BIOMATERIA

LS

Submitted by:
Manianglung, Clinton

Marquez, Megan
Miralo, Kaile
Ordoo, John Benedict
3-ChEA
BIOMATERIALS
Biomaterials are materials (synthetic and natural; solid and sometimes
liquid) that are used in medical devices or in contact with biological systems.
A biomaterial is a nonviable material used in a medical device, intended to
interact with biological systems. (Williams, 1987)
If the word "medical" is removed, this definition becomes more general and
still quite useful. And if the word nonviable is removed, the definition
becomes even more general and can address new tissue engineering and
hydrid artificial organ applications where living cells are used.
General requirements to be classified as a biomaterial are organisms
should not treat it as a foreign object, harmlessly degrade or dissolve in the
body, and possess mechanical stability which is equivalent or greater to
ensure high reliability of the graft.
Biomaterials are divided into two categories:
1.) Synthetic under this category some of the examples are metals,
ceramics, polymers and composites. New generations of synthetic
biomaterials are being developed at a rapid pace for use as threedimensional extracellular microenvironments to mimic the regulatory
characteristics of natural extracellular matrices (ECMs) and ECM-bound
growth factors, both for therapeutic applications and basic biological
studies
2.) Natural are protein-based, decellularized tissue. Mostly come in vivo
source therefore large quantities are constantly available. They already
have binding sites for cells and adhesion molecules so the
biocompatibility is not a major issue.
BIOMATERIAL CLASSIFICATION:
When a synthetic material is placed within the human body, tissue
reacts towards the implant in a variety of ways depending on the material
type. The mechanism of tissue interaction (if any) depends on the tissue
response to the implant surface. In general, there are three terms in which a
biomaterial may be described in or classified into representing the tissues
responses. These are bioinert, bioresorbable, and bioactive, which are well
covered in range of excellent review papers.
1.) Bioinert - refers to any material that once placed in the human body
has minimal interaction with its surrounding tissue, examples of these
are stainless steel, titanium, alumina, partially stabilised zirconia, and
ultra high molecular weight polyethylene. Generally a fibrous capsule

might form around bioinert implants hence its biofunctionality relies on

tissue integration through the implant.
2.) Bioactive - bioactive refers to a material, which upon being placed
within the human body interacts with the surrounding bone and in
some cases, even soft tissue. This occurs through a time dependent
kinetic modification of the surface, triggered by their implantation
within the living bone. An ion exchange reaction between the
bioactive implant and surrounding body fluids results in the formation
of a biologically active carbonate apatite (CHAp) layer on the implant
that is chemically and crystallographically equivalent to the mineral
phase in bone. Prime examples of these materials are synthetic
hydroxyapatite [Ca10(PO4)6(OH)2], glass ceramic A-W and bioglass.
3.) Bioresorbable - refers to a material that upon placement within the
human body starts to dissolve (resorbed) and slowly replaced by
advancing tissue (such as bone). Common examples of bioresorbable
materials are tricalcium phosphate [Ca 3(PO4)2] and polylactic
polyglycolic acid copolymers. Calcium oxide, calcium carbonate and
gypsum are other common materials that have been utilised during the
last

GENERAL CLASSES OF SYNTHETIC BIOMATERIALS

1.) Metallic biomaterials composed of sometimes pure metal, or an alloy.
Usually used for load bearing applications and must have sufficient
fatigue strength. Most commonly used metal in biomaterials is
Titanium (Ti).
2.) Ceramic biomaterials composed of metallic and nonmetallic elements
held together by ionic and/or covalent bonds. These materials are
highly inert, therefore, they are non-chemically reactive or materials
illicit no or minimal tissue response. Used for their hardness and wear
resistance for applications such as articulating surfaces in joints and in
teeth as well as bone bonding surfaces implants.
3.) Polymeric biomaterials used for their flexibility and stability, but have
also been used for low friction articulating surfaces.
A biomaterial should not be toxic, unless it is specifically engineered
for such requirements (for example, a "smart bomb" drug delivery system
that targets cancer cells and destroys them). Since the nontoxic requirement
is the norm, toxicology for biomaterials has evolved into a sophisticated
science. It deals with the substances that migrate out of biomaterials.

