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uring 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.1 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 today's
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
playa 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.
Technology Today. Fall 1995
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.2 It was also estimated that
170,000 people worldwide received artificial heart valves in 1994. 3
The biomaterials program at Southwest Research Institute (SwRI) is a cooperative effort primarily between the
Materials and Structures Division, the
Biosciences and Bioengineering Department, 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.
Orthopedic Biomaterials
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 tum to an orthopedic surgeon
Bone plates, introduced in the early 1900s
to assist in the healing of skeletal fractures,
were among the earliest successful biomedical implants. The plate is generally
removed once the bone has healed and the
bone can support loads without refracturing.
3
Artificial knee joints are implanted in patients with a diseased joint to alleviate
pain and restore function. After about 10 years of use, these artificial joints
often need to be replaced because of wear and fatigue-induced delamination
of the polymeric component. Institute engineers are developing improved
materials to extend the lifetime of orthopedic implants such as knees and hips.
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 advise joint replacement surgery in which the deteriorated
joint is removed and replaced with a manmade 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 d egenerative
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,
4
so they can design for sufficient structural integrity.
Ma terial 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 m a terials-related: wear of the
polymer cup in total joint replacements. 4
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
p olymer cup against the m etal 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 body's 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,
Senior Research Scientist Or. Cheryl R. Blanchard, of the Materials Development Department
in SwRI's Materials and Structures Division, conducts research aimed at improving biomaterials for medical implant applications. The atomic force microscope shown here is a powerful
tool used to study the fine structures of surfaces and interfaces important to an understanding of the interaction between biomaterials and the body.
Technology Today· Fall 1995
These micrographs, taken at a magnification of 20, OOOX on a scanning electron microscope, illustrate the wear
problem that occurs with an artificial
joint implant component (socket) constructed of ultrahigh molecular weight
polyethylene (UHMWPE). At left is
unworn UHMWPE. The UHMWPE sample at right has undergone a friction and
wear test versus cobalt chromium (artificial joint ball material). The fibrillation
and small particles are characteristic of
an adhesive wear mechanism, which
can result in surrounding bone loss and
the need for implant replacement.
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 loosening."
The average life of a total joint
replacement is 8-12 years 5 - 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. 6 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 no longer 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 loadbearing 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
Technology Today . Fall 1995
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.
Bioactive Materials
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 (A120 3) 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
5
Artificial mechanical heart valves are made of
pyrolytic carbon to prevent complications
associated with blood clotting, but this material can be subject to cyclic fatigue. The
Institute has developed an acoustic emissionbased system for detecting crack initiation
and the growth of existing flaws during controlled stress testing of artificial heart valves.
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 glassceramics that contain oxides of silicon,
sodium, calcium, and phosphorus (Si0 2,
Na20, CaO, and P 20 5) have been shown
to be the only materials known to form a
chemical bond with bone, resulting in a
strong mechanical implant/bone bond. 7
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.
6
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
Institute's 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
ceramic's 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 calcification8 (calcium from the blood stream
forms deposits on the implant), which
can result in mechanical dysfunction, vascular obstruction, or embolization of calTechnology Today. Fall 1995
cific 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,3 which may be revealed as a
thromboembolism or anticoagulationrelated 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 of
SwRI's Materials and Structures Division has predicted the calcification
mechanisms of poly ether 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 Materials
and Structures 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 manmade 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
Before new bone formation
Bioactive
implant
Body fluid
environment
Existing
bone
After new bone formation
Bioactive
implant
New
bone
Existing
bone
Biofilms are multilayered colonies of bacteria that often form on biomedical implants,
manifesting themselves as acute or chronic infections in a patient. This atomic force
microscope (AFM) image of the surface structure of a hydrated biofilm reveals microcolonies of bacteria, with channels that are believed to act as passageways carrying
nutrients to the bacteria. Institute scientists were the first to generate and study AFM
images of hydrated biofilms.
