Chapter 9 – Biomaterials and Biological

Materials
Pivotal Questions:
- What types of materials interact with biological
systems?
- What biological materials provide support and
what biomaterials interact with or replace them?
- What biomaterials serve a nonstructural
function in the body?
- What ethical issues are unique to biomaterials?
Basic Definitions
Other Pivotal Definitions
 Structural (or inert) Biomaterials provide physical
support for the body as their primary function
 Functional (or active) Biomaterials provide a
function other than structural support
 An Immune Response occurs when the body sends
white blood cells to attack and destroy foreign matter
in the body
 Biocompatibility is the ability of a material to
function within the body without triggering an
immune response
Structural Biomaterial and Biological
Materials
 Bone
 Prosthetic limbs
 Vascular stents
 Breast implants
 Teeth and dental fillings
Bone
 Bone is a naturally occurring
fiber-reinforced composite
that comprises the skeletal
system of most animals
 Organic collagen (a high-
strength structural protein)
fibrils are surrounded by a
calcium phosphate matrix in
the form of a mineral called
hydroxyapatite
Ca10(PO4)6(OH)2
 A schematic of a collagen
fiber is shown to the right
Types of bone cells
 Osteoblasts are cells located near the surface of the bone that
produce osteoid, a blend of structural proteins and hormones
that regulate the growth of bone
 Bone-lining cells serve as an ionic barrier and line the bone
 Osteocytes began as osteoblasts that became trapped in the
matrix and developed into star shaped cells that provide
pathways for the flow of nutrients and waste
 Osteoclasts are bone destroying cells that migrate to specific
bone areas and cluster in surface pits. They release acids and
other chemicals that dissolve the bone and allow the body to
reabsorb the calcium
Bone growth
 Osteoblasts initiate the process by secreting collagen
fibrils and osteoid
 During the growth of the matrix (called
mineralization), the osteoblasts release sealed
vesicles containing an enzyme that cleaves phosphate
bonds.
 Phosphate and calcium deposit on the vesicles which
serve as heterogeneous nuclei to facilitate crystal
growth
Bone replacement
 Bone is continuously reabsorbed and replaced through
a process called remodeling
 When microcracks form in bone, the piezoelectric
nature of bone creates a small voltage
 The electrical signal causes the osteoclasts to migrate
to the damage site and begin to reabsorb the damaged
bone
 Osteoblasts then produce new collagen and osteoid to
replace the bone without significantly changing its
shape
Use of biomaterials in bone
 Although bone is self-healing, larger breaks require
titanium screws, rods, or plates to hold the bone in
place
 When large segments of bone are damaged or missing,
the osteoblasts cannot reconnect the disjointed
pitches without help
 Powdered synthetic hydroxyapatite is added as a bone
filler that provides a framework to support the growth
of new bone
 The hydroxyapatite is a biomimetic material that
becomes part of the bone matrix through a process
called osseointegration
The Hip Joint
 The hip is a ball-and-
socket joint with the
femoral head extending
into the acetabulum
socket
 More than 300,000 hip
fractures occur in the
U.S. each year, many as a
result of osteoporosis
Hip Replacement
 The femoral head is
replaced with a titanium or
cobalt stainless steel
implant that includes a ball
shaped femoral head and
long stem that extends into
the femur
 The femural head is often
made of alumina, but
modern bioceramics such
as the Y-TZP femoral head
offer better strength and
wear rates
Challenges in hip replacements
 The implant materials are stronger than natural bone
and handle more of the load
 Wolf’s law dictates that less load on the bone results in
less bone, so the area around the metal becomes
thinner and weaker
 Naturally occurring synovial fluid can corrode the
metal and produce potentially toxic compounds
 Natural joint lubrication is often insufficient and
attempts to coat the implant have not been successful
 Hip replacements typically last between 10-20 years
Prosthethetic Legs History
 For centuries, wooden or metal stakes were secured to
the residual limb with straps. The amputee could walk
(with difficulty) but could do little else
 In 1696, the first non-locking foot appeared that used
external hinges to mirror the pivoting at the ankle
 By 1800, a pulley system that accounted for the
movement of the foot was added, but prosthetic legs
remained virtually unchanged from then until the end
of World War II
Modern Prosthetics
 In 1946, the American
Orthotics and
Prosthetics Association
was chartered to improve
prothetics
 Modern transtibial
prothesthes allow for a
much more natural
range of motion
The Keel
 To replace the missing tibia, all transtibial protheses
contain a long bar called the keel that must withstand the
compressive forces associated with walking
 The keel is usually made from titanium or carbon fiber
composites and must be stiff but have some ability to flex
 If the elastic modulus is too high, walking and running
would be painful as too much force would be transferred
into the residual limb
 If the elastic modulus was too low, it would be difficult to
maintain balance during walking or running
The SACH Foot
 Most transtibial protheses
are non-articulated (they
do not bend at the ankle)
 The most common foot is
the solid-ankle-cushion-
heel (SACH) foot
 The SACH foot contains a
compressible wedge at the
heel and a solid wooden
support at the bottom to
provide stability
Prosthetic Arms
 Prosthetics arms experience less load than prosthetic
legs and the elbow is no more complex than the knee
 However, the hand is far more complex and requires
more range of motion that the foot
 Until 1909, prosthetic arms consisted of a leather
socket that fit around the residual limbs and a
cumbersome steel frame that supported either a
simple hook (that remains popular in modern horror
movies) or synthetic hand that looked more realistic
but provided little functionality
The Dorrance Hook
 In 1909, Dr. D. W.
