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728 SECTION II.

4 Degradation of Materials in the Biological Environment

Rice, M. A., Sanchez-Adams, J., & Anseth, K. S. (2006). Exog- Tsuji, H., & Ikada, Y. (1998). Blends of aliphatic polyesters.
enously triggered, enzymatic degradation of photopolymer- II. Hydrolysis of solution-cast blends from poly(L-lactide)
ized hydrogels with polycaprolactone subunits: Experimental and poly(-caprolactone) in phosphate-buffered solution.
observation and modeling of mass loss behavior. Biomacro- J. Appl. Polym. Sci., 67, 405415.
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Rosen, H. B., Chang, J., Wnek, G. E., Linhardt, R. J., & Langer, R. polyesters. III. Biodegradation of solution-cast blends from
(1983). Bioerodible polyanhydrides for controlled drug deliv- poly(L-lactide) and poly(-caprolactone). J. Appl. Polym. Sci.,
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J. A. (2004). The effect of the linker on the hydrolysis rate of Hubbell, J. A. (2005). Poly(ethylene glycol) hydrogels formed
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bicarbonate ions. The principal cations are Na+, K+, Ca2+,


CHAPTER II.4.4 DEGRADATIVE EFFECTS
and Mg2+, but with smaller amounts of many others.
OF THE BIOLOGICAL ENVIRONMENT
Table II.4.4.1 presents the range of values for the anion
ON METALS AND CERAMICS
and cation concentrations in blood plasma and extracel-
David F. Williams1 and Rachel L. Williams2 lular fluid (Bundy, 1994). This represents an environment
1Wake Forest Institute of Regeneration Medicine Winston-Salem, with a chloride concentration of approximately a third of
North Carolina, USA
that of sea water (Hanawa, 2002). The concentration of
2Clinical Engineering, Institute of Ageing and Chronic Disease,
dissolved oxygen also influences the aggressive nature of
University of Liverpool, Liverpool, UK
the environment, and in venous blood is approximately
a quarter of that in air. The organic substances include
Metallic and ceramic biomaterials continue to be used low molecular weight species, as well as relatively high
in many medical device applications. Several of these molecular weight proteins and lipids. Table II.4.4.2 gives
materials now have more than 40 years clinical experi- examples of the concentration of various organic com-
ence, and the factors that control their performance and ponents of blood plasma. The protein content of the
the mechanisms by which they interact with the human environment is known to have a significant influence
body are well-known and understood. However, since on the corrosive nature of body fluids (Williams, 1985;
the biological environment to which they are exposed Khan etal., 1999a; Mueller etal., 2009). The pH in this
is both very aggressive and very susceptible to mate- well-buffered system is around 7.4, although because of
rial-provoked adverse responses (Williams, 2008), it is inflammation it may change for short periods following
important that the potential for degradative effects on surgery to as low as 4 or 5 (Bundy, 1994). The tempera-
these materials is kept clearly in mind as new materials ture remains constant at around 37C.
and new applications are introduced. On the basis of existing knowledge of the stability of
The environment to which biomaterials are exposed materials in various environments, we should predict that
during prolonged use (i.e., the internal milieu of the body) metals, as a generic group, should be relatively suscepti-
can be described as an aqueous medium containing var- ble to corrosion in this biological environment, whereas
ious anions, cations, organic substances, and dissolved ceramics should display a varying susceptibility, depending
oxygen. The anions are mainly chloride, phosphate, and on solubility. This correlates fairly well with experimental
Chapter iI.4.4 Degradative Effects of the Biological Environment on Metals and Ceramics 729

TAB L E I I . 4 . 4 . 1 Ionic Concentrations in Blood TABLE II.4.4.3 Chemical Composition


