JuanRodríguez-Hernández
Polymers against
Microorganisms
On the Race to E cient Antimicrobial
Materials
Polymers against Microorganisms
Juan Rodríguez-Hernández
Polymers against
Microorganisms
On the Race to Effi cient
Antimicrobial Materials
ISBN 978-3-319-47960-6 ISBN 978-3-319-47961-3 (eBook)
DOI 10.1007/978-3-319-47961-3
Library of Congress Control Number: 2016954979
© Springer International Publishing AG 2017
This work is subject to copyright. All rights are reserved by the Publisher, whether the whole or part of
the material is concerned, specifi cally the rights of translation, reprinting, reuse of illustrations, recitation,
broadcasting, reproduction on microfi lms 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 specifi c 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, express or implied, with respect to the material contained herein or for any errors
or omissions that may have been made.
Printed on acid-free paper
This Springer imprint is published by Springer Nature
The registered company is Springer International Publishing AG
The registered company address is: Gewerbestrasse 11, 6330 Cham, Switzerland
Juan Rodríguez-Hernández
Institute of Polymer Science & Technology (ICTP-CSIC)
Madrid , Spain
v
Pref ace
Bacterial contamination is still an unresolved problem present in cases in which a
biomaterial is required. This is an issue independent of the biomaterial considered
and is particularly serious in those cases in which long-term implants are employed.
In this context, polymers have been proposed as interesting candidates to improve
the biomaterial performance in order to prevent microbial contamination. Different
previous books have been published focusing their efforts on one of the aspects of
antimicrobial polymers: the synthesis, in the biology of the microorganisms in con-
tact with synthetic materials or related to their fi nal use (e.g., food packaging). This
book aims to present a complete overview of this rapidly evolving fi eld providing a
concise, clear, and precise image of the most important aspects involved in the use
of polymers to combat microorganisms.
As will be depicted throughout this book, polymers’ mode of action relies on
physiochemical parameters such as hydrophobicity and cationic charge, rather than
specifi c receptor-mediated interactions, so the activity of the polymers can be mod-
ulated by tuning key structural parameters. Taking into account the mechanism of
action, polymers exhibit important advantages that have motivated their investiga-
tion as antibacterial materials. These include that polymers do not provide toxicity
to the environment, do not develop resistance, and have an enhanced antimicrobial
action. Other important advantages are their versatility; polymers are easy to pro-
cess and cheap.
I hope that this text will be helpful for readers with very different backgrounds,
ranging from chemists, biochemists, materials scientists, and engineers, who aim to
have a general and complete overview of the use of polymers in the preparation of
antimicrobial materials. This book is not presented as a manual and will not provide
answers to all possible questions about polymers with antimicrobial properties. On
the contrary, this book is intended to provide an introductory view highlighting
important aspects including synthesis, surface functionalization and structuration,
and the extension of these important aspects to the preparation of antimicrobial
fi bers, hydrogels, or membranes among others.
vi
This text, devoted to the recent developments and ongoing works concerning the
use of polymers as antifouling and antimicrobials for different applications, is orga-
nized as follows. The fi rst part of this book (Chaps. 2 and 3 ) describes the basics of
bacterial infections and the main functional groups incorporated into polymeric
structures to avoid microorganism contamination. Chapter 4 depicts the use of
nanostructured polymer assemblies in solution as antimicrobials.
The design and fabrication of polymer surfaces is analyzed in Chaps. 5 and 6 .
Chapter 5 discusses the alternatives to modify the surface chemical composition in
order to introduce both antifouling and/or antimicrobial functional groups. Chapter
6 concerns those approaches that resort to both the modifi cation of the surface
topography and those that combine surface functionalization and patterning to
remove bacterial contamination and biofi lm formation.
Chapters 7 , 8 , and 9 are devoted to the use of antimicrobial polymers for the
elaboration of three different materials. The approaches developed for the fabrica-
tion of nano- and microstructured fi bers are depicted in Chap. 7 . In Chapter 8 , the
synthesis and modifi cation of hydrogels to improve the bacterial adhesion and to
introduce antimicrobial moieties are described. Finally, Chap. 9 focuses on the elab-
oration of membranes with enhanced antifouling properties.
