Metallic biomaterials

Metal elements:
Element Symbol Element Symbol
Molybdenum Mo Manganese Mn
Chromium Cr Vanadium V
Germanium Ge Gallium Ga

Levels of describe a property:

Superior, Excellent, Good, Poor

Some facts:
1. Materials corrode differently in the body versus air
- Materials that are inert in air are not necessarily inert in human body fluids. The
human body environment is quite corrosive. Corrosion is accelerated in the presence
of ions.

- Human body maintains a pH at around 7.35~7.45, but areas of inflammation or a site

of implantation can fall the pH down to 3~4, this can accelerate the corrosion speed.
- Some corrosion resistant materials can develop a passive metal oxide layer by
reacting with oxygen which protects the materials from corrosion. However, the
oxygen level in the human body (e.g. plasma) is only ~25% of that in atmosphere,
which slows down the speed of passive oxide layer formation if that initial passive
layer is broken or worn down.

2. Human body needs ions to maintain a healthy system [1]

Macro elements Trace elements
- O, C, H, N, S: proteins Metal ions Non-metal ions
- Na, K, Cl: electrolytes, Fe, Cu, Mn, Zn, Se, Co, I, B
pH and osmotic balance Mo, Cr, Ba, W, Ce, Ni, Sr
- Ca, P, Mg: bone/teeth
 structure

However, excess amount of ion concentration is often detrimental.

3. Alloying changes properties significantly

- Properties of metallic materials can change considerably with presence of alloying
elements
- Choice of alloying elements depends on the desired purposes

Characteristics of metals
Advantages Drawbacks
• Mechanically robust • Can be corrosive in the body
- High strength environment
- High fracture toughness • Ion release
- High stiffness - Most of these metallic ions are toxic at
- High hardness high, non-trace levels, which further
- Good wear resistance induce chronic inflammation and
- High fatigue life subsequent downstream effects (such as
• Excellent conductivity osteolysis, sensitization)
• Easy to sterilize - Wear particles can exacerbate such ion
• Well-established manufacturing release
process into complex shapes and surface • Fibrous tissue formation: implant
finishing procedures loosening from the surrounding tissue
• Stress shielding in bone: in a
composite material system, the
phase/material with the higher stiffness
takes more load, which causes less strain
on the other material. However, bone
remodeling depends on the strain levels
in bone
Stainless steel
There are many types of stainless steels classified based on the alloying elements and
concentrations.

316L stainless steel

- Fe-C system, austenitic
- Also contains Cr, Mo, Ni and Mn at specified concentrations
- Cr and Mo enhances corrosion resistance by forming ~2 nm thick chromium rich
oxide film
- Ni and Mn enhances toughness, ductility

The role of nickel

- For austenite formation, if only Fe-C, it won’t be stable for austenite under 727 ℃
- Austenite has FCC structure, which is more ductile and tough
Nickel stabilizes the austenite phase at room temperature.

Advantages Drawbacks
1. Good mechanical properties 1. Release of chromium and nickel ions,
2. Good biocompatibility potentially in lethal amounts if left
3. Processability is versatile and well- unchecked
established - Chromium:
4. Cheap - Cr3+: essential trace ion for sugar
regulation in the body, though high
concentrations cause DNA damage
- Cr6+: well-known carcinogen, also
hemotoxic and genotoxic
- Chromate salts can trigger allergic
reaction
- Nickel:
- Typical daily exposure to Ni2+
readily cleared by the body (average
adult 100-300 μg/day), but large
persistent doses shown to be toxic,
carcinogenic
- Nickel allergy
2. Still not that good at resisting
corrosion in the body.
3. Fatigue: stress corrosion cracking →
 brittle failure of normally ductile
materials (figure below).

Applications
1. Temporary fixation devices for bone repair, removed as soon as there is sufficient
healing. But there is research towards reduced-nickel stainless steel, with nitrogen
instead as the austenite-stabilizer. (Orthinox)
2. Surgical instruments (blades, scissors) that contact body fluids but not necessarily
implanted.

Cobalt-chrome alloys
- Excellent corrosion resistance by passive layer of Cr 2O3 formation, even in saline,
and chlorine rich environments
- Often alloyed with Mo or Ni
- Mo: increased corrosion resistance, increased strength
- Ni: increased corrosion resistance, increased strength, increased castability

Cobalt ions in the human body

- Essential trace element
- Vitamin B12 = cobalamin C63H88CoN14O14P
- Two main forms:
• Methyl-cobalamin: promotes methionine synthesis
• Deoxyadenosyl-cobalamin: key role in energy metabolism

- Toxic at higher concentrations

- Triggering of hypersensitivity, similar to that of nickel ions
• Damage surrounding tissues
- Systemic issues associated with high cobalt ion concentrations
• Neurological: decline in cognitive function, hearing and visual impairment
• Cardiovascular and endocrine deficits
• Muscle cramps, fatigue, headaches

