Classification of Modern

Biomaterials and Surface

Design

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How many different types of

biomaterials are in use today?

The FDA regulates 100,000 different products that represent at

least 1,700 Different Types of Biomedical Devices
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Microstructure
Atoms (<10-4 m)

Long range 3D arrangement of atoms in the

crystals and glasses

X-ray, STM
(>10-4 m)
Atoms arrange to form crystals (grains)
(10-3 - 10-2 m)

Light, TEM
Arrangements of grains can influence mechanical
properties

Analysis: Routine quality control, failure

analysis and research studies.
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Isotropy versus Anisotropy

E (Youngs Modulus) and G (Shear modulus)

materials (properties are same in all
Isotropic
directions)
crystals are anisotropic, when compacted
Single
become isotropic (metals, ceramics)
and natural tissues (bone, ligament) are
Polymers
anisotropic

Stronger in longitudinal versus transverse,

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Broad ClassificationTypes of Biomaterials

Ceramics (Al2O3)

1.

Inorganic Glasses (amorphous state; silicates,

phosphates)
Metals (316 SS)
Polymers (synthetic and natural) (pHEMA,
Gelatin)
Composites (Metal alloys)

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Ceramics

Inorganic compounds that contain metallic and non-metallic elements, for

which inter-atomic bonding is ionic or covalent, and which are generally formed
at high temperatures.
Derivation: From the Greek word "keramos" meaning the art and science of
making and using solid articles formed by the action of heat on earthy raw
materials.
Most ceramics occur as minerals:
(1) The abundance of elements and geochemical characteristics of the earths
crust govern mineral types.
(2) Composition of Earths Crust: [84% = O + Si + Al]
O = 50% Fe = 5% K = 2.5%
Si = 26% Ca = 3% Mg = 2%
Al = 8% Na = 2.5% H = 1%

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O = 65% Fe = 0.006%
K = 0.20%
Si = 0.002% Ca = 1.5%
Mg = 0.05%
Al = trace% Na = 0.15%
H = 10%

Ceramics

Advantages:
- inert in body (or bioactive in
body)
- high wear resistance
(orthopedic & dental applications)
- high modulus (stiffness) &
compressive strength (E)
- fine esthetic properties for
dental applications
Disadvantages:
- brittle (low fracture resistance,
flaw tolerance)
- low tensile strength (fibers are
exception)
- poor fatigue resistance (relates
to flaw tolerance)

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Ceramic Applications

femoral heads and cup inserts

for ceramic on polyethylene; or
ceramic on ceramic hip
replacement bearings;
knee prostheses;
spinal fusion devices;
orthopedic instrumentation;
dental-crowns;
bridges, implants and caps;
inner ear implants (cochlear
implants);
drug delivery devices.

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Ceramics

Alumina, Zirconium, Calcium phosphate, Silica, pyrrolytic carbon,

hydroxyapatite are common;
Porous ceramic materials exhibit much lower strengths but have
been found extremely useful as coatings for metallic implants;
The coating aids in tissue fixation of the implant by providing a
porous surface for the surrounding tissue to grow into and
mechanically interlock; and,
Certain ceramics are considered bioactive ceramics if they establish
bonds with bone tissue.
Hydroxyapatite (Ca5(PO4)3OH)2 (20- 80 m size)

SEM image of
Hydroxyapatite

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Metals

Closely packed crystal structure; the type of bonding in metals

and metal alloys render them valuable as load bearing implants
as well as internal fixation devices used for orthopedic
applications (bone screws) as well as dental implants;
When processed suitably they contribute high tensile, fatigue and
yield strengths; low reactivity and good ductility to the stems of
hip implant devices; and,
Their properties depend on the processing method and purity of
the metal, however, and the selection of the material must be
made appropriate to its intended use.

