2.2.1 Introduction

Millions of people are affected worldwide due to inflammatory and deteriorating problems pertaining to knee and hip arthroplasty. This reports for more than 50% of all chronic illness in adults over 55 years of age in developed countries and will likely increase in the next 10 years [1]. Orthopedic implants are thus employed to solve problems pertaining to repair and replacement of cartilage, bones, tendons, and ligaments. In maintenance of longevity and efficiency of implants, the right selection of biomaterial plays a crucial factor. Additionally, installing an implant within the highly corrosive body environment can result in toxic reactions, and hence, optimization of the biomaterial contributes to sustaining optimal function, while decreasing any negative tissue response. In knee and hip implants, the biomaterials aid in maximizing fatigue strength and wear resistance and alongside, reducing deterioration of implants due to corrosion [2, 3]. Pioneer scientists and surgeons therefore formulated implants with substances that not only were accessible but also possessed a thriving record within the surgical, aerospace, chemical, and mechanical industry [4, 5]. Biomaterials were therefore distributed into three generations where biomaterials were conceptually grouped into first generation based on its highly inert properties to decreased corrosiveness and product release such as ions after surgery. The second generation was categorized depending on the biodegradable and bioactive attributes and third generation materials were formulated to produce highly specialized biological responses [6].

During the late 1800s, knee and hip arthroplasty was first conducted by Gluck using femoral implants formed of ivory [7]. In the late 1950s, Walldius utilized acrylate and metallic spacers for hinged prosthesis, which was then later substituted by Charnley’s multiple rotation axis hip replacement model due to post‐surgery cases of inflammation and implant loosening issues. Then, in the late 1960s, stainless steel and polyethylene were employed in femoral stem and head, respectively, whereas polymethylmethacrylate (PMMA) was used for implant fixation [8–10]. Charnley’s model displayed >90% survival success rate in older patients (≥60 years) and, thus, established an extended record [11]. In the 1970s, the contemporary theory of low‐friction hip replacement was brought by Gunston who utilized polyethylene for the purpose [12–14]. With several theoretical and design changes employed in the surgical procedure of knee arthroplasty, Freeman and Swanson eliminated cruciate ligaments to improve stability in patients with osteoarthritis. As you can see, knee and hip arthroplasty has had a history of more than 40 years of critical developments and failures pertaining to surgical techniques (hinged, duo‐condylar, and total condylar) as well as selection of biomaterials in implant designing [15, 16].

This progression suggests that the current advancements in research are highly allocated to biomaterials, which based on their properties, can be classified as first or second generation. Moreover, advancements brought by newer generations do not certainly substitute the utilization of the former ones. Polymers created from the covalent linkage of monomers of smaller molecular weight or compounds with larger molecular weight are one such example due to their wide range of applications in hip and knee arthroplasty for more than 50 years. These include PMMA, which is utilized as bone cement since late 1950s, and ultra‐high molecular weight polyethylene (UHMWPE), which is used in implant shells since early the 1960s [5, 17, 18]. In recent studies pertaining to implant stiffness mimicking the bones, advancements of isoelastic hip stems have preceded the initiation of polyetheretherketone (PEEK) within the polyaromatic category of polymers. Similarly, PMMA has been utilized in surgeries with the purpose of preserving the implants and functions as an intermediary layer in mechanical and micromotion transport to bone from the implant. With decreased use in bone fixation in hip arthroplasties, alternative implant fixation techniques have been founded, and PMMA continues to remain a safe option in total knee arthroplasty due to their greater efficiency than that of uncemented knee replacement methods [19, 20].

Currently, metal alloys like titanium (Ti) and cobalt–chromium (Co–Cr) are used in hip and knee implants as they optimally stabilize the mechanical attributes of metal parts and provide improved resistivity to corrosion and flexibility than that of stainless steel. However, in terms of resistance to fatigue, stainless steel implants perform better than many other implants but remain prone to decreased biocompatibility [21]. Cast alloys, a subdivision of metal alloys, are typically utilized in production of implants due to their higher efficiency in generating net‐shaped components that are challenging to manufacture with machining techniques [22]. In addition to the use of different materials, coating and material treatment methods are also employed in elevating mechanical properties like wear and corrosion resistance. Several such techniques are plasma electrolytic oxidation, nano‐coatings, nitriding via glow discharge, and ion implantation. Additionally, wear due to friction is a crucial factor for biological attributes of metals as they can stimulate inflammatory responses. Due to this, there is a rise in surface engineering methods and their implementation in implants formed of titanium and titanium alloys [23, 24]. To enhance osseointegration properties, porous coatings on non‐cemented metal (Ti and Co–Cr) implants are used and are shown to stimulate bone growth than that of cemented implants [25]. On the contrary, cemented implants perform better in the long run than non‐cemented components such as femoral cups in total hip arthroplasty [26]. Various such porous coating techniques on metals are described in further sections of this chapter.

