TUTORIAL

BIOMATERIALS

Oleh:
dr. Hidayat
Pembimbing:
dr. Tjuk Risantoso,SpB,SpOT

Orthopaedi & Traumatologi Fakultas Kedokteran

Universitas Brawijaya Malang
2015

Definition
A biomaterial is a nonviable material used in a medical device, intended to interact with
biological systems. Defined by their application NOT chemical make-up.
The term biomaterials refers to synthetic and treated natural materials
that are used to replace or augment tissue and organ function.
Biomaterials must meet several criteria to perform successfully. They
must be biocompatible, or able to function in vivo without eliciting an
intolerable response in the body either locally or systemically; resistant to
corrosion and degradation, meaning that the body environment must not
adversely affect material performance; and possess adequate mechanical
properties, an especially important criterion for those biomaterials used in
devices intended to replace or reinforce load-bearing skeletal structures.
In addition, orthopaedic biomaterials intended for total joint replacement
must possess adequate wear resistance to maintain proper joint function
and to minimize biocompatibility problems caused by biologic reactions to
particulate debris. They must be capable of reproducible fabrication to the
highest standards of quality control and, of course, at a reasonable cost.
Biomaterials that meet these criteria are fundamental to the practice of
orthopaedic surgery. They have been used successfully to develop devices
for internal fixation of fractures, osteotomies and arthrodeses, wound
closure, softtissue reconstruction, and total joint arthroplasty that have
advanced significantly the treatment of musculoskeletal diseases. But at
the same time, limitations in biomaterial performance, failure of the
implant

designer

to

understand

the

limitations,

or

inappropriate

application of the technology often are directly related to clinical failure.

Therefore, an understanding of the physical and chemical properties of
orthopaedic biomaterials is an important consideration in selecting and
using implant devices and in providing a realistic expectation of clinical
performance. This chapter will discuss how a materials physical
properties result from its chemical composition and structure, and
fundamentals of mechanical performance in terms of the important
material properties that determine the behavior of implant structures.

Common metallic, polymeric, and ceramic orthopaedic biomaterials are

described

in

terms

of

their

molecular

structures,

microstructures,

composition, and properties, and how their properties are influenced by

processing and manufacturing variables is discussed as well.

Characteristics of Biomaterials
Physical Requirements
Hard Materials.
Flexible Material.
Chemical Requirements
Must not react with any tissue in the body.
Must be non-toxic to the body.
Long-term replacement must not be biodegradable.

History
More than 2000 years ago, Romans, Chinese, and Aztecs used gold in dentistry.
Turn of century, synthetic implants become available.
1937 Poly(methyl methacrylate) (PMMA) introduced in dentistry.
1958, Rob suggests Dacron Fabrics can be used to fabricate an arterial prosthetic.

1960 Charnley uses PMMA, ultrahigh-molecular-weight polyethylend, and stainless

steal for total hip replacement.
Late 1960 early 1970s biomaterial field solidified.

 1975 Society for Biomaterials formed.

First Generation Implants

ad hoc implants
specified by physicians using common and borrowed materials
most successes were accidental rather than by design

Examples Second generation implants

titanium alloy dental and orthopaedic implants

cobalt-chromium-molybdinum orthopaedic implants
UHMW polyethylene bearing surfaces for total joint replacements
heart valves and pacemakers

MED BOSC II Surakarta 2014

Third generation implants

bioengineered implants using bioengineered materials
few examples on the market
some modified and new polymeric devices
many under development

Example - Third generation implants

tissue engineered implants designed to regrow rather than replace tissues

Integra LifeSciences artificial skin
Genzyme cartilage cell procedure
some resorbable bone repair cements
genetically engineered biological components (Genetics Institute and Creative
Biomolecules BMPs)

Grow cells in culture.

Apparatus for handling proteins in

the laboratory.

Devices to regulate fertility in cattle.

Aquaculture of oysters.

Cell-silicon Biochip.

