Tissue and Organ Regeneration in Adults: Extension of the Paradigm to Several Organs

344 Pages·2015·11.34 MB·English

by  Ioannis V. Yannas (auth.)

Tissue and Organ Regeneration in Adults
Ioannis V. Yannas
Tissue and Organ
Regeneration in Adults
Extension of the Paradigm
to Several Organs
Second Edition
2123
Ioannis V. Yannas
Mechanical and Biological Engineering
Massachusetts Institute of Technology
Cambridge
Massachusetts
USA
Cover image is a selection of an anatomically well-defined defect for study or treatment of in-
duced peripheral nerve regeneration. Top: Complete transection. Bottom: The nerve stumps
have been inserted into a tube fabricated from an experimental biomaterial. The transected
nerve is an anatomically well-defined defect.
ISBN 978-1-4939-1864-5 ISBN 978-1-4939-1865-2 (eBook)
DOI 10.1007/978-1-4939-1865-2
Springer New York Heidelberg Dordrecht London
Library of Congress Control Number: 2014950147
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To the three nymphs, Alexandra, Marina, and
Sophia
Ioannis V. Yannas
Preface
Why This Volume?
The title of this volume reads like an oxymoron. After all, it is well known that,
whether animal or human, adults do not spontaneously regenerate any of their or-
gans that have been lost to accidental trauma or to surgery. If mammals could some-
how regenerate organs such as the skin of a hand lost to a burn or a breast lost to
mastectomy, scars should not fill the anatomical site of the lost organ; instead, a
regrown organ should emerge. If regeneration were possible, treatments might also
be developed for potentially lethal degenerative conditions such as a scarred heart
muscle or a cirrhotic liver.
The concept of induced organ regeneration in adults is relatively new. The de-
liberate modification of healing to achieve regrowth of lost tissue structures does
not follow directly from current mainstream paradigms of biological research. The
first tentative recognition that the healing process could be modified to induce re-
generation of the dermis, a tissue that does not spontaneously regenerate in adults,
appeared in reports published in the early 1980s. Eventually, other organs, including
peripheral nerves and the eye conjunctiva, were induced to regenerate in anatomical
wounds known to be incapable of supporting spontaneous regeneration. The data on
induced regeneration are scattered in a variety of journals, book chapters, abstracts,
and theses. It is time to marshal the extensive evidence. This is the main reason for
writing this volume.
Generic M ethodology
The emphasis throughout this volume is on systematic development of the view-
point that regeneration is an instance of synthesis of tissues and organs. Although
somewhat self-evident, this proposition has been hardly employed. It has three
simple consequences. The first is the requirement for a special kind of experimental
reactor, free of tissues that do not spontaneously regenerate. The second calls for
meticulous physicochemical and biological characterization of the end products of
such a reaction. The third requires the use of appropriate nondiffusible regulators
in the experimental reactor. These insoluble matrices induce adult cells to abandon
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their normal proclivity in closing up adult wounds in exchange for synthesizing
physiological tissues.
This approach appears to be independent of the organ under study. It is devel-
oped in substantial depth during the first several chapters by limiting the discussion
to just two organs that are quite different from each other, namely, skin and periph-
eral nerves. The conclusions from this analysis apply to either organ with roughly
equal strength. This intriguing result clearly suggests a generic methodology for
synthesis of other organs.
In Vitro or In Vivo?
Many researchers in tissue engineering have preferred to carry an organ synthesis
in vitro as extensively as possible before implanting the resulting construct in an
experimental animal model. The methodology developed in this volume applies
whether the bulk of the synthetic process is being carried in vitro or in vivo. Ir-
respective of whether the organ being synthesized in vitro is in advanced state of
completion or is simply a matrix seeded with cells, it is still necessary to eventually
implant it by inflicting a traumatic (surgical) injury at the correct anatomical site.
Once more, the implantation site can be construed as an experimental reactor and
the process of remodeling or regeneration that follows can be looked at as a syn-
thetic process. In short, the methodology of organ synthesis developed in this vol-
ume should apply in a large variety of protocols used in tissue and organ synthesis.
