**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.