Advantages Disadvantages
1. Superior wear and fatigue resistance 1. More difficult to machine/process →
 2. Excellent corrosion resistance versus
other metals.
3. Excellent strengths arising from its
crystal structure:
- A mix of close-packed HCP and
FCC (HCP introduced during post-
processing e.g. forging, cold working
etc.)
- Different crystal structure makes
hard for dislocation motion
- Solid solution strengthening: Cr and
Mo also makes hard for dislocation
motion through the effects of alloying
increased cost
2. Highest stiffness causing stress
shielding: The implant material will take
the load away from the bone → The
bone does not bear any stresses → No
strains will happen on the bone → Bone
stops building new bone → Bone
becomes weaker.

Applications of Co-Cr-Mo alloys – mostly used in joint implants

1. Used as the main stem components due to its corrosion resistance and high fatigue
strength
2. Used on articulating surfaces because of its excellent wear resistance
- Usually metal on polymer. Softer material always wears first, for polymers like
polyethylene it produces wear particles that causes chronic inflammation →
osteolysis.
Metal on metal will produce smaller wear particles however it’s not good to have this
combination.

Titanium and titanium alloys

- Passive TiO2 layer readily formed on the surface
- Titanium ions have no biological role in the body, but are not toxic in relatively large
doses.

Pure titanium (CpTi)

- Commercially pure titanium (CpTi) has alpha-phase (HCP) structure.
- The purer the titanium, the weaker, but more ductile
- Alpha stabilizing elements: Al, Ga, Ge

Standards for commercially pure titanium

Advantages Disadvantages
1. Light 1. Low wear resistance than other
 2. Corrosion resistant metals: although the passive TiO2 layer
3. Closer to the elastic modulus of bone can be readily formed for good
than other metals resistance to corrosion, but not
4. Kind of bioactive necessarily for resisting mechanical
forces. Easier mechanical surface
damage leads to increased roughness,
which increased the wear of both
articulating surfaces → loose of TiO2
debris → another abrading factor (see
figure below)
- Weak for load-bearing applications

Titanium alloys
Alloying titanium can improve the strength. Depending on alloying elements, there
are three material compositions:
- Alpha-titanium (HCP) alloys
- Alpha-beta titanium alloys
- Beta-titanium (BCC) alloys

Alpha-beta phase
- In the presence of both an alpha-stabilizer and beta-stabilizer in the appropriate
concentrations, one can get a hybrid α-β alloy.
- Generally stronger, less ductile

Ti-6Al-4V – most commonly used titanium alloy

- Alpha stabilizer: 6 wt% Al; beta stabilizer: 4 wt% V
- Al and V are not implicated in toxic or adverse reactions from use in titanium alloys,
but both ions show adverse effects in large concentrations. Potential long term health
problems include neuropathy, osteomalacia and Alzheimers.
- Result: stronger titanium alloy than CpTi.

Applications of titanium and titanium alloys

CpTi: non-load bearing, get as best biological and/or ductile properties as possible
- Pacemaker/cochlear hermetic case
- Dental/maxillafacial implants
- Housings for ventricular assist devices
- Mechanical heart valves

Ti-6Al-4V: load bearing

- The above, plus
- Joint replacement implants
- Fixation implants

Beta-titanium alloys
- If add beta-stabilizers, a stronger titanium alloy can be obtained.
- Beta-stabilizing elements: Mo, Nb, Cr, Fe, Si, Ta
- If add enough beta-stabilizers, pure beta-titanium alloys can be obtained, though
these stabilizers lead to concern on long-term biocompatibility
- Shows good strength and fracture toughness, but very low modulus

Aside: Research show TZNT alloys can reach to ~ 60 GPa (cortical bone: 10-30 GPa)
- Ti-4.6Zr-29Nb-13Ta: In vitro and short term seems fine in terms of non-toxic
outcomes [2].

Nitinol
- An alloy of nickel and titanium has ~55 wt% Ni (50/50 atomic%) to be stable at
room temperature.
- Other trace elements Hf, Pd, Pt, Zr, Au, used to control temperature of phase
transformation.
- Biocompatibility is better than stainless steel
- Titanium forms a corrosion-preventing TiO 2 passive layer which significantly
hinders the nickel release. So it has more nickel in nitinol, but less nickel released
than stainless steel.
 - Very inert in the body – minimal fibrous tissue formation, no negative deleterious
effects reported in humans
- In general, corrosion resistance is better than Co-Cr-Mo and stainless steel alloys.

