Dr. Alagiriswamy A A, (M.

Sc, PhD, PDF)

Asst. Professor (Sr. Grade),
Dept. of Physics, SRM-University,
Kattankulathur campus,
Chennai

ABCs of Biomaterials
UNIT III
Lecture 4

March 24, 2014

Skin/cartilage
Drug Delivery
Devices

Ocular
implants
Bone
replacements

Polymers

Orthopedic
screws/fixation

Metals

Dental
Implants

Synthetic
BIOMATERIALS

Ceramics

Heart
valves

Dental Implants

Implantable
Microelectrode
s

Semiconductor
Materials

Biosensors

Biological responses ; requirements

Changing the chemistry at the surface
Inducing roughness/porosity at the surface
Incorporate surface reactive materials (bioresorbable;

helps in slow replacement by tissue)

Should not secrete oxidizing agents
Reduce corrosion rate of biomaterials

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CLASSIFICATION OF BIOMATERIALS
Biomaterials can be divided into three major classes of
materials:
Metals
Polymers
Ceramics (including carbons, glass ceramics, and glasses).

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First Generation Implants

ad hoc implants
specified by physicians using common and borrowed

materials
most successes were accidental rather than by design
Examples First Generation Implants

gold fillings, wooden teeth, PMMA dental prosthesis

steel, gold, ivory, etc., bone plates
glass eyes and other body parts
dacron and parachute cloth vascular implants

METALLIC IMPLANT MATERIALS

Stainless steel

Must be corrosion resistant

Cobalt-chromium alloys Good fatigue properties

Titanium alloys
Other compatible issues
Metallic implants are used for two primary purposes.
To replace a portion of the body such as joints, long bones and skull plates
Fixation devices are used to stabilize broken bones followed by the healing
process
Either first generation or second ones
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CONSTITUENTS OF STEEL
Type

%C

%Cr

% Ni

%Mn

% other elements

301

0.15

16-18

6-8

2.0

1.0Si

304

0.07

17-19

8-11

2.0

1-Si

316, 18-8sMo

0.07

16-18

10-14

2.0

2-3 Mo, 1.0 Si

316L

0.03

16-18

10-14

2.0

2.3 Mo, 0.75Si

430F

0.08

16-18

1.0-1.5

1.5

1.0 Si, 0-6 Mo

LECTURE 3

Other features
less chromium content should be utilized (because Cr is a highly reactive
metal)
Make use of austenite type steel (less magnetic properties)
Lowered carbon content
Inclusion of molybdenum helps corrosion resistance
Electroplating technique (increases corrosion resistance)

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Devices

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Alloy Type

Jewitt hip nails and plates

316 L

Intramedullary pins

316 L

Mandibular staple bone plates

316L

Heart valves

316

Stapedial Prosthesis

316

Mayfield clips (neurosurgery)

316

Schwartz clips (neurosurgery)

420

Cardiac pacemaker electrodes

304

COBALT CHROMIUM ALLOYS

Cobalt based alloys
are used in one of
three forms
Cast; as prepared

Wrought
(fine
structure with low
carbon contents ;
pure forms)

Forged

Cobalt based alloys are better than stainless steel

devices because of low corrosion resistance

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More details
Cast alloy:
a wax model of the implant is made and
ceramic shell is built around the wax model
When wax is melted away, the ceramic mold has the shape
of the implant
Molten metal alloy is then poured in to the
shell, cooling, the shell is removed to obtain
metal implant.

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Wrought alloy:

possess a uniform
microstructure with fine
grains.

Wrought Co-Cr Mo alloy

can be further strengthened
by cold work.

Forged Alloy:

produced from a hot forging process.

Forging of Co-Cr Mo alloy requires

sophisticated press and complicated
tooling.

Factors make it more expensive to

fabricate a device

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TITANIUM BASED ALLOYS

The advantage of using titanium based alloys as implant
materials are
low density
good mechano-chemical properties

The major disadvantages

o relatively high cost
oreactivity.

