54.Berg-Sorensen, K & Flyvbjerg, H. (2004) Power spectrum analysis for optical tweezers. Review of Scientific Instruments 75, 594–612.

55.Odde, DJ & Renn, M.J. (2000) Laser-guided direct writing of living cells. Biotechnology and Bioengineering 67, 312– 318.

See also FIBER OPTICS IN MEDICINE; MICROSURGERY; NANOPARTICLES.

ORAL CONTRACEPTIVES. See CONTRACEPTIVE

DEVICES.

ORTHOPEDIC DEVICES, MATERIALS AND

DESIGN. See MATERIALS AND DESIGN FOR ORTHOPEDIC DEVICES.

ORTHOPEDIC DEVICES MATERIALS

AND DESIGN OF

AMIT BANDYOPADHYAY

SUSMITA BOSE

Washington State University

Pullman, Washington

INTRODUCTION

Musculoskeletal disorders are recognized as among the most significant human health problems that exist today, costing society an estimated $254 billion every year, and afflicting one out of seven Americans. Musculoskeletal disorders account for nearly 70 million physician office visits in the United States annually and an estimated 130 million total healthcare encounters including outpatient, hospital, and emergency room visits. In 1999, nearly 1 million people took time away from work to treat and recover from work-related musculoskeletal pain or impairment of function in the low back or upper extremities (1). There is still an ongoing debate on cause, nature and degrees of musculoskeletal disorders particularly related to work and how to reduce it. However, it is agreed unanimously that the number of individuals with musculoskeletal disorders will only increase over the coming years, as our population ages. According to the World Health Organization (WHO), these factors are called ‘‘work-related conditions’’, which may or may not be due to work exposures (1). Some of these factors include: (1) physical, organizational, and social aspects of work and the workplace, (2) physical and social aspects of life outside the workplace, including physical activities (e.g., household work, sports, exercise programs), economic incentives, and cultural values, and (3) the physical and psychological characteristics of the individual. The most important of the latter include age, gender, body mass index, personal habits including smoking, comorbidities, and probably some aspects of genetically determined predispositions

(1). Among the various options to treat musculoskeletal disorders, use of orthopedic devices is becoming a routine,

with the number of annual procedures approaching five million in the United States alone (2). Some of the common orthopedic devices include joint replacement devices for hip and knee and bone fixation devices such as pins, plates and screws for restoring lost structure and function.

Materials and design issues of orthopedic devices are ongoing challenges for scientists and engineers. Total hip replacement (THR) is a good example to understand some of these challenges. Total hip replacements are being used for almost past 60 years with a basic design concept that was first proposed by Charnley et al. (3). A typical lifetime for a hip replacement orthopedic device is between 10 and 15 years, which remained constant for the last five decades. From design point of view, a total hip prosthesis is composed of two components: the femoral component and the cup component. The femoral component is a metal stem, which is placed into the marrow cavity of the femoral bone, ending up with a neck section to be connected to the ball or head. The neck is attached to the head, a ball component that replaces the damaged femoral head. The implant can be in one piece where the ball and the stem are prefabricated and joined at the manufacturing facility, this is called a monobloc construction. It can also be in multiple pieces, called modular construction, which the surgeon put together during the time of the surgery based on patient needs, such as the size of the ball in the cavity. An acetabular component, a cup, is also implanted into the acetabulum, which is the natural hip socket, in the pelvic bone. The femoral component is typically made of metallic materials such as Ti or its alloys. The balls of the total prostheses are made either from metallic alloys or ceramic materials. The hip cups are typically made from UHMWPE (ultrahigh molecular weight polyethylene). Some part of the stem can be coated with porous metals or ceramics, which is called cementless implant, or used as uncoated in presence of bone cement, which is called cemented implants. Bone cements, which is primarily poly (methyl methacrylate) (PMMA) based, stabilizes the metallic stem in the femoral bone for cemented implants. However, for cementless implants, the porous coating helps in tissue bonding with the implants surface and this biological bonding helps implants to stabilize (Fig. 1).

Figure 1. An example of a modern cemented hip prosthesis design and various components.