Plasma and Extracellular Fluid of Implant Alloys
Blood Plasma Extracellular Fluid Implant Alloys Composition
Anion, Cation (mM) (mM) 316L stainless steel Cr, Mo, Ni, Mn, C, S, Si, P, Fe
Cl 96111 112120 CoCr based alloys Cast CoCrMo
HCO3 1631 25.329.7 Wrought CoCrMo
HPO42 11.5 193102 Wrought CoCrWNi
SO42 0.351 0.4 Wrought CoCrMoNi
H2PO4 2 Wrought CoCrMoNiFe
Na+ 131155 14115 Wrought CoCrMoNiWFe
Mg2+ 0.71.9 1.3 Cp titanium Ti + traces of O, N, C, H, Fe
Ca2+ 1.93 1.41.55 Titanium alloys Ti-6Al-4V
K+ 355.6 3.54 Ti-6Al-7Nb
Ti-15Mo
(Bundy, 1994) Ti-12Mo-6Zr-2Fe
Ti-13Nb-13Zr
Ti-15Mo-2.8Nb-0.2Si-0.26O
TAB L E I I . 4 . 4 . 2 Major Proteins and Other Organic Ti-16Nb-10Hf
Constituents of Blood Plasma Ti-15Mo-5Zr-3Al
Major Proteins and Organic Molecules in Blood Plasma TiNi
(gl1 Unless Stated Otherwise)
Albumin 3055
-Globulins 510 TABLE II.4.4.4 Chemical Composition
-Globulins 612 of Common Implant Ceramics
-Globulins 6.615 Implant Ceramics Composition
-Lipoproteins 3.54.5
Fibrinogen 1.74.3 Alumina Al2O3 + <0.3 wt% MgO
Total cholesterol 1.22.5 Zirconia Yttria stabilized tetragonal zirconia ZrO2
Fatty acids 1.94.5 + 23mol% Y2O3
Glucose 0.651.1 Calcium phosphates Ca3(PO4)2- or -tricalcium phosphate
Lactate 0.52.2 mM Ca10(PO4)6(OH)2hydroxyapatite
Urea 37 mM
(Bundy, 1994) and how is material selection (and treatment) gov-
erned by this knowledge?
observations and clinical experience, since it is well-known 2. Are there variables within this biological environment
that all but the most corrosion-resistant metals will suffer other than those described above that can influence
significant and destructive attack upon prolonged implan- these processes?
tation. Also, even the most noble of metals, and those that 3. What are the consequences of such corrosion and
are most strongly passivated (i.e., naturally protected by degradation phenomena?
their own oxide layer), will still show some degree of inter-
action. The important passivating implant alloys and their We review each of these questions in this chapter. It
compositions are presented in Table II.4.4.3. is particularly important to bear in mind some general
There are some ceramics that have a combination points as these questions are discussed.
of very strong partially ionic, partially covalent bonds
that are sufficiently stable to resist breakdown within 1. Material selection cannot be governed solely by con-
this environment, such as the pure simple oxide ceram- siderations of stability, and mechanical and physical
ics, and others in which certain of the bonds are read- properties especially may be of considerable impor-
ily destroyed in an aqueous medium so that the material tance. Since corrosion is a surface phenomenon,
essentially dissolves, for example certain calcium phos- however, it may be possible to optimize corrosion
phates. Typical implant ceramics and their compositions resistance by attention to, or treatment of, the sur-
are presented in Table II.4.4.4. face rather than by manipulation of the bulk chem-
With these general statements in mind, we have to istry (Trepanier et al., 1999, Singh and Dahotre,
consider the following questions in relation to the corro- 2007). This offers the possibility of developing suf-
sion and degradation of metals and ceramics: ficient corrosion resistance in materials of excellent
bulk mechanical and physical properties. Thus, noble
1. Within these groups, how does the susceptibility to metals such as gold and platinum are rarely used for
corrosion and degradation vary, by what precise structural applications (apart from dental restora-
mechanisms do the interfacial reactions take place, tion) because of their inferior mechanical properties,
730 SECTION II.4 Degradation of Materials in the Biological Environment