The last part of this book will analyze the eventual environmental concerns as
well as safety issues related to the use of nanoparticles. The last chapter will sum-
marize the future trends on the development of more sophisticated and effective
antimicrobial polymer systems.
Madrid, Spain Juan Rodríguez-Hernández
Preface
vii
Acknowledgements
I am indebted to many people that allowed this book to enter existence: my
coworkers at the Institute of Polymer Science and Technology (ICTP-CSIC), the
Macromolecular Engineering group (MEG) and also the Functionalization of
Polymers group (FUPOL). In addition, I would like to thank my wife Sonia, my
daughter Eva, and my parents and siblings who really encouraged me to complete
this project.
ix
Contents
1 Polymers Against Microorganisms ........................................................ 1
1.1 Infectious Diseases: Historical Context ........................................... 1
1.1.1 Mechanisms of Resistance to Antibacterial Agents ............. 6
1.2 Implant-Associated Infections ......................................................... 7
1.3 The Use of Macromolecules as Antimicrobials ............................... 8
1.4 About This Book .............................................................................. 9
References ................................................................................................. 10
2 Bacterial Infections: Few Concepts ....................................................... 13
2.1 Introduction ...................................................................................... 13
2.2 Bacterial Structure ........................................................................... 14
2.3 Interactions Mechanisms of Antimicrobials with Bacteria
in Solution ........................................................................................ 15
2.3.1 Bacterial Targets of Antibiotics ............................................ 15
2.3.2 Antibiotic Resistance Developed by Bacteria ...................... 16
2.3.3 Macromolecular Antimicrobials .......................................... 18
2.4 Biomaterials Surface: Device-Associated Infections ....................... 22
2.4.1 Adhesion, Adherence, and Attachment ................................ 23
2.4.2 Bacterial Adhesion to Biomaterials Surfaces ....................... 23
2.4.3 Biofi lm Formation ................................................................ 26
2.4.4 Antibiotic Resistance of Bacteria in Biofi lms ...................... 28
2.4.5 Approaches Developed to Achieve Polymeric
Biomaterials with Antibacterial Properties .......................... 30
2.5 Conclusions ...................................................................................... 31
References ................................................................................................. 32
3 Chemical Approaches to Prepare Antimicrobial Polymers ................ 39
3.1 Introduction ...................................................................................... 39
3.2 Types of Antimicrobial Groups Incorporated in Polymers .............. 40
3.2.1 Quaternary Ammonium/Phosphonium ................................ 41
3.2.2 N -Halamine and Other Halogen Containing Polymers ........ 43
x
3.2.3 Antimicrobial Peptides and Other Polymers
Mimicking Natural Peptides .............................................. 44
3.2.4 Other Antimicrobial Functional Groups............................. 47
3.3 Synthetic Strategies to Prepare Antimicrobial Polymers ............... 48
3.4 Interactions Between Bacteria and Polymeric Materials:
Role of the Macromolecular Parameters on the Antibacterial
Activity........................................................................................... 49
3.4.1 Hydrophilic/Hydrophobic Balance .................................... 49
3.4.2 Molecular Weight ............................................................... 51
3.4.3 Polymer Topology .............................................................. 52
3.4.4 Monomer Derivatization with Alkyl Chains:
Spacer Length and Alkyl Chain Effect ............................... 57
3.4.5 Other Macromolecular Parameters Involved
in the Antibacterial Activity ............................................... 57
3.5 Evaluation of the Antimicrobial Activity: In Vitro Testing ............ 59
3.6 Conclusions .................................................................................... 61
References ................................................................................................. 63
4 Nano-Micro Polymeric Structures with Antimicrobial
Activity in Solution ................................................................................. 71
4.1 Introduction .................................................................................... 71
4.2 Amphiphilic Antimicrobial Structures in Solution:
Key Variables to Take into Account ............................................... 72
4.3 Antimicrobial Random/Alternated Copolymers in Solution ......... 73
4.4 Self-Assembled Block Copolymer-Based Antimicrobial
Nanostructures ............................................................................... 76
4.5 Hybrid Organic/Inorganic Nano-Assemblies in Solution .............. 79