188 ORTHOPEDIC DEVICES MATERIALS AND DESIGN OF

As it can be seen that THR by itself is a complex device that incorporates multiple materials and designs. However, all of these artificial materials mimic neither the composition nor the properties of natural bone. The inorganic part of natural bone consists of 70 wt%, consists of calcium phosphate. Moreover, patient pool is different in terms of their age, bone density, physiological environment, and postoperative activities. To complicate matters further, surgical procedure and total surgery time can also be different for various patients. Because of these complications it is difficult, if not impossible, to point out the exact reason(s) for the low in vivo lifetime for these implants, which remained constant for the past 50 years. However, it is commonly believed that stress shielding is one of the key factors for limiting the lifetime of these implants. Because a metal stem is introduced into the bone, which has a complex architecture including an outer dense surface or cortical bone and an inner porous surface or cancellous bone, during the total hip surgery, the load distribution within the body shifts and the load transfer between tissue and implant does not match with normal physiological system. Typically, more load will be carried by the metal implants due to their high stiffness which will cause excess tissue growth in the neck regions. At the same time, upper part of the femoral bone will carry significantly less load and become weaker, which will make it prone to premature fracture. Both of these factors contribute to the loosening of hip implant that reduces the implant lifetime. This is also called stress-shielding effect, in general, which means the loss of bone that occurs adjacent to a prosthesis when stress is diverted from the area. To reduce stress-shielding, an ideal hip implant needs to be designed in a way that it has similar stiffness as natural femoral bone. However, current biomedical industries mostly use materials for load bearing implants that are typically designed and developed for aerospace or automotive applications, instead of developing new materials tailored specifically for orthopedic devices needs. But the time has come when materials need to be designed for specific biomedical applications to solve long-standing problems like stress-shielding in THR. Though THR is used as an example to show the complexity of materials and design issues in orthopedic devices but THR is not alone. Most orthopedic devices suffer from complex materials and design challenges to satisfy their performance needs.

FACTORS INFLUENCING ORTHOPEDIC DEVICES

There are several factors that need to be considered to design an orthopedic device. From the materials point of view, usually mechanical property requirement, such as strength, toughness, fatigue degradation becomes the most important issues as long as the materials are nontoxic and biocompatible. However, as the body tissue interacts with the surface of the device during in vivo lifetime, surface chemistry becomes one of the most important aspects for orthopedic devices. Most complex device functions cannot be accomplished using only one material, and require applications of structures made of multimaterials. As a result, compatibility of multimaterials in design and man-

Figure 2. Materials and design parameters for orthopedic devices.

ufacture becomes another issue. Figure 2 summarizes various parameters that are important toward design and development of an orthopedic implants. Four main areas of orthopedic devices include materials issues, design issues, biocompatibility issues and patient specific information. All four of them are complex in nature and their interactions are even more difficult to appreciate. The following section offers some basic understanding of all of those issues.

MATERIALS ISSUES IN ORTHOPEDIC DEVICES

Selection of appropriate material is probably the most important issue in successful design and development of orthopedic devices. Among various materials related issues, (1) physical and chemical properties, (2) mechanical properties, (3) surface properties, and (4) in vivo degradation or corrosion behavior are some of the most important ones. In general, it is most widely accepted to use metallic materials for load bearing, and polymers and ceramic–polymer composites for nonload bearing applications. Some ceramic compositions and glasses are also used for nonload bearing coatings and defect filling applications. Development of biomaterials and materials processing for different orthopedic device applications is currently a very active research area (4–6) and new materials are constantly being developed to meet the current and future needs.

Physical and Chemical Properties

Physical properties include density, porosity, particle size, and surface area type of information. Composition or chemistry is probably the most important chemical property. It is important to realize that orthopedic devices cannot be built with materials that are carcinogenic. Nontoxic materials that do not leach harmful metal ions in vivo are ideal. Apart from dense structures, partially or completely porous materials are also used for orthopedic devices. If a porous material is used, then some of the properties, such as pore size, pore volume, and pore–pore interconnectivity

become important. Typically, for most porous materials, an optimum pore size between 100 and 500 mm are used in which cells can grow and stay healthy. Higher pore volume usually adds more space for cells to grow and naturally anchor the device. However, this also exposes higher surface area of the device material that can cause faster degradation or corrosion, which sometimes can be a concern depending on the materials used. For polymeric materials, chemistry, and structure are important because materials with the same chemistry, but different structure can show different in vivo response. This is particularly important for biodegradable polymers, such as poly lactic acids (PLA) and polyglycolic acids (PGA) and their copolymers. Trace element is another important factor in materials selection. Sometimes even a small amount of impurities can cause harmful effects in vivo (7). However, in calcium phosphate based ceramics, small addition of impurity elements actually proved to be beneficial for mechanical and biological response (8).

