BIOMATERIALS FROM NATURE FOR ADVANCED DEVICES AND … · biomaterials from nature for advanced devices and therapies edited by nuno m. neves and rui l. reis

BIOMATERIALS FROM NATURE FOR ADVANCED DEVICES AND THERAPIESEDITED BY NUNO M. NEVES AND RUI L. REIS

BIOMATERIALS FROMNATURE FOR ADVANCEDDEVICES ANDTHERAPIES

WILEY - SOCIETY FOR BIOMATERIALS

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BIOMATERIALS FROMNATURE FOR ADVANCEDDEVICES ANDTHERAPIES

Edited by

NUNO M. NEVESUniversity of Minho

RUI L. REISUniversity of Minho

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Names: Neves, Nuno M., editor. | Reis, Rui L., editor.Title: Biomaterials from nature for advanced devices and therapies / edited by Nuno Neves, Rui L Reis.Description: Hoboken, New Jersey : John Wiley & Sons, Inc., [2016] | Includes index.Identifiers: LCCN 2016017315 | ISBN 9781118478059 (cloth) | ISBN 9781119178071 (epub)Subjects: LCSH: Biomedical materials–Therapeutic use.Classification: LCC R857.M3 B5726 2016 | DDC 610.28/4–dc23LC record available at https://lccn.loc.gov/2016017315

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CONTENTS

CONTRIBUTORS xix

PREFACE xxix

PART I

1 Collagen-Based Porous Scaffolds for Tissue Engineering 3Guoping Chen and Naoki Kawazoe

1.1 Introduction, 31.2 Collagen Sponges, 41.3 Collagen Sponges with Micropatterned Pore Structures, 71.4 Collagen Sponges with Controlled Bulk Structures, 101.5 Hybrid Scaffolds, 121.6 Conclusions, 13References, 14

2 Marine Collagen Isolation and Processing Envisaging BiomedicalApplications 16Joana Moreira-Silva, Gabriela S. Diogo, Ana L. P. Marques, Tiago H. Silva, andRui L. Reis

2.1 Introduction, 162.2 Extraction of Collagen from Marine Sources, 18

2.2.1 Extraction of Collagen from Fish, Jellyfish and Molluscs, 192.2.2 Extraction of Collagen from Other Sources: Marine Sponges, 22

v

vi CONTENTS

2.3 Collagen Characterization, 222.3.1 Fourier Transform InfraRed Spectroscopy (FTIR), 232.3.2 Differential Scanning Calorimetry (DSC), 232.3.3 Circular Dichroism (CD), 232.3.4 Sodium Dodecyl Sulfate Polyacrylamide Gel

Electrophoresis (SDS-PAGE), 242.3.5 Amino Acid Analysis, 24

2.4 Marine Collagen Wide Applications, 252.4.1 Marine Collagen-Based Biomaterials Properties, 252.4.2 Marine Collagen Applications in Tissue Engineering, 272.4.3 Other Tissue Engineering Applications, 31

2.5 Final Remarks, 32Acknowledgements, 34References, 34

3 Gelatin-Based Biomaterials for Tissue Engineering and Stem CellBioengineering 37Mehdi Nikkhah, Mohsen Akbari, Arghya Paul, Adnan Memic, AlirezaDolatshahi-Pirouz, and Ali Khademhosseini

3.1 Introduction, 373.2 Crosslinking of Gelatin, 383.3 Physical Properties of Gelatin, 393.4 Application of Gelatin-Based Biomaterials in Tissue Engineering, 40

3.4.1 Cardiovascular Tissue Engineering, 403.4.2 Bone Tissue Engineering, 423.4.3 Hepatic Tissue Engineering, 423.4.4 Ophthalmology, 433.4.5 Dermatology, 443.4.6 Miscellaneous Applications, 45

3.5 Gelatin for Stem Cell Therapy, 453.5.1 Embryonic Stem Cells, 453.5.2 Adult Stem Cells, 463.5.3 Induced Pluripotent Stem Cells, 48

3.6 Application of Gelatin in Delivery Systems, 493.7 Conclusion and Perspectives, 50Acknowledgements, 50Abbreviations, 50References, 51

