P8 037:
Introduction to Biomaterials
生醫材料導論
(Taught in English)
葉明龍
Phone: 63429
Email: mlyeh@mail.ncku.edu.tw
1
Alternative:
P8 017
Chemistry of Biomaterials
生物材料化學
張憲彰
Wed. 5-7
2
Time: Mon. 6-8 (2:10-5:00 PM)
 Office hours: Wednesday, Thursday
10AM -12PM (Biomedical Engineering
5751A)
 Grade:

Homework: 30%
 Tests: 50%
 Final paper and Presentation: 20%

3/68
Textbooks:
Intend for Non-Materials background
 Fundamentals of Materials Science and
Engineering (Chap 2-9)
By: William D. Callister Jr.

Biomaterials Science: An Introduction
to Materials in Medicine (Chap 1, 2)
By: Ruddy D. Ratner; Allan Hoffman; Frederick
Schoen and Jack Lemons
4/68

Introductory book:
生物醫學材料 王盈錦

References:
1. Biomaterials
by Sujata Bhat
2. Biomaterials: An Introduction
by Joon Bu Park
5/68
Students Self Introduction
1.
2.
3.
4.
5.
Fill your name, email, phone, Institute,
Grade (Year) and Advisor
Name, Institute, Grade (Year)
Advisor
Main focus of your lab
Possible research direction
6/68
Curriculum:
Week Content
1. Opening statement: Introduction (Biomaterials Page 1-9)
2. I. Materials Science and Engineering
Chap 2 Atomic Structure and Interatomic Bonding
Chap 3. Structures of Metals and Ceramics
3. Chap 4. Polymer Structure
Chap 5 Imperfections in Solids
4. Chap 6. Diffusion
Chap 7. Mechanical Properties
5. Chap 8. Deformation and Strengthening Mechanisms
Chap 9. Failure
6. Test I
7/68
Curriculum:
7. II. Biomaterials
1.4 Surface properties and surface characterization
1.5 Role of water in biomaterials
8. 2.2 Polymers
9. 2.3 Silicone Biomaterials
2.4 Medical fibers and biotextiles
10. 2.5 Hydorgels
2.6 Smart Polymers
11. 2.7 Bioresorbable and Bioerodible Materials
2.8 Natural Materials
12. 2.9 Metals
8/68
Curriculum:
13.
14.
15.
16.
17.
18.
2.10 Ceramics, Glasses, and Glass-Ceramics
2.11 Pyrolytic Carbon
2.12 Composite
2.13 Nonfouling surfaces
2.14 Physicochemical Surface modification
2.15 Textured and Porous Materials
2.16 Surface-Immobilized Biomolecules
Final presentation
Test II
9/68
Biomaterials: Definition

(1987, Williams) A biomaterial is a nonviable
material used in a medical device, intended to
interact with biological system.

(Bhat) Nondrug material that can be used to
treat, enhance or replace any tissue, organ, or
function in a organism.
(Bhat) Biological derived material that is used
for its structural rather than its biological
properties.

10/68
Definition:

(Merriam-Webster) Materials used for or
suitable for used in prostheses that
comes in direct contact with living
tissues.

Biocompatibility: ability of a material to
perform with an appropriate host
response in a specific application
11/68
Introduction


Biomaterials used in these devices:
 ophthalmology,
 cardiology,
 neuromuscular surgery,
 orthopedics and
 dentistry.
All biomaterials in common;



they must have intimate contact with patient’s tissue or body fluid,
providing a real physical interface.
The search for new, more reliable devices require a
disciplined scientific approach to the subject.
12/68
Introduction: Biocompatibility



Good biocompatibility is achieved when the
material exists within a living body without
adversely or significantly affecting it or being
affected by it.
The material should have adequate mechanical
strength, chemical and physical properties.
Thus biomaterials must be compatible with body
tissues mechanically, chemically as well as
pharmacologically.
13/68
Introduction

1.
2.
3.
To research these materials the
investigator need to have arrange of
techniques for
materials production,
measurement of strength and surface
properties and
in vitro and in vivo techniques for
biocompatibility evaluation.
14/68
Introduction

The functions of implants fall into one the
following categories:




Load bearing or transmission artificial joint, fracture
fixation
The control of fluid flow in order to stimulate normal
physiological function or situation vascular graft,
stent
Passive space filling either for cosmetic reasons or
functional reasons bone filling, skin
Generation of electric stimuli and transmission of light
and sound. electrode
15/68
Biomaterials: General perspective
Biomaterials was also used to

grow cells in culture,
 in apparatus for handling protein in
laboratory,
 devices to regulate fertility in cattle,
 in aquaculture of oyster, cell-silicon “biochip”.
Biomaterials are rarely used as simple
materials, integrated into devices (final
fabricated, sterilized form)


