Chitin. Fulfilling a Biomaterials Promise

143 Pages·2014·4.148 MB·English

by  Eugene Khor (Auth.)

Chitin
Fulfilling a Biomaterials Promise
Chitin
Fulfilling a Biomaterials Promise
Second Edition
By
Eugene Khor
Chiticore Enterprises Inc.
with Andrew C.A. Wan
Institute of Bioengineering and Nanotechnology
AMSTERDAM • BOSTON • HEIDELBERG • LONDON • NEW YORK • OXFORD
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Second edition 2014
Copyright © 2014, 2001 Eugene Khor. Published by Elsevier Ltd. All rights reserved.
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ISBN: 978-0-08-099939-5
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Acknowledgments
I was a member of the academic research community for 27 years, and for more than
20 of those years, involved with chitin. The latter 15 years were also intermingled
with starting and growing a commercial biomedical enterprise (while I remained in
academia). These experiences have provided the academic research and industry/
commercial perspectives presented in this book. This would not have been possible
without the goodwill extended to me throughout these years by so many. I am truly
grateful to the persons and organizations mentioned below.
It is without doubt that I might never have entered the research field of chitin and
chitosan if it were not for the challenge in artificial seeds posed to me by my former
colleague, C.S. Loh, of the Department of Biological Sciences, National University
of Singapore.
The funding and extensive research facilities including library resources for my
academic research in chitin and chitosan as well as support (institutional approval
and seed-funding) for my entrepreneurial endeavors were provided by the National
University of Singapore.
I gained medical products testing and business perspectives from my interactions
with BRASS P.L., NAMSA®, and Charles River Laboratories-EMD.
I received a tremendous kick start in chitin and chitosan research from the inspir-
ing mentorship of the late Professor Shigehiro Hirano, at Tottori University in 1992
through a JSPS1 visiting fellow award. JSPS also sponsored a second fellowship in
2000 at Fukui University under the fine tutelage of Professor K. Sakurai.
The interactions with faculty and students of the chitin and chitosan research com-
munity through the years have been one of cordial learning and warm respect. My
best wishes to all of you as you continue to push chitin forward.
Ms. Erin Hill-Parks, Ph.D. (Associate Acquisitions Editor, Elsevier) was resource-
ful in finding me after I had retired from NUS; her persistence secured my com-
mitment for this project; and facilitated my other book project through the Elsevier
system.
My wife Val provided the primary assistance and support on these two book pro-
jects (June 2012–March 2014).
My God, the God of the Bible, has blessed me with the talent appropriate for the
tasks, provided the circumstances and trials to gain the skills required, and bestowed
the opportunities to participate and contribute. This was the life He planned and I
lived. My God has been the constant throughout my life that continues until the day I
am called into His presence. To God be the Glory.
1 JSPS: Japanese Society for the Promotion of Science.
About the Author
Dr. Eugene Khor received his B.Sc. in Chemistry from Lakehead University, Thunder
Bay, ON, Canada and his Ph.D. in Chemistry from Virginia Tech, Blacksburg, VA.
Dr. Khor joined the NUS1 in April 1984 as a member of its Academic Staff in the
Department of Chemistry. Dr. Khor’s principal research program at NUS was on
chitin materials: their production, characterization, and biomedical applications. At
the end of November 2011, after 27 years of service to NUS, Dr. Khor retired from
academia, trading in his chemistry lab coat for a fishing vest and has gone fishing.
Dr. Khor was also the principal cofounder of BRASS,2 a Singapore Medical
Technology Tests Services company. He guided BRASS from its humble beginnings
to profit in 2005. He relinquished his responsibilities at BRASS in January 2007 but
returned briefly in mid-2009 to November 2010, at the request of his major share-
holders to steer the company forward in a changed business environment. He updated
the company’s name to its acronym BRASS P.L. and put in place a strong board of
directors and management team that resulted in progressive and continual growth
in revenue, profit, and market presence (www.brass-asiapacific.com). Charles River
Laboratories acquired BRASS P.L. in October 2013 (http://www.criver.com/about-us/
news-events/featured-stories/2013/brass).
1 NUS: National University of Singapore.
2 BRASS: Biomedical Research and Support Services Limited.
Preface to the Second Edition
Background
My first encounter with the chitin1 research field transpired in 1989 when I received
a request from a colleague in the Botany Department at the National University of
Singapore to assist him in improving the seed coat for his artificial seed research.
After a literature survey and evaluation, I recommended the chitosan-alginate coac-
ervation system to produce a two-coat artificial seed that proved useful for my col-
league [1]. This introduction to the world of chitin led to a long-term chitin research
program as it pertained to my interests in biomaterials and biomedical applications at
the National University of Singapore. Many fruitful years of chitin research ensued
that culminated in my writing the first edition of this book in 2001.