4 Hyaluronic Acid-Based Hydrogels on a Micro and Macro Scale 63A. Borzacchiello, L. Russo, and L. Ambrosio

4.1 Classification and Structure of Hydrogels, 634.2 Hyaluronic Acid, 65

CONTENTS vii

4.3 Hydrogel Mechanical Properties, 664.3.1 Dynamic Mechanical Analysis, 664.3.2 Stress Strain Behavior, 68

4.4 HA-Based Hydrogel for Biomedical Applications, 704.4.1 Regenerative Medicine, 704.4.2 Drug Delivery, 73

References, 75

5 Chondroitin Sulfate as a Bioactive Macromolecule for AdvancedBiological Applications and Therapies 79Nicola Volpi

5.1 CS Structure, 815.2 Biological Roles of CS, 815.3 Osteoarthritis Treatment, 845.4 Cardio-Cerebrovascular Disease, 845.5 Tissue Regeneration and Engineering, 855.6 Chondroitin Sulfate-Polymer Conjugates, 865.7 Conclusions and Future Perspectives, 87References, 88

6 Keratin 93Mark Van Dyke

6.1 Introduction, 936.2 Preparation of Keratoses, 986.3 Preparation of Kerateines, 1006.4 Oxidative Sulfitolysis, 1016.5 Summary, 102References, 102

7 Elastin-Like Polypeptides: Bio-Inspired Smart Polymers for ProteinPurification, Drug Delivery and Tissue Engineering 106Jayanta Bhattacharyya, Joseph J. Bellucci, and Ashutosh Chilkoti

7.1 Introduction, 1067.2 Recombinant Protein Production Using ELPs as Purification Tags, 107

7.2.1 ELP Expression, 1077.2.2 ELP Purification, 1087.2.3 Tag Removal, 1107.2.4 Biological Evaluation of Purified Protein, 111

7.3 Delivery of Therapeutics with ELPs, 1137.3.1 Systemic Delivery of Soluble ELP-Drug Conjugate, 1157.3.2 Systemic Delivery of ELP with Local Hyperthermia, 1177.3.3 Hyperthermia-Triggered Multivalency, 1177.3.4 Local Delivery by Thermal Coacervation, 118

viii CONTENTS

7.4 Tissue Engineering with ELPs, 1197.4.1 Coacervation of Soluble ELP, 1207.4.2 Covalent Crosslinking, 121

7.5 Conclusions, 122Acknowledgements, 122Abbreviations, 122References, 123

8 Silk: A Unique Family of Biopolymers 127A. Motta, M. Floren, and C. Migliaresi

8.1 Introduction, 1278.2 Main Silk Polymers, 129

8.2.1 Bombyx mori Silk, 1298.3 Fibroin Basic Processing: Regenerated Silk Fibroin, 131

8.3.1 Sericin Removal: Degumming, 1318.3.2 Fibroin Dissolution, 131

8.4 Materials Fabrication of Silk Proteins, 1318.4.1 Two Dimensional Platforms, 132

8.5 Advanced Material Applications of Silks, 1358.5.1 Biomedical Therapies, 1358.5.2 Silks as Photonic and Electronic Devices, 135

8.6 Conclusion, 136References, 137

9 Silk Protein Sericin: Promising Biopolymer for Biological andBiomedical Applications 142Sunita Nayak and Subhas C. Kundu

9.1 Introduction, 1429.1.1 Silks, 1429.1.2 Sericin, 1449.1.3 Biochemical Properties of Sericin, 145

9.2 Sericin Extraction and Processing, 1469.2.1 Directly from Glands, 1469.2.2 Heat Degradation, 1479.2.3 Acid Degradation, 1479.2.4 Alkali Degradation, 1479.2.5 Urea Method, 1479.2.6 Enzymatic Degradation, 147

9.3 Potential Applications of Sericin, 1479.3.1 Dietary Supplements, 1489.3.2 Antioxidant and Anticancer Properties, 1489.3.3 Sericin Bioconjugate, 149

CONTENTS ix

9.3.4 Sericin as Supplement in Animal Cell Culture, 1499.3.5 Sericin as Biomaterials, 150

9.4 Immunogenicity and Toxicity of Sericin, 1529.5 Conclusion, 153Acknowledgements, 154References, 154

10 Fibrin 159Markus Kerbl, Philipp Heher, James Ferguson, and Heinz Redl

10.1 Introduction, 15910.2 Fibrin Clotting, 16010.3 Fibrin Degradation, 16010.4 Fibrin Glue, 163

10.4.1 Modes of Application, 16310.4.2 Modification Options of Fibrin Glue, 16410.4.3 Usage, 166

10.5 Conclusion, 170Acknowledgement, 171References, 171

11 Casein Proteins 176Pranav K. Singh and Harjinder Singh

11.1 Introduction, 17611.2 Structures and Properties of Casein, 178

11.2.1 αS1-Casein, 17911.2.2 αS2-Casein, 18111.2.3 β-Casein, 18211.2.4 κ-Casein, 183

