The bone is typically processed by physical and chemical means to ensure safety, biocompatibility and clinical suitability. Processing steps can include physical shaping and resizing of the graft for a specific clinical purpose (e.g., an intervertebral body spacer), disinfection and sterilization, and preservation to increase shelf life and

Allograft use in bone grafting procedures dates back many decades, as evidenced by a nineteenth century publication from the Scottish surgeon William Macewen [21, 22]. He successfully reconstructed an infected humerus of a 4 year-old child using allograft tibial segments obtained while treating effects of rickets. Early in the twentieth century, Fred Albee published a book on bone graft applications, laying the foundation for a surge in bone transplantation procedures that is ongoing [23]. Allograft bone is now widely used for spinal, orthopedic, dental, and trauma applications. Notably, allograft usage in the treatment of degenerative cervical disc disease has increased from 14% in 1999 to 59% in 2008 [24]. Of particular interest here, the use of structural allografts in ACDF procedures dates back as early as 1958. Cloward described the use of frozen allograft bone in 46 patients undergoing ACDF [3]. A cylindrical iliac dowel, commonly known as the Cloward dowel, was implanted into the empty interbody space. Forty-four patients demonstrated complete interbody fusion at 3–4 months post-operative. Numerous studies have since been published discussing the use of various structural allografts in ACDF procedures [18]. Structural allografts continue to be used as interbody spacers due to their ability to support mechanical loads and resist failure. Such structural allografts are comprised of either cortical, cancellous or a combination of both cortical and cancellous bone. Cortical bone is more rigid and provides greater structural support, while cancellous bone confers less mechanical strength, but is more porous, providing an osteoconductive scaffold for neovascularization and osseointegration. Infection due to allograft transplantation remains a risk, albeit rare. A report released by the Centers for Disease Control and Prevention (CDC) in 2005 estimated an overall allograft-associated infection rate of 0.0004%, emphasizing the unlikely event of allograft-associated disease transmission [25]. This number was developed before additional advanced tissue processing methods, including terminal sterilization, were implemented by many tissue providers. Organizations, such as the American Association of Tissue Banks (AATB) and the Food and Drug Administration (FDA), maintain standards for tissue banking, including donor acceptance criteria, tissue procurement and processing methods, and allograft storage [26, 27]. Additionally, FDA published the Current Good Tissue Practice (CGTP) Final Rule, effective in 2005, setting requirements aimed at "preventing the introduction, transmission and spread of communicable diseases" [28]. AATB and FDA guidelines ensure that human allograft tissues are both clinically suitable and safe. Through the combination of rigorous donor screening and tissue processing, risk of disease transmission is virtually eliminated.

*DOI: http://dx.doi.org/10.5772/intechopen.88091*

**2.2 Synthetics: polyetheretherketone (PEEK) cages**

those forms of PEEK with increased mechanical strength [30].

Polyetheretherketone (PEEK) is a non-absorbable, semicrystalline polymer processed through a variety of techniques including extrusion, or injection and compression molding [29, 30]. Chemically, PEEK is made up of an aromatic backbone, interconnected by ketone and ether functional groups [30]. The chemical structure of PEEK gives it distinct qualities such as: stability at high temperatures, resistance to chemical and radiation damage, strength and stiffness. PEEK is available in several configurations including neat (unfilled) and carbon-reinforced PEEK (CRPEEK). The addition of composite fillers, such as carbon fiber, provides

simplify storage.

#### *Allograft Structural Interbody Spacers Compared to PEEK Cages in Cervical Fusion… DOI: http://dx.doi.org/10.5772/intechopen.88091*

sizes, based on clinical need, and can be either structural or non-structural. The bone is typically processed by physical and chemical means to ensure safety, biocompatibility and clinical suitability. Processing steps can include physical shaping and resizing of the graft for a specific clinical purpose (e.g., an intervertebral body spacer), disinfection and sterilization, and preservation to increase shelf life and simplify storage.