even though they have excellent corrosion resistance; electrochemical reactions take place on a metallic surface
instead, base metal alloys with passivated or pro- in an aqueous electrolyte. There are always two reactions
tected surfaces offer better all-around properties. that occur: the anodic reaction, which yields metallic
2. Medical devices are not necessarily used in mechanically ions, for example, involving the oxidation of the metal
stress-free conditions, and indeed the vast majority of to its salt:
those using metals or ceramics are structurally loaded. M M(n + ) + n(electrons) (1)
It is well-known that mechanical stress plays a very
important role in the corrosion of metals (Gilbert etal., and the cathodic reaction, in which the electrons so gen-
1993; Jacobs etal., 1998) and the degradation process erated are consumed. The precise cathodic reaction will
in ceramics (Piconi and Maccauro, 1999), both potenti- depend on the nature of the electrolyte, but two of the
ating existing effects and initiating others. This has to be most important in aqueous environments are the reduc-
taken into consideration. tion of hydrogen:
3. We cannot expect the biological environment to be con- 2H+ + 2e H2 (2)
stant. Within the overall characteristics described ear-
lier, there are variations (with time, location, activity, and the reduction of dissolved oxygen:
health status, etc.) in, for example, oxygen levels, avail- O2 + 4H+ + 4e 2H2 O (3)
ability of free radicals, and cellular activity, all of which
may cause variations in the corrosive nature of the envi- in acidic solutions:
ronment (Tengvall etal., 1989; Fonseca and Barbosa, O2 + 2H2 O + 4e 4OH (4)
2001). Most important, corrosion is not necessarily
a progressive homogeneous reaction with zero-order or in neutral or basic solutions.
kinetics. Corrosion processes can be quiescent, but In all corrosion processes, the rate of the anodic or
then become activated, or they can be active, but then oxidation reaction must equal the rate of the cathodic
become passivated and localized, with transient fluctua- or reduction reaction. This is a basic principle of elec-
tions in conditions playing a part in these variations. trochemically-based metallic corrosion. It also explains
4. The effects of corrosion or degradation may be two- how variations in the local environment can affect the
fold. First, and in the conventional metallurgical sense overall rate of corrosion by influencing either the anodic
the most obvious, the problem can lead to loss of struc- or cathodic reactions. The whole corrosion process can
tural integrity of the material and function. This may be be arrested by preventing either of these reactions.
undesirable, as in the case of many long-term prosthe- From a thermodynamic point of view, first consider
ses, or desirable, as in devices intended for short-term the anodic dissolution of a pure metal isolated in a solu-
function (e.g., ceramics for drug delivery systems) or tion of its salt. The metal consists of positive ions closely
where the material is replaced by tissue during the deg- surrounded by free electrons. When the metal is placed
radation process, as with ceramic bone substitution. In in a solution, there will be a net dissolution of metal ions
addition to this, however, and usually of much greater since the Gibbs free energy (G) for the dissolution reac-
significance with biomaterials, when released into the tion is less than for the reverse reaction. This leaves the
tissue, the corrosion or degradation products can have metal with a net negative charge, thus making it harder
a significant and controlling effect on that tissue (Bravo for the positive ions to leave the surface, and increasing
etal., 1990; Jacobs etal., 1998). Indeed, it is likely that the G for the dissolution reaction. There will come a
the corrosion process is the most important mediator of point when the G for the dissolution reaction will equal
the tissue response to metallic materials. It is therefore the G for the reverse reaction. At this point, a dynamic
important that we know both the nature of the reaction equilibrium is reached, and a potential difference will be
products and their rate of generation. In this respect it set up across the charged double layer surrounding the
is important to recognize that a very small release of metal. The potential difference will be characteristic of
certain metallic ions that cause adverse biological reac- the metal and can be measured against a standard ref-
tions may be more significant than a larger amount of a erence electrode. When this is done against a standard
less stimulating byproduct of corrosion or degradation. hydrogen electrode in a 1 N solution of its salt at 25C,
The implications of these effects on biocompatibility it is defined as the standard electrode potential for that
and the future uses of biomaterials have recently been metal (Table II.4.4.5). The position of a metal in the
discussed by Williams (Williams, 2008, 2009). electrochemical series primarily indicates the order with
which metals displace each other from compounds, but
it also gives a general guide to reactivity in aqueous solu-
METALLIC CORROSION tions. Those at the top are the noble, relatively unreactive
metals, whereas those at the bottom are the more reac-
Basic Principles
tive. This is the first guide to corrosion resistance, but, as
The most pertinent form of corrosion related to metal- we shall see, there are major difficulties related to the use
lic biomaterials is aqueous corrosion. This occurs when and interpretation of reactions from this simple analysis.
Chapter iI.4.4 Degradative Effects of the Biological Environment on Metals and Ceramics 731