Dorrance developed a split
hook system that gave the
user some ability to grasp
an object

 Most modern amputees

wear a modern variation of
the Dorrance Hook using a
polypropylene socket and
aluminum alloys, titanium
alloys, or carbon fiber
composites in the frame
Myoelectric Arms
 Myoelectric arms are artificial arms that respond to the
amputees’ muscle impulses to control the function of the
prosthetic
 Electrical impulses from the residual limb are transferred
through electrodes in the prosthetic shell to circuits in the
fingers
 Some are commercially available, but still lack durability and are
not covered by most insurance plans
 Dean Kamen, the inventor of the Segway, has a prototype of a so-
called “Luke Hand” named after the bionic hand given to Luke
Skywalker in The Empire Strikes Back
 His prototype has 19 degrees of motion and can emulate most of
the movements of a human hand
Angioplasty and Vascular Stents
 To reopen a clogged artery, a thin guide wire is fed
through the clogged area.
 A balloon is fed along the guide wire and inflated to
open the vessel and displace the blockage
 A metallic metal mesh called a vascular stent is
inserted to help keep the artery open after the
procedure
 Vascular stents come in two forms: Balloon
Expandable and Self-Expanding
The Palmaz Stent
 The first balloon
expandable stent,
developed in 1987
 The original stents were
made from stainless steel,
but these stents often
triggered retinosis, a
buildup of scar tissue
around the stent that
restricts blood flow
Nitinol Stents
 When stents are made
from a nickel-titanium
alloy called nitinol,
stenosis is largely
eliminated
 The alloy exhibits a shape
memory effect in which a
deformed lattice does not
regain its original shape,
but will return to its
original lattice position
when heated
Catheters
 Catheters are tubes that are inserted into vessels or ducts in the body to
promote either the injection or drainage of fluids
 A Foley Catheter is a flexible tube inserted through the tip of the penis
into the bladder to drain urine
 Foley catheters can be made from
 latex (which can induce allergic reactions and support bacterial
colonies)
 silicone (which offers the best performance but is the most
expensive) or
 polyvinyl chloride (which must be softened through the addition of
plasticizers)
Silicone Breast Implants
 Used a silicone rubber sac
filled with a silicone gel
 Formation of scar tissue led
to capsular contracture that
led to rupture of the implant
 Extracapsular silicone
migrated through the body
and may have led to other
health problems
 From 1992 to 2006, silicone
implants were banned in
Canada and restricted in the
U.S.