Allograft use in bone grafting procedures dates back many decades, as evidenced by a nineteenth century publication from the Scottish surgeon William Macewen [21, 22]. He successfully reconstructed an infected humerus of a 4 year-old child using allograft tibial segments obtained while treating effects of rickets. Early in the twentieth century, Fred Albee published a book on bone graft applications, laying the foundation for a surge in bone transplantation procedures that is ongoing [23]. Allograft bone is now widely used for spinal, orthopedic, dental, and trauma applications. Notably, allograft usage in the treatment of degenerative cervical disc disease has increased from 14% in 1999 to 59% in 2008 [24]. Of particular interest here, the use of structural allografts in ACDF procedures dates back as early as 1958. Cloward described the use of frozen allograft bone in 46 patients undergoing ACDF [3]. A cylindrical iliac dowel, commonly known as the Cloward dowel, was implanted into the empty interbody space. Forty-four patients demonstrated complete interbody fusion at 3–4 months post-operative. Numerous studies have since been published discussing the use of various structural allografts in ACDF procedures [18]. Structural allografts continue to be used as interbody spacers due to their ability to support mechanical loads and resist failure. Such structural allografts are comprised of either cortical, cancellous or a combination of both cortical and cancellous bone. Cortical bone is more rigid and provides greater structural support, while cancellous bone confers less mechanical strength, but is more porous, providing an osteoconductive scaffold for neovascularization and osseointegration.

Infection due to allograft transplantation remains a risk, albeit rare. A report released by the Centers for Disease Control and Prevention (CDC) in 2005 estimated an overall allograft-associated infection rate of 0.0004%, emphasizing the unlikely event of allograft-associated disease transmission [25]. This number was developed before additional advanced tissue processing methods, including terminal sterilization, were implemented by many tissue providers. Organizations, such as the American Association of Tissue Banks (AATB) and the Food and Drug Administration (FDA), maintain standards for tissue banking, including donor acceptance criteria, tissue procurement and processing methods, and allograft storage [26, 27]. Additionally, FDA published the Current Good Tissue Practice (CGTP) Final Rule, effective in 2005, setting requirements aimed at "preventing the introduction, transmission and spread of communicable diseases" [28]. AATB and FDA guidelines ensure that human allograft tissues are both clinically suitable and safe. Through the combination of rigorous donor screening and tissue processing, risk of disease transmission is virtually eliminated.

#### **2.2 Synthetics: polyetheretherketone (PEEK) cages**

Polyetheretherketone (PEEK) is a non-absorbable, semicrystalline polymer processed through a variety of techniques including extrusion, or injection and compression molding [29, 30]. Chemically, PEEK is made up of an aromatic backbone, interconnected by ketone and ether functional groups [30]. The chemical structure of PEEK gives it distinct qualities such as: stability at high temperatures, resistance to chemical and radiation damage, strength and stiffness. PEEK is available in several configurations including neat (unfilled) and carbon-reinforced PEEK (CRPEEK). The addition of composite fillers, such as carbon fiber, provides those forms of PEEK with increased mechanical strength [30].

*Clinical Implementation of Bone Regeneration and Maintenance*

allografts and conventional PEEK cages is provided.

clinical fusion rates in the cervical spine will be presented.

Allograft bone, sourced from deceased human donors, is readily available and commonly used [20]. Allogenic bone grafts come in various forms, shapes, and