BIOCOMPATIBILITY
More often than not, biocompatibility is defined in terms of
performance or success at a specific task. Thus, for a patient who is doing
well with an implanted Dacron fabric vascular prosthesis, few would argue
that this prosthesis is not "biocompatible." Biocompatibilty is the condition of
being compatible with the living tissue or a living system by not being toxic
or injurious and not causing immunological rejection. It arises due to the
differences in living and non-living materials.
RESPONSE TO IMPLANTATION
Before any implantation to be done, the host environment is first
evaluated to ensure safety. Some of the host factors are age, health status,
immunological/metabolic status.
Inflammation is a normal physiological reaction to trauma and the invasion
of foreign substance. It is the reaction of vascularized living tissue to injury.
Its function is to control, neutralize or isolate the damaging agent. The
inflammation process includes a sequence of events that is the generation of
new tissue via native parenchymal cells or the formation of fibrolastic scar
tissue.
Acute inflammation short term (minutes-day), it is characterized exudation
of fluid, plasma, proteins, leukocytes (neutrophils).
Chronic inflammation long term (>days) accompanied by the proliferation of
blood vessels and connective tissue.
Foreign body reaction indicated by the presence of foreign body giant cells
and the components of granulation tissue (macrophages, fibroblasts, and
capillaries in varying amounts).
Fibrosis and Encapsulation it is the final stage of the foreign body response
and healing process is the development of a fibrous encapsulation (porous
structures may be excluded from this stage). Repair involves two separate
processes: replacement of tissue by parenchymal cells of the same type or
replacement by connective tissue that constitute the fibrous capsule.
Healing - special processes are invoked when a material or device heals in
the body. Injury to tissue will stimulate the well-defined inflammatory reaction
sequence that leads to healing. Where a foreign body (e.g., an implant) is
present in the wound site (surgical incision), the reaction sequence is referred
to as the "foreign body reaction.
BIOCOMPATIBILITY TESTING
No one material will be appropriate for all medical device application.
The material, its composition and degradation products may affect host cells
and tissue. The host environment may also affect material properties and
device performance.

In vitro testing - (Latin for within the glass) refers to the technique of
performing a given procedure in a controlled environment outside of a living
organism.
Types of in vitro testing for estimating biocompatibility:
1.) Cytoxicity - ability to cause death or damage at the cellular level by
direct cell lysis or by fatally altering cellular metabolism. Inhibition of
enzyme activity, changes in cell membrane permeability and other sub
lethal effects. Some of the tests done are elution test, agar overlay,
and direct contact tests.
2.) Hemocompatibility - used to evaluate the effect of a material on blood
coagulation processes, thrombus formation and hemolysis (destruction
of red blood cells). Materials or their extracts are incubated with red
blood cells, isolated from rabbits, mice, or rats for three hours with
intermittent shaking to keep samples mixed and in contact with blood.
3.) Mutagenecity and Genotoxicity - capacity to modify the genome of a
host, so materials may be classified as genotoxic. Some of the tests
done are ames test, and hypersensitivity tests.
In vivo testing - (Latin for within the living) refers to experimentation using
a whole, living organism as opposed to a partial or dead organism. Animal
studies and clinical trials are two forms of in vivo research.
Types of in vivo testing for estimating biocompatibility:
1.) Short-term implantation tests subcutaneous, intramuscular and
intraperitoneal implantation tests to evaluate general tissue necrosis,
fibrosis and inflammation
2.) Long-term functional tests device or compositionally identical
prototypes are implanted in appropriate animal models to
replicate/simulate intended end-use in humans. Functionality of device
and histopatological evaluation if tissues /organs are performed.
3.) Animal tests under this are the nonfunctional, functional, and
cancerogenity tests. Under nonfunctional it is the first study of
interaction of the implant with physiological environment, nonspecific
acute toxic or inflammatory reaction, specialized sites such as the
cornea and cerebral cortex are used for materials. Histological
analyses may be scored or graded based on degree of tissue
necrosis/degeneration, fibrosis and types and amount of inflammatory.
Functional tests are the evaluation in soft tissues, much greater
complexity, also specific in-vivo physiological assessment tests
(genotoxicity, carcinogenityreproductive toxicity, etc). Some other
tests done are ocluded patch test, and open epicutaneous test.