11.3 Interaction of Caseins with Metal Ions, 18411.4 Conclusions, 185References, 186

12 Biomaterials from Decellularized Tissues 190Ricardo Londono and Stephen F. Badylak

12.1 Introduction, 19012.1.1 The Default Tissue Response to Injury in Adult Mammals, 19112.1.2 Extracellular Matrix Scaffolds, 19212.1.3 ECM Scaffolds – The Decellularization Process, 193

12.2 Host Response to Implanted ECM-Derived Biomaterials, 196References, 199

x CONTENTS

13 Demineralized Bone Matrix: A Morphogenetic ExtracellularMatrix 211A. Hari Reddi and Ryosuke Sakata

13.1 Introduction, 21113.2 Demineralized Bone Matrix (DBM), 21113.3 From DBM to Bone Morphogenetic Proteins (BMPs), 21313.4 BMPs Bind to Extracellular Matrix, 21613.5 BMP Receptors, 21613.6 Future Perspectives, 218Acknowledgements, 218References, 218

PART II

14 Recent Developments on Chitosan Applications in RegenerativeMedicine 223Ana Rita C. Duarte, Vitor M. Correlo, Joaquim M. Oliveira, and Rui L. Reis

14.1 Introduction, 22314.2 Chitosan and Derivatives, 224

14.2.1 Synthesis of Chitosan, 22414.2.2 Physicochemical Properties, 22514.2.3 Chemical Modification of Chitosan, 225

14.3 Regenerative Medicine Applications of Chitosan, 22714.3.1 Micro- and Nanoparticles Systems, 22814.3.2 Hydrogels and Scaffolds, 22914.3.3 Membranes and Tubular Structures, 230

14.4 Processing Methodologies, 23114.4.1 Freeze-Drying, 23214.4.2 Electrospinning, 23314.4.3 Layer-by-Layer Deposition, 23314.4.4 Supercritical Fluid Technology, 234

14.5 Final Remarks, 236Acknowledgments, 237References, 237

15 Starch-Based Blends in Tissue Engineering 244P.P. Carvalho, M.T. Rodrigues, R.L. Reis, and M.E. Gomes

15.1 Introduction, 24415.2 Starch, 24515.3 Modification of Starch for Biomedical Applications, 24715.4 Starch-Based Blends, 248

15.4.1 Starch Cellulose Acetate (SCA), 248

CONTENTS xi

15.4.2 Starch Ethylene-Vinyl Alcohol (SEVA-C), 25115.4.3 Starch Poly(Lactic Acid) [SPLA], 25115.4.4 Starch Polycaprolactone (SPCL), 252

15.5 Conclusions and Future Perspectives, 254References, 255

16 Agarose Hydrogel Characterization for Regenerative MedicineApplications: Focus on Engineering Cartilage 258Brendan L. Roach, Adam B. Nover, Gerard A. Ateshian, and Clark T. Hung

16.1 The Foundations of Agarose, 25816.2 Structure-Function Relationships of Agarose Hydrogels, 25916.3 Agarose as a Tissue Engineering Scaffold, 26116.4 Agarose in the Clinic, 26616.5 A Scaffold to Build On, 267Acknowledgements, 268References, 268

17 Bioengineering Alginate for Regenerative Medicine Applications 274Emil Ruvinov and Smadar Cohen

17.1 Introduction, 27417.2 Regenerative Medicine: Definition and Strategies, 275

17.2.1 Stem Cells, 27617.2.2 Biomaterials, 277

17.3 Alginate Biomaterial, 27717.3.1 Alginate Composition and Hydrogel Formation, 27717.3.2 Degradation of Alginate and its Hydrogels, 27917.3.3 Biocompatibility, 28017.3.4 Main Applied Forms of Alginate, 280

17.4 Alginate Implant: First in Man Trial for Prevention of HeartFailure, 281

17.5 Alginate Hydrogel as a Vehicle for Stem Cell Delivery andRetention, 28417.5.1 Cardiovascular Repair, 28517.5.2 Osteochondral Repair, 28617.5.3 Immunomodulation, 286

17.6 Engineering Alginate-Based Cell Microenvironments, 28717.6.1 Concept Design, 28717.6.2 Engineering Alginate Scaffold for Cardiac Tissue