Due to greater wear rates of metal–PE and metal–metal load‐bearing implants, ceramic implants serve as great alternatives in the replacement of knee and hip joints. Ceramics, similar to metals, are primarily applied in hip and knee replacements due to their outstanding wear resistance and strength. Ceramic crystals are considered as consisting of ions instead of atoms due to the fractional or complete ionic character within its bonds [5]. Several ceramics also contribute to surface properties and enrich bone attachment abilities. Different ceramics and coatings on ceramics display fluctuations in factors such as stiffness, tensile strength, wear resistance, and osteolysis due to debris and wear and, thus, remain superior to one another based on these attributes. Additionally, ceramic‐on‐ceramic bearings display exceptionally small wear rates as well as their inhibition of allergic responses and biocompatibility to ceramics are much better than that of metals and hence make an attractive alternative in joint arthroplasties. Alumina (Al₂O₃) was first presented around the 1970s in THA and then in partial knee arthroplasties (PKAs) yielding successful rates of implantation due to very small surface roughness which further provided superior friction and wear resistance characteristics [27]. The one limitation pertaining to its low tensile strength was shown to have been surmounted with thin diamond‐like carbon (DLC) coatings [28]. This prevented distortion of implants in cases of any tragic failures.

Zirconia is one such ceramic oxide which was used to induce bending strength around the mid‐1980s to substitute alumina. However, some studies have shown improved wear resistance in alumina components in hip replacement methods when compared to zirconia [29]. This brings forth an important remark on composites which allows properties of fracture resistance of zirconia in combination with biologic firmness of alumina. Furthermore, DLC and Titanium Nitride (TiN) can be employed in the form of thin coatings to enhance resistance to wear. The deposition procedure can be conducted through several coating methods like ion beam sputter deposition (IBSD), Chemical Vapor deposition (CVD), ion beam‐assisted deposition (IBAD), and Physical Vapor deposition (PVD) to induce resistance to corrosion offered by the hard layers of TiN.

Composite materials consist of constituents that are different chemically, wherein one of the two or more substances are polymers. Composites are frequently fabricated to optimize bulk or mechanical attributes like stiffness, resistance to fatigue, and strength [30]. Due to these properties, reinforced carbon fibers (CFRs) are typically utilized as prosthesis in athletes and patients with impaired limb joints [30, 31]. In the past few years, improvements have been made to enhance osseointegration using PEEK polymers. For this, PEEK is coated with HA or Ti to form permeable nets to promote the ingrowth of the bone [32, 33]. Additionally, nanocomposites such as the PMMA bone cement composed of HA nanofibers and magnesium phosphate (MgP) nanosheets also possess exceptional cytocompatibility and bioactivity and, hence, can serve as a prospective model for bone cements in knee and hip implants [34].

One of the most important considerations regarding implant surgeries is the complexities of antimicrobial infections, particularly infections in total knee replacements (TKRs) or the implantation pertaining to fixation of bones [35]. Due to prosthetic joint infections (PJIs), implantation surgeries have elevated to 2.18% from 2.05% and 1.99% for TKA and THA. The highest risk of infections post‐surgery was approximately 70% in the initial two years [36, 37]. With several ongoing research, antibiotic‐infused bone cements have significantly aided in treatment of TKA and THA. For this, antibiotic‐loaded bone cements have been impactful, especially in combination of gentamicin with preventive antibiotics such as vancomycin or cephalosporins to treat aggravated infections [38, 39]. Such antibiotic‐infused bone cements have been applied as spacers which consist of antibiotics in increased concentrations in contrast to that utilized for conventional implant fixation. For loading antibiotics, PMMA polymer and powders have been commonly used as gold standard as bone cement in orthopedic surgeries [39].