Saline Breast Implants
 Saline implant offer a
benign alternative
 Liquid saline is stored in
a room-temperature-
vulcanized (RTV) shell
that resist rupture
 They do not have the
natural look of silicone
implants
Gummy Bear Silicone Breast
Implants
 New form of silicone breast implants that uses a
cohesive gel that is far less likely to leak
 Used extensively outside of North America with many
fewer complications
 FDA approved first use in 2006
 A ten-year post-approval study is underway, following
40,000 women who received the implants
Teeth
 The living center of the tooth is
called dental pulp
 Three layers of material
surround the pulp
 Enamel – the hardest substance
in the body consists mostly of
hydroxyapatite
 Dentin – Yellow porous
material comprised of collagen
blended with a calcium
phosphate material called
dahlite
 Cementum – bony material
used to attach the periodontal
ligaments
Cavities and Dental Fillings
 Bacteria in the mouth react with sugars to produce lactic
acid which attacks the hydroxyapatite in all three layers
 Mercury compounds called amalgams are used to fill the
cavities
 Gamma-2 Phase Amalgam was used from 1895 through
about 1970 and contained 50% mercury and 50% of an alloy
with at least 65% silver, >29% tin, 6% copper and small
amounts of zinc and mercury
 In 1970, high-copper amalgam took over for economic
reasons. It contains 50% mercury, but the new alloy
contains only about 40% silver (the most expensive metal
in the alloy), >32% tin and nearly 30% copper
Dental Composites
 Are more expensive than amalgams and tend not to last as
long (~8 years compared to 10-15 for an amalgam filling)
 Look more like natural teeth and contain no mercury
 Made from a bis-GMA acrylic resin along with filler
materials including powdered glass
 Composite fillings bond with the enamel and are less likely
to fracture
 Amalgam fillings expand with age and can crack the tooth,
while composite fillings shrink with age and are more likely
to simple fall out
Functional biomaterials
 Serve a purpose beyond structure in the body
 Can be as involved as artificial organs replacing all or
some of the function of a body part
 Can be as simple as pacemakers that help control the
electrical signals that cause the heart to beat
 May be implanted in the body or may exist outside the
body with materials being taken from the body, passed
through the biomaterial, then returned to the body
Hemodialysis
 The blood of a patient is
removed by a catheter and
passed through a semi-
permeable membrane
 Dialysis fluid runs on the other
side
 Differential pressure causes
water to pass through the
membrane reducing excess fluid
and electrolytes in the blood
 Simultaneously, concentration
gradients cause urea and other
toxins to diffuse across the
membrane and out of the blood
Dialysis
The Dialysis Membrane
 Is the cornerstone of the dialysis process
 Is generally made from cellulose acetate (a relatively inexpensive
polymer that is permeable to the impurities, but has a pore size
small enough to prevent blood cells and proteins from passing
through)
 Must be:
 Permeable to urea and other waste products
 Impermeable to blood cells , plasma, and other key components
 Strong enough to withstand the differential pressures
 Biocompatible enough to not trigger and immune response from
the blood
Issues with Cellulose Acetate
Membranes
 Biocompatibility tends to be a challenge and
significant numbers of negative reactions have been
reported
 Hollow tubes made from PMMA, PAN, and
polysulfone have been used with the blood running
through the center and the dialysis fluid on the
outside
 These tubes have fewer biocompatibility issues but are
more expensive
Artificial Hearts
 The heart is responsible for
pumping blood throughout the
body
 The Jarvik-7 Artificial Heart
(shown here) was implanted in a
patient in 1982. He lived for 112
days
 Numerous issues (blood cell
destruction, need for external
power sources, biocompatibility,
etc.) has shifted the emphasis to
Ventricular Assist Devices
(VADs)
Ventricular Assist Device (VAD)
 VADs help a damaged heart increase its functionality
and throughput
 Internal VADs are implanted directly into the left
ventricle of a damaged heart and or in the abdominal
cavity. Both are viewed as bridges to transplant and
are designed to remain in a patient for several months
until a donor heart is found
 Inside a titanium case, a small motor causes a titanium
impeller to spin increasing the blood flow to the heart
 External VADs are used during open heart surgery
Skin
 Skin protects internal organs from pathogens, keeps
water in, and accounts for more than 15% of the weight
of the body
 The epidermis (outer layer) contains no blood cells
and receives nutrition from the inner layer (dermis)
 The dermis contains follicles, nerves, sweat glands,
and muscles
Renewal of skin
 Over 90% of the epidermis consists of keratinocytes,
cells that produce the structural protein keratin
 Other structural proteins (collagen and elastin)
enhance strength and flexibility
 As skin cells move toward the surface of the epidermis,
they change shape and produce more keratin.