Engineering, 28817.6.3 Engineering Alginate Scaffold for Cartilage Tissue

Engineering, 28917.7 Alginate Hydrogel Carrier for Growth Factor Delivery, 289

xii CONTENTS

17.8 Engineering Alginate for Affinity Binding and Presentation ofHeparin-Binding Growth Factors, 29217.8.1 The Concept of Affinity-Binding Alginate Biomaterial, 29217.8.2 Case Study: Myocardial Repair, 29317.8.3 Case Study: Osteochondral Repair, 29717.8.4 Conclusions and Future Perspectives, 299

References, 300

18 Dextran 307Rong Wang, Pieter J. Dijkstra, and Marcel Karperien

18.1 Introduction, 30718.2 Structure and Properties, 30818.3 Dextran Derivatives, 310

18.3.1 Dextran Esters, 31018.3.2 Dextran Carbonates, 31218.3.3 Dextran Carbamates, 313

18.4 Dextran Copolymers, 31418.4.1 Graft Copolymers, 31418.4.2 Block Copolymers, 315

18.5 Degradation, 31618.6 Outlook, 316References, 316

19 Gellan Gum-based Hydrogels for Tissue Engineering Applications 320Joana Silva-Correia, Joaquim Miguel Oliveira, and Rui Luıs Reis

19.1 Introduction, 32019.2 Gellan Gum and its Derivatives, 322

19.2.1 Low and High Acyl Gellan Gum: Structure and Properties, 32219.2.2 Gellan Gum Derivatives, 323

19.3 Tissue Engineering Applications, 32519.3.1 Cartilage, 32619.3.2 Meniscus, 32719.3.3 Bone, 32719.3.4 Osteochondral, 32819.3.5 Peripheral Nerve, 32919.3.6 Intervertebral Disc, 329

19.4 Final Remarks, 331Acknowledgments, 332References, 332

CONTENTS xiii

PART III

20 Biomedical Applications of Polyhydroxyalkanoates 339L.R. Lizarraga-Valderrama, B. Panchal, C. Thomas, A.R. Boccaccini, and I. Roy

20.1 Introduction, 33920.2 Skin Tissue Engineering, 34120.3 Nerve Tissue Engineering, 34420.4 Cardiac Tissue Engineering, 348

20.4.1 Pericardial Patch, 35120.4.2 Cardiovascular Stents, 35120.4.3 Congenital Cardiovascular Defects: Artery Augmentation, 35220.4.4 Heart Valves, 35320.4.5 Vascular Grafts, 355

20.5 Dental Tissue Engineering, 35620.6 Bone Tissue Engineering, 35820.7 Cartilage Tissue Engineering, 36620.8 Osteochondral Tissue Engineering, 36820.9 Drug Delivery, 37020.10 Conclusions and the Future Potential of PHAs in Biomedical

Applications, 373References, 373

21 Bacterial Cellulose 384Hernane S. Barud, Junkal Gutierrez, Wilton R. Lustri, Maristela F.S. Peres,Sidney J.L. Ribeiro, Sybele Saska, and Agniezska Tercjak

21.1 Introduction, 38421.2 BC Dressings, 38521.3 Bacterial Cellulose for Tissue Engineering and Regenerative

Medicine, 38821.4 Concluding Remarks, 393Acknowledgments, 394References, 394

PART IV

22 Molecularly Imprinted Cryogels for Protein Purification 403Muge Andac, Igor Yu Galaev, and Adil Denizli

22.1 Introduction, 40322.2 Molecularly Imprinted Cryogels for Protein Purification, 405

22.2.1 Cryogels, 40522.2.2 Magic of Freezing (Mechanisms of Ice Formation and

Polymerization in Cryogels), 406

xiv CONTENTS

22.3 Some Selected Applications of Molecularly Imprinted Cryogels(MIC) for Macromolecules, 414

22.4 Concluding Remarks and Future Perspectives, 421References, 423

23 Immunogenic Reaction of Implanted Biomaterials from Nature 429Martijn Van Griensven and Elizabeth Rosado Balmayor

23.1 Introduction, 42923.2 Implantation Leads to Tissue Injury, 43023.3 Inflammatory Responses, 431

23.3.1 Acute Inflammation, 43123.3.2 Chronic Inflammation, 433

23.4 Foreign Body Reaction, 43323.5 Immunogenic Reactions Towards Natural Biomaterials, 435

23.5.1 Collagens, 43523.5.2 Fibrin, 43523.5.3 Hyaluronic Acid, 43623.5.4 Alginate, 43623.5.5 Chitosan, 43623.5.6 Fibroin, 43723.5.7 Combinations, 437