of ions takes place. In other words, the corrosion process


TAB L E I I . 4 . 4 . 5 Electrochemical Series
takes place only transiently, but is effectively stopped
Metal Potential (V) once this equilibrium is reached.
Gold 1.43 In reality, we usually have neither entirely homoge-
Platinum 1.20 neous surfaces nor solutions, nor complete isolation of
Mercury 0.80 the metal from other parts of the environment, and this
Silver 0.79 equilibrium is easily upset. If the conditions are such that
Copper 0.34 the equilibrium is displaced, the metal is said to be polar-
Hydrogen 0 ized. There are several ways in which this can happen.
Lead 0.13
Two main factors control the behavior of metals in this
Tin 0.14
Molybdenum 0.20 respect, and determine the extent of corrosion in prac-
Nickel 0.25 tice. The first concerns the driving force for continued
Cobalt 0.28 corrosion (i.e., the reasons why the equilibrium is upset
Cadmium 0.40 and the nature of the polarization), and the second con-
Iron 0.44 cerns the ability of the metal to respond to this driving
Chromium 0.73 force.
Zinc 0.76 It is self-evident that if either the accumulating posi-
Aluminum 1.33
tive metal ions in the surrounding media or the accumu-
Titanium 1.63
Magnesium 2.03
lating electrons in the metal are removed, the net balance
Sodium 2.71 between the dissolution and the replacement of the ions
Lithium 3.05 will be disturbed. This will occur in the biological envi-
ronment surrounding implanted alloys, due to the inter-
action of the proteins with the metal ions. Metal ions
Now consider a system in which the metal is in an can form complexes with proteins (Steinemann, 1996;
aqueous solution that does not contain its ions. In this Jacobs et al., 1998; Bdinger and Hertl, 2000; Munoz
situation, the electrode potential at equilibrium (i.e., and Mischler, 2007) and these complexes can be trans-
when the rate of the anodic reaction equals the rate of ported away from the immediate vicinity. This removes
the cathodic reaction) will be shifted from the standard the metal ions from the charged double layer at the inter-
electrode potential and can be defined by the Nernst face allowing further release of metal ions to re-establish
equation: the equilibrium. Similarly, relative movement between
E = E0 + (RT / nF In(aanod / acath ) the implant and the tissue, for example, at a bearing sur-
face or on a cyclically loaded implant, will cause mix-
where E0 is the standard electrode potential, RT/F is a ing at the interface and will modify the composition of
constant, n is the number of electrons transferred, and the electrolyte, and may modify the surface of the alloy
a is the activity of the anodic and cathodic reactants. (Khan etal., 1999b). The equilibrium is established pre-
At low concentrations, the activity can be approxi- cisely because of the imbalance of charge, so that if the
mated to the concentration. In this situation, there is a charge balance is disturbed, further corrosion will occur
net dissolution of the metal and a current will flow. At to attempt to re-establish the balance. The result will be
equilibrium, the rate of the metal dissolution is equal continued dissolution as the system attempts to achieve
to the rate of the cathodic reaction, and the rate of the this equilibrium, in other words, sustained corrosion.
reaction is directly proportional to the current density An environment that allows the removal of electrons in
by Faradays law; therefore: contact with the metal or stirring of the electrolyte will
ianodic = icathodic = icorrosion achieve this.
The process of galvanic corrosion may be used to dem-
and the Nernst equation can be rewritten: onstrate this effect. Consider a single homogeneous pure
E = E0 = In(icorr / i0 ) metal, A, existing within an electrolyte (Figure II.4.4.1).
The metal will develop its own potential, VA, with respect
where is a constant and i0 is the exchange current den- to the electrolyte. If a different metal electrode, B, is
sity, which is defined as the anodic (or cathodic) current placed into the same electrolyte, but without contacting
density at the standard electrode potential. Current den- A, it will develop its own potential VB. If VA is not equal
sity is the current, measured in amperes, normalized to to VB, there will be a difference in the numbers of excess
the surface area of the metal. free electrons in each. This is of no consequence if A and
These conditions represent convenient models for B are isolated from each other, but should they be placed
the basic mechanisms of corrosion, but they are hardly in electrical contact, electrons will flow from that metal
realistic. Indeed, in this situation of a homogeneous pure with the greater potential in an attempt to make the two
metal existing within an unchanging environment, an electrodes equipotential. This upsets the equilibrium and
equilibrium is reached in which no further net movement causes continued and accelerated corrosion of the more
732 SECTION II.4 Degradation of Materials in the Biological Environment

VA VB oxidation leaves an impervious oxide layer firmly adher-


ent to the metal surface; thus all other forms of cor-
rosion may be significantly reduced because the oxide
A B layer acts as a protective barrier, passivating the metal.
+ +
The manufacturing process for implant alloys may
+ + include a passivating step to enhance the oxide layer
+ + prior to implantation, for example nitric acid treatment
+ + of 316L stainless steel (Fraker and Griffith, 1985; Yoo
+
+ etal., 2008).
In summary, the basic principles of corrosion deter-
mine that:

VA > VB 1. In theory, corrosion resistance can be predicted from


standard electrode potentials. This explains the nobil-
ity of some metals and the considerable reactivity of
V others, but is not useful for predicting the occurrence
of corrosion of most alloy systems in practice.
2. Irrespective of standard electrode potentials, the cor-
rosion resistance of many materials is determined by
their ability to become passivated by an oxide layer
that protects the underlying metal.
3. Corrosion processes in practice are influenced by
variations in surface microstructural features, and
in the environment that disrupt the charge transfer
equilibrium.