 After about 30 days, epidermal cells dry and flake off to
make room for the next tier through a process called
keratinization
Healing of Skin
 Damage that does not extend beyond the epidermis
heals naturally through keratinization
 When damage reaches the dermis, the body responds
by laying new collagen fibers across the wound site
that provide a matrix for skin growth
 The collagen fibers result in a scar
 Regrown dermal tissue with support epidermal cells
and provide a barrier to water loss and infection, but
hair follicles, and sweat glands are not replaced
Severe skin damage
 When large areas of skin are damaged (such as with
burn victims), the body cannot repair itself effectively
 Until 1986, victims who received third-degree burns to
over 50% of their body were almost certain today
 Since 1986, an artificial skin has provided new hope
Artificial skin
 A synthetic matrix is applied to the wound site
 The matrix is made of a blend of collagen fibers from
cows and glycosaminoglycan fibers from shark
cartridge for dermal cells and a simpler polysiloxane
mesh is used to support epidermal cells
 The soft mesh mimic natural biological materials and
allow new growth to occur without scarring
Artificial Bladders
 Until recently, patients with damaged bladders were
forced to wear an external bag for urine collection
 The first artificial bladder was made in 1999
 Artificial bladders are made from the patient’s own
intestine so it is a biological material rather than a
biomaterial
 Surgeons remove approximately three feet of small
intestine and reshape it like a grapefruit
 It is replaced in the body and connected to the ureter
and kidneys
Heart Valves
 The mitral valve separates
the left ventricle and the left
atrium
 The tricuspid valve
separates the right atrium
from the right ventricle
 The pulmonary valve
controls the flow of blood
into the lungs
 The aortic valve regulates
the flow of oxygenated blood
into the body
Defective heart valves
 Defective heart valves experience one of two problems:
 Regurgitation which occurs when the valve fails to seal
properly allowing some blood to leak back into the previous
chamber and forcing the heart to work harder.
 Stenosis which is a hardening of the valve that prevents it
from opening properly and results in a build up of blood
pressure and am enlarging of the heart
 Mechanical replacement valves have been used to replace
defective heart valves since 1952
Caged-Ball Valves
 Caged-ball valves contain a
ball that is pushed forward
into a cage under pressure
then drops back to fill the
hole at rest
 The original caged ball valves
were made from acrylic with a
silastic silicone rubber ball
 Many patients experienced
thrombosis (blood clotting)
because of the body’s
reaction to the acrylic
The Starr-Edwards Valve
 The Starr-Edwards valve is the only caged-ball valve
in use today
 The ball is made from a silicone rubber polymer
impregnated with barium sulfate
 The cage is made from a cobalt-chromium alloy
 Nearly 70% of recipients live for at least five years
Tilting Disk Valves
 Tilting disk valves use a single
circular disk to regulate flow
 The most common tilting
disk valve, the Medtronic
Hall valve, is made with four
titanium struts and a carbon-
coated disk
 The disk can tilt up to 75
degrees
 The design of the valve is
unchanged since the early
1980s
The St. Jude Bileaflet Valve
 Features two leaflets that
swing apart when opened and
create three regions of flow
 The valve is made from
pyrolitic carbon deposited
over graphite
 The resulting blood flow is
much closer to the
hemodynamic conditions of
flow through a normal heart
valve
 Over 500,000 patients have
received an implant since
1977
Performance of Valves
 The performance of an artificial heart valve is estimated by
the Effective Orifice Area (EOA)
EOA = Q/(51.6P0.5)
where Q is the volumetric flow rate and P is blood pressure
 A higher EOA means less energy loss by the blood passing
through the valve.
