Table Of ContentTISSUE ENGINEERING INTELLIGENCE UNIT 6
Patrick Vermette, Hans J. Griesser, Gaétan Laroche
and Robert Guidoin
Biomedical Applications
of Polyurethanes
T
ISSUE
E
NGINEERING
I
NTELLIGENCE
U 6
NIT
Biomedical Applications
of Polyurethanes
Patrick Vermette
Hans J. Griesser
CSIRO Molecular Science
Clayton South, Australia
The Cooperative Research Centre
for Eye Research and Technology (CRCERT)
The University of New South Wales
Sydney, Australia
Gaétan Laroche
Robert Guidoin
Institut des Biomatériaux du Québec,
Hôpital St-François d'Assise
Centre Hospitalier Universitaire de Québec
Québec, Canada
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IOMEDICAL PPLICATIONS OF OLYURETHANES
Tissue Engineering Intelligence Unit
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Library of Congress Cataloging-in-Publication Data
Biomedical applications of polyurethanes / Patrick Vermette...[et al.].
p. ; cm. -- (Tissue engineering intelligence unit)
Includes bibliographical references and index.
ISBN 1-58706-023-X
1. Polyurethanes in medicine. 2. Biomedical engineering. 3. Artificial organs. 4.
Biomedical materials. I. Vermette, Patrick. II. Series.
[DNLM: 1. Biocompatible Materials. 2. Polyurethanes. 3. Artificial Organs. 4.
Prostheses and Implants. QT 37 B6147 2000]
R857.P64 B56 2001
610'.28--dc21
00-037184
CONTENTS
1. Synthesis, Physicochemical and Surface Characteristics
of Polyurethanes.....................................................................................1
Martin Castonguay, Jeffrey T. Koberstein, Ze Zhang, and Gaétan Laroche
1.1 Introduction....................................................................................1
1.2 Chemistry........................................................................................2
1.3 How to Control Physicochemical and Mechanical Properties
of Polyurethanes?...........................................................................8
1.4 Thermotropic Behavior of Polyurethanes.......................................13
1.5 Comparison of Mechanical Properties
of Biomedical Polyurethanes with Other Biomedical Grade
Polymers .....................................................................................14
1.6 Surface Characteristics of Polyurethanes ........................................16
1.7 Conclusion....................................................................................19
2. Commercial Production of Polyurethanes............................................22
Stéphane Lévesque, Denis Rodrigue, Patrick Vermette,
and Pathiraja Gunatillake
2.1 Introduction..................................................................................22
2.2 History ..........................................................................................22
2.3 Manufacture of Polyurethane.........................................................28
2.4 Conclusion....................................................................................48
2.5 Acknowledgments..........................................................................48
3. Additives in Biomedical Polyurethanes.................................................55
Nathalie Dubé, Sahar Al-Malaika, Gaétan Laroche, and Patrick Vermette
3.1 Introduction..................................................................................55
3.2 Classification of Plastics’ Additives.................................................55
3.3 Additives Used in Biomedical-Grade Polyurethanes.......................57
3.4 Conclusion....................................................................................74
4. Biocompatibility of Polyurethanes .......................................................77
Yves Marois and Robert Guidoin
4.1 Introduction..................................................................................77
4.2 Biocompatibility............................................................................78
4.3 Blood Compatibility of Polyurethanes...........................................81
4.4 Biocompatibility of Polyurethanes.................................................86
4.5 Effect of Protein Adsorption on Polyurethanes ..............................89
5. Biomedical Degradation of Polyurethanes............................................97
Patrick Vermette, Stéphane Lévesque, and Hans J. Griesser
5.1 Introduction..................................................................................97
5.2 Methods for the Assessment of Polyurethane Degradation...........100
5.3 Influence of Manufacturing Process on Polyurethane Stability.....109
5.4 Biodegradation of Polyurethanes..................................................114
5.5 Biological Activity Involved in Polyurethane Biodegradation.......118
5.6 Pathways of Polyurethanes Biodegradation..................................120
5.7 Accelerated Testing Models.........................................................128
5.8 Conclusion..................................................................................151
6. Developments in Design and Synthesis
of Biostable Polyurethanes.................................................................160
