Biomaterials

Class #02 – Introduction to Biomaterials

Biomaterials/Biomateriais
Biomaterials/Biomateriais
MIEQ/MIEB/MEMAT
2015/2016

Herminio Sousa/Jorge Coelho

Departamento de Engenharia Química
Faculdade de Ciências e Tecnologia
Universidade de Coimbra
 Summary

Definition
History
Classification
Applications
 Definition

“… is any material, natural or man-made, that comprises whole or part

of a living structure or biomedical device which performs, augments, or
replaces a natural function”

“… is a nonviable material used in medical device, intended to

interact with a biological systems”

“… is a synthetic or natural material used to replace part of a living

system or to function in intimate contact with living tissue”
 Definition

“A biomaterial can be defined as

any material used to make devices
to replace a part or a function of
the body in a safe, reliable,
economic, and physiologically
acceptable manner.”

Park Joon, Lakes R.S., “Biomaterials – An Introduction”, 3rd edition, Springer;

 Definition

“… is a systematically and pharmacologically inert substance designed for

implantation within or incorporation with living systems”

“… constitute part of medical implants, extracorporeal devices, and

disposables that have been utilized in medicine, surgery, dentistry, and
veterinary medicine as well as in every aspect of patient health care”

“… is any substance (other than a drug) or combination of substances,

synthetic or natural in origin, which can be used for any period of time, as a
whole or as a part of a system which treats, augments, or replaces any
tissue, organ, or function of the body”
 Definition

WHAT??????

There is universally accepted no

definition of a biomaterial!

in our lectures, we will address biomaterials as materials

(synthetic, artificial and natural) that are used in contact with
biological systems (including biological fluids)
 History

Dental Implants in Early Civilizations

Nacre teeth
Mayan People from sea shells

600 A.D.

200 A.D.

Iron and gold teeth Romans

 History

Sutures

600 A.D.
Egyptians

Linen Sutures
200 A.D.

1816 Greeks Gold wire sutures

Philip Physick Lead wire sutures 1849

Silver wire sutures J. Marion Sims

 History

Contact Lenses

1508 1860 1961

Leonardo DaVinci Adolf Fick Otto Wichterle

Contact lenses concept Glass contact lens “Modern” hydrogel

contact lens
 History

20th Century – Materials Revolution

Early 1900’s Bone plates used to fix fractures

1930’s Introduction of stainless steel
and cobalt-chromium alloys
1938 First total hip prosthesis (P. Wiles)

Most implants prior to 1939 had a low probability of success

because of poor understanding of biocompatibility and sterilization
 History

1940’s Polymers in medicine: PMMA bone repair;

cellulose for dialysis; nylon sutures
1952 Mechanical heart valve
1953 PET (polymer fiber) vascular grafts
1958 Cemented* (PMMA) joint replacement
1960 First commercial heart valves
1970’s PEO** (polyethyleneoxide) protein
resistant thin film coating
1976 Artificial heart (W. Kolff, Prof. Emeritus)
 History

1980 “Cleaned up” commodity materials used

extensively
Lycra, Teflon, Polyethene, GoreTex, Silastic, Dacron

1987 New definition of a biomaterial (Williams)

“A biomaterial is a nonviable material used in a medical
device, intended to interact with biological systems”

1994 The word “nonviable” is removed from

the definition of a biomaterial
“A biomaterial is a material used in a medical device,
intended to interact with biological systems”

Current IUPAC definition (2012):

“Material exploited in contact with living tissues,
organisms, or microorganisms”
Note: The notion of exploitation includes utility for applications
and for fundamental research to understand reciprocal
perturbations as well.”
 History

After 1980 – Tissue Engineering Revolution

1980 Yannas et al: artificial skin made from
collagen and glycosaminoglycans
1993 R. Langer and C. Vacanti

Definition of “Tissue Engineering”