VA > V > VB INFLUENCE OF THE BIOLOGICAL


FIGURE II.4.4.1 When electrical contact is made between elec- ENVIRONMENT
trodes A and B, electrode B acts as an electron sink, thus upsetting It is reasonable to assume that the presence of biological
the equilibrium and causing continued dissolution of A.
macromolecules will not cause a completely new corro-
sion mechanism. However, they can influence the rate of
corrosion by interfering in some way with the anodic or
active metal (anodic dissolution), and protects the less
cathodic reactions discussed earlier. Four ways in which
active metal (cathodic protection).
this could occur are discussed next.
Galvanic corrosion may be seen whenever two dif-
ferent metals are placed in contact in an electrolyte. It 1. The biological molecules could upset the equilibrium
has been frequently observed with complex, multicom- of the corrosion reactions by consuming one or other
ponent surgical implants such as modular total joint of the products of the anodic or cathodic reaction.
designs consisting of titanium alloy femoral stems and For example, proteins can bind to metal ions and
cobalt alloy femoral heads (Jacobs etal., 1998; Virtanen transport them away from the implant surface. This
etal., 2008). It is not necessary for the components to be will upset the equilibrium across the charged double
macroscopic, monolithic electrodes for this to happen, layer and allow further dissolution of the metal; in
and the same effect can be seen when there are differ- other words, it will decrease G for the dissolution
ent microstructural features within one alloy, such as the reaction.
multiphase microstructure evident in implants of sensi- 2. The stability of the oxide layer depends on the elec-
tized stainless steel where the grain boundaries become trode potential and the pH of the solution. Proteins
depleted in chromium and corrode preferentially to the and cells can be electrically active and interact with
remaining surface (Disegi and Eschbach, 2000). In prac- the charges formed at the interface, and thus affect the
tice, it is the regional variations in electrode potential electrode potential (Bundy, 1994). Bacteria (Laurent
over an alloy surface that are responsible for much of the et al., 2001) and inflammatory cells (Fonseca and
generalized surface corrosion that takes place in metallic Barbosa, 2001; Hanawa, 2002; Messer etal., 2009)
components. can alter the pH of the local environment through the
Many of the commonly used surgical alloys contain generation of acidic metabolic products that can shift
highly reactive metals (i.e., with high negative electrode the equilibrium.
potentials), such as titanium, aluminum, and chromium. 3. The stability of the oxide layer is also dependent on
Because of this high reactivity, they will react with oxy- the availability of oxygen. The adsorption of proteins
gen upon initial exposure to the atmosphere. This initial and cells onto the surface of materials could limit the
Chapter iI.4.4 Degradative Effects of the Biological Environment on Metals and Ceramics 733