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Metals

One complication that can occur from the use of metals in

orthopedic applications is the phenomenon of stress
shielding;
In some situations, such as hip implantation, the high strength
of the metal in the implant (210-230 GPa) induces it to
assume more than its share of responsibility for the load in
that region (10-18 Gpa);
This decreases the load born by the surrounding tissue and
therefore shields it from experiencing stress;
Lack of stress causes bone density to decrease as bone
tissue resorbs, eventually causing complications in the
implant/tissue interface.
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Other Uses of Metals

Medical Tubing

Stents

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Catheters

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Polymers

consist of small repeating units strung together in long chains;

flexible structure of polymers has enabled this group of materials
to be useful in applications from plastic garbage bags (PS) to
rubber tires;
In many materials, processing conditions can induce the polymer
chains to link with each other along the length of the chain to
produce a wide variety of mechanical properties;
These parameters are easily varied in order to suit current
biomedical applications.

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Polymers
Hydrophilic

(PEG)
Hydrophobic (polyvinylpyridine)
Biostable
Biodegradable (PLLA)
Natural (Collagen, Gelatin, Hyaluronic Acid)
Synthetic (pHEMA)
Highly processable
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15

Contact angle

SG= SL + LG cos
The energy of the surface (SG), which is directly related to its
wettability (), is a useful parameter that has often correlated strongly
with biological interaction.
Eg. Polytetrafluorethylene: 19 dyne/cm (Blood vesels)
Polyacrylonitrile: 50 dyne/cm (Vesico-ureteral reflux and urinary
incontinence)

Why need a hydrophilic surface?

The first stage of implant integration is the adsorption of blood and extracellular
fluids onto the implant surface.
These body fluids, which contain around 90% water, carry proteins and ions
which adsorb on the surface, and most of these components are hydrophilic. A
hydrophobic surface, i.e. a surface which repels water, will be a bad substrate
for adsorption of water soluble components.
Later on, the adsorbed proteins serve as the substrate for bone cell growth.
albumin (BSA), fibrinogen (Fbg), and fibronectin (Fn)
Because of this, a hydrophilic surface is a better substrate for bone cell growth
than a hydrophobic one.
The interaction between an implant and the hydrophilic body liquids becomes
even more important for porous structures, such as for example metal foams
for spinal fusion, or implants with a layer of plasma sprayed titanium. For these
types of structures capillary forces become more dominant and will augment
the difference between hydrophilic and hydrophobic surfaces. A drop of water
placed on a hydrophobic porous foam will stay on top of the foam without
penetrating its inner structure.
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Left image: dyed water drop on unmodified PEEK.

Right image: water on HAnano Surface treated PEEK.

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High Surface Energy

The surface energy can be described as the force
required to create a new surface of a certain
material.
Surface energy depends on chemistry and
topography poly(ethylene) has lower surface
energy than titanium, and a rough titanium surface
has a higher surface energy than a polished one.
Increasing the surface energy for a material
increases the number of contact points for bone cells
to attach to, which in turn leads to a better
osseointegration and mechanical stability.
Nanoparticles deposited on a surface increases the
surface energy of a substrate.
Measuring the surface energy gives a broader
information on the characteristics of an implant
surface. The surface energy can be calculated by
measuring the contact angle between the test
surface and for different liquids with known surface
energies. Hydrophilicity and surface energy are
closely linked, a hydrophilic surface also has a high
surface energy.
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Composites

individual strengths and weaknesses of polymers, ceramics, and

metals benefit different applications;
The porosity and hardness of ceramics support tissue integration
into the tissue/implants interface, but these properties could
hardly suit a ligament replacement;
A composite material incorporates the desired characteristics of
different materials to meet the stringent demands of living tissue;
Most composite designs combine strength and flexibility by
reinforcing a relatively flexible material with a harder, stronger
one (fiberglass); and,
In some cases, one or more of these materials may be
degradable in order to encourage tissue integration (polymer
composites- bone screws and bone plates; eg: CF/PMMA)

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Bio-inertness vs. Bioactivity

Bioactive materials play a more aggressive role in the
body. While a biocompatible material should affect
the equilibrium of the body as little as possible, a
bioactive material recruits specific interactions
between the material and surrounding tissue.