The main purposes that prompted me to write the first edition were:
1. To organize in a general way the growing amount of information as it pertained in one way
or another of chitin as biomaterials and to biomedical applications.
2. To present the material in a perspective for academic and applied research of chitin to pro-
gress into true and mainstream biomedical applications.
3. To summarize some of the challenges that had to be met for chitin to be biomaterials at par
with some of the other more successful (in terms of biomedical applications) biomaterials
from nature, collagen, and hyaluronan in particular.
In the second half of 2012, I was approached by Elsevier Science to update Chitin:
Fulfilling a Biomaterials Promise as a second edition. While I remain satisfied with
the first edition, about a dozen years had elapsed since the first edition was published.
The passage of time in the modern world present the following realities:
1. A lot has taken place in the research field of chitin, chitosan, and their derivatives as bio-
materials and for biomedical applications since 2001, both in subject matter as well as
participants.
2. The success of chitin and chitosan in biomedical applications is becoming more of a reality.
Consequently, it is now more critical than ever to firmly establish chitin and chitosan as
biomaterials whose promise will be fulfilled.
Accordingly, I embarked on preparing a second edition to expand what was pre-
sented in the first edition and discuss on the vital link to bring chitin, chitosan, and
their derivatives, from the research lab bench to commercialization since 2001.
1 The term chitin is used to denote chitin, chitosan, and their derivatives when italicized.
xiv Preface to the Second Edition
Format
In many ways, writing a second edition is tricky. There is a greater degree of difficulty
in improving on the original effort to make it interesting to justify the work because
the obvious and straightforward aspects have been covered. Providentially, science
is not stagnant. Any researcher in the field knows the tremendous progress made in
chitin and chitosan research, especially in the bio-frontiers such as tissue engineering,
stem cells, gene and drug delivery, and nanotechnology. In addition, you are provided
an opportunity to incorporate aspects you may have chosen to omit in the first edition
but now feel worthy of inclusion. Furthermore, your knowledge and understanding of
the subject matter matures, offering plausibly a more objective and unbiased, suitably
informed and perhaps better-rounded veteran’s perspective.
The main goals for this second edition were to:
1. Review some of the work that is ongoing as it pertains to chitin as biomaterials and their
biomedical applications. A thorough review of the field was deemed unnecessary in light of
the comprehensive topical reviews available in the scientific literature. Therefore, a high-
lighting strategy with examples on some of the fascinating progress made with chitin as a
biomaterial has been used.
2. Present some of the trends, challenges, and concerns of biomaterials as discussed by thought
leaders and the place of chitin amidst these exciting activities.
3. Present some of the commercial (product development and manufacturing) and regulatory
aspects of biomedical products and chitin’s biomaterials role in this undertaking.
To retain the original chapter format of the first edition would disregard the
advances made and insights gained since. Therefore, this second edition adopts a
more updated format with specific biomedical applications topics covered in their
own chapters. While this may make reference back to the original first edition more
challenging, it recognizes the importance of maintaining currency.
An overview chapter on chitin research in perspective lays the groundwork for the
biomedical focus of this book. This leads into a presentation on the status of the bio-
medical commercialization of chitin to provide the impetus for the research content
that follow. Four chapters survey the use of chitin, chitosan, and their derivatives in
specific biomedical research topics:
1. For “traditional” biomedical applications
2. In tissue engineering and stem cell research
3. In nanotechnology
4. The relationship between chitin and chitosan to collagen and hyaluronan complete the
research survey
In most instances, each chapter contains a preview section on the specific topic,
followed by a literature research roundup, and concludes with a “Trends” section
focusing on a discussion of the potential and issues of the chapter content.
Finally, two chapters highlight some of the further considerations for biomedical
commercialization that leads to the final chapter on “what next” for chitin and chitosan.
This second edition remains essentially my effort. However, I have been blessed
to procure the assistance of one of my former graduate students, Dr. Andrew C.A.
Preface to the Second Edition xv
Wan to participate in this update, as well as pass on the mantle to him for posterity’s
sake. Among Dr. Wan’s current research interests are tissue engineering and stem cell
applications. He provided vital background literature searches and critical comments
on my draft chapters, invaluable to the integrity of this book’s content. His contribu-
tions despite his busy schedule as a principal research scientist at the Institute of
Bioengineering and Nanotechnology, Singapore, are gratefully noted.