16/68
Biomaterials science


The physical and biological study of materials and their
interaction with the biological environment.
Traditionally investigation:




biomaterials synthesis, optimization, characterization,
testing
the biology of host-material interactions.
Most biomaterials introduce a non-specific, stereotyped
biological reaction.
Current effort:


toward the development of engineered surfaces that could
elicit rapid and highly precise reactions with cells and
proteins,
tailored to a specific application.
17/68
Biocompatibility
Indeed, a complementary definition
essential for understanding the goal (i.e.,
specific end applications ) of biomaterials
science is that of “biocompatibility”.
 "Biocompatibility” is the ability of a material
to perform with an appropriate host
response in a specific application
(Williams, 1987).

18/68
Biocompatibility

Examples of "appropriate host responses"
include
the resistance to blood clotting,
 resistance to bacterial colonization, and
 normal, uncomplicated healing.

19/68
Biocompatibility

This general concept of biocompatibility
has been extended recently in the broad
approach called "tissue engineering"

careful selection of cells, materials, and
metabolic and biomechanical conditions to
regenerate functional tissues.
20/68
Classic Examples of
Biomaterials
21
Classic Examples: Table 1 (Ratner)
22/68
Classic Examples: Table 1 (Ratner)
23/68
Classic Examples: Table 1 (Ratner)
24/68
Biomaterials and
health care market
25
26/68
27/68
Classic Examples


Substitute Heart
valves: Heart valve
prostheses are fabricated
from carbons, metals,
elastomers, fabrics and
natural (e.g. pig) valves and
other tissues chemically
pretreated to reduce their
immunologic reactivity and
enhance durability.
Problem: degeneration of
tissue, mechanical failure,
postoperative infection, and
induction of blood clot.
28/68
Classic Examples




Artificial Hip Joint: The
human hip joint is subjected to
high mechanical stress and
undergoes considerable
abuse.
Hip joints are fabricated from
specific high-strength alloy,
ceramics, composites, and
ultrahigh molecular weight
polyethylene.
In most cases, good function
is restored, and even athletic
activities are possible.
After 10-15 years, the implant
may loosen, necessitating
another operation.
29/68
Classic Examples


Dental implant:
Titanium implants, which
form an artificial tooth
root on which crown is
affixed.
A special requirement of
a material in this
application is the ability
to form a tight seal
against bacterial
invasion where the
implant traverses the
gingival (gum).
30/68
Classic Examples

Intraocular Lenses:
Intraocular Lenses
(IOLs) made by poly
(methyl methacrylate),
silicone elastomer, or
other materials are
used to replaced a
natural lens when it
become cloudy and
cataractous.
31/68
Characteristics of Biomaterials
Science
Multidisciplinary
 Many diverse materials
 Development of biomaterials devices
 Magnitude of the field
 Success and failure

32/68
Characteristics of Biomaterials
Science: Multidisciplinary


More than any other field of contemporary
technology, biomaterials science brings
together researchers from diverse
backgrounds who must communicate clearly.
Figure 6 lists some of the disciplines that are
encountered in the progression from
identifying the need for a biomaterial or
device to its manufacture, sale, and
implantation.
33/68
34/68
Many Diverse Materials:
The biomaterials scientist will have an
appreciation of materials science.
 This may range from

an impressive command of the theory and
 practice of the field demonstrated by the
professional materials scientist to
 a general understanding of the properties of
materials that might be demonstrated by the
physician or biologist investigator involved in
biomaterials-related research.

35/68
Many Diverse Materials:

A wide range of materials is routinely
used and no one researcher will be
comfortable synthesizing and designing
with all these materials.
36/68
Many Diverse Materials:




Hard tissue replacement biomaterials: metals,
ceramics, used in orthopedic and dental
materials.
Soft tissue replacement biomaterials: polymers,
cardiovascular and general plastic surgery
materials.
Some devices involved both soft and hard tissue.
There is need for a general understanding of all
class of materials.
37/68
Development of biomaterials
devices: Fig 6.
It provides a perspective on how
different disciplines work together,






starting from the identification of a need for
a biomaterial through
development,
manufacture,
implantation, and
removal from the patient.
38/68
Characteristics of Biomaterials
Science
39/68
Magnitude of the field.