With an aim to enhance the quality and expectancy of life, next generation implants have gained a lot of momentum in the field of research and development. These implants essentially are medical devices or fabricated tissues that bear the capability to be a replacement for a lost part of the body. Such tissues can also aid in the formation of new bone tissues and components. Silver (Ag) and silver nanoparticles (AgNPs) have also gained a lot of interest, and the development of Ag in the form of nanotubes has been researched upon due to their potential in treating post‐surgical infections of orthopedic implants [40, 41]. Ag is a transition metal bearing distinct chemical and physical properties with well‐recognized antibacterial traits. Ag has also been utilized in the form of wound dressings to prevent PJIs and has been effective in THA and total knee arthoplasty (TKA) in the form of Aquacel Ag [42]. Another probable solution to decrease infection risk of the gene as well as the generation of bacterial biofilm includes implants coated with thin layers of silver. The primary use of Ag lies in external fixation pins employed for the purpose of joint stabilization. Several in vivo and in vitro research have shown effective reduction of microbial colonies and rates of infections after application of such external fixation pins coated with Ag [43].

2.2.2 Ultra‐High Molecular Weight Polyethylene (UHMWPE) and Polyethylene (PE)

To promote prolonged outcomes in TKA and THA, UHMWPE has played a primary role. In bulk form, UHMWPE is known for its biocompatibility as well as capabilities in comparison to several synthetic polymers. One such example is polytetrafluoroethylene (PTFE), in contrast to which UHMWPE shows better resistance to wear and bear increased toughness against fractures and thus indicates its massive utilization in joint arthroplasties [44]. Subsequently, it is extensively used as shell bearings in fractures of acetabulum in THA and as the tibial plateau interposition substance in TKA [45, 46]. Polymerization of monomers (ethane) into forms of increased molecular weight allows formation of polyethylene and be conducted via Ziegler’s catalytic method [5]. The extent of polymer cross‐linking, casting characteristics, resistance to wear, density, flexibility, and oxidization can be characterized by the four subtypes – linear low density (LLDPE), low density PE (LDPE), UHMWPE, and high‐density PE (HDPE). Resistance to deterioration and fitting mechanical properties contribute toward the biocompatibility aspect of PE. Regarding inflammatory responses, the amount of free wear debris and their proportions, volume, and rate are highly significant factors [47, 48]. While antioxidants can be utilized to slightly regulate the immune response in hosts, other factors such as the substance fatigue, factures, and removal of lamination especially in the fabrication of thinner implant parts highly cause mechanisms of wear. The designing disparity also leads to a difference in mechanism of wear in hip versus knee implants.

While ethylene oxide (EtO) was initially utilized to sterilize UHMWPE, deterioration of bone tissue due to failure in cross‐linking further promoted usage of peroxides in combination with vitamin E has shown reduced fatigue risk and higher wear resistance [49, 50]. Radiation sterilization of UHMWPE has shown favorable effects in reducing the rates of osteolysis and wear. While the most commonly used UHMWPE sterilization doses range from 20–40 kGy, the 85 kGy dosage (in irradiation) in combination with vitamin E has shown better results of oxidation and wear defiance than that of the conventional ones [5, 51]. In several cases, the conventional methods (gamma radiation) have shown weakening of mechanical attributes as well as deterioration of the material due to oxidation and free radical production. Through irradiation, conducted in an environment with vacuum or inert gas, there are still chances of removal of lamination due to oxidation in the long run [52]. In addition, irradiation results in highly cross‐linked polyethylene (HXLPE) have also been researched upon and display enhanced resistance to wear in dosages 55–100 kGy. As an advantage, this technique is just as cost‐effective as the traditional ones.

Properties such as the type of resin applied also influence the cause of loosening of implants and osteolysis. UHMWPE fits best since the resin bears a melt flow index of zero which suggests that the particles (diameter 100 μm) maintain their form and are prevented from flowing. Therefore, the slower melting procedure, although intricate, allows production of UHMWPE with enhanced toughness and resistance to wear, thereby leading to increased success rates of implants in TKR and THR. Therefore, as an involuted material, the mechanical attributes and tribological behavior of UHMWPE depend highly on cross‐linking, sterilization, and radiation methods. This includes not only the fabrication of implant parts but also capabilities in absorption of shock, forbearance to edge wear mechanisms, and negligible issues pertaining to alignment. In all, PE biomaterial categorized under first generation may show higher wear resistance but compromises on oxidation and fatigue defiance. Although PE under second generation improvises on these concerns, it has yet to undergo advancements [18, 53].

