Tissue Engineering: Engineering Principles for the Design of Replacement Organs and Tissues

538 Pages·2004·9.99 MB·English

by  W. Mark Saltzman

Tissue Engineering
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Tissue Engineering
Engineering Principles for the Design of
Replacement Organs and Tissues
W. MARK SALTZMAN
1
2004
3
Oxford NewYork
Auckland Bangkok BuenosAires CapeTown Chennai
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Sa˜oPaulo Shanghai Taipei Tokyo Toronto
Copyright #2004byOxford University Press, Inc.
PublishedbyOxfordUniversityPress,Inc.,
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OxfordisaregisteredtrademarkofOxfordUniversityPress
Allrightsreserved.Nopartofthispublicationmaybereproduced,
storedinaretrievalsystem,ortransmitted,inanyformorbyanymeans,
electronic,mechanical,photocopying,recording,orotherwise,
withoutthepriorpermissionofOxfordUniversityPress.
LibraryofCongressCataloging-in-PublicationData
Saltzman,W.Mark.
Tissueengineering:engineeringprinciplesforthedesignofreplacementorgansand
tissues/W.MarkSaltzman
p.cm.
Includesbibliographicalreferencesandindex.
ISBN0-19-514130-X
1.Tissueengineering. I.Title.
R857.T55S3582004
617.905—dc21 2003049865
9 8 7 6 5 4 3 2 1
PrintedintheUnitedStatesofAmerica
onacid-freepaper
To Melissa,
my best friend during the years that fell into this text
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Preface
What It Means to Me
It is awkward to admit that, although I have now written a book on the
subject, I am reluctant to tell people that tissue engineering is one of my
primary academic interests. It is a reluctance of the heart, not the head,
although several practical reasons for this aversion have occurred to me.
Tissue engineering is difficult to define. There are few examples of successful
tissue engineering that one can use to illustrate a definition; therefore, telling
someone that you are a tissue engineer can lead to a long and unsatisfying
conversation. Sometimes, in the right company, I feel like a lengthy conversa-
tion; now, on those other occasions, I can recommend this book. There is
another emotional barrier: the concept of making replacement tissues sounds
so fantastic, insinuating science fiction more than actual engineering practice,
that I find it difficult to stake so bold a claim.
In spite of these reservations, I am certain that tissue engineering is a
concept whose time has arrived. Within its embrace is the real possibility of
newtoolsforplasticsurgery,fortreatmentofdiabetes,forrepairofspinalcord
injuries;thesenewdiscoverieswillchangethelengthandqualityoflifeofmany
individuals in the coming decades. In breaking the subject down into chapters
and headings, I hope that tissue engineering will become accessible to anyone
interested in engineering and modern medicine.The goals of tissue engineering
are grand and important and increasingly achievable; even a modest step
toward progress in the area is worthy of effort and sacrifice.
Tissue Engineering is my second book; my first, Drug Delivery, was pub-
lished in 2001. These two books were born conjoined, in the early 1990s, as a
single project with the working title ‘‘Biomaterials for Drug Delivery and
Tissue Engineering’’ (affectionately, BDDTE). Five years of work on this
initial project earned me two bulging notebooks of chapter drafts and little
hope that they could be corralled to even a tentative conclusion. I was for-
tunatetohavetwoadvisorsatthattime,DougLauffenburgerofMITandBob
Rogers, then of Oxford University Press, who, at a breakfast meeting on a
mid-November Chicago day, confirmed my suspicion that my ambition for
BDDTE was running far ahead of my accomplishment. One possible solution
viii Preface
was to split the project, publish Drug Delivery first (since it was the more
manageable of the two subjects), and leave Tissue Engineering to ripen and
(hopefully) find its own path to harvest.
ThatTissueEngineeringsurvived,andevenprospered,isduelargelytothe
generosityoftheWhitakerFoundation,whichprovidedagrantthatpermitted
metotakeatwo-semestersabbaticalduringthe2000–2001academicyear.The
most important elements of this book—the themes that toil to hold it
together—were developed during that period. I am grateful to members of
the Whitaker Foundation for their enthusiasm and support for this project. I
especially thank John Linehan, who supplied vital encouragement at several
key points and enthusiasm continuously.
My own interest in tissue engineering was born in 1986, when I was for-
tunate to work with two irreplaceable mentors, Joseph Vacanti and Robert
Langer.Bobisaforceofnature,anditisimpossibletomovewithinhisfieldof
action without absorbing some of his enthusiasm. For the subject of tissue
engineering, as in drug delivery, Bob is my first and best teacher. Jay is a
scientist-surgeon and extraordinary person. He showed me the connection
between transplant surgeons and biomedical engineers. He taught me that