Pathiraja A. Gunatillake, Gordon F. Meijs, and Simon J. McCarthy
6.1 Introduction................................................................................160
6.2 Biostability and Polyurethane Structure.......................................161
6.3 Development of Degradation-Resistant Polyurethanes.................163
6.4 Conclusion..................................................................................170
7. Surface Modification of Polyurethanes...............................................175
Hans J. Griesser
7.1 Introduction................................................................................175
7.2 Rationale for Surface Modification ..............................................176
7.3 Common Pitfalls in Surface Modification....................................178
7.4 Surface Modification Types.........................................................185
7.5 Synthetic Functionalization with Chemical Groups.....................186
7.6 Plasma Surface Modifications ......................................................188
7.7 Surface Immobilization of Biologically Active Molecules.............191
7.8 “Non-fouling” Polyurethane Surfaces ..........................................200
7.9 Coatings for Cell Colonization ....................................................205
7.10 Surface Modifying Additives and End Groups...........................206
7.11 Other Surface Modifications......................................................208
7.12 Summary and Conclusions........................................................209
8. Biomedical Applications of Polyurethanes..........................................220
Mylène Bergeron, Stéphane Lévesque, and Robert Guidoin
8.1 Introduction................................................................................220
8.2 Polyurethanes for Cardiovascular Applications.............................220
8.3. Polyurethane for Reconstructive Surgery.....................................235
8.4. Gynecology and Obstetrics.........................................................240
8.5 Conclusion..................................................................................241
9. The Future of Polyurethanes..............................................................252
Robert Guidoin and Hans J. Griesser
9.1. Cardiovascular Applications........................................................254
9.2. Reconstructive Surgery ...............................................................256
9.3. Gynecology and Obstetrics.........................................................257
9.4. Organ Regeneration in Tissue Engineering.................................258
9.5. Medical Supplies.........................................................................258
9.6. Summary....................................................................................259
Abbreviations.....................................................................................261
Index..................................................................................................265
EDITORS
Patrick Vermette
Hans J. Griesser
CSIRO Molecular Science
Clayton South, Australia
The Cooperative Research Centre
for Eye Research and Technology (CRCERT)
The University of New South Wales
Sydney, Australia
e-mail: [email protected]
Chapters 2, 3, 5, 7, 9
Gaétan Laroche
Robert Guidoin
Institut des Biomatériaux du Québec,
Hôpital St-François d'Assise
Centre Hospitalier Universitaire de Québec
Québec, Canada
e-mail: [email protected]
[email protected]
Chapters 1, 3, 4, 8, 9
CONTRIBUTORS
Sahar Al-Malaika Martin Castonguay
Polymer Processing and Performance Institut des Biomatériaux du Québec
Research Unit Hôpital St-François d'Assise
Aston University Centre Hospitalier Universitaire de
Birmingham, England, U.K. Québec
e-mail: [email protected] Québec, Canada
Chapter 2 e-mail:
[email protected]
Mylène Bergeron Chapter 1
Institut des Biomatériaux du Québec
Hôpital St-François d'Assise Nathalie Dube
Centre Hospitalier Universitaire de Institut des Biomatériaux du Québec
Québec Hôpital St-François d'Assise
Chapter 8 Centre Hospitalier Universitaire de
Québec
Départment de Chirurgie
Université Laval
Sainte-Foy, Québec, Canada
e-mail: [email protected]
Chapter 2
Pathiraja Gunatillake Gordon F. Meijs
Cooperative Research Centre for Cardiac Cooperative Research Centre for Cardiac
Technology Technology
CSIRO Molecular Science CSIRO Molecular Science
Clayton South, Victoria, Australia Clayton South, Victoria, Australia
e-mail: e-mail: [email protected]
[email protected] Chapter 6
Chapters 2, 6
Simon J. McCarthy
Jeffrey T. Koverstein Cooperative Research Centre for Cardiac
Institute of Materials Science Technology
Department of Chemical Engineering CSIRO Molecular Science
and Applied Chemistry Clayton South, Victoria, Australia
New York, New York, U.S.A. Chapter 6
e-mail: [email protected]
Chapter 1 Denis Rodrigue
Départment de Génie Chimique
Stéphane Lévesque Université Laval
Institut des Biomatériaux du Québec Québec, Canada
Hôpital St-François d'Assise e-mail: [email protected]