MED BOSC II Surakarta 2014

Examples of Biomaterial
Applications

Metals
Metallic alloys have found widespread use in orthopaedic surgery. Alloys are metals
composed of mixtures or solutions of metallic and nonmetallic elements. The combination of

elements is used to impart the high strength, ductility, and elastic modulus, the corrosion
resistance, and the biocompatibility required for load-bearing applications, such as fracture
fixation devices and implant components for total joint arthroplasty. The 3 common alloys
used in orthopaedics are stainless steel, cobalt chromium alloy, and titanium alloy. None of
these alloys were developed specifically for orthopaedic or biomedical applications.
Instead,their proven strength and corrosion resistance in the aerospace, marine, and chemical
industries have led them to be adopted for implant use. Their specific properties can be
understood from their molecular structure, microstructures, and composition.
Stainless Steel
The most common form of stainless steel used in orthopaedic applications is 316L, grade 2,
designated by the American Society for Testing and Materials (ASTM) specification F138.
The numeric designation 316 places the alloy within the so-called austenitic stainless
steels; the L denotes low carbon concentration (typically below 0.03 wt%). As with all
steels, 316L stainless steel is an alloy of iron and carbon. The other major alloying elements
include chromium, nickel, and molybdenum, with minor amounts of manganese,
phosphorous, sulfur, and silicon. The alloying elements affect the microstructure and hence
the mechanical and corrosion properties of the steel. Chromium in the microstructure forms a
strongly adherent oxide (Cr2O3) on the surfaces of the metal that are exposed to the
environment, thus providing corrosion resistance by forming a passive layer between the
environment and the bulk material. Stainless steel devices are passivated by immersion in a
strong nitric acid bath as part of the manufacturing process to assure the creation of the oxide
layer. The creation of a passive oxide layer limits the rate of electrochemical corrosion by
about a thousand to a million times compared to the rate of corrosion in the absence of the
oxide. Most of the metallic alloys are highly reactive with oxygen, so that the oxide layer
forms naturally as the base metal is exposed to the atmosphere. Standardized methods (such
as the nitric acid bath) are used to enhance the layer and ensure appropriate resistance to
corrosion. Though chromium provides the stainless quality to the steel, it also stabilizes the
ferritic, body-centered cubic phase that is weaker than the face-centered cubic austenitic
phase. Molybdenum, added to provide additional corrosion resistance, and silicon, added
with manganese to aid in the manufacturing process, also stabilize the ferritic phase. To offset
this tendency, nickel is added to stabilize the austenitic phase and thus assure an appropriately
strong microstructure.

Carbon concentration must be kept low in 316L stainless steel to maintain corrosion
resistance. At higher carbon concentrations, there is a tendency for the carbon to combine
with the chromium to form a brittle carbide that robs the microstructure of much of the
chromium and that tends to segregate to the grain boundaries, significantly weakening the
material by making it prone to corrosionrelated fracture. Such a condition, called
sensitization, has been directly responsible for mechanical failures of orthopaedic implants
made from stainless steels in which carbon content has been too high. ASTM specifications
for 316L stainless steel call for an austenitic microstructure free of carbides or inclusions that
might remain from the steel-making process (and that can reduce corrosion resistance). The
recommended grain size is small (about 100 microns in any dimension) to assure adequate
strength for orthopaedic applications. Grain size can be controlled by the solidification
process and by postsolidification heat treatments and cold working of the material.
Stainless steel is typically cold-worked by about 30% for orthopaedic applications.
Mechanical properties of 316L stainless steel are provided in Table 2 in both the annealed
(not cold-worked) and 30% cold-worked condition. A potential disadvantage of stainless steel
in implant applications is its susceptibility to crevice and stress corrosion. In any corrosion
process, there are 2 reactions, an anodic reaction in which the metal is oxidized to its ionic
form (M Mn+ + n electrons) and a cathodic reaction in which the electrons are consumed
(in an aqueous solution with dissolved oxygen, O2 + 2H2O + 4e 4OH). These reactions
could initially be progressing at an even rate over the surface of a stainless steel implant, such
as a bone plate or a bone screw. But as the reactions progress in the crevice between the
underside of the head of the screw and the countersunk area of the plate, the crevice becomes
depleted of oxygen. The anodic reaction continues in the crevice while the remainder of the
plate and screw undergo the cathodic reaction. The oxygen concentration is not readily
replenished by the fluids outside of the crevice, though smaller chlorine ions flow into the
crevice, drawn there by the metal ions being released by the anodic reaction.
The crevice region decreases in pH, causing accelerated metal oxidation. Stress corrosion
cracking results when the combination of an applied stress and a corrosive environment lead
to mechanical failure of the material, even though the environment or load in and of itself
would be insufficient to cause failure. Stress corrosion cracking has been shown to occur
even under low levels of constant stress, such as might occur in an implant with residual
stresses. Crack initiation is accelerated by the corrosion process, as is the subsequent crack
growth that occurs under the applied stress. Because of concerns about corrosion and