Magnitude expresses both a magnitude
of need and magnitude of a commercial
market.
Needless to say, a conflict of interest can
arise with pressure from both the
commercial quarter and from the ethical
consideration.
40/68
Success and Failure





Most biomaterials and medical devices perform
satisfactorily, improving the quality of life for the
recipient or saving lives.
However, no manmade construct is perfect.
All manufactured devices have a failure rate.
Also, all humans are different with differing
genetics, gender, body chemistries, living
environment, and degrees of physical activity.
Furthermore, physicians implant or use these
devices with varying degrees of skill.
41/68
Success and Failure


The other side to the medical device success
story is that there are problems, compromises,
and complications that occur with medical
devices.
Central issues for the biomaterials scientist,
manufacturer, patient, physician, and attorney
are,
(1) what represents good design,
(2) who should be responsible when devices perform "
with an inappropriate host response," and
(3) what are the cost/risk or cost/benefit ratios for the
implant or therapy?
42/68
Success and Failure




Some examples may clarify these issues.
Clearly, heart valve disease is a serious medical
problem. Patients with diseased aortic heart
valves have a 50 % chance of dying within 3
years.
Surgical replacement of the diseased valve
leads to an expected survival of 10 years in 70
% of the cases.
However, of these patients whose longevity and
quality of life have clearly been enhanced,
approximately 60 % will suffer a serious valverelated complication within 10 years after the
operation.
43/68
Subjects Integral to
Biomaterials Science
44
Subjects Integral to
Biomaterials Science









Toxicology
Biocompatibility
Functional tissue structure and
pathobiology
Healing
Dependence on specific anatomical site
Mechanical and Performance requirements:
Industrial involvement
Ethics (Table 3)
Regulation
45/68
Toxicology:


It deals with the substances that migrate
out of biomaterials. Ex: for polymers,
many low-molecular-weight “leachables”
exhibit some level of physiologic activity
and cell toxicity.
It is reasonable to say that a biomaterial
should not give off anything from its
mass unless it is specifically designed to
do so.
46/68
Biocompatibility:





The understanding and measurement of
biocompatibility is unique to biomaterials
science.
Unfortunately, we do not have precise
definitions or accurate measurements of
biocompatibility.
It is defined in terms of performance or
success at a specific task.
However, this operational definition offers us
little to use in designing new or improved
vascular prostheses.
In fact, biocompatibility may have to be
uniquely defined for each application.
47/68
Functional tissue structure and
pathobiology


1.
2.
3.
Biomaterials incorporated into medical devices
are implanted into tissues and organs.
Critical considerations to workers in the field.
The key principles governing the structure of
normal and abnormal cells, tissues, and
organs,
the techniques by which the structure and
function of normal and abnormal tissue are
studied, and
the fundamental mechanisms of disease
processes
48/68
Healing




Injury to tissue will stimulate the well define
inflammatory reaction sequence that lead to
healing.
When a foreign body is involved, the reaction
sequence is referred to as “foreign body
reaction”.
The normal response of body will be
modulated because of the solid implant.
This reaction will differ in intensity and duration
depending upon the anatomical sites involved.
49/68
Dependence on specific
anatomical site:

Each site challenges the biomedical
device designer with special
requirements for geometry, size,
mechanical properties, and bioreaction.
50/68
Mechanical and Performance
requirements:


Each biomaterial and device has imposed
upon in mechanical and performance
requirements that originate from the physical
(bulk) properties of the material.
These requirements can be divided into three
categories:
 mechanical performance,
 mechanical durability, and
 physical properties (functional).
51/68
Industrial involvement

The balance between the desire to
alleviate loss of life and suffering, and
the corporate imperative to turn a profit
force us to look further afield (out of the way)
for guidance.
52/68
53/68
Ethics (1)

Is the use of animals justified? Specifically, is the
experiment well designed and important so that
the data obtained will justify the suffering and
sacrifice of the life of a living creature?

How should research using humans be
conducted to minimize risk to the patient and
offer a reasonable risk-to-benefit ratio? How can
we best ensure informed consent?
54/68
Ethics (2)




Companies fund much biomaterials research and own
proprietary biomaterials.
How can the needs of the patient be best balanced with
the financial goals of a company?
Consider that someone must manufacture devices - these would not be available if a company didn’t choose
to manufacture them.
Since researchers often stand to benefit financially from
a successful biomedical device and sometimes even
have devices named after them, how can investigator
bias be minimized in biomaterials research?
55/68
Ethics (3)

For life-sustaining devices, what is the
trade-off between sustaining life and the
quality of life with the device for the Patient?
Should the Patient be permitted to "Pull
the plug" if the quality of life is not
satisfactory?
56/68
Ethics (4)

With so many unanswered questions
about the basic science of biomaterials, do
government regulatory agencies have
sufficient information to define adequate
tests for materials and devices and to
properly regulate biomaterials?
57/68
Ethics (5)

Should the government or other "thirdparty payers" of medical costs pay for the
health care of patients receiving devices
that have not yet been formally approved
for general use by the FDA and other
regulatory bodies?
58/68
Ethics (6)