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More details
a light metal
Titanium exists in two allotropic forms,
The low temperature -form has a close-packed hexagonal
crystal structure with a c/a ratio of 1.587 at room temperature
Above 882.50C -titanium having a body centered cubic
structure which is stable

Ti-6 Al-4V alloy is generally used in one of three conditions

wrought, forged or cast

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POLYMERS
Elastomers; able to withstand large deformations and
return to their original dimensions after releasing the
stretching force.

Plastics; are more rigid

materials
Thermoplastic (can be
reused, melted)

Thermosetting (cant)
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Elastomers
include,
butyl
rubber,
chlorosulfonated
polyethylene,
epichlorohydrin,rubber,
polyurethane,natural rubber and silicone
rubber.
Polymers toxicity

Residual monomers due to incomplete

polymerization/catalyst
used
for
polymerization may cause irritations.

15

Polymer

Specific Properties

Biomedical uses

Polyethylene

Low cost, easy Possibility excellent

Tubes for various
electrical
insulation
properties,
catheters,
hip
excellent
chemical
resistance,
joint, knee joint
toughness and flexibility even at low
prostheses
temperatures

Polypropylene

Excellent chemical resistance, weak

Yarn for surgery,
permeability to water vapors good
sutures
transparency and surface reflection.

Chemical
inertness,
exceptional Vascular
and
weathering and heat resistance,
auditory
Tetrafluoroethylene
nonadhesive, very low coefficient of
prostheses,
friction
catheters tubes

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Polyethylene structures
The first polyethylene [PE,(-CH2-CH2-)n] was made by
reacting
ethylene gas at high pressure in the presence of a peroxide
catalyst for starting polymerization; yielding low density
polyethylene (LDPE).

By using a Ziegler-Natta catalyst, high-density polyethylene

(HDPE)
can be produced at low pressure; (first titanium-based
catalysts)
The crystallinity usually is 50-70% for low density PE and
70-80%
for high density PE
ultra high molecular weight polyethylene (UHMWPE)
??????

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ACRYLIC RESINS (organic glass)

The most widely used polyacrylate is poly(methyl
methacrylate, PMMA) ; The features of acrylic polymers ;
high toughness/strength,
good biocompatibility properties

brittle in comparison with other polymers

excellent light transparency
high index of refraction.

Causes allergic reactions

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BONE CEMENT MIXING AND INJECTION

PMMA powder + MMA liquid
mixed in a ratio of 2:1 in a dough, to
cure
Injected in the femur (thigh bone)
The monomer polymerizes and
binds
together
the
preexisting
polymer particles.

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Hydrogels
Interaction with H2O, but
not soluble

PHEMA; absorbs 60 % of Water,

machinable when dry

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Interesting features

HYDROGELS

(1) The soft, rubbery nature coupled with minimal

mechanical/frictional irritation to the
surrounding
tissues.

(2) Low or zero interfacial tension with surrounding

biological fluids and tissues, thereby, minimizing the
driving force for protein adsorption and cell adhesion
(3) Hydrogels allow the permeating and diffusion of low
molecular weight metabolities,waste products and salts
as do living tissues.
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POLYURETHANES
Polyther-urethanes; block copolymers (variable length blocks that
aggregate in phase domains)
Good physical and mechanical characteristics

Are hydrophilic in nature

Good biocompatibility (blood compatibility)
Hydrolytic heart assist devices
Non-cytotoxic therapy

Consists of hard and soft segments

LECTURE 5

BIOMATERIALS

22

POLYAMIDES (Nylons)
Obtained through condensation of diamine and
diacid derivative.
Excellent fiber forming properties due to interchain hydrogen bonding and high degree of
crystallinity, which increases the strength in the
fiber direction.
Hydrogen bonds play a major role
As a catheter
Hypodermic syringes
Diamino hexane

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BIOMATERIALS

adipic acid

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Next-Generation biomaterials for