Mechanical Properties

Mechanical properties are important in selecting materials for orthopedic devices. Among various mechanical properties, uniaxial and multiaxial strength, elastic modulus, toughness, bending strength, wear resistance, fatigue resistance are some of the most important ones. Mechanical property requirements are tied to specific applications. For example, for the stem in THR, it should have high strength, low modulus, and very high fatigue resistance. As a result, due their low modulus, Ti and its alloys are usually preferred over high modulus metal alloys for the stem part of THR. However, for the acetabular component, high wear resistance requirement is the most important one and high-density polymers are preferred for the acetabular component. Mechanical properties are also linked on how they are processed. For example, casting devices in their near final shape can be a relatively inexpensive way to make complex shapes. However, material selection is critical in casting. The use of cast stainless steel for femoral hip stems is one experience that led to a high failure rate. This result generated significant debate in 1970s regarding processing of load bearing implants using casting and the options were considered by the ASTM Committee F04 on Medical and Surgical Materials and Devices to ban cast load bearing implants (8). For devices made of degradable polymers, strength loss due to degradation is an important factor. For example, materials compositions and structures in resorbable sutures are designed for different degradation times to achieve desired strength loss characteristics.

In vivo Degradation

Some orthopedic devices require materials to be bioresorbale or biodegradable, which will dissolve in body fluid as natural tissue repairs the site. Except for a few polymer and ceramic compositions, most materials are nondegradable in Nature. The degradation behavior is controlled by three basic mechanisms and they are (1) physiologic dissolution, which depends on pH and composition of calcium phosphate; (2) physical disintegration, which may be due to

biochemical attack at the grain boundaries or due to high porosity; and (3) biological factors, such as phagocytosis.

In most materials, not just one mechanism but a combination of all three mechanisms control biodegradation behavior. Among them, biological factors are probably the most interesting ones. Though the actual process is quite complex (9), a simplistic action sequence can be viewed as osteoclastic cells slowly eat away the top surface of the foreign material and stimulate osteoblast cells. Osteoblast cells then come and deposit new bone to repair the site. Such dynamic bone remodeling is a continuous process within every human body. The rate at which osteoblastic deposition and osteoclastic resorption are taking place changes with the age of the person. This process controls the overall bone density. In terms of materials, in vivo degradation of polymeric materials is probably the most well-characterized field. Numerous products are available in which degradation kinetics has been tailored for specific applications. However, the same is not true for ceramics. Controlled degradation ceramics are not commercially available though degradation behavior of some calcium phosphate based ceramics is well documented (10). For metallic implants, the most serious concern regarding in vivo degradation is metal ion leaching or corrosion of the implants, which can cause adverse biological reactions. Corrosion products of nickel, cobalt, and chromium can form metal–protein complexes and lead to allergic reactions (7,11). Early reports of allergic reactions were reported with metal on metal (MOM) total hips (12). The inflammatory response to metallic wear debris from these devices may have been enhanced due to the high corrosion rate of the small wear particles. However, there is a lack of a predictable relationship between corrosion and allergies except in a few cases, such as vitallium implants (13,14). The number of patients with allergic reactions is not large, and it remains to be proven whether corrosion of devices causes the allergy, or the reactions are only manifest in patients with preexisting allergies. Most materials that are currently used in load bearing dental and orthopedic devices are plates and screws and they show minimum long-term degradation and health related concerns such as allergies.

Surface Properties

Surface property of materials is another important parameter for orthopedic device design. Once implanted, it is the surface that the body tissue will see first and interact. As a result, surface chemistry and roughness both are important parameters for device design. Devices that are designed for different joints, where wear is a critical issue, smooth surface is preferred there. For example, in knee joints UHMWPE is used to reduce wear debris. But most other places, where tissue bonding is necessary, rough surface or surface with internal porosity is preferred primarily to enhance physical attachment. However, biomechanical and biochemical bonding to device surfaces are still subject of active scientific investigation (15). Tailoring internal porosity and chemistry of metallic implants is still an active research area. Either metal on metal or ceramic on metal coatings are used to achieve this goal. Different

manufacturing techniques are used to modify surfaces of metal implants. Among them, partial sintering of metal powders on metallic implants is one approach (16). For example, Ti powders are sintered on cp-Ti or Ti6Al4V devices, where after sintering the sintered layers leave some porosity in the range of 100–500 mm for osteointegration by bone tissues. Similar techniques are also used for metal fibers to create a mesh with varying porosity for improved osteointegration (17). For ceramic coatings, such as calcium phosphate on Ti or Co–Cr based devices, plasma-spray technique is used. Typically, a direct current (DC) plasma gun is used under a controlled environment to coat metallic device with several hundred microns of calcium phosphate-based ceramics. Because of significantly better bioactivity of calcium phosphates, these coated devices show improved tissue–materials interaction and better long-term tissue bonding (18). In case of THRs, ceramics coated cementless implants are placed without any bone cement during surgery. During healing, body tissue forms strong bonds with the coating and anchors the device. This biological fixation is believed to be equal or better than cemented implants in which bone cement is used during surgery to anchor the device. Though the idea of cementless implants is great, but lack of interfacial strength at the implant metal and ceramic coating interface is still a concern and subject of active research. Formation of amorphous calcium phosphate during processing of plasma-sprayed ceramic coatings increase potential biodegradation rate for the coating material, which is another major concern for these devices. In general, though coated implants are promising, a significant number of uncoated implants are still used in surgery every day that has worked for a long time. In fact there are more research data available today on uncoated implants than on the coated ones.

DESIGN ISSUES IN ORTHOPEDIC DEVICES

Design of orthopedic devices is focused on the needs for that particular problem. As a result, for the same device (spinal grafting cage or THR), different designs can be found from various device makers. These devices can be in single piece or multiple-piece, made from the same or different material(s). As a result challenges are significantly different for multiple piece multimaterial devices like THR than single piece ones like bone screws or plates. For multiple piece multimaterial devices, compatibility among different

materials/pieces and overall functionality becomes a more serious design issue.

Current practice in device design usually starts from biomechanical analysis of stress distribution and functionality of a particular device. If it is a joint related device, it is important that the patient can actually move the joint along multiple directions and planes to properly restore and recover functionality of that joint. Figure 3 shows some of the recent trends in orthopedic device designs. During the past 10 years, computer aided design (CAD) and rapid prototyping (RP) based technologies have played a significant role in orthopedic device design. Using this approach, real information from patients can be gathered using a computed tomography (CT) or magnetic resonance imaging (MRI) scans, which then can be visualized in three dimensions (3D). This 3D data can be transformed to a CAD file using different commercially available software.

The CAD file can be used to redesign or modify orthopedic devices that will be suitable to perform patient’s need. If necessary, the device can also be tested in a virtual world using finite element analysis (FEA) to optimize its functionality. Optimized device can then be fabricated using mass manufacturing technologies such as machining and casting. If small production volume is needed, then RP technologies can be used. In RP, physical objects can be directly built from a CAD file without using any part specific tooling or dies. Rapid Prototyping is an additive or layer by layer manufacturing process in which each layer will have a small thickness, but the X and Y dimensions will be based on the part geometry. Because no tooling is required, batches as small as 1 or 2 parts can be economically manufactured. Most RP processes are capable of manufacturing polymer parts with thermoset or thermoplastic polymers. Some of the RP techniques can also be used to manufacture metal parts. Figure 4 shows a life-sized human femur made of Ti6Al4V alloy using laser engineered net shaping (LENS) process. The LENS technology uses metal powders to create functional parts that can be used in many demanding applications. The process uses up to 2 kW of Nd:YAG laser power focused onto a metal substrate to create a molten puddle on the substrate surface. Metal powder is then injected into the molten puddle to increase the material volume. The substrate is then scanned relative to the deposition apparatus to write lines of the metal with a finite width and thickness. Laser engineered net shaping is an exciting technology for orthopedic devices because it can directly build functional parts that can be used for different applications instead of

Figure 4. A life-sized human femur made of Ti6Al4V alloy using LENS.

other RP parts that are typically used for ‘‘touch and feel’’ applications. Commercial RP processes have also been modified to make ceramic parts for orthopedic devices. Figure 5 shows one such example in which reverse

engineering of horse’s-knuckle was used to show how fused deposition modeling (FDM), a commercial RP process, can be used to create tailored porosity bone implants in which pore size and pore volume can be varied simultaneously keeping the outside geometry constant (19,20). The FDM process was used to make polymer molds of to cast porous ceramic structures. The mold was designed from the CAD file of the horse’s knuckle. The CAD file was created from the 3D volumetric data received from the CT scan of the bone. Such examples demonstrate the feasibility of patient specific implants through novel design and manufacturing tools.

BIOCOMPATIBILITY ISSUES IN ORTHOPEDIC DEVICES

Biocompatibility issue is an important issue in orthopedic device design and development, but it is usually considered during materials selection and surface modification. From cell materials interaction point of view, materials can be divided into three broad categories: (1) toxic; (2) nontoxic and bioinert, and (3) nontoxic and bioactive. For any application in the physiological environment, a material must be nontoxic. A bioinert material is nontoxic, but biologically inactive such as Ti metal. A bioactive material is the one that elicits a specific biological response at the interface of the biological tissue and the material, which results in formation of bonding between tissue and material. An