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Regenerative
Medicine and
Plastic Surgery
Elements, Research Concepts
and Emerging Technologies
Dominik Duscher
Melvin A. Shiman
Editors
123

Regenerative Medicine
and Plastic Surgery

Dominik Duscher • Melvin A. Shiman
https://t.me/medicina_free
Editors
Regenerative Medicine
and Plastic Surgery
Elements, Research Concepts
and Emerging Technologies

Editors
https://t.me/medicina_free
Dominik Duscher
Department for Plastic Surgery and
Hand Surgery
Division of Experimental Plastic Surgery
Technical University of Munich
Munich
Germany
Melvin A. Shiffman
Private Practice
Tustin, CA
USA
ISBN 978-3-030-19957-9 ISBN 978-3-030-19958-6 (eBook)
https://doi.org/10.1007/978-3-030-19958-6
© Springer Nature Switzerland AG 2019
This work is subject to copyright. All rights are reserved by the Publisher, whether the whole or
part of the material is concerned, specically the rights of translation, reprinting, reuse of
illustrations, recitation, broadcasting, reproduction on microlms or in any other physical way,
and transmission or information storage and retrieval, electronic adaptation, computer software,
or by similar or dissimilar methodology now known or hereafter developed.
The use of general descriptive names, registered names, trademarks, service marks, etc. in this
publication does not imply, even in the absence of a specic statement, that such names are
exempt from the relevant protective laws and regulations and therefore free for general use.
The publisher, the authors, and the editors are safe to assume that the advice and information in
this book are believed to be true and accurate at the date of publication. Neither the publisher nor
the authors or the editors give a warranty, expressed or implied, with respect to the material
contained herein or for any errors or omissions that may have been made. The publisher remains
neutral with regard to jurisdictional claims in published maps and institutional afliations.
This Springer imprint is published by the registered company Springer Nature Switzerland AG
The registered company address is: Gewerbestrasse 11, 6330 Cham, Switzerland

To Aura, the love of my life
https://t.me/medicina_free
Dominik Duscher

Foreword
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Plastic surgery, by its very nature, takes care of nearly every part of the
human body including the skin, muscles, bones, nerves, and blood vessels.
As Joseph G.McCarthy, my former Chief at NYU, once said, plastic surgeons are problem- solvers. They are called upon by other practioners to
develop creative solutions to unsolvable problems in nearly every anatomic
region. Thus, it is not surprising that plastic surgeons have ocked to the
burgeoning eld of regenerative medicine, which promises even more elegant solutions to clinical problems found everywhere in the human body.
Regenerative medicine proposes using cellular and molecular processes to
recreate the exact same tissues that plastic surgeons perform long operations to recreate.
It is logical that plastic surgery would be at the forefront of the eld of
regenerative medicine. And this is indeed the case at stem cell conferences
and tissue engineering symposia, where plastic surgeons often outnumber all
the other clinical attendees combined. However, up until now, there did not
exist an authoritative reference documenting all the ways that plastic surgical
practice and regenerative medicine science overlap or provide a road map for
the future of both specialties. Drs. Duscher and Shiffman have provided a
valuable service by gathering in one place the leading voices in these two
elds in clear and concise manner.
Reading through this work, one is impressed by both the breadth of plastic
surgery practice and the enormous potential of regenerative medicine to cure
a multitude of human diseases. One also sees the potential for regenerative
medicine to be integrated into clinical plastic surgery. With beautiful clinical
images and artwork, this book will be a central companion to both practicing
plastic surgeons who wish to remain abreast of upcoming technological
advances and regenerative medicine researchers who wish to understand the
current state of the art of surgical reconstruction. The analogies between the
two disciplines are clearly laid out, and the possibilities for advances in clinical care leap off the pages.
Ultimately, regenerative medicine may make many operations plastic surgeons perform obsolete. This is familiar territory for plastic surgeons who
always need to look for the next clinical arena for innovation. I am condent
that clinical plastic surgeons will remain at the forefront and become leaders
in this emerging eld. In your hands is a comprehensive encyclopedia of two
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rapidly converging elds. Drs. Duscher and Shiffman have done an outstanding job of highlighting the interdependent relationship between plastic
surgery and regenerative medicine. Ultimately, this is to the benet of both
elds.
Stanford, CA GeoffreyC.Gurtner
Foreword