Tissue implantation

Skin implantation

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Primary
exposed
underlying

Preserve
viability of
structures

THERAPY GOALS

Promote
controlled

Prevent
infection

Long term
reconstruction

optimize
later

Permit
mobility of

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Durable
skin cover

healing

Sensation
to key areas

25

Spine,

Cranial
maxillofacial

Dental

Vascular

Bone
Cartilage

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Types of Implants

Implants
may be

Cemented
Porous coated
Mesh of holes on
implant surface
Secured as bone in
grows

Types of coated implants

Requirements
Non-toxic, noncarcinogenic, nonallergic,
Biocompatible

Sterilizable,

Low cost, ofcourse

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Excellent physical
properties,
corrosion resistant,
fatigue strength

Choice of design

Rate, modes of
degradation should
follow the intended
ways

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Three so-called 'generations' of biosensors;

First generation; normal product of the reaction diffuses to

the transducer and causes the electrical response.
Second generation; involve specific 'mediators' between
the reaction and the transducer in order to generate
improved response.
Third generation; reaction itself causes the response and no
product or mediator diffusion is directly involved.

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Brief applications of biosensor(s)

Clinical diagnosis and biomedicine

Farm, garden and veterinary analysis

Process control: fermentation control and

analysis food and drink

production and analysis
Microbiology: bacterial and viral analysis

Pharmaceutical and drug analysis

Industrial effluent control
Pollution control and

monitoring/Mining, industrial and toxic

gases
Military applications

LECTURE 3

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Tissue engineering (also referred to as

regenerative medicine)
By

restoring,
maintaining,
enhancing the tissue, and finally
functionalize the organs

Tissue can be grown inside or

outside

To create products that improve tissue

function or heal tissue defects.
Replace diseased or damaged tissue

Finally to exploit the living cells in

many ways

Because
Donor tissues and organs are in short
supply
We want to minimize immune system
response by using our own cells or
novel ways to protect transplant

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Tissue engineering
Regenerate
Identify the cues that allow for

regeneration without scarring

Like growing a new limb
Repair
Stimulate the tissue at a cell or
molecular level, even at level of
DNA, to repair itself.
Replace
A biological substitute is created
The cells themselves
in the lab that can be implanted
Non-soluble factors within the extracellular
to replace the tissue or organ of
matrix (ECM) such as laminins,collagens,and
interest
other molecules
Soluble factors such as cytokines, hormones,
nutrients, vitamins, and minerals

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Normal strategies
cell isolation
cell culture
scaffold material choice

cell scaffold co-culture studies

implantation in animals
human trials
SUCCESSFULLY ENGINEERED
TO SOME EXTENT

Skin
Bone
Cartilage
Intestine

Advances in
Biomaterials Technology
Cell matrices for 3-D growth and tissue reconstruction

Biosensors, Biomimetic , and smart devices

Controlled Drug Delivery/ Targeted delivery

Biohybrid organs and Cell immunoisolation

New biomaterials - bioactive, biodegradable, inorganic
New processing techniques

Test Conditions:
pH
pO2
Temperature
Mechanical Stress
Stress Cycles (per year)

Value
6.8
7.0
7.15-7.35
2-40
40
100
37
28
4x107 N m-2
4x108 N m-2
3x105
5x106 - 4x107

Location
Intracellular
Interstitial
Blood
Interstitial (mm Hg)
Venous
Arterial
Normal Core
Normal Skin
Muscle (peak stress)
Tendon (peak stress)
Peristalsis
Heart muscle contraction

Length of implant: Day: Month: Longer:

where used: skin/blood/brain/mucosal/etc.

Challenges

To more closely replicate complex tissue architecture

and arrangement in vitro
To better understand extracellular and intracellular
modulators of cell function

To develop novel materials and processing techniques

that are compatible with biological interfaces
To find better strategies for immune acceptance

Skin
Implantation

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Biosensors (invitro/invivo);

analytical devices which convert

biological response into a useful electrical
signal
to determine the concentration of
substances either directly or indirectly
areas of biochemistry, bioreactor
science,
physical
chemistry,
electrochemistry, electronics and software
engineering, and others

http://www.lsbu.ac.uk/biology/enztech/

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Principle of biosensors (bio-recognition systems)

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WORKING PRINCIPLE OF BIOSENSOR

biocatalyst (a) converts the substrate to product.