diffusion of oxygen to certain regions of the surface. is sometimes used for its antibacterial activity; and plati-
This could cause preferential corrosion of the oxygen- num-group metals (Pt, Pd, Ir, Rh) are used in electrodes.
deficient regions and lead to the breakdown of the The second approach involves the use of the pas-
passive layer. Alternatively, the biomolecule adsorp- sivated metals. Of the three elements that are strongly
tion layer could act as a capacitor, preventing the dif- passivated (i.e., aluminum, chromium, and titanium),
fusion of molecules from the surface (Hiromoto etal., aluminum cannot be used on its own for biomedical pur-
2002). poses because of toxicity problems; however, it has an
4. The cathodic reaction often results in the formation important role in several titanium alloys. Chromium is
of hydrogen, as shown earlier. In a confined locality, very effectively protected, but cannot be used in bulk. It
the build-up of hydrogen tends to inhibit the cathodic is, however, widely used in alloys, especially in stainless
reaction, and thus restricts the corrosion process. If steels and in the cobaltchromium-based alloys, where it
the hydrogen can be eliminated, then the active cor- is normally considered that a level of above 12% gives
rosion can proceed. It is possible that bacteria in the good corrosion resistance, and about 18% provides excel-
vicinity of an implant could utilize the hydrogen, and lent resistance. Titanium is the best in this respect, and is
thus play a crucial role in the corrosion process. used as a pure metal or as the major constituent of alloys
(Long and Rack, 1998; Geetha etal., 2009). In alloys the
There is sufficient evidence to support the premise that passivating layer promoting the corrosion resistance is
the presence of proteins and cells can influence the rate of predominantly composed of one of these metal oxides.
corrosion of some metals (Williams, 1985; Khan etal., For example, chromium oxide passivates 316L stainless
1999a,b; Hanawa, 1999, 2002). Studies have examined steel and CoCr-based alloys, and Ti oxide passivates
these interactions electrochemically, and have found Ti alloys. The other alloying elements may be present in
very few differences in many of the parameters measured the surface oxide and this can influence the passivity of
(e.g., electrode potential, polarization behavior, and cur- the layer (Sittig etal., 1999). Careful pretreatment of the
rent density at a fixed potential). However, analysis of alloys can be used to control the passivity of these alloys
the amount of corrosion through weight loss or chemical (Trepanier etal., 1998; Shih etal., 2000). In particular,
analysis of the electrolyte has shown significant effects production procedures need to be controlled because
from the presence of relatively low concentrations of of their influence on the surface oxides, for exam-
proteins. These effects have varied from several-fold ple, cleaning (Aronsson et al., 1997) and sterilization
increases for some metals under certain conditions, to (Thierry etal., 2000) procedures.
slight decreases under other conditions. Although these metals and alloys have been selected
It has been shown that proteins adsorb onto metal for their corrosion resistance, corrosion will still take
surfaces and that the amount adsorbed appears to be place when they are implanted in the body. Two impor-
different in a range of metals (Williams and Williams, tant points have to be remembered. First, whether noble
1988; Wlivaara etal., 1992). Similarly, proteins have or passivated, all metals will suffer a slow removal of
been shown to bind to metal ions, and it is suggested ions from the surface, largely because of local and tem-
that they are transported away from the local site as a poral variations in microstructure and environment.
proteinmetal complex and distributed systemically in This need not necessarily be continuous, and the rate
the body (Jacobs etal., 1998). It is therefore likely that may either increase or decrease with time, but metal ions
proteins will influence the corrosion reactions that occur will be released into that environment. This is particu-
when a metal is implanted, although there is no direct larly important with biomaterials, since it is the effect
evidence to explain the mechanism of the interaction at of these potentially toxic or irritant ions that is the most
this time. important consequence of their use. Even with a strongly
passivated metal, there will be a finite rate of diffusion of
ions through the oxide layer, and possibly dissolution of
CORROSION AND CORROSION CONTROL the layer itself. It is well-known that titanium is steadily
IN THE BIOLOGICAL ENVIRONMENT released into the tissue from titanium implants (Jacobs
The need to ensure minimal corrosion has been the etal., 1998; Hanawa etal., 1998). Second, some specific
major determining factor in the selection of metals and mechanisms of corrosion may be superimposed on this
alloys for use in the body. Two broad approaches have general behavior; some examples are given in the next
been adopted. The first has involved the use of noble section.
metals, that is, those metals and their alloys for which
the electrochemical series indicates excellent corrosion
Pitting Corrosion
resistance. Examples are gold, silver, and the platinum
group of metals. Because of cost and relatively poor The stainless steels used in implantable devices are pas-
mechanical properties, these are not used for major sivated by the chromium oxide that forms on their sur-
structural applications, although it should be noted that face. It has been shown, however, that in a physiological
gold and its alloys are extensively used in dentistry; silver saline environment, the driving force for repassivation
734 SECTION II.4 Degradation of Materials in the Biological Environment

FIGURE II.4.4.2 This etched metallographic micrograph demonstrates the pitting corrosion of stainless steel.