subsequent long-term biocompatibility, stainless steel has been used primarily in fracture and
spinal fixation applications. These applications often allow removal of the device or require
strength only until healing occurs. Permanent implants, such as femoral components of the
Charnley design of hip replacements, have also been made from stainless steel, demonstrating
that stainless steel can be used safely even in these high-demand applications.
Cobalt-Chromium Alloys
Cobalt-chromium alloys include compositions intended to be manufactured by casting
(ASTM F75 alloy) and by forging (ASTM F799 alloy), as well as alloy compositions that
obtain excellent mechanical properties through cold working (ASTM F90 and F562). All of
these alloys are primarily cobalt with significant amounts of chromium added for corrosion
resistance. As with stainless steel, the chromium forms a strongly adherent oxide film that
provides a passive layer shielding the bulk material from the environment. The F75 and F90
alloys contain about 60% cobalt with about 28% chromium. The F799 and F562 alloys have
less cobalt and chromium, and in their place have large amounts of other alloying elements
(about 15% tungsten in F799 and about 35% Ni in the F562).
The alloys display a range of mechanical properties that can be understood from the
processes and the resulting microstructures used to fabricate devices from the materials. The
F75 alloy, for example, has commonly been used for investment (or so-called lost wax)
casting. Waxmolds of near-final dimensions of devices such as total hip femoral stems are
coated with a ceramic slurry. The slurry is fired in a furnace (and the wax is lost as it melts
away from the inside of the ceramic mold). Molten F75 alloy is poured or pressurized into the
molds and allowed to solidify. The ceramic mold is broken away from the underlying metal
part, which can then be finished into the final device. Quality control can be a problem during
the casting process. If solidification proceeds too slowly, grains have ample time to grow
quite large, thus significantly diminishing the materials strength (Fig. 12). If solidification
proceeds too quickly, air from inside the mold and gases that are released during the
solidification process can become entrapped in the microstructure, causing undesirable stress
concentrations that can cause premature failure. Finally, if cooling conditions are not ideal,
carbides that naturally occur within the alloys microstructure segregate to too great a degree,
which can weaken the material, reduce ductility, and decrease corrosion resistance. To
overcome these problems, the alloy can be fabricated by powder metallurgy. Fine powder of
the alloy is compacted and sintered together to form a near net shape. The shape is then
forged under pressure and heated into the final shape. The resulting microstructure has a