**2. Bone graft substitutes as intervertebral spacers in ACDF**

Structural bone allografts have been used successfully in a broad range of clinical applications including ACDF procedures [11–13]. Although lacking direct osteogenic potential, structural allografts have similar osteoconductive properties to autograft while avoiding complications such as donor site morbidity [14]. Furthermore, studies have shown similar clinical outcomes when comparing the use of allograft to autograft in ACDF procedures [15, 16]. Other commonly used implants include interbody cages made of various materials, including metals, ceramics, and polymers. Metal implants have been widely used as spinal cages for ACDF procedures. In particular, titanium implants offer mechanical strength, maintenance of vertebral disc height, and are available in various forms including mesh and box implants [4]. However, there are concerns regarding the use of titanium implants due to their mismatched mechanical properties compared to native bone. The difference in elastic modulus between bone and titanium can cause stress shielding, weakening the surrounding bone and increasing risk of peri-prosthetic fractures [17]. Bioactive ceramics serve as an attractive alternative due to their demonstrated biocompatibility, osteoconductive potential, and availability [9]. Despite these advantages, varying porosity of ceramics can lead to brittleness, thus making them less ideal implants for load-bearing applications [18]. Finally, various polymers are used in biomedical applications due to their biocompatibility, chemical and mechanical stability, and wide ranging compositions. However, some polymers are not ideal for orthopedic implants due to their malleable nature and weak mechanical properties [19]. One polymer with desirable mechanical properties is polyetheretherketone (PEEK). Compared to autograft, PEEK cages offer shorter operating time and reduced donor site morbidity [4]. This chapter will focus on the properties of structural allograft bone compared to conventional PEEK implants due to their similar mechanical properties and common use. Pre-clinical studies examining mechanical properties, osteoconduction and osseointegration, and

Robinson and Smith described this technique in 1955 [2]. Their approach involved implantation of a horseshoe-shaped bone graft harvested from iliac crest, followed by immobilization. Patients treated with this technique demonstrated promising clinical outcomes [2]. In 1958, Cloward described a similar technique, however, it included decompression of the neural structures and implantation of a bone dowel in the interbody space [3]. Regardless of the approach, a graft was used as a spacer to restore disc height, provide stability, and help promote bone fusion. Autograft, generally taken from the iliac crest, is often considered to be the gold standard for interbody fusion [4]. The use of autograft has led to high fusion rates and clinical success, although there are several disadvantages, such as extended operating time, donor site pain, limited supply, and variable quality depending upon the patient's health [5–8]. In an effort to avoid the complications seen with autografts, there has been a decades-old shift towards the use of alternative interbody spacers for treatment of degenerative disc disease [9, 10]. Two of the most common choices have been structural allograft bone or synthetic cages manufactured using polyetheretherketone (PEEK) [10]. Here, a comparison of the material properties and clinical performance of structural

**64**

**2.1 Structural allograft**

Developed in 1978, PEEK was initially commercialized for industrial applications such as aircraft and turbine blades due to its high chemical and mechanical resistance [29, 31]. However, in the late 1980s, it emerged as a potential biomaterial for surgical implantation and rapidly gained acceptance as a medical device. In the late 1990s, PEEK was introduced as a spinal cage implant and has also been used for other orthopedic and dental applications [19]. PEEK cages have become a popular choice due to inherent biocompatibility and favorable mechanical properties compared to traditional metal-based cages. PEEK has undergone numerous biocompatibility and cytotoxicity tests in accordance with both FDA and ISO 10993 standards. Morrison et al. evaluated the response from mouse fibroblasts and rat osteoblasts *in vitro* and found PEEK to display excellent biocompatibility [32]. Rivard et al. demonstrated that PEEK particles implanted in New Zealand white rabbits elicited no apparent necrosis or swelling, leading the authors to suggest that it is "harmless" to the spinal cord [33].

Compared to other synthetic implants such as titanium cages, PEEK has an elastic modulus similar to that of native bone, thus reducing the potential impact of stress shielding on the bone healing process [19, 34]. Another advantage of PEEK is radiolucency which allows for radiographic assessment of fusion [35]. Furthermore, due to its ability to resist radiation damage, PEEK is able to be sterilized by electron beam or gamma irradiation. Despite noted advantages, several concerns have been raised due to how PEEK's inert nature and low-surface energy might affect the body's biological response. Adsorption of water at the implant surface plays an important role in protein-surface interactions, and thus cell-surface interactions, which can determine the success of an implant [36]. The hydrophobic nature of PEEK can potentially limit cellular adhesion. This undesirable property has been recently reported in studies finding that conventional smooth PEEK implants have limited osteoconductive properties and limited bone fixation at the implant interface [29, 37]. For example, Phan et al. described a case in which a patient underwent anterior lumbar interbody fusion (ALIF) with a PEEK implant [38]. The authors found evidence of poor integration between the implant and surrounding bone causing the "halo-effect" on CT scans.