This reaction is determined by the transducer (b)

which converts it to an electrical signal.
The output from the transducer is amplified (c),

output
distribution of charges
light-induced changes

mass difference

processed (d) and displayed (e).

LECTURE 6

BIOMATERIALS

41

Special materials

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Autograft
A graft, or portion of living tissue, taken from one part of the
body and placed in another site on the same individual.

Allograft
Grafts between two or more individuals allogenic (genetically different
although belonging to or obtained from the same species) at one or more loci.

Xenograft
Grafts from one species of tissues to other species; Bone marrow engineering

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THREE CLASSES OF CERAMICS (according to their reactivity)

completely resorbable

More reactive (Calcium phosphate) over a span of times

Yielding mineralized bone growing from the implant surface

surface reactive

Bioglass ceramics ; Intermediate behavior

Soft tissues/cell membranes

nearly inert

Less reactive (alumina/carbons) even after thousands of hours

how minimal interfacial bonds with living tissues.

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DIFFERENT VARIETIES OF CARBON (NEARLY INERT CERAMICS)

Pyrolitic carbon;

Pyrolysis of hyrdocarbon gas (methane) 15000 degrees

Low temperature isotropic (LTI) phase

Good bonding strength to metals (10 Mpa 35 Mpa)

Inclusion of Si with C, wear resistance increases drastically

Vitreous carbon (glassy carbon);

controlled pyrolysis of a polymer such as phenol formaldehyde

resin, rayon and polyacrylonitrile

Low temperature isotropic phase

Good biocompatibility, but strength and wear resistance are not good as LTI carbons

Turbostratic carbon (Ultra low temperature isotropic carbons (ULTI))

Carbon atoms are evaporated from heated carbon source and

condensed into a cool substrate of ceramic, metal or polymer.

Good biocompatibility

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Alumina (Aluminium oxide)

Natural single crystal alumina known as sapphire
High-density alumina ; prepared from purified alumina
powder by isostatic pressing and subsequent firing at 150017000C.
-alumina has a hcp crystal structure (a=0.4758 nm and
c=1.2999nm)

load bearing hip prostheses and dental implants, hip and knee
joints, tibial plate, femur shaft, shoulders, vertebra, and ankle
joint prostheses

Alumina ceramic
femoral
component

Porous network ;
SEM images

high corrosion resistance

wear resistance
Surface finishing
small grain size
biomechanically correct design
exact implantation technique

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Glass Ceramics

Bioglass

To achieve a controlled surface reactivity that will

induce a direct chemical bond between the implant and the
surrounding tissues.

Bioglass and Ceravital; fine-grained structure with

excellent mechanical and thermal properties
The composition of Ceravital is similar to bioglass in Sio2
content but differ in CaO,MgO,Na2O.

Ceravital

Bioglass implants have several advantages like

high mechanical properties

surface biocompatible properties.

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GLASS CERAMICS
Bioglass and Ceravital are two glass

ceramics,

fine-grained structure with excellent

mechanical/thermal properties, which are used in
implants.
Bioglass (composed of SiO2, Na2O, CaO and
P2O5)
Ceravitals composition is similar to bioglass in
Sio2 content but differ in CaO,MgO,Na2O.

highly reactive to aqueous medium and

bioactive
Drawbacks:

brittleness, low fracture-resistance due to

mechanical weakness

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Resorbable Ceramics (first resorbable implant material-Plaster of Paris).

Should not have variable resorption rates

Should not have poor mechanical properties.

Two types of orthophosphoric acid salt namely -tricalcium phosphate (TCP)

and hydroxyapatite (HAP) (classified on the basis of Ca/P ratio).
The apatite- [Ca10 (PO4)6 (OH)2] crystallizes into the hexagonal rhombic
system. The unit cell has dimensions of a = 0.9432 mm and c = 0.6881 nm.
The ideal Ca/P ratio of hydroxyapatite is 10/6 and the calculated density is
3.219 g/ml.

The substitution of OH- with F- gives a greater structural stability due to the
fact that F- has a closer coordination than the hydroxyl, to the nearest calcium.

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Questions?

March 24, 2014