of the surface is not high (Seah etal., 1998). Thus, if the


passive layer is broken down, it may not repassivate and
Crevice Corrosion
active corrosion can occur. The area between the head of the bone screw and
Localized corrosion can occur as a result of imperfec- countersink on the fracture fixation plate can also be
tions in the oxide layer, producing small areas where the influenced by the crevice conditions that the geometry
protective surface is removed (Rondelli and Vicentini, creates (Figure II.4.4.3) (Cook et al., 1987). Porous
1999). These localized spots will actively corrode, and coated implants may also demonstrate crevice corrosion
pits will form in the surface of the material. This can (Seah et al., 1998). Accelerated corrosion can be initi-
result in a large degree of localized damage, because the ated in a crevice by restricted diffusion of oxygen into
small areas of active corrosion become the anode and the crevice. Initially, the anodic and cathodic reactions
the entire remaining surface becomes the cathode. Since occur uniformly over the surface, including within the
the rate of the anodic and cathodic reactions must be crevice. As the crevice becomes depleted of oxygen,
equal, it follows that a relatively large amount of metal the reaction is limited to metal oxidation, balanced by
dissolution will be initiated by a small area of the sur- the cathodic reaction on the remainder of the surface.
face, and large pits may form (Figure II.4.4.2). In an aqueous sodium chloride solution, the build-up of
metal ions within the crevice causes the influx of chloride
ions to balance the charge by forming the metal chloride.
Fretting Corrosion
In the presence of water, the chloride will dissociate to
The passive layer may be removed by a mechanical pro- its insoluble hydroxide and acid. This is a rapidly accel-
cess (Khan etal., 1999b; Okazaki, 2002). This can be a erating process, since the decrease in pH causes further
scratch that does not repassivate, resulting in the forma- metal oxidation.
tion of a pit, or a continuous cyclic process in which
any reformed passive layer is removed. This is known
as fretting corrosion, and it is suggested that this can
Intergranular Corrosion
contribute to the corrosion observed between a fracture As mentioned earlier, stainless steels rely on the for-
fixation plate and the bone screws attaching the plate to mation of chromium oxides to passivate the surface.
the bone. There are four reasons why fretting can affect If some areas of the alloy become depleted in chro-
the corrosion rate. The first is due to the removal of the mium, as can happen if carbides are formed at the grain
oxide film as just discussed. The second is due to plas- boundaries, the regions adjacent to the grain boundar-
tic deformation of the contact area; this can subject the ies become depleted in chromium. The passivity of the
area to high strain fatigue and may cause fatigue corro- surface in these regions is therefore affected, and pref-
sion. The third is due to stirring of the electrolyte, which erential corrosion can occur (Figure II.4.4.4). Although
can increase the limited current density of the cathodic this problem can easily be overcome by heat treating
reaction. The fourth, especially seen with titanium, is the alloys (Disegi and Eschbach, 2000), it has been
the influence of fretting on hydrogen absorption, and observed on retrieved implants (Walczak et al., 1998)
the consequential hydrogen embrittlement (Rodrigues and can cause severe problems, since once initiated it
etal., 2009). will proceed rapidly and may well cause fracture of the
Chapter iI.4.4 Degradative Effects of the Biological Environment on Metals and Ceramics 735

FIGURE II.4.4.3 Crevice corrosion is evident in the screw hole in this fracture fixation plate.

FIGURE II.4.4.4 Intergranular corrosion is demonstrated on this etched stainless steel specimen.

implant and the release of large quantities of corrosion it is a potential source of failure for implanted devices,
products into the tissue. although to date there has been little evidence that it
occurs extensively in clinical practice.
Stress Corrosion Cracking
Galvanic Corrosion
Stress corrosion cracking is an insidious form of cor-
rosion, since an applied stress and a corrosive environ- If two metals are independently placed within the same
ment can work together and cause complete failure of a solution, each will establish its own electrode poten-
component, when neither the stress nor the environment tial with respect to the solution. If these two metals
would be a problem on their own. The stress level may are placed in electrical contact, then a potential differ-
be very low, possibly only residual, and the corrosion ence will be established between them, electrons pass-
may be initiated at a microscopic crack tip that does not ing from the more anodic to the more cathodic metal.
repassivate rapidly. Incremental crack growth may then Thus, equilibrium is upset and a continuous process of
occur, resulting in fracture of the implant. Industrial uses dissolution from the more anodic metal will take place.
of stainless steels in saline environments have shown This accelerated corrosion process is galvanic corro-
susceptibility to stress corrosion cracking, and therefore sion. It is important if two different alloys are used in
736 SECTION II.4 Degradation of Materials in the Biological Environment

FIGURE II.4.4.5 Extensive corrosion on the titanium stem of a modular hip prosthesis.

