Wear Particles Affect Implant Success, Failure

Wear debris creates concern about longevity of implants;

FDA has strict requirements.

Dr. Janet Cotton and Simon Demnitz

A range of engineering materials currently are used for orthopedic devices: cobalt chromium alloys; titanium alloys; ceramics such as alumina and zirconia; polymers such as PEEK and UHMWPE; and elastomers such as silicone, polyurethane, etc.

Implant design and materials choices can restrict the concentration of particles that develop during the life cycle of an implant; however, some wear particles are unavoidable. Photo courtesy of Janet Cotton.

These materials are considered to be biocompatible, which means they can coexist with living tissue. Some implants made from these materials slide against each other during the normal operation of the device. Examples include artificial hips, knees, and, more recently, total disc replacement, posterior dynamic fixators and facet joint replacements.

As a consequence of the sliding action of the joint replacement devices, wear particles form in the joint space. Implant, design and materials selection can limit the concentration and size of the particles that develop during the expected life cycle of the implant, but essentially it is unavoidable. It is the presence of the wear particles, at certain concentrations and specific size ranges, that largely contributes to osteolysis (bone cell death) through various cell responses in the body. The formation of wear debris undoubtedly has created considerable concern about the long-term longevity of implants. For this reason, the U.S. Food and Drug Administration requires manufacturers to show the wear particle size, shape distribution and concentration development during biomechanical testing. They must demonstrate that the particles produced are outside of the bioactive size range and also are of low concentration.<sup>1

Orthopedic Device Materials</sup>
Historically, titanium and titanium alloys have been selected for large joint implant materials primarily
because these materials have excellent boney in-growth properties. Titanium and its alloys, however, make poor wear couples when they are matched with ultra-high molecular weight polyethylene (UHMWPE), and in some cases, when the motion is against bone. The oxide layer, which gives titanium and its alloys excellent bone compatibility, is not tenacious and breaks off easily. The titanium oxide layer, which becomes dislodged, creates a hard third body in the joint space resulting in exponential wear. This is especially the case for historical products such as titanium alloy femoral heads, which wear against an UHMWPE acetabular cup. In such cases, a large volume of titanium and UHMWPE wear debris would be generated in the joint space leadingto osteolysis.

Additionally, bone screws manufactured using titanium alloys and subject to considerable micromotion against bone also resulted in wear debris because of the micromotion effects. In response, implant designers sought other metallic materials for articulating implants and abandoned the use of titanium and its alloys for those specific applications. Consequently, stainless steels were considered for the same applications but were quickly replaced by cobalt chromium alloys with far superior wear resistance against materials such as UHMWPE and bone. Cobalt chromium alloys also are excellent wear couple against themselves, and hence the development of metal-on-metal wear couples seen in total hip replacement and total disc replacement. Cobalt chromium alloys are not immune to the development of wear debris, and in addition to the size effects of the debris, the particles release ions that can have cytotoxic and genotoxic effects. This remains a concern to implant manufacturers. Therefore, the quest for more wear-resistant material continues. Examples include:

Ceramic Materials
The development of ceramic materials for orthopedic applications has been motivated by the need for more wear-resistant materials that produce less wear debris during articulating applications. The significant advantage of ceramic materials in articulating applications is that they produce low-volume fractions of wear debris. Historically, alumina has been used for acetabular cups in total hip replacement. In recent years, other ceramics such as various grades of stabilized zirconia have been used. Ceramics fell out of favor because they showed a tendency to fracture catastrophically in vivo. These types of failures were not a widespread problem but created caution in the industry around the use of ceramic materials. More recently, hot isostatically-pressed alumina has been widely used in the industry, and the most contemporary development is the use of zirconia-toughened alumina. Wear particles generated by ceramic materials are generally very fine and do not leach out ions that can have cytotoxic or genotoxic effects. Certainly, if fracture toughness issues can be overcome in the future, these materials will make attractive alternatives.

Polymeric Materials
UHMWPE widely has been used for acetabular cups in artificial hips, tibial trays in artificial knees and meniscus core for total disc replacement. When this material wears against a hard counterface such as cobalt chromium or alumina, wear debris is generated. Although wear particles do not leach out ions, the particles produced from UHMWPE elicit cell responses that lead to osteolysis. This is because the particles generated are within the bioactive size range. For this reason, more wear-resistant polymers such as PEEK have been investigated for these applications.

Elastomeric Materials
Elastomeric materials such as silicone and polyurethane are used for spinal nucleus pulposus (the jelly-like substance in the middle of the spinal disc) replacement devices. These materials also have applications in total disc replacement. Traditionally, these materials have been used in finger joints and breast implants. These materials are not subjected to significant wear or articulations; however, failure is linked to localized thermal fatigue and environmental stress cracking. Both of these failure modes can result in the generation of debris, which also will result in a response ultimately leading to osteolysis.