2.2.3 Polyetheretherketone (PEEK)

In developing advanced methods pertaining to tough plates in fixating fractures and isoelastic stems for THR, an era of materials comprised of multiple aromatic polymers emerged. During the late 1900s, PEEK and its composites with CFRs were implemented for total knee and hip arthroplasties in the form of bearing material to mimic natural properties of bones [54]. Regarding PEEK’s chemical structure, groups ether and ketone form linkage with the rings within the backbone, and this allows it to sustain in extremely elevated temperatures (>290°C). In addition, the material remains protected from any damage stimulated by radiation or chemicals and can be safely utilized alongside CFRs, highly robust metals, and even glass. The concept of introducing CFRs was brought forward during 1971 with UHMWPE, which showed excellent tribological results but demonstrated poor strain resistance. One such property of carbon‐reinforced polymers is the elastic modulus, wherein PEEK can be modified to simulate 110 and 18 GPa of Ti alloys and cortical portion of the bone, respectively. This is highly remarkable as on its own, the elastic modulus of PEEK (~4 GPa) is closer to the bone, yet not the same, and can thus be improved with implementation of CFR. Additionally, the elastic modulus and toughness of these carbon. PEEK composites rely on the length, arrangement, size, and percentage amount of the fibers utilized [55].

PEEK also remains inert to thermal and chemical damage due to resonance [56, 57]. Like UHMWPE, PEEK bears great defiance against electron beam, gamma radiation and irradiation. In terms of water absorption, PEEK performs poorly in surroundings containing increased fluids (>0.5 weight percent) in vivo and negatively affects its crystallinity, as shown in several studies [58–60]. Other such studies have shown biocompatibility of PEEK which however compromises osseointegration within the tissue environment. Also, while PEEK continues to remain biocompatible, a few studies (relating to new generation modifications) have shown its slight reaction within the tissue environment. HA composites have therefore been utilized to enhance surface properties of PEEK bone. PEEK coated with HA or Ti is also implemented to elevate the growth of bone inside the porous surface of implants [5, 61, 62]. HA‐coated PEEK exhibits increased roughness and a more hydrophilic surface allowing for increased osteoblast growth than that of uncoated PEEK (Figure 2.2.1; [62]). For this, PEEK is often plasma‐coated directly with hydroxyapatite (HA), or through double‐coating method using Ti before HA is applied by the thermal plasma spray method. The main purpose of this is to make certain of the bone and implant apposition in supplement to its resorption with HA.

With several biomaterials implemented in femoral stems for about five decades, PEEK remains the most effective in displaying compatibility in a biologic environment and yet remains easily accessible and fabricable. There are still several ongoing clinical studies testing the long‐term performance of PEEK. One such is the Epoch system, wherein Ti metal, PEEK resin, and Co–Cr alloys are utilized in the fabrication of outer, intermediate, and core layers, respectively. Hence, in the form of bearing material, PEEK remains a desirable target in THA and TKA [63].

2.2.4 Polymethylmethacrylate (PMMA)

PMMA, categorized as first‐generation biomaterials, are commonly used in the form of bone cement to fixate the implants with bone in TKA and THA. Like PEEK, these are also utilized as intermediate layers in implants to aid in mechanical load bearing and micromotion of implant–bone. PMMA in the early 1930s was patented under the name “Plexiglass” by Dr. Rohm. In 1938, the PMMA powdered mixture was first used to treat defects of crania in monkeys. Similar was utilized for dental fixtures and orthopedic stems by Kulzer and Degussa in the early 1940s [64, 65]. Due to several mechanical and compatibility failures, this plexiglass was improvised by Dr. Charnley, who renamed the latter as “bone cement” which remained a prominent means of anchoring prosthesis in most joint arthroplasties [55, 65].

Most PMMA bone cements are formulated with two parts, each of which are colored with pigments extracted from chlorophyll which enables the translucent PMMA to be clearly detectable to the human eye and therefore offers easier controllability. Alongside copolymers, PMMA powder when polymerized remains in the latter portion of the mixture which allows effortless regulation of physical characteristics of the bone cement. Besides, this makes it easier to adjust the radio‐opacifying agents (zirconium dioxide: ZrO₂ or barium sulfate: BaSO₄) as well as the initiator isomer (toluidine) to provide cleaner imaging results (Figure 2.2.2).