smaller grain size and more evenly distributed carbides than the cast alloy, leading to
improved properties F75 alloy is used to fabricate porous coatings for biologic fixation of
orthopaedic implants. The resulting properties of the porous-coated device will depend on the
microstructure of the substrate metal and the porous beads, as well as the thermal sintering
process that is used to connect the two. Sintering involves very high temperatures (near the
1225C melting temperature), which can significantly decrease the fatigue strength of the
substrate material.
Together with the stress concentrations caused at the attachment points with the porous
coating, the result is a fatigue strength of only about 200 MPa, even after additional thermal
treatments are used to restore some of the strength. This strength is well below that achieved
for other cobalt alloys that are not porous-coated. The forging alloy, F799, possesses
mechanical properties that are superior to that of the cast alloy. Hot forging effectively
reduces grain size, heals pores through the combination of pressure and heat, and breaks up
the carbides into an even distribution. The thermomechanical forging operation also induces
an additional microstructural phase that contributes to the improved properties.
The F90 and F562 alloys obtain substantial mechanical properties through more than 40%
cold-working. The tungsten addition in F90 improves machinability and fabrication via coldworking. The cold working of F562 alloy provides additional energy for the transformation of
some of the face-centered cubic phase into a hexagonal phase that emerges as fine platelets
throughout the microstructure. The combination of a very fine grain size (the facecentered
cubic grains are less than 0.1 in any dimension) and the dispersed platelets impede plastic
deformation, strengthening the material. In addition, the material can be thermally treated to
precipitate a uniform distribution of very fine cobalt-molybdenum (Co3Mo) precipitates that
act to further strengthen the material. The result is among the strongest of the orthopaedic
implant alloys.
The ease of fabrication and the range of properties available for cobalt alloys make them deal
for a wide range of orthopaedic applications, including all metallic components of all joint
replacements as well as fracture fixation devices. The chromium content of these alloys
provide excellent corrosion resistance, with superior resistance to crevice corrosion than
stainless steel. Long-term clinical use has proved that these alloys also have exceptional
biocompatibility in bulk form
Titanium and Titanium Alloys
Titanium and its alloys are of particular interest for biomedical applications because of their
outstanding biocompatibility and corrosion resistance. Their corrosion resistance, provided

by an adherent passive layer of titanium oxide (TiO2), significantly exceeds that of stainless
steel and the cobalt alloys. Uniform corrosion even in saline solutions is extremely limited,
and resistance to pitting and intergranular and crevice corrosion is excellent. Experimental
studies in animal models and long-term clinical use in humans confirm truly superior
biocompatibility. Furthermore, the oxide surfaces of titanium and its alloys are well tolerated
in contact with bone, becoming osseointegrated with little evidence of a fibrous layer
between bone and implant.
CP-titanium (ASTM F67) is used more extensively in dental implants, but is used in
orthopaedic surgery primarily in the form of wire mesh for porous coatings that is sintered
onto titanium alloy joint replacement components. The properties of CP-titanium depend on
the amount of oxygen contained in the metal. At small concentrations, increased oxygen
content improves the mechanical properties. Grade IV CP-titanium, for example, with an
oxygen concentration of 0.40 wt% has a yield strength of about 485 MPa, while grade I with
an oxygen concentration of 0.18 wt% has a yield strength of only 170 MPa. The CP-titanium
microstructure consists of grains of a single, hexagonal close-packed phase, and the material
can be cold-worked. Additional strengthening of the microstructure comes from interstitial
solid solution strengthening, in which atoms of oxygen, carbon, and particularly nitrogen
harden the material by being encased in the interstices of the crystalline, hexagonal
arrangement of titanium atoms.
The most common form of titanium used in orthopaedic applications is titanium-aluminumvanadium alloy (ASTM F-136). The primary alloying elements, aluminum and vanadium, are
limited to 5.5 wt% to 6.5 wt% and 3.5 wt% to 4.5 wt%, respectively (Fig. 13), so that the
alloy is often called Ti-6Al-4V or simply Ti-6-4. Developed by the aerospace industry as a
high strength-to-weight ratio material, the alloy is used in orthopaedic implants in the extra
low interstitials form, in which the oxygen concentration is kept very low to avoid
embrittlement and to maximize strength and ductility. The microstructure of Ti-6Al-4V
contains 2- phase grains, the alpha phase being a hexagonal-close packed phase that is
stabilized by the aluminum alloying element and the body-centered cubic beta phase
stabilized by the vanadium. The distribution and amount of the phases dictate the materials
properties and can be altered by prior thermal treatments. The alloy can also be mechanically
worked to alter its properties. Typically, the microstructure is a fine-grained alpha phase with
the beta phase present as isolated particles that precipitate at the grain boundaries; this
microstructure possesses excellent fatigue resistance compared to other forms of titanium
alloy microstructures.