Should the CEO of a successful multimillion
dollar company that is the sole manufacturer a
polymer material (that is a minor but crucial
component of the sewing ring of nearly all heart
valves ) yield to the stockholders, demands that
he/she terminate the sale of this material
because of litigation concerning one model of
heart valve with a large cohort of failures?
The company sells 32 Pounds of this material
annually, yielding revenue of approximately $40,
000?
Cohort: a group of individuals having a statistical factor (as age or class
59/68
Ethics (7)

Should an orthopedic appliance company
manufacture two models of hip joint
prostheses: one with an expected "lifetime”
of 20 years ( for young, active recipients )
and another that costs one-fourth as much
with an expected lifetime of 7 years ( for
elderly individuals ), with the goal of saving
resources so that more individuals can
receive the appropriate care?
60/68
Regulation


To prevent inadequately tested devices and
materials from coming on the market, and to
screen out individuals clearly unqualified to
produce biomaterial, a complex national
regulatory system has been erected by the
United States government through the Food
and Drug Administration (FDA).
Through the International Standards
Organization (ISO), international regulatory
standards have been developed for the world
community.
61/68
Regulation
The cost to meet the standards and to
demonstrate compliance with material,
biological, and clinical are enormous.
 Introducing a new biomedical device to the
market require a regulatory investment of
many millions dollars.
 Are the regulations and standards truly
addressing the safety issue ?

62/68
Regulation
Is the cost of regulations inflating the cost
of health care and preventing improved
devices from those who need them?
 Under this regulation topic, we see the
interaction of all the players in the
biomaterials community: government,
industry, ethics and basic science.

63/68
Summary:


A broad overview of the biomaterials
field. It provides a vantage point from
which the reader can gain a perspective
to see how the sub-themes fit into the
larger whole.
Biomaterials science may be the most
multidisciplinary all the sciences.
64/68
Summary:


Consequently, biomaterials scientists must
master certain key material from many fields of
science, technology, engineering, and medicine
in order to be competent and conversant in this
profession.
The reward for mastering this volume of material
is immersion in an intellectually stimulating
endeavor that advances a new basic science of
biointeraction and contributes to reducing
human suffering.
65/68
Summary:
Basic definition of biomaterials
 Example of biomaterials application
 Characteristics of biomaterials Science

Multidisciplinary
 Many diverse materials
 Development of biomaterials Devices
 Magnitude of the field
 Success and failure

66/68
Summary:

Subjects Integral to Biomaterials Science









Toxicology:
Biocompatibility
Functional tissue structure and pathobiology
Healing:
Dependence on specific anatomical site
Mechanical and Performance requirements:
Industrial involvement:
Ethics (Table 3)
Regulation
67/68
Home work I:
Due: Next week (9/20/2010)
I.
II.
III.
Find an abstract from the least issue of “Biomaterials”
and write your opinion about this paper. (100-300
words) (30%)
End Note: Following question I, copy the text of
Introduction or Discussion with 10-20 references from
that paper and use End Note to cite these reference.
Build a End Note file for these reference. (45%)
What is your opinion about the ethical concerns
related to biomaterials science? Please answer “one”
of the issues from Table 3 (in page 8). Choose
anyone from that table. (25 %) (100-300 words)
68/68
69/68

Some helpful dictionary sites:






http://www.m-w.org/
http://dictionary.reference.com/
http://dict.vghtpe.gov.tw/search.php
http://tw.dictionary.yahoo.com/
http://www.hk-doctor.com/html/dict.php ????
http://www.google.com.tw/
70/68
To be continued…….
71
Success and Failure




Another example involves LVADs.
A clinical trial called Randomized Evaluation of
Mechanical Assistance for the Treatment of
Congestive Heart Failure (REMATCH) led to the
following important statistics (Roseetal., 2001).
Patients with an implanted Heartmate LVAD
(Thoratec Laboratories) had a 52 % chance of
surviving for 1 year, compared with a 25 %
survival rate for patients who took medication.
Survival for 2 years in patients with the
Heartmate was 23 % versus 8 % in the
medication group.
72/68
Success and Failure



Also, the LVAD enhanced the quality of life for
the patients 一 they felt better, were less
depressed, and were mobile.
Importantly, patients participating in the
REMATCH trial were not eligible for a heart
transplant.
In the cases of the heart valve and the LVAD,
long 一 term clinical complications associated
with imperfect performance of biomaterials do
not preclude clinical success overall.
73/68
Success and Failure


These five characteristics of biomaterials
science : (1)multidisciplinary, (2)multimaterial,
(3)need-driven, (4)substantial market, and
(5)risk-benefit, flavor all aspects the field.
In addition, there are certain subjects that are
particularly prominent in our field and help
delineate biomaterials science as a unique
endeavor · Let us review a few of these.
to describe, portray, or set forth with accuracy or in detail
74/68