It is not the biocompatibility of orthopedic materials that is the problem; it is the release of wear particles during the normal operation of the device that ultimately facilitates the failure of the implant. The nature of the wear particles, sizes and concentrations cause various physiological cell responses, which result in a cascade of cell reactions that lead to osteolysis. The primary effect is the size of the particles; particles within a specific size range have greater effects than particles that are out of this range.

How Osteolysis Develops

Wear particles are the debris released between two articulating parts of an orthopedic device.

The presence of wear debris invokes a cascade of cell responses that lead to the formation of osteoclasts (specialized cells responsible for breaking down bone tissue) and loosening of the implant. Further, the presence of debris also inhibits the formation of osteo-blasts (cells responsible for bone formation) and thus adversely affects osteointegration, the connection between living bone and an artificial implant.

Bone is constantly remodeled and is in a repetitive process of resorption and reformation. Both processes are controlled through cell-signaling substances, or cytokines. Osteoclasts, the bone cells responsible for breaking down bone tissue, are activated through the release of cytokines by cells called macrophages, as well as by fibroblast and osteoblast cells. Osteo-blast cells, which build up new bone material through maturation, transition into inactive osteocytes. Similarly, fibroblast cells are those that build up fibrous tissue. Macrophages are cells that phagocytose foreign bodies by engulfing them.

When macrophages encounter foreign bodies in the tissue surrounding implants, such as wear particles, they respond by phagocytosing and engulfing the particles in an attempt to destroy the particles. Since wear debris produced by orthopedic devices cannot be phagocytosed in this way, the process of phagocytosis becomes interrupted. When this happens, cytokines are released. These cytokines disrupt the natural bone-remodeling process, eventually leading to bone resorption. This article describes the influence of various particles on cytokine release. If this can be properly understood, the influence of wear debris on the natural remodeling of bone can thus be understood as well. Consequently, the success or failure of an implant can be predicted to some degree.

Mechanical factors also may contribute to osteolysis. Factors such as load mismatch or stress-shielding and the action of micromotion can lead to the release of cytokines and may result in eventual loosening of the prosthesis. Other mechanical factors also can lead to the development of wear debris through micromotion at the bone-implant interface, which can then result in cytokine release.

Physiological Responseto Wear Debris

During the normal functioning of the device, a concentration of wear debris migrates into the tissue adjacent to the bone, the periprosthetic tissue, and when it does so, macrophages already in the vicinity respond to the foreign particles. At this point, the macrophages release cytokines, which recruit further macrophages to the site. This causes further vascularization through the development of a fibrous membrane around the joint space, allowing blood flow to place macro-phages and cytokines to the area.

When the particle concentration is low, particles can be removed by the body’s lymphatic system through the release of leukocytes. If the particle concentration is too high to be removed by the lymphatic system, the macrophages in the vicinity attempt to engulf the wear particles by phagocytosis.

The purpose of phagocytosis is to remove the particle from the joint space and destroy it. The byproducts of such a process normally would be taken away from the joint space through the lymphatic system. If the foreign body cannot be destroyed, then the process of phagocytosis is disrupted. The disruption of the process causes expression of cytokines, and through a cascade of reactions, ultimately leads to osteolysis. The reactions cause the activation of osteoclast cells, which lead to bone dissolution at the joint site. This is what causes the implant to loosen, which leads to the failure of the implant.²

The Influence of Various Particles on Osteolysis

In the case of polymeric particles such as UHMWPE and PEEK, it is the presence of these particles that cause phagocytosis as they release negligible levels of toxic ions.

The size range of particles released from metallic materials, which is considered to be acceptable in terms of contrast, can have a cytotoxic and genotoxic effect as a result of release of ions.

Metallic materials such as cobalt chromium alloys produce fine debris, which has less of a size effect than UHMWPE particles for example, but the particles release chromium and cobalt ions. In certain valency states, chromium can be genotoxic (causing DNA damage) and cytotoxic (toxic to cells). Soluble metal corrosion products and particulate metallic debris may promote both local and systematic exposure since they are easily circulated around the body. These soluble elements have been found in the liver, spleen and para-aortic lymph nodes.³

To a lesser extent, cobalt chromium alloys and stainless steels also form a passive layer spontaneously, and for this reason, are second to titanium alloys in their potential cyctoxicty and genotoxicity effect. Ceramics are generally biocompatible, and particles have limited cytotoxic effects and foreign body inflammatory response.

Elastomeric particles also have been shown to have toxic effects, Silastic, a silicone polymer used in hand joint replacements and increasingly in spinal intervention products, has been shown to produce wear debris of the order of 10-100 m in particle size when used for finger joint replacements.