These issues have led to several modifications in an attempt to increase PEEK's bioactivity, including surface coating with synthetic osteoconductive material such as titanium, increasing surface roughness and porosity through chemical modifications, and incorporating bioactive particles [34, 39]. Despite these promising modifications, conventional PEEK is still commonly used and is the focus in this chapter.


**9. Mechanical properties of Al-Cu-Mn-Zr alloy**

#### **9.1 Hardness and tensile properties**

Similar to other age hardening Al-Cu alloys, primary strengthening mechanism for peak-aged Al-Cu-Mn-Zr alloys is Orowan looping where matrix dislocations bow around the coarse θ0 precipitates [52]. Apart from this, solid solution and grain boundary strengthening (by Hall–Petch mechanism) also contributes to the overall strength of the Al-Cu-Mn-Zr alloys. Analytical calculations, however, suggest that Orowan looping plus other strengthening mechanisms together are inadequate to account for experimentally measured yield strength of Al-Cu-Mn-Zr alloys [52]. This calls for the consideration of additional strengthening mechanisms e.g. stress-free transformation strain (SFTS). The formation of θ0 precipitates in the α-Al matrix is usually associated with transformation strain fields which can interact and potentially restricts dislocation movement, thereby increasing the alloy strength further.

**Figures 3c–d** indicates that the room temperature tensile properties for peak aged Al-Cu-Mn-Zr alloy is inferior compared to the conventional peak-aged Al-Cu alloy. For example, the ultimate tensile strength(UTS) of Al-5Cu alloy is �490 MPa whereas it is �300 MPa for Al-Cu-Mn-Zr alloy at room temperature [48]. In addition, the yield strength of the later alloy is nearly half compared to the base Al-Cu alloy. However, after prolonged thermal exposure at 300°C, the trend reverses; Al-Cu-Mn-Zr alloy possess nearly twice the UTS and yield strength compared to the base Al-Cu alloy. Similarly, Al-5Cu-Mg alloy possess higher hardness than Al-Cu-Mn-Zr alloys at room temperature (**Figure 7**). With increase in pre-conditioning temperatures (heat treatment for 200 hours), non- Al-Cu-Mn-Zr alloys show drastic decrease in hardness around 200°C, while Al-Cu-Mn-Zr alloys can sustain the room temperature hardness without any significant degradation until 350°C.

Bahl. et al. [52] further showed that the hardness and yield strength of peak-aged Al-Cu-Mn-Zr alloy drop marginally during post-aging thermal exposure but remained

**Figure 7.** *Room temperature hardness for various conventional Al-Cu and Al-Cu-Mn-Zr alloys as a function of pre-conditioning temperatures [48].*

almost constant during prolonged thermal treatment up to 5000 hours. This accounts for a stable microstructure with almost constant precipitate volume fraction, thickness, diameter, aspect ratio, equivalent diameter, number density and interprecipitate spacing for Al-Cu-Mn-Zr alloys on extended thermal exposure. The ductility of Al-Cu-Mn-Zr alloys are further influenced from Cu content although it does not vary the yield strength and UTS much. For example, increasing the Cu content from 6 wt% to 9 wt% causes the fracture strain to reduce by 50% primarily due to the increased amount of brittle intermetallics at α-Al matrix grain boundaries [80].