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. 9 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. lO 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 biomaterialassociated biofilm (irreversible infection)
The mechanism of new bone formation
and bone bonding to a bioactive ceramic
implant is illustrated at left. Immediately
following implantation, an ion-exchange
reaction takes place between the implant
and the surrounding body fluid during
which chemical species from the ceramic
diffuse into the fluid and vice versa. Over
time, this results in the formation of chemically graded layers that become hydrocarbonate apatite, or new bone.
Technology Today· Fall 1995
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 Sanford's
7
The wrist joint is a complicated one, allowing
flexion, extension, adduction, and abduction,
primarily through the radiocarpal joint.
Though not subject to the severe wear problems encountered in other orthopedic
implants, artificial wrist joints will benefit from
improved biomaterials, particularly those
designed to incorporate biological factors to
enhance bone attachment, as well as materials with improved mechanical integrity and
corrosion resistance.
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 d etermine the effects of varying
surface parameters on biofilm formation .
In mid-1995, SwRI researchers generated
the first AFM images of hydrated biofilm.
Studying h ydrated 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
micro colonies of bacteria that had grown
in columns and were completely embedd ed in a slime matrix. The matrix consisted of numerous pores and channels
with diameters of 0.25 and 0.50 pm,
respectively. It is believed that these channels act as passageways for nutrients to
reach all layers of the biofilm, ther eby
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
pm) 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 b e 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
8
stable. Silver-coated samples, tested in the
modified Robbins device w ith 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 d evice manufacturers,
restructuring of FDA approval procedures, patient expectations, and the
health care reform movem ent 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 m anufacturers to
refuse the use of their products in medical
applications. As a result, new materials
and suppliers w ill 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 implant's 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 .•:.
Technology Today· Fall 1995
References
1. J.B. Park and R.S. Lakes, Biomaterials: An Introduction, Plenum Press,
NY, NY (992).
2. CM. Sharkness, et aI., "Prevalence
of Artificial Hips in the United States,"
Journal of Long-Term Effects of Medical
Implants, 2 0), 1-8 (1992).
3. F.J. Schoen, "Clinical Performance
of Mechanical Heart Valve Prostheses
w ith Pyrolytic Carbon Components:The
Cardiac Pathology Perspective," Journal
of Heart Valve Disease (in press).
4. The Journal of Bone and Joint Surgenj, 75-A (6), 1993 (issue d evoted to
aseptic loosening of total joint arthroplasties).
5. W.H. Harris, "Osteolysis and Particle Disease in Hip Replacement: A
Review," Acta Orthopaedica Scandinavica,
65 (1), 113-123 (994).
6. B. Ingersoll and R. Gutfeld,
"Implants in Jaw Joint Fail, Leaving
Patients in Pain and Disfigured," Wall
Street Journal, August 31, 1993, p. 1.
7. L.L. Hench and J. Wilson, "Bioceramics," Materials Research Society
Bulletin, 16 (9), 62-74 (991).
8. R.J. Levy, et aI., "Cardiovascular
Implant Calcification: A Survey and
Update," Biomaterials 1991, 12, 707-714
(991).
9. A.L. Bisno and FA Waldvogel,
eds., Infections Associated with Indwelling
Medical Devices, American Society for
Microbiology, Washington, D.C (989).
10. J. Dankert, A. H . Hogt, and J.
Feijen, "Biomedical Polymers: Bacterial
Adhesion, Colonization, and Infection,"
Chemical Rubber Company Critical
Reviews in Biocompatibility, 2, 219-301
(986).
11. [pg. 9 opposite] RA Smith, CR.
Blanchard, and J. Lankford, "Nonantigenic Keratinous Protein Material,"
United States Patent No. 5,358,935,
issu ed October 25,1994.
12. [pg. 9 opposite] Collagen Corporation Press Release, "Collagen Wins Court Case Filed by Woman Claiming
Treatments Are Defective," United
Press International, October 16, 1991.