23.6 Final Remarks, 438References, 438

24 Chemical Modification of Biomaterials from Nature 444J.C. Rodrıguez Cabello, I. Gonzalez De Torre, M. Santos, A.M. Testera, and M. Alonso

24.1 Protein Modification, 44424.1.1 Biological Incorporation of Non-Natural Amino Acids

in Target Protein Using a Genetic Modification System, 44524.1.2 Labeling of Expressed Protein by Bioconjugation of

Natural Amino Acids, 44624.1.3 Bio-Orthogonal Reactions of Proteins with

Non-Natural Functional Groups, 44824.1.4 Enzymatic Site-Specific Modification, 44924.1.5 Ligand-Directed Labeling Chemistries, 449

24.2 Lipid Modifications, 45124.2.1 Acetylation, 45224.2.2 Epoxidation and Hydroxylation, 45224.2.3 Hydrogenation, 45524.2.4 Esterification, 456

24.3 Polysaccharide Chemical Modifications, 45724.3.1 Modifications Guided by Saccharide Oxygen Acting as

Nucleophile, 457

CONTENTS xv

24.3.2 Modifications Guided by Saccharide Carbon Acting asElectrophile, 461

24.3.3 Polysaccharides Modificated by Oxidation, 46224.3.4 Reactions of Carboxilic Groups of Polysaccharides, 46324.3.5 Modifications Guided by Saccharide Nitrogen Acting

as Nucleophile, 464References, 466

PART V

25 Processing of Biomedical Devices for Tissue Engineering andRegenerative Medicine Applications 477Vitor M. Correlo, Albino Martins, Nuno M. Neves, and Rui L. Reis

25.1 Introduction, 47725.2 Processing Techniques of Naturally Derived Biomaterial, 478

25.2.1 Gelation, 47825.2.2 Electrospinning, 47825.2.3 Emulsion/Freeze-Drying, 47925.2.4 Wet-spinning, 48025.2.5 Solvent Casting, 48125.2.6 Microparticles Fabrication and Agglomeration, 48125.2.7 Supercritical Fluids, 482

25.3 Processing Techniques of Natural-Based Polymeric Blends, 48325.3.1 Melt Fiber Extrusion, 48325.3.2 Compression Molding and Particle Leaching, 48425.3.3 Rapid Prototyping, 48525.3.4 Hot-Embossing, 485

References, 487

26 General Characterization of Physical Properties of Natural-BasedBiomaterials 494Manuel Alatorre-Meda and Joao F. Mano

26.1 Introduction, 49426.2 Bulk Properties, 495

26.2.1 Bulk Microstructure, 49526.2.2 Porosimetry, 49626.2.3 Water Content, 49826.2.4 Thermal Properties, 49926.2.5 Mechanical Properties, 500

26.3 Surface Properties, 50726.3.1 Wettability and Interfacial Free Energy, 50826.3.2 Topography and Roughness, 509

xvi CONTENTS

26.4 Concluding Remarks, 512Acknowledgments, 512References, 512

27 General Characterization of Chemical Properties of Natural-BasedBiomaterials 517Manuel Alatorre-Meda and Joao F. Mano

27.1 Introduction, 51727.2 Molecular Weight and Elemental Composition, 518

27.2.1 Viscosimetry, 51827.2.2 Mass Spectrometry, 51927.2.3 Nuclear Magnetic Resonance, 52127.2.4 FT-IR and UV Spectroscopies, 522

27.3 Physiological Degradation, 52427.4 Concluding Remarks, 527Acknowledgments, 529References, 529

28 In Vitro Biological Testing in the Development of New Devices 532Marta L. Alves Da Silva, Albino Martins, Ana Costa-Pinto, Rui L. Reis, andNuno M. Neves

28.1 Introduction, 53228.2 Cytotoxicity Assays, 53328.3 Evaluation of Cell Morphology and Distribution, 533

28.3.1 Scanning Electron Microscopy (SEM), 53328.3.2 Fluorescence Microscopy, 53428.3.3 Micro-Computed Tomography (μCT), 534