Tissue engineered skin

Metallic tantalum foam for bone scaffolds

History
 History

Biomaterials Today

Protein adsorption

Bio-specific biomaterials

Non-fouling materials

Healing and foreign body reaction

 History

Biomaterials Today
Controlled release

Tissue engineering

Regenerative medicine

Biomimetics

“Nanobiotechnology”

Biomimetics is the process of understanding and applying biological principles to

human designs. Ex. when scientists make a machine that mimics what an organism
does
Biomaterials - Classification
 Biomaterials - Classification

Polymers
Natural polymers,
biopolymers/biomacromolecules

Polymers

Modified/artificial Synthetic polymers and

biopolymers/biomacromolecules biopolymers
Biomaterials -Polymers
 Biomaterials -Polymers

Nylon , Silicone , Rubber , Polyester , Polytetrafluoroethylene

 Biomaterials -Polymers

Advantages (generic!)
Resilient; “easy” to fabricate (or “easier” to fabricate than
ceramics or metals); high elasticity; low density; price
Disadvantages (generic!)
Not “strong” (or not as “strong” as ceramics or metals); low
mechanical strain; may deform with time; may degrade

Examples:
Sutures, blood vessels, other soft tissues, hip socket, tissue
engineering scaffolds, etc.
 Biomaterials -Ceramics

Alumina
Calcium Phosphates

Carbon (pyrolitic) Calcium

Hydroxyapatite
Ceramics Ceramic glasses
Silicates
Glasses
Bioglasses

Titania

Zirconia

http://en.wikipedia.org/wiki/Bioactive_glass
http://www.azom.com/Details.asp?ArticleID=3625
 Biomaterials -Ceramics

Alumina, Zirconia , Calcium Phosphates (including Hydroxyapatite ), Carbon

Biomaterials -Ceramics
 Biomaterials -Ceramics

Ceramics
Advantages (generic!)
Good compatibility; corrosion resistance; inert

Disadvantages (generic!)
Brittle; not resilient; week in tension; “difficult” to manufacture (or
more “difficult” to manufacture than polymers); high density;
expensive;

Examples:
Dental and orthopedic implants, neuro-estimulation
 Biomaterials - Metals

Platinum

Gold

Titanium-based Alloys

Metals Cobalt-based Alloys

Stainless Steels

Silver
 Biomaterials - Metals

Ti and its alloys , Co-Cr alloys , Au , Ag Stainless Steels

Biomaterials - Metals
 Biomaterials - Metals

Metals
Advantages (generic!)
High tension force; high use resistance; strong; tough; ductile;

Disadvantages (generic!)
Corrosion in physiological medium; high density; low
biocompatibility, “difficult” to make (or more “difficult” to make than
polymers); price

Examples:
Joint replacements, dental root implants, pacer and suture wires,
bone plates and screws
 Biomaterials - Composites

Hydrogels/PET fibers

Fiber-reinforced

Composites
Particle-reinforced

PE / HA particles

• Composites are engineered materials made from two or more constituent materials with
significantly different physical or chemical properties and which remain separate and distinct on a
macroscopic level within the finished structure.
Biomaterials - Composites

Composites
 Biomaterials - Composites

Composites
Advantages (generic!)
Good compatibility; corrosion resistance; usually inert; strong or
soft (depending on final intended application); tailor-made

Disadvantages (generic!)
“Difficult” to manufacture; price

Examples:
Bone cement, dental resin, artificial valves
Biomaterials - Composites
 Biomaterials

Non-carcinogenic, non-pyrogenic,
non-toxic, non-allergenic, blood
compatible, non-inflammatory, non-
degradable (only if that is intended)

Not destroyed or changed by

typical sterilizing techniques such
as autoclaving, dry heat,
radiation, ethylene oxide

Mechanical, Chemical, Physical, Capacity to be… machinable,

Surface and Biological properties moldable, extrudable, etc…
 Biomaterials - Features

To be used as biomaterials:

Right density
Biocompatible
Sterilizable
Adequate mechanical strength
Chemically inert and stable (if intended)
Non-toxic and non-carcinogenic
Biomaterials - Features
 Biomaterials - Features

To be used as biomaterials:

The material must not leach or release soluble components

into the living/biological systems, unless that release is
intentional

The living/biological systems must not degrade the implant,

unless this degradation is intentional

Relatively inexpensive, reproducible and easy to fabricate

and to process on a large scale
Biomaterials – Main Characterizations

Chemical analyses
Physical analyses
Biocompatibility analyses
“in vivo” tests
“in vitro” tests
Surface characterization
 Ideal Biomaterial

Should carry out the task for which was designed and
must NOT cause:

Cancer
Hemolysis and thrombosis
Destruction of enzymes
Toxic or allergic reactions
Adverse immune responses
Damage to adjacent tissues
Alteration of plasma proteins
Biomaterials – Applications
Biomaterials – Applications
 Biomaterials – Applications

The need for biomaterials stems from the inability to treat many
diseases, injuries and conditions with other therapies or procedures:

Replacement of body part sthat lost function (total hip, heart)

 Biomaterials – Applications

Correct abnormalities (spinal rod)

 Biomaterials – Applications

Assist in healing (sutures, drug release)

 Biomaterials – Applications

Improve /replace function (intraocular lenses)

 Biomaterials – Applications

Intraocular lenses usually replace the

existing crystalline lens because it has
been clouded over by a cataract, or as a
form of refractive surgery to change the
eye’s optical power.

It usually consists of a plastic

lens with plastic side struts,
called haptics, to hold the lens
in place within the capsular bag.
 Biomaterials – Applications

Intraocular
lenses

There are foldable intraocular lenses made of acrylic or silicone (simple

surgery) or non-flexible lenses (typically made of PMMA) that require a
larger incision.

Major complications:
Capsule opacification caused by proliferation and migration of residual
lens epithelial cells into the visual axis (the term “secondary cataract” is
used but it is not correct)
 Biomaterials – Applications

Cataract is a clouding that develops in the crystalline

Intraocular lens of the eye or in its envelope, varying in degree
lenses from slight to complete opacity and obstructing the
passage of light.

The lens is a transparent, biconvex structure in the eye that, along with the cornea,
helps to refract light to be focused on the retina.
 Biomaterials – Applications

Intraocular
lenses
 Biomaterials – Applications

Improve function (pacemaker, stent)

 Biomaterials – Applications

Stents

A stent is either an expandable wire form or perforated tube that is inserted

into an artery, blood vessel, or other duct to hold the structure open.

They are used to unblock and to keep open tube-shaped structures in the
body.
 Biomaterials – Applications

Stents

An intra-luminal coronary artery

stent is a small, self-expanding,
metal mesh tube that is placed
inside a coronary artery after
balloon angioplasty to prevent
the artery from reclosing.

Risks of stents and stent placement may include:

Blood clot
Allergic reaction to stent materials
Rupture of the duct or vessel when the stent is inserted
 Biomaterials – Applications

Suture strands

Can be
extremely thin

Plastic surgery
 Biomaterials – Applications

Suture strands Non-absorbable

Generally made from

nylon, polypropylene, or
silk and used to close
skin or muscle.

Biodegradable sutures are usually

made of poly(lactic acid-co-glycolic
acid) (PLGA)
 Biomaterials – Applications

Staples

Metallic

Stainless
steel or
titanium

Biodegradable Poli(lactic acid-co-glycolic acid)

(PLGA)
 Biomaterials – Applications

Adhesive strips advantages

•rate of wound infection is
less with adhesive strips
than with stitches.
•less time to apply;
•no need for a painful
injection of anaesthetic

disadvantages
•less precision in bringing wound
edges together than suturing.
•areas with hair or secretions are
not suitable for taping.
Biomaterials – Applications