even busy people can find the time to be kind.
Hereisanothergoodreasontobeatissueengineer:yougettohaveterrific
colleagues. Many of them proofread chapters and provided homework pro-
blems. Each homework problem has an acknowledgement to indicate the
donor (where no one is indicated, I am the donor). I thank Keith Gooch,
Linda Griffith, Erin Lavik, Song Li, Christine Schmidt, Michael Sefton,
Rebecca Kuntz Willits, and Peter Zandstra for contributing problems from
theircourses.Ioweaspecialthanks toLinda,whoprovided somespectacular
exercisesandalsoencouragedmetoaddasectiononmasstransferfundamen-
tals.IthankMalcolmSteinbergandMartinKlugerfortheircriticalreviewsof
Chapters3and10,respectively.IthankChristineSchmidtandherstudentsfor
their helpful and thorough review of the entire book, which led to several
changes that improved the quality of the text. I thank Greg Rutkowski,
Robert Sah, William Olbricht, William Miller and Elizabeth Geller for their
comments.Everypicturesavedmeathousandwords(thisismostacutelytrue
forthepicturesthatIgotfromfriends):IappreciatethegenerosityofGuenter
Albrecht-Buehler, Kristi Anseth, Peter Fong, Steven Goldstein, Erin Lavik,
Peter Ma, and Andrew Zydney who provided photographs. I thank Sylvia
Yoo, Chris Anker, Chun Kuo, and Michael McWay for helping with figure
preparation.IthankSaraRoyceforhelpwithorganizationandpreparationof
solutions to the exercises. I thank Kirk Jenson of Oxford University Press for
hispatientandthoughtfulguidancethroughoutthisperiod.And,withaspecial
enthusiasm,IthankMalgorzataCartiera,whohelpedmeintoomanydifferent
waystoenumerate(fromproofreadingtocopying),alwayswithasmile,always
perfect and prompt, and always wonderful.
Lastly,IthankAlisonWittenbergforherencouragement,herenthusiasm,
and her voice—patient, wise, and soothing—which leads me when I lose my
own.
Preface ix
How To Use This Book
This book was prepared from lecture notes that I have used over the past 10
years to teach senior undergraduate and graduate students at Johns Hopkins,
Cornell, and Yale.The courseissuedin different disguises, but always with an
accompanying numerical code (to certify and legitimize); it was Biomaterials
for Drug Delivery and Tissue Engineering (540.641) at Hopkins from 1993 to
1995, Artificial Organs and Tissue Engineering (ENGRG 606.2) at Cornell,
1997–2002, and Senior Seminar in Biomedical Engineering (BENG 480) at
Yale in 2002. I thank my colleagues for allowing me to teach these courses
(all but one were done voluntarily as an overload on my regular teaching
schedule).
The book is, as the courses were, intended for engineering students. I
have found some non-engineering students who enjoyed and profited from
the material, although, in all of these cases, these students had strong mathe-
matics backgrounds. Some background in biology, particularly cell and
molecular biology, is useful but not necessary. Most students find that
they profit from extra reading on biology topics that are unfamiliar or
difficult; the latest editions of the Molecular Cell Biology books by
Lodisch et al.—or Alberts et al.—and some aptitude with use of an
index—are highly recommended for that purpose. I have included back-
ground information on two subjects that are particularly important for tissue
engineering—polymers and mass transfer—in the appendix. I realize that
these tutorials will be unnecessary for many readers, particularly those
who are studying chemical engineering, but by adding this background I
hope to make the textbook accessible to biomedical engineering, electrical
engineering and mechanical engineering, and other students who do not
usually take separate courses in these areas.
Oneofthemostinfluentialearlypapersintissueengineeringwasareview,
publishedin1993,thatdefinedthefieldbybreakingitdownaccordingtotissue
types and approaches [1]. An encyclopedic and important book, Textbook
of Tissue Engineering, follows a similar outline, but adds flesh to it by also
incorporating chapters on materials science and biological science in areas of
importance [2]. Both of these works are valuable and serve their purposes,
for introduction and explication, admirably.
This textbook explores the same wooded region, but encourages you to
wander along a different path by first presenting developmental biology as a
foundational science and then exploring certain areas of biology (adhesion,
growth, and motility of cells) that are presumed fundamental to the practice
of tissue engineering. It is now possible to write about these fundamentals in
quantitative terms, to think about rates of cell movement, to define rate con-
stants for cell growth processes, and to develop models of the physics cell
adhesion. Only in the third section of the book are the core elements of tissue
engineering—basedontheuseofsyntheticmaterials—presented.Withaquan-
titativebackgroundinthefundamentalsbehindthem,afewreaderswillbeable
to distinguish something bright and alluring between the lines in the third