Centre Hospitalier Universitaire de Chapter 2
Québec
Départment de Chirurgie Ze Zhang
Université Laval Institut des Biomatériaux du Québec
Sainte-Foy, Québec, Canada Hôpital St-François d'Assise
e-mail: [email protected] Centre Hospitalier Universitaire de
Chapters 2, 5, 8 Québec
Québec, Canada
Yves Marois e-mail: [email protected]
Institut des Biomatériaux du Québec Chapter 1
Hôpital St-François d'Assise
Centre Hospitalier Universitaire de
Québec
Québec, Canada
e-mail: [email protected]
Chapter 4
PREFACE
Polyurethanes form a large family of polymeric materials with an enormous
diversity of chemical compositions and properties. They have found wide
spread application in a number of technological areas and a range of com-
modity products, such as polymers for clothing (Lycra® being a well-known ex-
ample), automotive parts, footwear, furnishings, construction, and in paints and
coatings for appliances. The wide range of properties that can be achieved with
polyurethane chemistry also attracted the attention of developers of biomedical de-
vices who saw promise in, for instance, the mechanical flexibility of these materials
combined with their high tear strength. Thus, polyurethanes were tried in a number
of biomedical applications, as discussed in this book. However, a number of drawbacks
quickly became apparent, most importantly their unexpected lack of stability in the
living host environment. Early studies were mostly done with “available” polyure-
thanes developed for quite different uses; hence, in retrospect, their failure to meet
the requirements of biomedical applications may not be altogether surprising. The
clinical findings of adverse consequences with early polyurethanes led to a large
number of studies aiming to elucidate the reasons for polymer degradation in the
biomedical environment, and the synthesis of customized polyurethanes guided by
biomedical considerations. This work is still continuing; promising improved mate-
rials have been developed and are now undergoing detailed testing, and this raises
the possibility of commercialization in the near future of the “ultimate” biomedical
polyurethane(s) optimized for specific biomedical requirements.
Another avenue towards improving the biomedical performance of polyurethanes,
which is of more recent origin than synthetic approaches, comprises the application of
surface modification or coating technologies. This type of approach has been featured
in a substantial number of studies. It offers the promise of enabling use of an “available”
polyurethane whose biomedical response has been improved by the alteration of its
surface chemistry.
The literature on the development and evaluation of polyurethanes intended
for biomedical applications is enormous and, on account of its multidisciplinary
nature, spread over a wide range of primary scientific and applied technological
journals. Biomedical polyurethanes also are featured in many patents. Of course the
subject of biomedical polyurethanes has been covered in many reviews, as well as an
excellent book (Lelah MD, Cooper SL. Polyurethanes in Medicine. Boca Raton, FL:
CRC Press, 1986); these previous surveys of the field, or parts thereof, are invalu-
able in conveying the history and status (at the time) of progress on applying poly-
urethanes to various biomedical applications. Yet, the field has over the last few
years continued to progress rapidly, and several conceptually new polyurethanes
have recently become available for detailed clinical testing. In addition, the applica-
tion of surface modification and coating techniques, the use of polymer additives
and their effects on the biological response of polyurethanes and the development
of novel biostable polyurethanes were surveyed only very briefly in the most recent
book (Lamba NMK, Woodhouse KA, Cooper SL. Polyurethanes in Biomedical Ap-
plications. Boca Raton, FL: CRC Press LLC, 1998) dedicated to these materials.
Hence, we perceived a need for an up-to-date text, and we hope that the present work will
meet this need and convey information to both the novice and the expert in the field.
While presuming some background knowledge of biomaterials science, for the reader
who is a relative novice to the field we present and discuss a number of concepts that are
relevant to biomedical polyurethanes, in the hope of conveying the multifaceted task that
faces the developers of improved biomedical materials. Such materials must meet a diverse
number of criteria, some of which may be poorly defined. Of course some of these issues,
such as the question of what is “biocompatibility” and how one assesses it, applies to other
classes of biomedical materials as well. An exhaustive discussion of all aspects of biomedi-
cal requirements, tests, and responses obviously is beyond the scope of this work, and the
reader is encouraged to consult standard textbooks on biomaterials science, such as:
• Ratner BD, Hoffman AS, Schoen FJ, Lemons JE, Eds. Biomaterials Science: An
Introduction to Materials in Medicine. San Diego: Academic Press, 1996.