Focus shifted towards tailoring materials to elicit specific

responses

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Remove
Replace
Regrow

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Commonly Used Biomaterials

Material
Silicone rubber
Dacron
Poly(methyl methacrylate)

Applications
Catheters, tubing
Vascular grafts
Intraocular lenses, bone
cement

Polyurethanes

Catheters, pacemaker
leads

Stainless steel
Collagen (reprocessed)

Orthopedic devices, stents

Cosmetic surgery, wound
dressings

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Requirements of Biomaterials
A biomaterial must be:
Inert (bulk) and specifically interactive (surface)
biocompatible
mechanically and chemically stable or
biodegradable
processable (for manufacturability)
nonthrombogenic (if blood-contacting)
sterilizable
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Break! (5 min)

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What we want to know...

What properties of a biomaterial surface
mediate biological response?

To what extent?

Example: Bacterial Adhesion

Bacteria take advantage of surface effects to gain a foothold then they
rework the surface!

Example: Foreign Body Response

Surface properties have been shown to mediate the FBR to a
certain degree

Scanning electron microscopy images of an Elasthane 80A Polyurethane

surface from an in vivo cage study showing the morphological progression of
the foreign body reaction. The sequence of events at the Polyurethane surface
includes (A) monocyte adhesion (0 days), (B) monocyte-to-macrophage
development (3 days), (C) ongoing macrophage-macrophage fusion (7 days),
and (D) foreign body giant cells (14 days).
James M. Anderson , Analiz Rodriguez , David T. Chang
Seminars in Immunology, Volume 20, Issue 2, 2008, 86 - 100

Foreign body reaction to biomaterials

http://dx.doi.org/10.1016/j.smim.2007.11.004

Example: Surface Coagulation

Hageman Factor
(Factor XII) is surface
activated!

So control adsorption to
control coagulation..
how?
Surface energetics?
Serum albumin
adsorption if higher
than fibrinogen ~
an important and
well known
criterion for
promoting a lower

Protein Adsorption to Surfaces

Plays a significant role in:
Complement activation (IgG, IgM)
Coagulation activation (Hageman Factor)
Fouling of contact lenses (lysozyme)
Where transport is important (drug delivery)
The goal has shifted from understanding the adsorption properties of
unmodified materials to intelligent design of materials to mediate the
adsorption process.
To facilitate the attachment of cells, implant surfaces have been coated
with pyrolitic carbon, collagen, albumin, gelatin, and drug-releasing gels.

Protein Coating
Adsorption of proteins to a surface creates a new surface

Surface

Protein Solution

New Surface

Surface Design

Surface Design

Surface Design

Surface Design

Surface Design

Protein Resistant Surfaces

PolyEthylene Oxide (PEO) is a highly mobile, hydrophilic polymer that can
be grafted onto a surface (or protein) to render resistance to adsorption.
This is a very effective way to control complement and coagulation
activation.
Activation + Resistance

Tissue Engineering
Many tissue engineering design strategies rely on seeding a biomaterial
construct with cells. Different strategies are then employed to get the cells to
migrate, differentiate, and ultimately to develop into functional tissue.
Surface modification strategies employed include:
Topographic modification (cell alignment)
Spatial patterning of cell adhesive zones
Integration of adhesion epitopes
Switchable

Activated Surfaces
Use the preceding techniques to add functional groups to the surface.
Examples are:
Avidination / Biotinylation
Epitopes (e.g. RGD for promoting cell adhesion)
Plasma treatment (promotes protein adhesion)
Adsorption of whole bioactive molecules (patterns)

Recapitulation/ Summary
1 Surfaces have unique properties
2 We can (and do) measure these properties
3 Surface properties affect biocompatibility
4 Engineering surfaces to make them bioactive