an implantable device when the more reactive may cor- on polymers. However, there is increasing interest in the
rode freely. possibility of using magnesium alloys that are known to
Whenever stainless steel is joined to another implant degrade in the body, and are potentially resorbable.
alloy, it will suffer from galvanic corrosion. If both alloys As reviewed by Staiger etal. (Staiger etal., 2006) and
remain within their passive region when coupled in this Witte (Witte, 2010), magnesium itself corrodes readily in
way, the additional corrosion may be minimal. Some the body, and magnesium samples can disappear in rela-
modular orthopedic systems are made of titanium alloys tively short times. The rapid loss of strength, and the doubt-
and cobalt-based alloys on the basis that both should ful biocompatibility of such a rapidly degrading structure,
remain passive, but evidence of corrosion has been has to be viewed with caution, even though it would appear
reported (Gilbert et al., 1993). Certainly, as shown in that the magnesium ions are relatively well-tolerated, mag-
Figure II.4.4.5, titanium stems of modular prostheses can nesium being an essential element in humans. Develop-
exhibit extensive corrosion. Galvanic corrosion may also ments with this element have concentrated on alloying
take place on a microscopic scale in multiphase alloys additions that reduce the corrosion rate, without inducing
where phases are of considerably different electronega- significant cytotoxicity or radically altering the mechani-
tivity. In dentistry, some amalgams may show extensive cal properties (Xu et al., 2007; Li et al., 2008; Kannan
corrosion because of this mechanism. and Raman, 2008). Alloys of MgMnZn and MgCa,
wherein all alloying additions are also essential elements,
figure prominently in these developments. It is a little early
Intentional Corrosion and Resorption to predict the likely clinical success with these alloys.
of Implantable Alloys
The vast majority of applications of metallic systems in
CERAMIC DEGRADATION
medical devices are predicated on the assumption that the
device will remain in the patients body for their full life The rate of degradation of ceramics within the body can
or until it is intentionally removed surgically. As discussed differ considerably from that of metals, in that they can
elsewhere in this book, there are some situations where be either highly corrosion resistant or highly soluble. As
permanence is not required, and indeed could be disad- a general rule, we should expect to see a very significant
vantageous. Two situations may be mentioned here: the resistance to degradation with ceramics and glasses. Since
use of temporary supports during tissue healing (as with the corrosion process in metals is one of a conversion
bone fracture plates), and the use of intravascular stents of a metal to a ceramic structure (i.e., metal to a metal
that support blood vessels after angioplasty procedures. oxide, hydroxide, chloride, etc.) we must intuitively
In both of these situations, an intentionally degradable conclude that the ceramic structure represents a lower
and resorbable material may be considered as an alterna- energy state, in which there would be less driving force
tive. With bone fracture plates, a range of biodegradable for further structural degradation. The interatomic bonds
polymers have been used clinically, and there is some good in a ceramic, being largely ionic but partly covalent, are
clinical success. With stents, clinical experience is only strong directional bonds and large amounts of energy are
just beginning, and again attention is being concentrated required for their disruption. As extraction metallurgists
Chapter iI.4.4 Degradative Effects of the Biological Environment on Metals and Ceramics 737

know, it takes a great deal of energy to extract aluminum rate seen at different implantation sites. It is possible that
metal from the ore aluminum oxide, but as we have seen, cellular activity, either by phagocytosis or the release of
the reverse process takes place readily by surface oxida- free radicals, could be responsible for such variations.
tion. Thus, we should expect ceramics such as Al2O3, In between the extremes of stability and intentional
ZrO2, TiO2, SiO2, and TiN to be stable under normal degradability lie a small group of materials in which
conditions (Dalgleish and Rawlings, 1981). This is what there may be limited activity. This is particularly seen
is observed in clinical practice. There is limited evidence with a number of glasses and glass ceramics, based on
to show that some of these ceramics (e.g., polycrystalline Ca, Si, Na, P, and O, in which there is selective dissolu-
Al2O3 and ZrO2) do show aging phenomena (Piconi tion on the surface involving the release of Ca and P, but
and Maccauro, 1999; Marti, 2000), with reductions in in which the reaction then ceases because of the stable
some mechanical properties, but the significance of this is SiO2-rich layer that remains on the surface. This is of
unclear. With some variations in structure, there is clear considerable interest because of the ability of such sur-
evidence that problems may arise if incorrect structural faces to bond to bone, and this subject is dealt with else-
forms are used. Zirconia is often used in the transforma- where in this book.
tion toughened state; as with most oxide ceramics, the On the basis of this behavior, bioceramics are nor-
material is inherently brittle but this can be ameliorated mally classified under three headings:
by the use of doping elements which cause the formation
Inert
or nearly inert ceramics
and retention of a metastable state. This is achieved by the
Resorbable ceramics
addition of small amounts of the rare earth oxide yttria
Ceramics of controlled surface reactivity.
to the zirconia. The toughening arises from the transfor-
mation of crystallographic structure at a crack tip under This area is discussed in detail in other chapters within
strain, which causes blunting of the crack and prevents its this book.
catastrophic propagation. However, this metastable state
can transform under other conditions. Many batches of
improperly heat-treated zirconia hip replacement com-
SUMMARY
ponents underwent such changes over a short time after This chapter has attempted to demonstrate that met-
implantation, causing significant structural failure under als are inherently susceptible to corrosion, and that the
load (Deville etal., 2005; Chevalier, 2006). greatest care is needed in using them within the human
Alternatively, there will be many ceramic structures body. In general, ceramics have much less tendency to
that, although stable in the air, will dissolve in aqueous degrade, but care still has to be taken over aging phe-
environments. Consideration of the classic fully ionic nomena. The human body is very aggressive toward all
ceramic structure NaCl and its dissolution in water dem- of these materials.
onstrates this point. It is possible, therefore, on the basis
of the chemical structure, to identify ceramics that will
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