• Von Recum AF, Ed. Handbook of Biomaterials Evaluation. New York: Macmillan,
1986.
• Silver FH, Doillon C. Biocompatibility: Interactions of Biological and Implanted
Materials, Vol 1—Polymers. New York: VCH Publisher, 1989.
One challenge we faced in writing and editing this book is the wide range of techno-
logical fields that apply to the development and testing of biomedical materials. We
approached this challenge by assembling editors and authors from diverse technological
backgrounds — and geographical locations. Only once did the four editors meet in one
room to assess whether the contents might end up forming a cohesive unit. Nor did we
have an opportunity to meet all contributors in person in the course of writing. However,
modern communication technology has eliminated the obstacles of geographical location,
and all of us are richer for the experience of collaborating on his book across oceans,
different mother tongues, and different cultural backgrounds. There were misunderstand-
ings, delays, and mishaps, but above all an overriding sense of goodwill and collaboration
that so much characterizes the international community of scientists.
A further challenge in writing and editing this book lies in the vague nature of some
of the terminologies used by many researchers. A prominent example is the term
“biocompatibility”. Innumerable biomaterials publications declare the development of
biocompatible materials, and polyurethanes are well represented in this. Why, then, is
development and testing still ongoing? If those publication titles were to be true in their
literal meaning, the challenge of developing the “ultimate” biomedical polyurethane would
appear to have been solved long ago; as a corollary, there would be no need for this book.
It is also regrettable that many researchers fail to acknowledge that “biocompatibility”
requirements may differ considerably for different biomedical applications. Thus, a poly-
urethane that performs well in one host body location may be unsuitable for another
biomedical purpose. Likewise, a number of publications report “blood-compatible (or
hemocompatible) polyurethanes”. Why is it, then, that these materials have not led to the
fabrication of “perfect” cardiovascular devices and efforts are continuing on improving the
hemocompatibility of these materials? Is it perhaps because informed researchers and device
manufacturers realize the true value of such claims based on tests that do not fully replicate
the real in vivo requirements? Regrettably, though, this situation leads to confusion for
novices and should be addressed.
Language is a wonderful communication tool but needs to be used with precision.
The term “biocompatible” means exactly that, i.e., full compatibility with all require-
ments; it does not mean “almost biocompatible” or “more compatible than polymer X”. It
is a pity that so many researchers use loose, ill-defined terminology instead of bringing
precision to their reports and declaring an improvement in performance in this-and-that
application as measured by this-and-that test. While of course such details are contained
in the body of reports, the use of unqualified, broad, imprecise statements in abstracts and
conclusions sections should be discouraged.
Having said this, we admit to using in this book terminology that is not always well
defined or implicitly clear in its meaning. Some terms have widely accepted usage in the
field, and we do rely in many instances on an implicit understanding of the contents and
limits of such usage. We beg the reader’s indulgence for such compromises and any confusion
and uncertainty we may bring about with our writing.
We hope that this book will prove to be of value to readers from various technical
backgrounds. Research and development of biomedical materials requires the expertise of
materials scientists, engineers, chemists, clinicians, surface scientists, biologists, and others,
pooled into a collective effort. It is difficult to structure a text such that it addresses the
needs of such a diverse audience and starts at realistic levels of pre-existing knowledge.
Those who have worked in the biomaterials field for a while may wish to skip many
sections, while others will undoubtedly feel that we left out some useful background
information. We do hope that every reader will derive some benefit.
Editing this book has been a challenging but most rewarding task. We thank all the
contributing authors for their efforts and timeliness; it has been a pleasure working with
you. We also express our sincere thanks to the reviewers who graciously consented to
donate their time for the careful review of draft Chapters and whose suggestions, much
appreciated by the authors, led to substantial improvements. We wish to acknowledge
partial financial support by the Fonds pour la Formation des Chercheurs et l’Aide à la Recher-
che (Fonds FCAR, Québec, Canada), the Cooperative Research Centre for Eye Research
and Technology, (Sydney, Australia) and the National Sciences and Engineering Research
Council of Canada (NSERC, Canada). Finally, we thank our loved ones for their
understanding and patience during the hours we spent on this book. It is to them that we
dedicate this work.
Patrick Vermette
Hans J. Griesser
Gaétan Laroche
Robert Guidoin
Clayton, Australia
Québec, Canada
January 2000