Preface
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A surgical success will impactthe patient in question, but a research success
can impact a global population.This thought came to me at the end of medical school and still is the main reason for my fascination for science today.
Driven by my desire to create knowledge and discover new things, I found the
seemingly endless possibilities of the young eld of regenerative medicine
particularly enchanting.
Through channelling the power of stem cells to repair or replace damaged
tissues, regenerative therapies are making their way into mainstay clinical
routine. As both case-based stem cell therapy and global understanding
evolve, we are entering an era in which we can design treatments for some of
the world’s most devastating diseases. Innovative therapeutic concepts borne
of the intersection of clinical medicine, engineering, and cell biology have
potential to change the way we practice medicine.
The international efforts put into this eld have created an unyielding body
of literature. Staying abreast of the genetic, epigenetic, cellular, stromal,
hematopoietic, and pathologic research emerging each year is critical. A
comprehensive, up-to-date reconnaissance of these parameters in the eld of
regenerative medicine is therefore a valuable tool. The expertise required to
generate such a text far exceeded that of its editors, and the roots of this book
are nourished in the soul of collaboration. I am indebted to the scores of
renowned specialists who have contributed their expertise and ingenuity to
this work. This book is intended for surgeons and scientists, for biologists and
engineers, and for students of medicine, biomedical engineering, cell biology, and biotechnology, simply for everyone who is interested in the extraordinary potential that regenerative medicine has to offer. The rst edition of
this book represents an attempt to organize the current knowledge in the eld.
However, knowledge is of no value unless you put it into practice. Thus, we
all need to strive for the clinical translation of the principles presented here to
make the dream of tissue and organ regeneration become reality.
You can have results or excuses. Not both.
—Arnold Schwarzenegger
Munich, Germany DominikDuscher
ix

Contents
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Part I Elements of Regenerative Medicine
1 Definitions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3
Dominik Duscher, Matthias M. Aitzetmüller,
and Elizabeth A. Brett
2 History of Regenerative Medicine . . . . . . . . . . . . . . . . . . . . . . . . . 5
Maximilian Zaussinger and Dominik Duscher
3 Basic Principles and Current Approach for Soft Tissue
Regeneration . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 7
Matthias M. Aitzetmüller, Elizabeth A. Brett,
Matthias A. Sauter, and Dominik Duscher
4 Sophisticated Biocomposite Scaffolds from Renewable
Biomaterials for Bone Tissue Engineering . . . . . . . . . . . . . . . . . . 17
Yavuz Emre Arslan, Eren Ozudogru, Tugba Sezgin Arslan,
Burak Derkus, Emel Emregul, and Kaan C. Emregul
Part II Research Concepts
5 Mechanotransduction in Wound Healing and Scar Formation . 35
Dominik Duscher
6 Stromal Cell-Derived Factor 1 (SDF-1) Signaling
and Tissue Homeostasis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 47
Zeshaan N. Maan, Mimi R. Borrelli,
Khosrow Siamak Houschyar, and Geoffrey C. Gurtner
7 Stem Cell Differentiation Directed by Material
and Mechanical Cues . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 61
Caitlyn A. Moore, Alexandra Condé-Green, Pranela
Rameshwar, and Mark S. Granick
8 Bacteriophages: A New (Yet Old) Weapon Against Infections . . 69
Stephen K. Mathew and Reba Kanungo
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9 Bacteriophages as Biocontrol Agents of Biofilm Infections
Associated with Abiotic Prosthetic Devices . . . . . . . . . . . . . . . . . 81
Shilpa Deshpande Kaistha, Pramila Devi Umrao,
Ravish Katiyar, and Neelima Deshpande
10 Extracellular Vesicles Derived from Mesenchymal
Stem/Stromal Cells: Current Approaches to Enhance Their
Release and Therapeutic Potential . . . . . . . . . . . . . . . . . . . . . . . . 101
Richard Schäfer, Benjamin Koch, and Patrick C. Baer
11 Anti-Biofilm Activity of Viruses, Bacteria, Fungi,
and Lichens: Mechanisms and Impact on Clinical Practice . . . . 113
Oana Săndulescu, Anca Streinu-Cercel, Mihai Săndulescu,
and Adrian Streinu-Cercel
Part III Emerging Technologies
12 Bionic Reconstruction: The New Frontier . . . . . . . . . . . . . . . . . . 125
Stefan Salminger, Johannes A. Mayer, and Oskar C. Aszmann
13 Carbohydrates in Regenerative Medicine: From Scaffolds
to Cell Fate Modulators . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 129
Roberto Guizzardi, Mattia Vacchini, and Laura Cipolla
Contents
14 Biomimetics: A New Abstraction for Bone Implant Design . . . . 151
Elizabeth A. Brett, Matthias A. Sauter, and Dominik Duscher
15 The Role of Microbiota in Skin Regeneration . . . . . . . . . . . . . . . 159
Angela Faga, Marco Mario Tresoldi, and Giovanni Nicoletti
16 Erythropoietin: An Innovative Therapeutic Approach
in Thermal Trauma . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 165
Christina Irene Günter and Hans-Günther Machens
17 Targeting C-Reactive Protein in Inflammatory Disease . . . . . . . 173
Johannes Zeller and Steffen U. Eisenhardt
18 Stem Cell Therapies for Tissue Regeneration and Wound
Healing: Strategies to Enhance Therapeutic Effectiveness . . . . . 187
Silvia Mihalceanu, Matthias M. Aitzetmüller,
Hans- Günther Machens, and Dominik Duscher
19 Iron Chelators & HIF-1α: A New Frontier for
Skin Rejuvenation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 201
Andrea Pagani, Matthias M. Aitzetmüller,
and Dominik Duscher
Part IV Translational Aspects
20 How to Overcome the Valley of Death from Basic Science to
Clinical Trials . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 213
Kelly Bridgham, Akash Chandawarkar, Halley Darrach,
and Justin M. Sacks
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