Polymers in Regenerative Medicine

Biomedical applications of Polymers from Scaffolds to
Nanostructures

The ability of polymers to span wide ranges of mechanical
properties and morph into desired shapes makes them useful for a
variety of applications, including scaffolds, self-assembling
materials, and nanomedicines. With an interdisciplinary list of
subjects and contributors, this book overviews the biomedical
applications of polymers and focuses on the aspect of regenerative
medicine. Chapters also cover fundamentals, theories, and tools for
scientists to apply polymers in the following ways:

• Matrix protein interactions with synthetic surfaces

• Methods and materials for cell scaffolds

• Complex cell-materials microenvironments in bioreactors

• Polymer therapeutics as nano-sized medicines for tissue
  repair

• Functionalized mesoporous materials for controlled
  delivery

• Nucleic acid delivery nanocarriers

Concepts include macro and nano requirements for polymers as
well as future perspectives, trends, and challenges in the field.
From self-assembling peptides to self-curing systems, this book
presents the full therapeutic potential of novel polymeric systems
and topics that are in the leading edge of technology.

Autorentext

Manuel Monleón Pradas is Professor at the Technical
University of Valencia, Spain, where he founded and headed the
Centre for Biomaterials and Tissue Engineering (1999-2009).
He was Head of the Biomaterials Unit at the Centro de
Investigación Príncipe Felipe (Valencia, Spain), and has
been visiting professor at the University of Paris-XI. He has
authored over 160 papers in the fields of polymer science and
biomaterials.

María J. Vicent is Head of the Polymer Therapeutics
Laboratory at Centro de Investigación Príncipe Felipe
(Valencia, Spain). She has expertise in several aspects of polymer
therapeutics field, from synthesis of nanopharmaceutics to their
biological evaluation in different cell and in vivo models. Dr.
Vicent has coauthored over 70 papers and 7 patents in the field.
Furthermore, in 2012, she cofounded a spin-off company named
Polypeptide Therapeutic Solutions SL, Spain, based on a family
patent from her own group.

Zusammenfassung

Biomedical applications of Polymers from Scaffolds to Nanostructures

The ability of polymers to span wide ranges of mechanical properties and morph into desired shapes makes them useful for a variety of applications, including scaffolds, self-assembling materials, and nanomedicines. With an interdisciplinary list of subjects and contributors, this book overviews the biomedical applications of polymers and focuses on the aspect of regenerative medicine. Chapters also cover fundamentals, theories, and tools for scientists to apply polymers in the following ways:

• Matrix protein interactions with synthetic surfaces
• Methods and materials for cell scaffolds
• Complex cell-materials microenvironments in bioreactors
• Polymer therapeutics as nano-sized medicines for tissue repair
• Functionalized mesoporous materials for controlled delivery
• Nucleic acid delivery nanocarriers
  Concepts include macro and nano requirements for polymers as well as future perspectives, trends, and challenges in the field. From self-assembling peptides to self-curing systems, this book presents the full therapeutic potential of novel polymeric systems and topics that are in the leading edge of technology.

Inhalt

Preface xi

Contributors xvii

Part A Methods for Synthetic Extracellular Matrices and Scaffolds 1

1 Polymers as Materials for Tissue Engineering Scaffolds 3
Ana Vallés Lluch Dunia Mercedes García Cruz Jorge Luis Escobar Ivirico Cristina Martínez Ramos and Manuel Monleón Pradas

1.1 The Requirements Imposed by Application on Material Structures Intended as Tissue Engineering Scaffolds 3

1.2 Composition and Function 5

1.2.1 General Considerations 5

1.2.2 Some Families of Polymers for Tissue Engineering Scaffolds 8

1.2.3 Composite Scaffold Matrices 12

1.3 Structure and Function 14

1.3.1 General Considerations 14

1.3.2 Structuring Polymer Matrices 15

1.4 Properties of Scaffolds Relevant for Tissue Engineering Applications 24

1.4.1 Porous Architecture 24

1.4.2 Solid State Properties: Glass Transition Crystallinity 25

1.4.3 Mechanical and Structural Properties 26

1.4.4 Swelling Properties 28

1.4.5 Degradation Properties 29

1.4.6 Diffusion and Permeation 30

1.4.7 Surface Tension and Contact Angle 31

1.4.8 Biological Properties 31

1.5 Compound Multicomponent Constructs 32

1.5.1 Scaffold-Cum-Gel Constructs 32

1.5.2 Scaffolds and Membranes Containing Microparticles 34

1.5.3 Other Multicomponent Scaffold Constructs 34

1.6 Questions Arising from Manipulation and Final Use 35

1.6.1 Sterilization 35

1.6.2 Cell Seeding Cell Culture Analysis 36

1.6.3 In the Surgeon's Hands 37

References 37

2 Natural-Based and Stimuli-Responsive Polymers for Tissue Engineering and Regenerative Medicine 49
Mariana B. Oliveira and João F. Mano

2.1 Introduction 49

2.2 Natural Polymers and Their Application in TE & RM 52

2.2.1 Polysaccharides 52

2.2.2 Protein-Based Polymers 60

2.2.3 Polyesters 65

2.3 Natural Polymers in Stimuli-Responsive Systems 65

2.3.1 pH-Sensitive Natural Polymers 67

2.3.2 Temperature Sensitive Natural Polymers 67

2.3.3 Natural Polymers Modified to Show Thermoresponsive BehaviorModifying Responsive Polymers
and Agents 71

2.3.4 Light-Sensitive PolymersPotential Use of Azobenzene/-Cyclodextrin Inclusion Complexes 72

2.4 Conclusions 73

References 74

3 Matrix Proteins Interactions with Synthetic Surfaces 91
Patricia Rico Marco Cantini George Altankov and Manuel Salmerón-Sánchez

3.1 Introduction 91

3.2 Protein Adsorption 92

3.2.1 Cell Adhesion Proteins 93

3.2.2 Experimental Techniques to Follow Protein Adsorption 94

3.2.3 Effect of Surface Properties on Protein Adsorption 97

3.3 Cell Adhesion 109

3.3.1 Experimental Techniques to Characterize Cell Adhesion 112

3.3.2 Cell Adhesion at CellMaterial Interface 115

3.4 Remodeling of the Adsorbed Proteins 122

3.4.1 Protein Reorganization and Secretion at the CellMaterial Interface 122

3.4.2 Proteolytic Remodeling at CellMaterials Interface 126

References 128

4 Focal Adhesion Kinase in CellMaterial Interactions 147
Cristina González-García Manuel Salmerón-Sánchez and Andrés J. García

4.1 Introduction 147

4.2 Role of FAK in Cell Proliferation 149

4.3 Role of FAK in Migratory and Mechanosensing Responses 150

4.4 Role of FAK in the Generation of Adhesives Forces 152

4.5 Influence of Material Surface Properties on FAK Signaling 156

4.5.1 Effect of Mechanical Properties on FAK Signaling 156

4.5.2 Effect of Surface Topography on FAK Signaling 160

4.5.3 Effect of Surface Chemistry on FAK Signaling 163

4.5.4 Effect of Surface Functionalization in FAK Expression 165

References 168 5 Complex CellMaterials Microenvironments in Bioreactors 177
*Stergios C. Dermenoudis and Yannis F. M...