Who Should Benefit by Reading This Volume?
A second reason for writing this volume is the need for a single-author textbook on
organ synthesis. Lack of a unifying text has frustrated both university students and
practitioners in industry. For years, my graduate students have had to confront a
motley array of lecture notes. This volume is partly based on the author’s notes for
undergraduate and graduate classes in biomaterials–tissue interactions, tissue engi-
neering, and design of medical devices at Massachusetts Institute of Technology.
This work should be of interest to three groups of investigators: biologists, experi-
mental surgeons, and biomedical engineers. Biologists should be interested in the
molecular biological basis of induced regeneration, a process that appears to reverse
the developmental process that normally converts the wound-healing response of
the fetus to that of the adult.
Experimental surgeons interested in organ regeneration should benefit from a
fresh approach toward making their experimental protocols more quantitative and
standardized. Biomedical engineers will gain a new look at the treatment of old
ailments. In particular, it is hoped that the generic organ-blind methodology de-
scribed in this volume should be useful to most students and practitioners of tissue
engineering.
Preface ix
Outline
This volume is divided into four major sections. Loss of organ function, the basic
medical problem treated in this volume, is defined in Chap. 1. The basic methodol-
ogy of organ synthesis in vivo is described in Chaps 2–4. Application to adult skin
and peripheral nerves is treated in detail in Chaps 5–7. Finally, detailed mechanistic
hypotheses of induced tissue and organ regeneration are presented in Chaps 8–10,
leading to generic methodology for organ regeneration.
Newton, MA, USA Ioannis V. Yannas
Preface to Second Edition
Five developments have marked the field of tissue and organ regeneration since the
First Edition was published in 2001.
The role of contractile cells in wound healing and their specific interactions with
ligands on the surface of a regeneratively active collagen scaffold have been largely
elucidated. Improved understanding of this interaction and its consequences has
introduced the concept of surface biology, an exciting landscape in which cell phe-
notype changes from repair to regeneration via specific molecular interactions of
cells with the active surface.
Decellularized matrices have been studied by a large number of investigators and
led to regeneration of several organs, including the urethra, large defects in the ab-
dominal wall, the bladder, Achilles tendon, the larynx, the lungs, and other organs.
A possible mechanism of the regenerative activity of decellularized matrices, one
which may improve functional outcomes from the use of these matrices, has been
presented.
In the two organs, skin and peripheral nerves, where repair and regeneration
have been studied most extensively by investigators, the differences in their respec-
tive healing processes have been shown to be much smaller than originally thought
to be. This finding simplifies greatly the description of repair and regeneration and
inspires its extension to other organs.
Scar formation has been the perennial explanation in the literature for lack of
regeneration in adults. There is now evidence that scar is a derivative process to
wound contraction. Future efforts to induce regeneration must apparently be direct-
ed primarily towards modification of wound contraction rather than scar formation.
Not least is the increasing clinical use of the regeneratively active collagen scaf-
fold, dermis regeneration template, as a treatment for skin loss in massive burns,
plastic surgery and closure of chronic skin wounds. The mechanism of activity of
this clinical treatment appears to derive from surface biological interactions that
have been described in a preliminary fashion in this volume.
Cambridge, MA, USA Ioannis V. Yannas
xi
Acknowledgments for the Second Edition
In addition to students and research associates mentioned in the first edition, I wish
to thank Melissa Buydash, Kathy Miu, Amit Roy, Eric Soller, Peter Stasikelis,
Dimitrios Tzeranis, and David Wong, who were responsible for obtaining data on
regeneration for their thesis research or during postdoctoral research. Peter So was
a thoughtful colleague.
Most of the illustrations were prepared by Wayne Hsiao. Alex Springer assisted
with the references and with the graphics.
The outline of this book was composed while I was recovering from a tough
medical condition. I thank my daughter, Tania Kluzak, and my sister, Elizabeth
Sitinas, who helped me caringly and made my recovery possible.
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