4.) Irritation tests including the inflammatory response of the ocular from
ophtalmological materials, irritation experienced by the skin through
the appearance of allergies, and mucosal.
DEGRADATION OF BIOMATERIALS
The degradation of the biomaterial should be controlled precisely to
give enough time for the cells to lay down their own extracellular matrix and
regenerate the injured bone, and at the same time to ensure that the scaffold
does not last longer than needed. It is important for an engineer to
understand the mechanisms involved in process of enhancing the service
efficiency of the materials, and to develop technique to avoid or delay the
degradation process.
CORROSION OF METALS
Corrosion is the gradual degradation of materials are caused by an
electrochemical attack. As a material starts to corrode, the dissolution of
metal will lead to erosion which in turn will eventually lead to brittleness and
fracture of the implant. Corrosion gets accelerated due to increase in the
amount of exposed surface area. If metal fragments are not surgically
extracted, further dissolution and fragmentation may occur, which may result
in the inflammation of the surrounding tissues. Implants with rough
surfaces as are especially susceptible due to the increased amount of area
exposed to corroding substances. The implants face severe corrosion
environment which includes blood and other constituents of the body fluid (i.
e. Water, Na+, proteins, plasma, and amino acids). These biological molecules
upset the equilibrium of the corrosion reactions of the implant by consuming
the products due to anodic or cathodic reaction.
The corrosion resistance of an implant material influences its functional
performance and durability and is a primary factor governing biocompatibility.
The tolerable corrosion rate for metallic implant systems should be about 2.5
x 10-4 mm/yr, or 0.01 mils/yr
Ions released from the implant:
Are potentially cytotoxic
Can reduce the biocompatiblity of the implant and jeopardize its
function
The most common forms of corrosion that occur:
Uniform Corrosion
Intergranular
Galvanic and Stress Corrosion Cracking,
Pitting
Fatigue Corrosion.
DEGRADATION OF CERAMICS

Ceramics, being compounds between metallic and nonmetallic

elements, may be thought of as having already been corroded and has a high
corrosion resistance which makes it an ideal material for biological use. Its
high corrosive resistance is due to its chemical inertness in corrosive
environment. Ceramics hardly degrade except under extreme temperatures
and loads or through simple chemical dissolution.
DEGRADATION OF POLYMERS
The degradation of plastics is not termed as corrosion but often termed
"ageing. Polymeric materials degrade by non-corrosive processes and only
degrades under varying physiochemical conditions.
Polymer degradation is a change in the properties. As a biomaterial
which is placed in the biological system, its properties and function are of
importance and are usually placed for a reason making these changes in the
properties of polymers, usually undesirable.
BIOLOGICAL MATERIALS
Biological materials are materials produced by biological systems. (i.e.
bone, teeth, tendons and ligaments).
EXTRACELLULAR MATRIX (ECM)
The extracellular matrix (ECM) is a collection of extracellular molecules
and serves as a structural scaffold for the human cells. The ECM initiates
crucial biochemical and biomechanical cues that are required for tissue
morphogenesis, differentiation and homeostasis. The components of the ECM
are produced intracellularly by resident cells and secreted into the ECM
via exocytosis.
HARD TISSUE
Hard tissues are a collection of cells that has become mineralized and
is a kind of connective tissue.
Most Common Hard Tissues:
Bone
Cartilage
Teeth
BONE
The bone is a specialized form of connective tissue and is the main
component of your skeletal system. Unlike other connective tissue, bone is a
hard tissue that becomes calcified. It provides internal support for your body
and offer a place for muscles and tendons to attach. It also protects organs:
the skull for your brain, the ribs for your heart and lungs. Bones are strongest
and most stiff in the direction that they are generally loaded during normal
daily activities. Bones are also much stronger in compression than tension.
Two types of bony tissues:
Cortical
also called as compact

comprises the outer structure of the cortex of the bone.

higher density; is stronger and stiffer than the cancellous
bone, but is more brittle
yields and fractures, when strain exceed 2.0%
Cancellous
also called as trabecular
loosely meshed and porous
may sustain strain level of 50% before it fractures

Types of Bone Fractures

Tensile Fractures occurs in bones that are highly
cancellous such as bone adjacent to the Achilles tendon.
Shear- like tensile fracture, it also occur more commonly
in highly cancellous bone
Compressive loading- found mostly in vertebrae.
Bending- cause both compressive and tensile stresses in
the bone; long bones are susceptible to this
Torsional- also occur in the long bones of the human body
Combined-2 or more of the loading types stated above
may be present
SOFT TISSUE
Soft tissues are the tissues that connect, support, or surround other
structures and organs of the body, not being bone.
Most Common Soft Tissue
tendons

ligaments fascia
skin
fibrous tissues
fat
membranes
TENDON AND LIGAMENT
A ligament is a fibrous connective tissue which attaches bone to bone,
and usually serves to hold structures together and keep them stable. It acts
as a passive stabilizers of the joints.
A tendon is a fibrous connective tissue which attaches muscle to bone.
It aids in the transferring forces generated by muscle contractions. Loads in
tendons are generally higher
CELL-MATERIAL INTERACTION
Cell-material interactions can be positive, negative, or neutral. In the
interaction of our cells to our implants, we desire bioactivity, the beneficial or

adverse effects of the reaction of our body to the implant, and we avoid bioincompatibility or those having toxic or injurious effects on the biological
system.
BIOMATERIALS : DESIGN AND CHARACTERIZATION
Metallic Implant Materials
Metals have been used in various forms as implants. The first metal
developed specifically for human use was Sherman Vanadium Steel,
which was used to manufacture bone fracture plates and screws. Most
metals used for manufacturing implants (e.g., Fe, Cr, Co, Ni, Ti, Ta, Mo,
and W) can be tolerated by the body in minute amounts.