Comments on literature survey and references
A project of this magnitude typically requires a comprehensive review of the scientific
literature published. Since 2001, the year the first edition was published, new journal
titles have come about, and existing journals have increased their number of annual
issues and/or created subspecialty areas. The outcome of all this is an overwhelm-
ing amount of information that has to be evaluated for their relevance to the matter
at hand. For example, a search of the terms chitin and chitosan of the ScienceDirect
database yields upwards of 11,000 citations. Limiting the search to the years from
2002 to 2013 reduces the number to around 8400. Similarly, more than 4000 citations
were obtained for the John Wiley online library search for the same period. The reality
is that while the task of sifting through the citations is surmountable with effort, it is
more appropriately (and has been) covered by invited or self-initiated review articles
in many journals and, specialty books that are compilations of expert papers on the
research topics put together by an editor. Therefore, to duplicate such effort here is
redundant and counterproductive.
In contrast, this book adopts a strategic approach of surveying a limited number
of relevant key journals and articles, especially reviews mentioned in the previous
paragraph. The rationale for this tactic was based on the following:
1. This book presents a research that can more readily lead into commercialization perspective
rather than the traditional research overview reports.
2. Most germane topics found in any specialty journal would be represented in the major
established journals referenced in this work.
3. Elsevier publications dominate the reference lists because of the ready access to their exten-
sive database provided to the lead author.
4. Where a reference transcends two or more topics, it was the lead author’s judgment to place
it where relevant and/or duplicate its placement.
The survey covers publications that appeared between the years 2002 and 2013
(June as cutoff). References to publications prior to 2002 or after June 2013 may
appear based on the relevance of the information. Each chapter’s references are com-
piled when used for completeness and convenience. Duplication of the same reference
in other chapters where they occur is believed a worthwhile expediency.
It is within these defined scope and boundaries in mind that this second edition
came to its completion.
Eugene Khor
February 28, 2014
xvi Preface to the Second Edition
Reference
[1] (a) L.F. Tay, L.K. Khoh, C.S. Loh, E. Khor, Alginate-chitosan coacervation in produc-
tion of artificial seeds, Biotechnol. Bioeng. 42 (4) (1993) 449–454.
(b) C.S. Loh, W. Shu, E. Khor, High frequency production of embryos from liquid flask
cultures of oilseed rape, Biotechnol. Bioeng. 54 (3) (1997) 231–238.
(c) E. Khor, W.F. Ng, C.S. Loh, Two-coat systems for encapsulation of Spathoglottis
plicata (Orchidaceae) seeds and protocorms, Biotechnol. Bioeng. 59 (5) (1998)
635–639.
(d) T.K. Tan, W.S. Loon, E. Khor, C.S. Loh, Infection of Spathoglottis plicata
(Orchidaceae) “artificial seeds” by mycorrhizal fungus, Plant Cell Rep. 18 (1–2)
(1998) 14–19.
Preface to the First Edition
The incessant search for alternative and better ways to treat bodily ills is filled with
challenges and opportunities. When it concerns replacement of body parts with artifi-
cial substitutes, state-of-the art technology developments such as Tissue Engineering
are fueling the quest for better biomaterials that can meet a myriad of challenges.
Central to this issue is the potential for the utilization of materials from nature.
Among the candidates, chitin has been poised to be one such natural material that can
be the answer to a variety of needs in the biomedical field. Ask any chitin researcher
about the benefits of chitin and you will receive an earful of its capabilities as wound
dressings, in bone substitutes, and as drug delivery carriers, conveyed in a manner that
is almost magical. Such is the passion, yet more is the accompanying confusion and
lack of consensus that confronts chitin as it strives to be a fully qualified member of
the biomaterials club.
Why is the situation unclear as to whether chitin will blossom into a fully accepted
medical material? The ever-looming impediment to the full-scale launch of chitin
as a biomaterial remains the production of high-purity grades of the material and
the daunting requirements of regulatory approval. Chitin biomedical products have
appeared, and there has been a noticeable effort toward the introduction of biomedi-
cally suitable chitin. Nonetheless, the widespread proliferation of chitin-based medi-
cal products has not really taken off. The key question now is whether chitin will be
a contender that truly makes it! With so much information amassed from chitin
research over the past 40 years, what more can and should be done with or for chitin?
For all its purported therapeutic benefits, can chitin succeed in vying for a market
share in niches already occupied by cellulose, collagen, hyaluronic acid, and the up-
and-coming chondroitin and keratan sulfates. Will chitin be sidelined by these other
biopolymers or newer technologies on the horizon? Will chitin, having exploded with
promise, find itself falling short of erupting with profits?
So far, little has been discussed on the groundwork necessary for chitin to claim
its rightful place as a biomaterial. This book is written with the aim to underscore
the factors that must increasingly transpire in standardizing chitin processing and
characterization. It attempts to capture the essential interplay between chitin’s assets
and limitations as a biomaterial, placing the past promises of chitin in perspective,
addressing its present realities and offers insight into what is required to realize chi-
tin’s destiny (that includes its derivative, chitosan) as a biomaterial of the twenty-first
century. For both the industrialists and researchers with a vested interest in commer-
cializing chitin, I hope this book will serve as a primer toward this goal.