Important to note that no comprehensive study is yet to report the results pertaining to full-scale tensile testing, especially the strain hardening response as well as the fracture characteristics of Al-Cu-Mn-Zr alloys whether at room or elevated temperatures. The earliest available work of Shyam et al. [48] showed certain true stress–strain curves for Al-Cu-Mn-Zr alloy from tensile tests carried out at room temperature and 300°C in comparison to regular Al-Cu alloy (**Figure 3**). The purpose of the tensile tests was however, to establish the superiority for the former alloy at elevated temperature. Important to note that the alloys (Al-Cu and Al-Cu-Mn-Zr alloys) were used in peak-aged condition for room temperature tensile tests and after pre-conditioning at 300°C for 200 hours for elevated temperature tests.

The true stress–strain curves from room temperature tensile tests suggest that peak-aged Al-Cu-Mn-Zr alloy possesses marginally higher strain hardening rate compared to the conventional Al-5Cu-Mg alloy at least in the initial part of the plastic regime. The hardening rates although do not vary much at the later part (below UTS) representing almost similar slopes for both alloys. During 300°C tensile tests, both Al-Cu-Mn-Zr and Al-5Cu-Mg alloys exhibit substantial strain softening, however at significantly differing rates; the rate of softening is greater for Al-Cu-Mn Zr alloy compared to the conventional Al-Cu-Mg alloy. The ductility for the former alloy is also always higher than the later alloy irrespective of the test temperature. The strain hardening response for precipitate hardened systems at room temperature is generally attributed to the isotropic hardening of α-Al matrix plus kinematic hardening due to dislocation pile up at the precipitate locations from continued Orowan looping [81–83]. The strain softening at elevated temperature can possibly be attributed to dynamic recovery of piled-up dislocations which reduces dislocation density at precipitate cites and increases ductility by delaying the final fracture.

*New-Age Al-Cu-Mn-Zr (ACMZ) Alloy for High Temperature-High Strength Applications… DOI: http://dx.doi.org/10.5772/intechopen.104533*

### **9.2 Creep response**

The excellent high temperature stability of Al-Cu-Mn-Zr alloys enhances their creep properties as well. Miligan et al. [84] conducted creep tests under different stress levels for various Al-Cu-Mn-Zr alloys with varying grain sizes at 300°C and compared their creep resistance with base Al-Cu alloy as well as Al-Sc alloy which is known for its excellent creep resistance. **Figure 8** represents the steady state creep strain rate as a function of applied stress for these alloys. At low stress level, stress exponents for Al-Cu-Mn-Zr alloys are close to unity signifying for diffusional creep being the dominant mechanism. On the other hand, dislocation creep is the mechanism for conventional Al-Cu alloy as identified from a higher stress exponent. The dislocation movement though α-Al grain interiors is difficult at low stress levels for Al-Cu-Mn-Zr alloys due to the enhanced thermal stability of θ0 precipitates; rather grain boundary diffusion dominates at high temperature making diffusional Coble creep as the rate controlling mechanism. At higher stress levels however, the controlling mechanism switches to dislocation creep even for Al-Cu-Mn-Zr alloys since the grain boundary precipitates effectively slow down the movement of vacancies. This in turn restricts grain boundary diffusion as well as grain boundary sliding.

#### **9.3 High temperature deformation response**

One of the prime motivations for the development of Al-Cu-Mn-Zr alloy is to replace conventional cast Aluminum alloys (e.g. Al-Si-Cu based 319 alloy) for making light weight components in automotive engines [48, 85]. The Al-Cu-Ni based RR350 alloy with 0.2 wt% Mn and 0.17 wt% Zr, which can be considered as a variant of Al-Cu-Mn-Zr alloys, is also used as light weight and high temperature resistant alloys for high end automobile engine applications over the years [86]. Shower et al. [87] has compared the effect of microstructural stability on the high temperature deformation response of RR350 alloy vis-à-vis 319 alloy in as-cast