Stainless Steels
Chromium is a major component of corrosion-resistant
stainless steel. The minimum effective concentration of
chromium is 11 w/o. The chromium is a reactive element, but it
and its alloys can be passivated to give excellent corrosion
resistance. The austenitic stainless steels especially types 316
and 316L are most widely used for implants. These are not
hardenable by heat-treatment but can be hardened by coldworking. These groups of stainless steels are nonmagnetic and
possess better corrosion resistance than any others. The
inclusion of molybdenum enhances resistance to pitting
corrosion in salt water.

Co-BASED ALLOYS
These materials are usually referred to as cobaltchromium alloys. There are basically two types: one is the
CoCrMo alloy, which is usually used to cast a product, and the
other is CoNiCrMo alloy, which is usually wrought by (hot)
forging. The castable CoCrMo alloy has been in use for many
decades in dentistry and in making artificial joints. The wrought
CoNiCrMo alloy has been used for making the stems of
prostheses for heavily loaded joints (such as the knee and hip).

Ti AND Ti-BASED ALLOYS

The lightness of titanium (4.5 g/cm3 compared to 7.9
g/cm3 for 316 stainless steel, 8.3 g/cm3 for cast CoCrMo, and
9.2 g/cm3 for wrought CoNiCrMo alloys) and good
mechanochemical properties are salient features for implant
application.

Dental Metals: Dental Amalgam

An amalgam is an alloy in which one of the component
metals is mercury. Mercury reacts with other metals such as
silver and tin and form a plastic mass that can be packed into
the cavity, and which hardens (sets) with time.

Dental Metals: Gold

Gold and gold alloys are useful metals in dentistry as a
result of their durability, stability, and
corrosion resistance. Gold fillings are introduced by two
methods: casting and malleting. Cast restorations are made by
taking a wax impression of the prepared cavity, making a mold
from
this impression in a material such as gypsum silica, which
tolerates high temperature, and casting molten gold in the mold.
Malleted restorations are built up in the cavity from layers of
pure gold foil. The foils are degassed before use, and the layers
are welded together by pressure at room temperature

Ceramic Implant Materials

Ceramics are refractory, polycrystalline compounds, usually
inorganic, including silicates, metallic oxides, carbides, and various
refractory hydrides, sulfides, and selenides. Oxides such as Al2O3,
MgO, SiO2, etc. contain metallic and nonmetallic elements. Ionic salts
(NaCl, CsCl, ZnS, etc.) can form polycrystalline aggregates, but soluble
salts are not suitable for structural biomaterials. Diamond and
carbonaceous structures like graphite and pyrolized carbons are
covalently bonded. The important factors influencing the structure and
property relationship ofthe ceramic materials are radius ratios (2.2.2)
and the relative electronegativity between positive and negative ions.
Ceramics have been used for some time in dentistry for dental
crowns by reason of their inertness to body fluids, high compressive
strength, and good aesthetic appearance in their resemblance to
natural teeth. Some carbons have also found use as implants,
especially for blood interfacing applications such as heart valves. Due
to their high specific strength as fibers and their biocompatibility, they
are also being used as a reinforcing component for composite implant
materials and tensile loading applications such as artificial tendon and
ligament replacements. Although the black color can be a drawback in
some dental applications, this is not a problem if they are used as
implants. They have such desirable qualities as good biocompatibility
and ease of fabrication. Calcium Phosphate is used to make artificial
bone. Hydoxyapatite is the most important among the calcium
compounds since it is found in natural hard tissues as mineral phase. It
acts as reinforcement in hard tissues and it is responsible for the
stiffness of bone, dentin, and enamel
Polymeric Implant Materials
Polymers can be easily fabricated into many forms: fibers,
textiles, films, rods, and viscous liquids. It Bear a close resemblance to
natural polymeric tissue components such as collagen. It is possible to
achieve a bond between synthetic polymers and natural tissue
polymers.