Biological Adhesives

The idea of using an adhesive was born in

1787 when someone realized that “many
workers glued their wounds with solid glue
dissolved in water” (Haring, 1972).
 Biomaterials – Applications

Biological Adhesives

• To bond two organic segments usually

apart
• To stop blood flow or air leaks from an
organ surface;

• To close quickly and efficiently incisions

in any biological material.
 Biomaterials – Applications

Biological Adhesives

- Must hold tissues together

- lack of toxicity

- no allergy, mutagenicity, or
carcinogenicity effects,

- easy to apply

- biodegradability

- biocompatibility
Biomaterials – Applications

More common Biological Adhesives

-cyanoacrylates
-fibrin/thrombin

Already commercialized
Biomaterials – Applications

BioGlue

compósito de
albumina sérica
bovina (BSA) e
glutaraldeído
 Biomaterials – Applications

Advantages of fibrin glues and sealants

• control of blood loss

• tissue adhesion
• sealing of organs or tissues

Disadvantages of fibrin/thrombin glues and sealants

They don’t possess hardness enough to be applied

where mechanical strength is necessary. Risk of
blood diseases transmission
 Biomaterials – Applications

Focal Seal-L

hidrogéis de
polietilenoglicol
fotopolimerizáveis

Controlo de fugas de ar
 Biomaterials – Applications

Cyanoacrylates

C N C N

CH 2 C CH2 C

COOR COOR
n

Poli(alkyl-2-cyanoacrylate) % of degradation
Methyl 52,2 More toxic
Ethyl 3,10 with
Propyl 1,99 increasing
Isobutyl 1,52
degradation
Butyl 0,73
 Biomaterials – Applications

Dermabond

2-octil-cianoacrilato

mantém-se no local pelo período

de 7 a 10 dias
Biomaterials – Applications
 Biomaterials – Applications

Cyanoacrylates degradation
CN CN CN CN
-
CH2 C CH2 C + OH CH2 C CH2 OH + -C

C O C O C O C O

O O O O

R R R R

CN CN
-
-C + H2O HC + OH

C O C O

O O

R R

CN CN

C-
-
CH2 C CH2 OH + OH CH2 + CH2 O + H2 O

C O C O

O O
formaldehyde
R R
Biomaterials – Applications
 Further references

RATNER, B.; HOFFMAN A.; SCHOEN, F.; LEMONS, J.; “Biomaterials

Science”, 2nd Edition, Elsevier
DEE, K.; PULEO, D.; BIZIOS, R.; “ Tissue-Biomaterial Interactions”, Wiley
PARK, J.; LAKES, S.; “Biomaterials: An Introduction”, 3rd Edition, Springer
CALLISTER J., “Material Science and Engineering: An Introduction”, 6th
Edition, Wiley
GIL, H.; ROCHA, J.; BRANQUINHO, J.; ALVES, P.; CALVINHO, P.; “Polymeric
Biomaterials”, Open and Distance Learning for Training in Biotechnology,
Universidade de Coimbra
 Further references

Articles
-Ryou, M., Thompson, C. C. (2006) Tissue Adhesives: A Review. Tech. Gastrointest. Endosc. 8(1):33-37
-Donkerwolcke, M., Burny, F., Muster, D. (1998) Tissues and bone adhesives-historical aspects. Biomaterials
19(16):1461-1466.

Figures References
http://www.medsurge.in/images/sutures_img.jpg http://www.insorb.com
http://www.scf-online.com http://www.diginfo.tv
http://mistyart.com http://www.vas-reversal.com
http://www.gasdetection.com http://www.medgadget.com
http://www.hfa.ie http://www.maleinfertility.org
http://www.nycpba.org http://neurobio.drexel.edu
http://www.visualsunlimited.com
 Acknowledgement

For the content of this lecture:

Carlos Boto
Rita Gabriel
Eduardo Palmieri
Nathália Schmidt
Vinicius Magalhães
Joana Mendes
Mariline Alves