Additionally, PMMA may be loaded with antibiotics like vancomycin or gentamicin since the amalgamation of PMMA and preventive antibiotics like tobramycin and cephalosporins can reduce or eradicate the infections that are rooted deeply within the implants [35, 38]. One such study by Bistolfi et al. revealed that when vancomycin and gentamicin were both loaded with PMMA, the antibacterial resistance increased than that of PMMA spacers with only gentamicin [66]. Subsequently, when gentamicin‐loaded PMMA is blended commercially compared to the manually mixed gentamicin‐PMMA, the industrial one shows enhanced antibiotic release and relatively more inhibition to Staphylococcus aureus bacteria than that of the manual one over time (Figure 2.2.3). However, there is a need for more such studies on the mixing procedures to confirm the aforementioned.

Antibiotic‐loaded PMMA has also been utilized as spacers, which consist of antibiotics in increased concentrations than the ones utilized normally in fixating implants. Several studies have shown improvement in success rates (~95%) of the second phase revision surgery in treatment of microbial infection in total joint arthoplasty (TJA) [67]. Another study performed by Uchiyama et al. showed similar success rates, wherein 119 clinical trials of revision surgeries were conducted on patients to treat implant loosening due to infection [68]. For this, antibiotic‐loaded PMMA cement beads were utilized as spacers. This was then followed up after five years through radiographs to determine the prevention of infection. Regarding the rates of infection modulation, 95% success was observed.

The next component of the bone cement, the liquid part, consists of the monomer methyl methacrylate (MMA) along with a stabilizer compound (hydroquinone) to inhibit any monomeric units from curing amongst each other in the fluid and an accelerator substance (N,N‐dimethyl‐p‐toluidine) to enable polymerization as well as prevent any deposition of poisonous monomeric units of MMA in a different place other than that of the implant site. Due to their mechanical attributes such as the load bearing and relocating ability, the performance of implants depends highly on the PMMA bone cement. In relation to this, about 18 separate brands have implemented PMMA into manufacturing as bone cements for TJA and THA [65, 66]. They can be categorized as high, medium, and low viscose depending on the transition phases (curing of cement) as well as the mixing ratio of powder to liquid, temperature, and cement composition. The most moldable and movable of them all lie in the initial mixing phase with lowest viscosity, and the hardened one remains in the setting phase with increased viscosity and increased temperature than the former waiting and working phases. The PMMA thus performs best in sealing the void between bone implants. Also for prolonged time, when the viscosity is medium‐to‐high, as it reduces the risk of fractures and probable entrapment of blood [7, 69]. In the first generation, PMMA‐based bone cements were manually applied, but in the following generation, they were treated using cement guns or intermedulary plugs (IM) plugs.

In recent years, the most widely employed approach is that of the third generation, which is cement pressurization in the targeted bone, centrifugation, and application of the PMMA pre‐coat on the interface. This not only lessens the porosity but also sustains a long‐lasting durability of the implant–cement interface and instant anchorage with no need of biologic osseointegration [69, 70]. Then, the cement permeates into the spongy part of the bone and latches onto the tiny irregular forms of implant surface. A similar occurrence takes place when the cement shrinks throughout the curing process.

While PMMA bone cement remains useful in TJA, TKA, and other orthopedic applications, it may interfere with bone restoration and healing due to its inert as well as heat‐releasing characteristics and bears inadequate osseointegration. This exothermic trait of the PMMA can result in necrosis of the surrounding tissue over the course of the curing process. Additionally, the lack of primary stability can induce the development of the scar tissue capsule over implant to further form the synovial‐like interface membrane (SLIM). As a result, aseptic loosening of the implant occurs [5, 71]. Nevertheless, PMMA continues to be utilized as bone cement and indeed remains the most widely employed polymer cement.

Since numerous advancements in alternative techniques for fixating implants have been introduced and researched upon, the utilization of bone cement in THR has thus reduced. Regardless, PMMA‐based bone cements have been regularly utilized in TKR since the total knees fixated using this method perform functions superior compared to non‐cemented knees. Moreover, in many THR, the patients requiring cemented fixations are elderly with serious osteoporosis. The bone cement therefore enables swift remobilization post‐surgery. On the contrary, young adults and highly active patients bear an increased threat of implant loosening due to increased mobility.

2.2.5 Metal Implants