#### **Figure 8.**

*Creep curves showing the steady state creep strain rate as a function of applied stress for various Al-Cu-Mn-Zr alloys (RR350, Al-7Cu SG and Al-7Cu LG where SG and LG refers to small and large grains, respectively) plus base Al-Cu and Al-Sc alloys [84].*

**Figure 9.**

*(a) Comparison of flow stress variations with test temperatures for 319 and RR350 alloys at different strain rates, and (b) post-compression (at 300°C and 1 s*�*1 strain rate) SEM micrograph of RR350 alloy showing shear band formation and bending of θ*0 *precipitates within α-Al grains having <100> direction nearly parallel to the compression axis [87].*

condition by conducting isothermal hot compression tests at different temperature-true strain rate combinations. At all strain rates, compressive flow stress of 319 alloy is greater than that for RR350 alloy up to 200°C (**Figure 9a**). However, within 250–300°C, RR350 alloy possesses higher flow stress which can be attributed to the stability of strengthening θ0 precipitates. In this temperature range, 319 alloy losses its flow stress by 40%. At lower strain rates (e.g. 10�4 s �1 & 10�3 s �1 ), primary deformation mechanism for both alloys is strain hardening at room temperature, which changes to dynamic recovery and cross slip of dislocation at 250°C. Afterwards, dynamic recrystallization becomes predominant at 300°C while grain boundary sliding is the primary deformation mechanism at 350°C. In addition, RR350 alloy shows formation of shear bands as well as bending of θ0 precipitates within α-Al grains having <100> direction nearly parallel to the compression axis in the microstructure of specimens deformed at 300°C (**Figure 9b)**.

### **10. Fatigue response**

The excellent high temperature stability of Al-Cu-Mn-Zr alloys also make them a prime candidate for fracture critical engineering applications where fatigue properties are crucial consideration. Bahl et al. [88] studied the effect of Cu concentration on the high temperature (250°C) low cycle fatigue (LCF) properties of Al-Cu-Mn-Zr alloys that led to a correlation between LCF life and monotonic tensile fracture strain. At low strain amplitude (0.1%), Al-Cu-Mn-Zr alloys with either 6 wt% or 9 wt% of Cu do not undergo failure even after 105 number of cycles. However, at higher strain amplitudes (0.2% and 0.3%), the alloys fail within these many cycles of testing. This suggests that the fatigue life of Al-Cu-Mn-Zr alloys decreases with increasing strain amplitude.

For the peak-aged Al-Cu-Mn-Zr alloys with varying Cu content that underwent a further thermal exposure at 250°C for 100 hours, initiation of fatigue cracks almost always occur from the surface pores rather than from coarse grain boundary precipitates [80]. The fracture surfaces correspondingly do not contain much of the traces of intermetallic precipitates. Finite element modeling (FEM) also indicates that stress concentration at the pores are higher compared to that at the grain

#### *New-Age Al-Cu-Mn-Zr (ACMZ) Alloy for High Temperature-High Strength Applications… DOI: http://dx.doi.org/10.5772/intechopen.104533*

boundary precipitates. The low strain amplitude in the fatigue testing possibly led to the pore assisted crack initiation since otherwise the cracking from grain boundary precipitates would require higher stress concentration and their decohesion from the matrix which is only possible at larger strains [88].

Furthermore, since the variation in Cu content only affects the volume fraction of grain boundary intermetallic precipitates, it does not influence the cracking and in turn, low cycle fatigue behavior of Al-Cu-Mn-Zr alloys [80]. The thermal stability of θ0 precipitates also does not influence the fatigue property of these alloys since both crack initiation and propagation occur at a larger microstructural scale (from surface pores). It therefore appears that controlling the casting defects (predominantly shrinkage pores) is the most crucial factor to enhance the LCF life for Al-Cu-Mn-Zr alloys. Overall, these alloys exhibited moderate to excellent high temperature low cycle fatigue life making them suitable for components meant for elevated temperature applications.