 Because EOA does not account for the size of the valve, a
dimensionless term called Performance Index (PI) is
calculated by dividing the EOA by a standard
PI = EOA/EOAstd
Complications with Artificial Valves
 All three types subject the blood to stresses that can
result in thrombosis so patients must take
anticoagulants
 The caged-ball valves develop high stresses along the
walls of the struts
 Tilting disk valves tend to develop clots behind the
struts
 Bileaflet valves has both high stresses and areas of
stagnation making clot formation common
 All valves lose material over time due to erosion and
frictional losses
Valves made from Biological Materials
 Homografts – heart valves are removed from a
cadaver and frozen in liquid nitrogen. The valves are
thawed and used as a direct replacement in the
recipient
 Autografts – Surgeons remove tissue from other parts
of the patient’s body (usually the pericardium) and
mold it around stainless steel stents to form a new
valve
 Xenografts – Surgeons implant valves from other
species (usually pigs but cows have been used. These
may be natural heart valves or pericardial tissue
molded around stents
Use of Homografts
 Natural heart valves cause no thrombosis and do not
require the use of anticoagulants
 Hemodynamic properties are far superior to
mechanical valves
 Supply is limited
 The valves must be the right size and compatible for
transplant
 The recipient must take immunosuppressants
 The implant surgery is difficult and dangerous
Use of Autografts
 Do not trigger an immune response because the
patient’s own tissue is used
 The material used was not specifically designed to
serve as a valve
 Efficiency tends to be low
Use of Xenografts
 Porcine valves are more available than human donors
 The surgery is less complex than that for implanting
artificial valves
 Patients must take immunosuppressants
 Hemodynamic properties lie between mechanical
valves and homografts
 Some patients have religious or ethical issues with the
xenograft
Blood
 The primary functions of blood is to transport oxygen
to the cells of the body and to transport waste products
away
 Blood consists of about 60% plasma (a yellow liquid)
and 40% corpuscles (a mixture of white and red blood
cells)
 The red corpuscles contain an iron-based protein
called hemoglobin that stores oxygen and releases it to
the cells
 As the blood travels through the body, lower partial
pressures trigger the release of more oxygen
Artificial Blood
 The search for artificial blood (more properly called
oxygen therapeutics) has led to two competing
technologies, neither of which is approved for use in
the United States
 The first technique uses perfluorocarbons (PFCs),
organic molecules with an oxygen solubility nearly 100
times greater than the surrounding plasma
 A Japanese company ran clinical trials with a PFC
emulsion, but the results were less successful than
hoped
Artificial Blood – Method 2
 The second method involves the extraction of
hemoglobin from expired blood products and
injecting it into the body
 Initial trials proved disastrous as the injection of free
hemoglobin caused capillaries to collapse
 In late 2003, a new hemoglobin-based substitute called
polyheme began clinical trials and is awaiting FDA
approval
Artificial Pacemakers
 One of the most successful functional biomaterials
 In a normal heart, the sinus node causes the heart to beat 60 to
80 times per minute
 When the sinus node malfunctions, an irregular heartbeat called
brachycardia results and can result in death
 Artificial pacemakers are implanted directly in the heart
 They consist of a biocompatible titanium casing that houses a
long-lasting battery, a microprocessor, and a header that sends
small wires to the right atrium or ventricle and the device sends
an electrical signal to regulate the heart when an irregular beat is
detected
 Over two million pacemakers have been installed since 1958
Controlled Release Agents
 Traditionally, most pharmaceuticals are ingested orally
or injected into the bloodstream with a hypodermic
syringe
 The dosage is difficult to control as the initial level is
very high and gradually declines
 The pharmaceutical must be transported through the
body to the desired site
 The implantation of controlled release devices into the
body provides several benefits
Classes of Controlled Release
Systems
 Diffusion Systems have the
pharmaceutical suspended in a
polymer matrix that allows the
drug to diffuse out gradually
 Solvent-Activated Systems are
dry implants that absorb water
causing a membrane to swell.
Osmotic pressure drives the
drug into the body at a
controlled rate
 Polymer Degradation Systems
have the pharmaceutical
encased in a polymer that
gradually dissolves and allows
the drug to escape
Polymers used in Controlled
Release Systems
 A variety of polymers are used in controlled release
systems
 Vinyl acetate is commonly used because its
permeability is easily regulated
 Polyurethanes provide elasticity
 Polyethylene does not swell and adds strength to the
matrix
 Methylmethacylates are transparent and strong
 Polyvinyl alcohol has a strong affinity for water
Use of Transdermal Patches
 Not all controlled release agents are implanted in the
body
 One of the largest commercial applications is the use
of nicotine patches that are affixed to the skin of the
arm of smokers who are attempting to quit
 The FDA has approved transdermal patches for more
than 35 different applications ranging from birth
control to motion sickness
Parts of Transdermal Patches
 Transdermal patches have five parts:
 Liner – protects the patch during shipping. It is removed and
discarded prior to use
 Adhesive – holds the patch together and affixes it to the skin
 Pharmaceutical – The product to be delivered at a
controlled rate. It is generally stored in a reservoir but may be
distributed through the adhesive
 Membrane – controls the release of the pharmaceutical from
the reservoir
 Backing Material – protects the patch from damage while on
the skin
Bioethics
 The ethical issues raised in the use of biomaterials are
legion
 Cost, fairness, access, and safety take on additional
significance when human life is at stake
 The issues are so complex that an entire field of study
called bioethics has been created to deal with the
many dilemmas
 Bioethicists are not hired for their personal opinion,
but for their knowledge of the history and research in
the field
 Religious bioethicists have particular challenges of
balancing scientific advances with religious doctrines