The mechanical properties of Ti-6Al-4V are more than adequate for most orthopaedic
applications The elastic modulus for the alloy is about half that of stainless steel and the
cobalt alloys, making the alloy an ideal candidate for lowering the structural stiffness of a
device without changing its shape. For example, the axial, bending, and torsional stiffnesses
of a bone plate fabricated from titanium alloy will be half that of a bone plate of the same size
and shape made from stainless steel or cobalt alloy. Thus, the severity of stress shielding
when the plate is rigidly attached to the bone (so that the bone and the plate share
load) would be less for the titanium alloy plate. This mechanical consideration has led to the
use of titanium alloy in fracture and spinal fixation devices, including plates, nails, and
screws. The same consideration has led to the use of titanium alloy in stems for total joint
replacements.
A disadvantageous trait of titanium alloy is its notch sensitivity. A stress concentration, such
as a notch or scratch, on the surface of a titanium alloy implant significantly reduces the
fatigue life of the part. The same is true for the type of stress concentrations that occur when a
porous coating is applied to the surface of a titanium alloy total joint component. The severe
changes in geometry that result from the sharp angles that are created wherever the coating is
sintered to the substrate act as points of stress concentration. Therefore, care must be taken in
designing porous-coated total joint implants with titanium alloy.
Another disadvantage of titanium alloy is its lower hardness (in comparison, for example, to
the cobalt alloys). An ambiguous term, hardness encompasses a number of mechanical
properties, but mostly measures the materials resistance to elastic and plastic deformation.
Several standard tests for measuring hardness exist, most involving the forced indentation of
a fixed geometry indentor into the surface of a material. Hardness measurements are
determined from the geometry of the resulting indentation (for example, the depth or the
circumference). Hardness can be empirically related to other properties, such as yield
strength, but in general it is most useful in terms of comparison between materials.
Microhardness measurements, for example, in which a diamond-tipped, pyramidshapedindentor is pressed into the surface under a 10-g load, show titanium alloy to be about
15% softer than cast cobalt alloy. The decreased hardness of titanium alloy that must be
considered in total joint applications is due to its wear resistance.
Clinical observations have demonstrated significant scratching and wear of total hip femoral
heads made from titanium alloy. Measurements of the levels of titanium and aluminum in the
tissues and fluids taken from the hip joint have confirmed the release of significant amounts
of these elements from the femoral head. These observations suggest that titanium alloy that

has not undergone additional surface processing (for example, ion implantation) should not
be used as an articulating surface. Despite the longterm clinical evidence of the excellent
biocompatibility of titanium alloy, the concern that the release of cytotoxic elements such as
vanadium could cause local and systemic problems has led to the limited introduction of
other titanium alloys in which the vanadium has been replaced by more inert elements such
as niobium. Beta titanium alloys have also been advocated for orthopaedic implants. These
alloys have molybdenum concentrations greater than 10% to allow the beta phase to be stable
at room temperature. Beta alloys can be processed to possess lower elastic modulus (by about
20%) and slightly better crevice corrosion resistance than Ti-6Al-4V, while maintaining other
important mechanical properties at levels comparable or better than the conventional
aluminum-vanadium alloy. Together with excellent formability, the beta alloys are candidates
for a wide range of orthopaedic applications

Problems/test for with Biomaterials

Acute toxicity (cytotoxicity) arsenic
Sub chronic/chronic Pb
Sensitization Ni, Cu
Genotoxicity
Carcinogenicity
Reproductive &/or developmental Pb
Neurotoxicity
Immunotoxicity
Pyrogen, endotoxins