The accumulation of these particles has been found to promote a significant foreign body reaction ranging from the presence of macrophages and giant cells and may cause silicone synovitis (inflammation of the synovial membrane). Polyurethane also has been investigated as an acetabular cup material for total hip replacements and shows good wear properties both in vivo⁴ and in laboratory studies.⁵

Wear Particle Analysis

Wear particle analysis is conducted during biomechanical testing of a device. The device is placed in the tester within a reservoir of fluid to simulate the lubrication conditions of the human body when the device is in vivo. This fluid is either saline or bovine serum, and the tests are usually run at 37 degrees Celcius up to 10 million wear cycles. usually after each million wear cycles, a sample of the test fluid is taken for wear particle analysis. The volume of the fluid taken is approximately 10 ml.

If the fluid is bovine serum, the particles must be digested out of the serum by means of an acid treatment or an enzyme treatment. The type of treatment depends on the wear particle material; acid treatments are used for ceramic and UHMWPE wear particles, whereas enzymatic treatments are used for metallic and elastomeric particles.

Once the particles have been isolated by means of an enzyme or acid treatment, the remaining fluid with the suspended wear particles is sequentially filtered through four microscopic filters. First, it is filtered through a 10 µm filter, then a 1 µm, then a 0.1 µm filter and finally a 0.015 µm filter.

These filters are imaged in scanning electron microscopes; the fine filters imaged with field emission gun SEMs in order to resolve very fine particles on the nanometer size range. The images captured from each filter are processed so that the graphical information is captured electronically. This is processed in order to generate particle parameter histograms.

Replacement Combinations

The levels of wear debris must be reduced for implants to show longer life cycles in vivo. Wear debris generation is a concern for large joint replacement, finger joint replacement and, more recently, spine arthroplasty devices. The traditional metal-on-poly combinations have been replaced by metal-on-metal combinations in an attempt to reduce wear particle concentrations that ultimately develop over time. In spite of this, the concern about metallic wear debris and possible long-term systemic effects of ion release from the particles cannot be ignored. Consequently, other materials are being considered, such as ceramics and various coatings on metallic substrates for joint replacement.

References

1. Kondrashov, D.G., Hannibal, M., Hsu, K., Zucherman, J., Orthopaedic Surgery, “US Musculoskeletal Review 2006,” 58-60; www.touchbriefings. com/pdf/1857/kondrashov.pdf.

2. Athanasou N.A. “The Pathology of Joint Replacement. Current Diagnostic Pathology.” (2002) 8, 26-32.

3. Wang J.Y., Wickland B.H., Gustilo R.B., Tsukayama D.T. “Titanium, Chromium and Cobalt Ions Modulate the Release of Bone-Associated Cytokines by Human Monocytes/ Macro-phages In Vitro.” Biomaterials. (1996) 17, 2,233-2,240.

4. Imran Khan, Nigel Smith, Eric Jones, Dudley S. Finch, Ruth Elizabeth Cameron; “Analysis and Evaluation of a Biomedical Polycarbonate Urethane Tested in an in vitro Study and an Ovine Arthroplasty Model; Biomaterials” 26 (2005), 633–643.

5. Christian J. Schwartz, Shyam Bahadur; “Development and Testing of a Novel Joint Wear Simulator and Investigation of the Viability of an Elastomeric Polyurethane for Total-Joint Arthroplasty Devices,” Wear, 262 (2007), 331–339.

Janet Cotton, director of 6° of Freedom, completed her undergraduate studies at the University of Cape Town in metallurgical engineering in 1995 and started her Ph.D. in 1996. Her Ph.D. focused on the development of a cast Cromanite alloy for Columbus Stainless, specifically on microstructure-property relationships of a Cromanite base composition with additions of precipitate (fine particles that harden the steel) forming elements. Cotton finished her Ph.D. in 2000 and worked for two more years at UCT as a post-doctoral fellow. Cotton is now the director of One Eighty (Pty) Ltd., a sister company to 6° of Freedom, and over the last few years has completed more than 200 projects for the manufacturing industry in South Africa, including research and development work, failure investigation or forensic engineering and general problem solving. The primary business of 6° of Freedom is to complete wear particle analysis for implant manufacturers in accordance with ISO and ASTM standards. 6° of Freedom has developed unique enzymatic digestion procedures for the processing of metallic and elastomeric debris in bovine serum. Addition-ally, 6° of Freedom has the capacity to analyze nano-sized particles by means of a high-resolution field emission gun scanning electron microscope. Some of the clients of 6° of Freedom include Medtronic Sofamor Danek, Abbott Laboratories, Synthes Spine, Blackstone Medical, DePuy Orthopaedics and Aesculap.

Simon Demnitz studied mechanical engineering at the University of Cape Town and completed his BSc degree in 2003. The following year, he undertook his MSc with the Sasol Advanced Fuels Laboratory at UCT. His area of research involved the development of an experimental app-roach designed to test a newly developed fuel auto-ignition model, based on data acquired from literature and chemical kinetics simulations. The model was applied to the physical conditions in a motored engine under autoignition conditions in order to investigate the feasibility of its numerically determined underlying parameters. He graduated in 2007 and currently is involved in research work with Cotton in the field of orthopedic implant materials.