28.4 Cell Viability Assays, 53528.5 Cell Proliferation Assays, 53628.6 Biochemical Analysis, 537

28.6.1 Glucose Consumption and Lactate Production, 53728.6.2 Protein Synthesis, 539

28.7 Genotypic Expression Analysis, 54128.8 Histological Assessment, 542

28.8.1 Hematoxylin–Eosin, 54228.8.2 Immunodetection of Specific Proteins, 543

28.9 In Vitro Engineered Tissues, 54328.9.1 Bone, 54328.9.2 Cartilage, 547

28.10 Concluding Remarks, 548References, 548

CONTENTS xvii

29 Advanced In-Vitro Cell Culture Methods Using NaturalBiomaterials 551Marta L. Alves Da Silva, Rui L. Reis, and Nuno M. Neves

29.1 Introduction, 55129.2 Bioreactors, 55229.3 Hypoxia, 55329.4 Co-Cultures, 55529.5 Transfection, 55529.6 Nanoparticles and Related Systems, 55829.7 Concluding Remarks, 559References, 559

30 Testing Natural Biomaterials in Animal Models 562Ana Costa-Pinto, Tırcia C. Santos, Nuno M. Neves, and Rui L. Reis

30.1 Laboratory Animals as Tools in Biomaterials Testing, 56230.2 Inflammation and Host Reaction, 564

30.2.1 Host Reaction Models, 56630.3 Animal Models for Tissue Engineering, 568

30.3.1 Cartilage Tissue Engineering, 56930.3.2 Bone Tissue Engineering, 571

30.4 Final Remarks, 574References, 575

PART VI

31 Delivery Systems Made of Natural-Origin Polymers for TissueEngineering and Regenerative Medicine Applications 583Albino Martins, Helena Ferreira, Rui L. Reis, and Nuno M. Neves

31.1 Introduction, 58331.2 Advantages and Disadvantages of Natural Polymers-Based

Delivery Systems, 58531.3 Fundamentals of Drug Delivery, 586

31.3.1 Diffusion Controlled Systems, 58731.3.2 Chemically Controlled Systems, 58831.3.3 Solvent-Activated Systems, 58931.3.4 Externally Triggered Systems, 58931.3.5 Self-Regulated Delivery Systems, 589

31.4 In Vitro and In Vivo Applications of Natural-Based DeliverySystems, 59131.4.1 Drug Delivery Systems, 59131.4.2 Protein Delivery Systems, 59331.4.3 Gene Delivery Systems, 600

xviii CONTENTS

31.5 Concluding Remarks, 601References, 602

32 Translational Research into New Clinical Applications 612M. David Harmon and Sangamesh G. Kumbar

32.1 Introduction, 61232.2 Cardiovascular System Applications, 61332.3 Integumentary System Applications, 61632.4 Musculoskeletal System Applications, 61832.5 Nervous System Applications, 61932.6 Respiratory System Applications, 62132.7 Gastrointestinal System Applications, 62232.8 From Idea to Product, 624Acknowledgements, 626References, 626

33 Challenges and Opportunities of Natural Biomaterials forAdvanced Devices and Therapies 629R.L. Reis and N.M. Neves

33.1 Introduction, 62933.2 Challenges of Natural Biomaterials, 63033.3 Opportunities of Natural Biomaterials, 63133.4 Final Remarks, 631References, 632

34 Adhesives Inspired by Marine Mussels 634Courtney L. Jenkins, Heather J. Meredith, and Jonathan J. Wilker

34.1 Introduction, 63434.2 Requirements for a Bioadhesive, 63534.3 Marine Mussels, 63634.4 Bulk Adhesion Testing, 63834.5 Extracted Mussel Adhesive Proteins, 64034.6 Mimics of Mussel Adhesive, 64134.7 Conclusions, 645Acknowledgement, 645References, 645

35 Final Comments and Remarks 649R.L. Reis and N.M. Neves

INDEX 651

CONTRIBUTORS

Mohsen Akbari, Center for Biomedical Engineering, Department of Medicine,Brigham and Women’s Hospital, Harvard Medical School, Boston, MA, 02139,USA

Harvard-MIT Division of Health Sciences and Technology, MassachusettsInstitute of Technology, Cambridge, MA, 02139, USA

Laboratory for Innovations in MicroEngineering (LiME), Department ofMechanical Engineering, University of Victoria, Victoria, BC, Canada

Manuel Alatorre-Meda, 3B’s Research Group – University of Minho; Headquartersof the European Institute of Excellence on Tissue Engineering and RegenerativeMedicine, AvePark, Parque de Ciencia e Tecnologia, Zona Industrial da Gandra,4805-017 Barco GMR – