Biomaterials: Body Parts of the Future
During the last 90 years, man-made materials and devices have been developed to the point at which they can be used successfully to replace parts of living systems in the human body. These special materials able to function in intimate contact with living tissue, with minimal adverse reaction or rejection by the body are called biomaterials. Devices engineered from biomaterials and designed to perform specific functions in the body are generally referred to as biomedical devices or implants.
The earliest successful implants were bone plates, introduced in the early 1900s to stabilize bone fractures and accelerate their healing. Advances in materials engineering and surgical techniques led to blood vessel replacement experiments in the 1950s, and artificial heart valves and hip joints were under development in the 1960s. As early as the first bone plate implants, surgeons identified material and design problems that resulted in premature loss of implant function, as evidenced by mechanical failure, corrosion, and poor biocompatibility. Design, material selection, and biocompatibility remain the three critical issues in todays biomedical implants and devices.
As advances have been made in the medical sciences, and with the advent of antibiotics, infectious diseases have become a much smaller health threat. Because average life expectancy has increased, degenerative diseases are a critical issue, particularly in the aging population. More organs, joints, and other critical body parts will wear out and must be replaced if people are to maintain a good quality of life. Biomaterials now play a major role in replacing or improving the function of every major body system (skeletal, circulatory, nervous, etc.). Some common implants include orthopedic devices such as total knee and hip joint replacements, spinal implants, and bone fixators; cardiac implants such as artificial heart valves and pacemakers; soft tissue implants such as breast implants and injectable collagen for soft tissue augmentation; and dental implants to replace teeth/root systems and bony tissue in the oral cavity.
The number of implants in use in this country indicates their importance to health care and the economic impact of the biomaterials industry. For example, it was estimated in 1988 that 674,000 adults in the U.S. were using 811,000 artificial hips.  It was also estimated that 170,000 people worldwide received artificial heart valves in 1994.
The biomaterials program at Southwest Research Institute (SwRI) is a cooperative effort primarily between the Mechanical and Materials Engineering Division, the Automation and Data Systems Division, and the Chemistry and Chemical Engineering Division. The program includes such diverse activities as biomaterials development and testing, bioengineering and device design, and drug delivery. This article highlights some emerging technologies in the field of biomaterials at the Institute.
Imagine that you are a 65-year-old woman who has suffered from chronic hip pain for the last 10 years because of degenerative arthritis. Able to walk only with difficulty and losing your independence, you turn to an orthopedic surgeon for help. Or, you are a 30-year-old man who cannot walk without experiencing unbearable knee pain as a result of a football injury sustained in high school, and are restricted from any form of athletics except swimming. In cases such as these, when improvement cannot be gained through physical therapy, nonsurgical treatments, or surgical repairs, orthopedic surgeons often advised joint replacement surgery in which the deteriorated joint is removed and replaced with a man-made device.
Artificial joints consist of a plastic cup made of ultrahigh molecular weight polyethylene (UHMWPE), placed in the joint socket, and a metal (titanium or cobalt chromium alloy) or ceramic(aluminum oxide or zirconium oxide) ball affixed to a metal stem. This type of artificial joint is used to replace hip, knee, shoulder, wrist, finger, or toe joints to restore function that has been impaired as a result of arthritis or other degenerative joint diseases or trauma from sports injuries or other accidents. Joint replacement surgery is performed on an estimated 300,000 patients per year in the U.S. In most cases, it brings welcome relief and mobility after years of pain.
One might think that only surgeons and bioengineers would be involved in improving the design and performance of these implants. Not so. Materials and design engineers must consider the physiologic loads to be placed on the implants, so they can design for sufficient structural integrity. Material choices also must take into account biocompatibility with surrounding tissues, the environment and corrosion issues, friction and wear of the articulating surfaces, and implant fixation either through osseointegration (the degree to which bone will grow next to or integrate into the implant) or bone cement. In fact, the orthopedic implant community agrees that one of the major problems plaguing these devices is purely materials-related: wear of the polymer cup in total joint replacements.
Although the wear problem is one of materials, it plays out as a biological disaster in the body. Any use of the joint, such as walking in the case of knees or hips, results in cyclic articulation of the polymer cup against the metal or ceramic ball. Due to significant localized contact stresses at the ball/socket interface, small regions of UHMWPE tend to adhere to the metal or ceramic ball. During the reciprocating motion of normal joint use, fibrils will be drawn from the adherent regions on the polymer surface and break off to form submicrometer-sized wear debris. This adhesive wear mechanism, coupled with fatigue-related delamination of the UHMWPE (most prevalent in knee joints), results in billions of tiny polymer particles being shed into the surrounding synovial fluid and tissues. The biological interaction with small particles in the body then becomes critical. The bodys immune system attempts, unsuccessfully, to digest the wear particles (as it would a bacterium or virus). Enzymes are released that eventually result in the death of adjacent bone cells, or osteolysis. Over time, sufficient bone is resorbed around the implant to cause mechanical loosening, which necessitates a costly and painful implant replacement, or revision. Since the loosening is not caused by an associated infection, it is termed "aseptic
The average life of a total joint replacement is 8-12 years even less in more active or younger patients. Because it is necessary to remove some bone surrounding the implant, generally only one revision surgery is possible, thus limiting current orthopedic implant technology to older, less active individuals."
A relatively recent incident in the biomedical device field serves to illustrate the importance of materials choice and engineering on implant performance. The temporomandibular joint (TMJ) provides all jaw mobility and is crucial for chewing, talking, and swallowing. This joint can deteriorate from disease or trauma which, in severe cases, necessitates replacement by an artificial joint. For many years, less than optimum technologies existed for TMJ implants. In the late 1970s, a TMJ replacement using polytetraflouroethylene (PTFE) as the bearing counterface was invented, and, in 1983, the inventors received FDA approval to market the PTFE implant, which was called the Interpositional Implant (IPI). In theory, PTFE would seem an appropriate choice for an implant material, as it exhibits a low coefficient of friction and has been used extensively as a bearing surface in other engineering applications. However, of the more than 25,000 PTFE TMJ implants received by patients, most failed.
Materials engineers know that the reason PTFE exhibits such a low coefficient of friction is that a thin film of the material is continuously transferred onto the opposing bearing surface. Although this transfer film acts as a lubricant, it also, by virtue of its formation, subjects the material to an adhesive wear mechanism. In the case of the PTFE TMJ implants, surrounding tissues quickly became overwhelmed by wear debris, and the immune system response resulted in osteolysis, causing massive destruction of the joint and surrounding tissues. For those people who received the implants, this was truly a tragedy; many suffered severe facial deformities, and most experienced unbearable pain and were nol onger able to chew, swallow, or sleep.
At the time the IPI was developed, evidence did exist that PTFE was not an appropriate implant material. In the late 1950s, Dr. John Charnley, then with Wrightington Hospital in the U.K., pioneered the first total hip replacements using PTFE as the cup bearing surface. Dr. Charnley reported massive wear of the PTFE part and early clinical failure as a result of aseptic loosening. These findings, reported widely in the open literature and in later caveats from researchers testing the IPI implant, should have been sufficient warning that PTFE was not an appropriate material to use as a load-bearing surface in the body.
Work at SwRI is addressing the wear problem in UHMWPE total joint prostheses. In collaboration with scientists at the University of Texas Health Science Center at San Antonio(UTHSCSA), through the Center for the Enhancement of the Biology/Biomaterials Interface (CEBBI)funded by the National Science Foundation, SwRI scientists and engineers are studying the wear process and biological responses to wear debris. Results of these studies have led to novel ideas for materials modification and development. The Institute is also developing new composite materials to defeat the fatigue-induced delamination observed in the UHMWPE component of knee implants.
Studies of wear debris extracted from actual tissue samples of patients whose implants failed as a result of aseptic loosening have generated significant information regarding wear particle size, shape, and surface morphology. Institute scientists were the first to use the atomic force microscope (AFM) to produce detailed, high resolution images of wear particles. A few hundred nanometers in size, the UHMWPE wear debris studied at SwRI sometimes exhibits a cauliflower-like surface morphology. Scientists at the Health Science Center will use similar particles to study the biological response elicited by the particles. By combining wear debris and cellular response studies, engineers and biologists will be able to better understand implant failure and to re-engineer implants to prevent future problems.
When a man-made material is placed in the human body, tissue reacts to the implant in a variety of ways depending on the material type. Therefore, the mechanism of tissue attachment (if any) depends on the tissue response to the implant surface. In general, materials can be placed into three classes that represent the tissue response they elicit: inert, bioresorbable, and bioactive. Inert materials such as titanium, UHMWPE, and alumina (Al2O3) are nearly chemically inert in the body and exhibit minimal chemical interaction with adjacent tissue. A fibrous tissue capsule will normally form around inert implants. Tissue attachment with inert materials can be through tissue growth into surface irregularities, by bone cement, or by press fitting into a defect. This morphological fixation is not ideal for the long-term stability of permanent implants and often becomes a problem with orthopedic and dental implant applications. Bioresorbable materials, such as tricalcium phosphate and polylactic-polyglycolic acid copolymers, are designed to be slowly replaced by tissue (such as bone) or for use in drug-delivery applications.
Certain glasses, ceramics, and glass-ceramics that contain oxides of silicon, sodium, calcium, and phosphorus (SiO2, Na2O, CaO, and P2O5) have been shown to be the only materials known to form a chemical bond with bone, resulting in a strong mechanical implant/bone bond.  These materials are referred to as bioactive because they bond to bone (and in some cases to soft tissue) through a time-dependent, kinetic modification of the surface triggered by their implantation within living bone. In particular, an ion-exchange reaction between the bioactive implant and surrounding body fluids results in the formation of a biologically active hydrocarbonate apatite (calcium phosphate) layer on the implant that is chemically and crystallographically equivalent to the mineral phase in bone. This equivalence is responsible for the relatively strong interfacial bonding.
Although bioactive materials would appear to be the answer to biomedical implant fixation problems, available bioactive glasses (i.e., Bioglass®) are not suitable for load-bearing applications, and so are not used in orthopedic implants. In fact, their use for other implants, even some dental applications, is limited because they have a low resistance to crack growth. However, there are stronger ceramic materials, crystalline in structure, that are not as bioactive. Recent work at SwRI, funded by the Institutes Internal Research Biomaterials Initiative, has used ion beam surface modification to change the atomic structure and chemistry at the surface of these crystalline ceramics to allow the material to react (ion-exchange) upon implantation. In vitro assays have shown that a ceramics bioactivity can be increased through surface modification. Efforts continue in this area to improve the mechanical integrity of bioactive ceramics while maintaining a useable level of bioactivity.
Heart Valve Materials
The science of replacing organs or parts of organs that are crucial to our existence is both exciting and potentially dangerous. Success can mean years of healthy living; failure can mean death. An example of the successful development of a critical implant technology is the artificial heart valve. Although poor heart valve designs resulted in clinical failures in the past, the current limiting factor for long-term success is the materials themselves.
Two types of materials are used for artificial heart valves: soft bioprosthetic materials such as denatured porcine aortic valves or bovine pericardium, and hard man-made materials used in mechanical heart valves, the most successful being pyrolytic carbon. Both categories of material exhibit problems when implanted.
Bioprosthetic valves, which must be used in children, often fail due to calcification (calcium from the blood stream forms deposits on the implant), which can result in mechanical dysfunction, vascular obstruction, or embolization of calcific deposits. Bioprosthetic valves are also susceptible to mechanical fatigue. The cyclic loading of the valves can facilitate fatigue crack growth, often resulting in catastrophic failure. The principal problem with mechanical heart valves is thrombosis, which may be revealed as a thromboembolism or anticoagulation-related hemorrhaging. Graphite coated with pyrolytic carbon has become the material of choice for mechanical heart valves, because of its excellent thromboresistance. Pyrolytic carbon is also being studied to assess its susceptibility to fatigue damage.
Institute researchers have investigated the calcification process in heart valves by using molecular modeling and have developed improved lifetime assurance technology for pyrolytic carbon valves. Dr. Mark Lupkowski, formerly of SwRIs Mechanical and Materials Engineering Division, has predicted the calcification mechanisms of polyether urethane implant materials using computer simulations. His work has shown that a complexation mechanism controls the calcification process wherein the calcium is attracted to the oxygen in the polymer, and the polyether subsequently wraps around the calcium and traps it. Further calcification studies will include systematic evaluation of the effect of ion size, molecular weight, steric hindrance, and solvent effects on complexation.
It has been suggested that the service lives of pyrolytic carbon heart valves may be limited by cyclic fatigue, because cyclic crack growth is possible in this material. Thus, predicting the lifetime of pyrolytic carbon heart valves has been a topic of great interest to a number of parties, including the FDA, heart valve manufacturers, attorneys, scientists, and, of course, implant recipients. Proof testing to evaluate the structural integrity of heart valves is an appropriate next step. Dr. James Lankford, also of the Mechanical and Materials Engineering Division, has developed an acoustic emission-based system for detecting crack nucleation and the growth of existing flaws during controlled stress testing of artificial heart valves. The technique is expected to have an important bearing on quality control for the heart valve industry.
Acute or Chronic Infection in Some Biomaterial Applications
Regular bacterial growth can often be eradicated by cleaning a surface with a disinfectant or by treating our bodies with antibiotics. However, bacteria may irreversibly adhere to surfaces (both man-made and natural, such as human tissue) that are surrounded by fluids. Once the bacteria adhere, they can multiply, form complex multilayered colonies, and produce a slimy matrix material that encases the bacterial cells. Called a biofilm, this structure is difficult and often impossible to eradicate in the body with antibiotics, because the slime matrix acts as a physical and chemical barrier to protect the bacteria.
Biofilms routinely foul ship hulls, submerged oil platforms, and the interiors of pipeworks and cooling towers. The damage caused by these wildly procreating bacteria includes corrosion and failure of metal components. Biofilm formation is also a serious medical problem that manifests itself as biomaterial- associated infections of devices such as endotracheal tubes, intravenous catheters, urinary catheters, and contact lenses, and of prosthetic implants such as heart valves, joint replacements, dental implants, and spinal implants. In fact, the increased use of biomedical devices and implants in humans in recent years has resulted in a concomitant rise in bacterial infections, with Staphylococcus epidermis emerging as the most common cause. Depending on the organism involved, these infections can be acute (symptoms appear relatively soon after material insertion) or chronic (may take months for symptoms to appear). The formation of a biomaterial- associated biofilm (irreversible infection) usually leads to removal or revision of the affected device or implant, with obvious devastating results for the patient.
The pervasiveness of biofilm formation is magnified by the fact that it is a poorly understood phenomenon, making it difficult for researchers to combat. The key to biofilm formation appears to be the interaction between the body and the implant more specifically, the interface between the biomaterial surface and the bacteria as well as the associated environments (for example, plasma proteins deposited onto the implant material surface can condition the surface for biofilm formation).
The surface characteristics and properties of a biomaterial roughness and area, hydrophobicity, porosity, and chemistry have a significant effect on bacterial adherence and colonization. Scientists at the Institute and UTHSCSA, with funding provided by the National Science Foundation through the CEBBI, are studying biofilm formation on several important biomaterials (UHMWPE, polyvinyl chloride, titanium, and cobalt chromium) and are formulating novel material modifications to resist or block biofilm formation.
To better understand how biofilms form and continue to function and persist, scientists in Dr. Barbara Sanfords laboratory at UTHSCSA test various biomaterial samples in a modified Robbins device that cultures, feeds, and flows bacteria over materials to observe biofilm formation in vitro. Institute scientists have studied and characterized material surfaces to determine the effects of varying surface parameters on biofilm formation. In mid-1995, SwRI researchers generated the first AFM images of hydrated biofilm. Studying hydrated biofilm (instead of a dry, chemically fixed biofilm, necessary for scanning electron microscope characterization), as it would exist in vivo, can provide details regarding the feeding and proliferation of bacteria. Prior to AFM, the only techniques available to study hydrated biofilms required first altering the biofilm.
The AFM biofilm studies revealed microcolonies of bacteria that had grown in columns and were completely embedded in a slime matrix. The matrix consisted of numerous pores and channels with diameters of 0.25 and 0.50 µm, respectively. It is believed that these channels act as passageways for nutrients to reach all layers of the biofilm, thereby maintaining its viability and ability to proliferate, while the slime matrix protects the bacteria from the attack of antibiotics.
To eradicate the biofilm problem, SwRI scientists are altering the surfaces of certain biomaterials to make them less attractive to bacteria. A variety of chemical treatments, thin coatings, and ion beam surface modifications are being studied and tested in cooperation with Dr. Sanford. The most successful treatment observed to date has been with a thin (»1.0 µm) coating of silver on PVC. Silver has been recognized as bactericidal for many years, but it is expensive, and, in the wrong form or amount, can be deleterious. The Ion-Beam Assisted Deposition (IBAD) silver coating applied to PVC samples at SwRI is adherent to the substrate and believed to be relatively chemically stable. Silver-coated samples, tested in the modified Robbins device with Staphylococcus epidermidis, exhibited less prolific biofilm formation than did uncoated materials. These studies will continue, to assess other surface treatments and their effects on various strains of bacteria.
The Future of Biomaterials
Biomaterials research is an exciting and rapidly growing field. Lawsuits against medical device manufacturers, restructuring of FDA approval procedures, patient expectations, and the health care reform movement are changing the future of the medical device community and shaping the direction of biomaterials research. For example, lawsuits have prompted long-term material suppliers and device manufacturers to refuse the use of their products in medical applications. As a result, new materials and suppliers will be required to meet FDA standards. Another important issue not often discussed is that implant recipients expect an implant to function as well as its biological counterpart, and to last forever. This misconception has been fostered by the popular press and some physicians, and will only be corrected by properly educating potential recipients.
Biomaterials and implant research at SwRI will continue to concentrate on serving the needs of medical device manufacturers and recipients, as well as medical professionals, and on developing technologies to meet those needs. Future biomaterials will incorporate biological factors (such as bone growth) directly into an implants surface to improve biocompatibility and bioactivity. New projects will be directed at materials development for improved mechanical integrity, corrosion resistance, and biocompatibility. Institute engineers will also apply statistical finite element analysis, stereoimaging strain analysis, and composite materials to the biomaterials program.
Published in the Fall 1995 issue of Technology Today®, published by Southwest Research Institute. For more information, contact Joe Fohn.