 Composite Implants
Composite materials offer a variety of advantages in comparison
with homogeneous materials. However, in the context of biomaterials,
it is important that each constituent of the composite be
biocompatible, and that the interface between constituents not be
degraded by the body environment. Composites currently used in
biomaterial applications include the following: dental filling
composites; bone particle or carbon fiber reinforced methyl
methacrylate
bone
cement
and
ultrahigh-molecular-weight
polyethylene; and porous surface orthopedic implants. Moreover,
rubber used in catheters, rubber gloves, etc. is usually filled with very
fine particles of silica to make the rubber stronger and tougher.
SURFACE MODIFICATION OF BIOMATERIALS
Surfaces of the biomaterials are needed to be modified because
they need to be un-reactive chemically and physically with the
body, as well as integrate when with tissue. Surface modifications
affect surface
energy, adhesion, biocompatibility, chemical
inertness, lubricity, sterility, asepsis, thrombogenicity, susceptibility
to corrosion, degradation, and hydrophilicity.

Abrasive blasting

It is forcibly propelling a stream of abrasive material against a

surface under high pressure to smooth a rough surface, roughen
a
smooth
surface,
shape
a
surface,
or
remove
surface contaminants.
Plasma modification
The surface is subjected to high levels of excited gases that alter
the surface of the material. It affects the adhesion,
biocompatibility, chemical inertness, lubricity, and sterilization
of the material.

Thermal spraying

Melted (or heated) materials are sprayed onto a surface. The

"feedstock(coating precursor) is heated by electrical (plasma or
arc) or chemical means (combustion flame).

Physical vapor deposition (PVD)

It is a variety of vacuum deposition methods used to deposit thin
films by the condensation of a vaporized form of the desired film

material
onto
various
onto semiconductor wafers).

work

piece

surfaces

(e.g.,

Chemical vapor deposition (CVD)

It is used to produce high-purity, high-performance solid
materials. The process is often used in the semiconductor
industry to produce thin films. The wafer (substrate) is exposed
to
one
or
more volatile
precursors,
which react and/or decompose on the substrate surface to
produce the desired deposit. Frequently, volatile by-products are
also produced, which are removed by gas flow through the
reaction chamber.

Self-assembled monolayers (SAM)

The molecular assemblies formed spontaneously on surfaces by
adsorption and are organized into more or less large ordered
domains.

Layer-by-Layer (LbL) deposition

The films are formed by depositing alternating layers of
oppositely charged materials with wash steps in between.

APPLICATION OF BIOMATERIALS
Devices
1) Cardiac

Pacemaker

2) Vascular
Graft

Materials
Titanium or titanium
alloy
Polyurethane
Silicon

Uses
To regulate
the
heartbeat of
a person
To Treat dead
arteries or to
patch injured
arteries.

Polytetrafluoroethylene
or PTFE
Polyethylene
terephthalate or Darcon
Polyurethanes

Titanium
Graphite
Pyrolytic carbon
Double velour polyester
Silicone
Rubber

To treat a
heart with
vulgar heart
Disease.

Cardiovasc
ular
Medical
Devices

3) Artificial
cardiac
Valve
4) Heart
Catheter

Used for
direct

Orthopedic
implants

Nitinol
Nylon
Polyurethane
Polyethylene
terephthalate (PETE)

Hip
Replaceme
nt
Knee Cap
Replaceme
nt
Joint
Replaceme
nt
Bone
grafting
Jaw
Replaceme
nt

Stainless Steel
Co-Based Alloys
Ti-Based Alloys
POLYMETHYLMETHACRY
LATE (PMMA)

Pure titanium
Titanium Alloy
Titanium-Nickel alloy
Artificial sapphire
Glass-ceramics
Sintered ceramics

Dental
Implants

Tooth
Implant

Dental
Ceramics

Ceramic
Teeth

Dental
Cement

Dental
Cement

Zinc oxide
Polycarboxylate

Bone
Cement

Bone
Cement

Polymethylmethacrylate
(PMMA)

Opthalmolo
gic
application
s

Intraocular
Lens (IOL)

Uses poly-methylmethacrylate (PMMA)

Acrylic polymers
Silicon elastomeres

determinatio
n of blood
pressure and
for giving
drugs of
other fluid
inside a vein
or the heart.
To replace a
broken bone
or to support
an
injured/fractu
red bone.

To replace
the tooth
lost.
Used for
dental inlays,
onlays,
veneers,
crowns or
bridges.
To place
crown tooth
in place or
without
slipping
Use to hold
in place
newly
operated
bones in
place.
Used for
treating
cataract or
myopia