4.6 Polymeric Nanocapsules ................................................................ 82
4.7 Polymeric Nanoparticles ................................................................ 82
4.8 Core/Shell Nanoparticles ............................................................... 84
4.9 Fabrication of Microspheres for Antibacterial Purposes................ 85
4.10 Responsive Nanoparticles/Assemblies .......................................... 87
4.11 Conclusions .................................................................................... 90
References ................................................................................................. 91
5 Antimicrobial/Antifouling Surfaces Obtained
by Surface Modification ......................................................................... 95
5.1 Introduction .................................................................................... 95
5.2 Polymer Surface Modifi cation ....................................................... 97
5.3 Techniques to Functionalize Polymer Surfaces ............................. 98
5.4 Anti-Adhesive Polymer Surfaces: Antifouling .............................. 99
5.5 Antibacterial Coatings ................................................................... 102
5.5.1 Biocide-Releasing Antibacterial Coatings ......................... 102
5.5.2 Intrinsically Bioactive Materials: Contact-Active
Biocidals ............................................................................. 102
Contents
xi
5.6 Dual-Function Antibacterial Surfaces for Biomedical
Applications ..................................................................................... 107
5.6.1 Repelling and Releasing Surfaces ........................................ 107
5.6.2 Contact-Killing and Repelling ............................................. 107
5.6.3 Releasing and Contact-Killing ............................................. 108
5.7 Responsive Antibacterial Surfaces ................................................... 109
5.7.1 Thermoresponsive Surfaces ................................................. 111
5.7.2 pH-Responsive Surfaces ...................................................... 112
5.7.3 Bioresponsive Surfaces ........................................................ 112
5.7.4 Other Responsive Interfaces ................................................ 113
5.8 Conclusions ...................................................................................... 115
References ................................................................................................. 115
6 Nano/Microstructured Antibacterial Surfaces ..................................... 125
6.1 Introduction ...................................................................................... 125
6.2 Fabricating Micro- and Nanometer Size Patterns
on Polymer Surfaces ........................................................................ 127
6.2.1 Innovative Lithographic Techniques .................................... 127
6.2.2 Laser-Based Micro-Nanopatterning ..................................... 128
6.2.3 Writing Using Electron and Ion Beams ............................... 128
6.2.4 Molding ................................................................................ 129
6.2.5 Pattern Formation by Surface Instabilities ........................... 129
6.3 Micro/Nanostructured Antimicrobial Surfaces in Nature ................ 131
6.3.1 Nanostructured Surfaces that Repel/Kill Bacteria
in Nature .............................................................................. 132
6.3.2 Hierarchically Structured Surfaces with Antifouling
Properties ............................................................................. 134
6.4 Engineering Bioinspired Surfaces with Either Micro-
or Nanostructured Topographic Structures ...................................... 134
6.4.1 Synthetic Structured Polymer Surfaces with Micrometer
Size Patterns ......................................................................... 135
6.4.2 Nanoscale Surface Patterns in Polymeric Materials
as Antimicrobial Materials ................................................... 135
6.5 Engineered Surfaces with Micro/Nanostructured
Topographic Features and Chemically Controlled Surface ............. 138
6.6 Nanostructured Composite Films .................................................... 143
6.7 Nanostructured Responsive Surfaces ............................................... 145
6.8 Conclusions ...................................................................................... 148
References ................................................................................................. 148
7 Antimicrobial Fibers and Fabrics Obtained
by Electro/Melt Spinning ....................................................................... 155
7.1 Introduction ...................................................................................... 155
7.2 Approaches for Fiber Fabrication .................................................... 156
7.2.1 Melt, Solution, and Emulsion Spinning ............................... 156
7.2.2 Electrospinning .................................................................... 157
7.2.3 Melt Blowing ....................................................................... 158
Contents