Phases of Nitinol
It is unique in that it has two stable phases about a phase transition temperature
- A stronger austenitic (FCC) phase, at temperatures higher than the phase transition
temperature
- A weaker martensite (BCT) phase, at temperatures lower than the phase transition
temperature

- Normally, metals undergo elastic deformation of up to only < 1% for most metals,
before they reach plastic deformation (because of stretching of atomic bonds). For
nitinol (starting as austenitic FCC, at temperature higher than phase transition), usual
elastic deformation to yield does not involve plastic deformation, but a phase
transition to martensitic BCT (stress induced phase transformation), this phase change
allows for the change in shape (i.e. increase in strain) upon stress. If the stress is
released prior to the second elastic deformation (usually around 10% strain), the strain
will be recovered through re-conversion of the BCT to FCC.

Shape memory effect of nitinol [3]

- Initial shaping (e.g. shape A) of implant occurs in its FCC austenitic phase at the
temperature beyond phase transition temperature. The temperature is then cooled
below phase transition temperature, the material phase converts to BCT martensite,
regardless of presence of stress/strain. Implant is then reshaped to a new shape (e.g.
shape B) while in this BCT martensite phase. Then the temperature is heated above
phase transition temperature, the BCT revert to FCC and the shape goes back to shape
A.

Nitinol as expandable stents in

opening obstructed biological vessels
- Imagine the phase transition temperature is ~ 30 ℃
- Manufacture the expanded stent initially (FCC).
- Crimp/scrunch it at room temperature (< 30 ℃) (BCT).
- Encase it in a retractable sheath so it doesn’t prematurely expand.
- Minimal invasive insertion into blood vessel and release the stent, let it expand to
original manufactured shape at 37 ℃.

Applications:
- This can be used to expand the narrowed arteries due to atherosclerosis, though
patient needs to take anticoagulants until sufficient endothelialization around the stent
has occurred
- Can be also used to expand narrowed gastrointestinal/urological tracts due to cancer
or benign tumors
- Braces/orthodontics

Nitinol as bulk material

Can’t really be used as joint stems and other bone-related implants for its properties as
- Fatigue strength isn’t too great
- Again, afraid of Ni release under more intense loading conditions
- Fabricating/machining is very difficult
- Though we can make use of its superelasticity to make screw-less bone anchors
Platinum alloys – metals for electrodes
• Electrodes are very important for stimulating impaired muscle (e.g. skeletal, cardiac)
and nerves (cochlear, deep brain). Platinum alloys, often alloyed with iridium, are
used as the material for electrodes due to,

1. Low impedance between electrode and tissue by minimizing fibrous capsule

formation (i.e. bioinert metal) → Lower current needed to stimulate surrounding
tissue → Longevity of the electrode and less irritation of the surrounding tissue,

2. Needs to allow for reversible charge transfer, i.e. minimize chemical changes and
material loss during stimulation,
3. Balance of stiffness and flexibility at the same time to withstand both insertion and
cyclic loading, which are the requirements for an electrode material.

Future of metallic implants

Magnesium alloys
• Magnesium is a benign element with various biological roles (involved in ~300
biochemical reactions), it can be excreted readily by the kidney.
• Commonly alloyed with Zn, Ca in small amounts
- Primarily to increase tensile strength
- No big concerns over these elements as they are not adverse to the body
• Has biodegradability
- New tissue grows where there was metal
- No fibrous tissue formation

• Decent mechanical properties

- Closer stiffness to bone: ~ 45 GPa for Mg alloys versus 10-30 GPa for bone
- Strength = 180-280 MPa which is lower than other metals, but expected for a
degradable metal. It is still much stronger polymers, and tougher than ceramics
though.

Degradation of magnesium alloys [4]

- The mechanism of degradation: Mg + H2O → Mg(OH)2 + H2, which produces gas.
- Gas is bad for bone and wound healing but can remove by puncturing gas cavity
- Need to also consider rate of degradation
- Ideally match the rate of bone ingrowth

References
[1]. Chen, Q., Thouas, G. 2014. Metallic implant biomaterials. Materials Science and
Engineering R, 87 (2015), pp.1–57
[2]. Niinomi, M., Liu, Y., Nakai, M., Liu, H. and Li, H., 2016.  Biomedical titanium alloys with
Young’s moduli close to that of cortical bone. Regenerative Biomaterials, 3(3), pp.173–185
[3]. Action Lab Shorts. (2016, October 26). Nitinol Amazing Shape Memory Alloy [Video].
YouTube. https://www.youtube.com/watch?v=QGhkOGDszt0
[4]. Lee, J., Han, H., et al., 2015. Long-term clinical study and multiscale analysis of in vivo
biodegradation mechanism of Mg alloy. PNAS, 113 (3), pp.716-721
[5]. DMG MORI. (2017, February 16). New method of manufacturing using powder bed:
Additive Manufacturing with Selective Laser Melting [Video]. YouTube.
https://www.youtube.com/watch?v=te9OaSZ0kf8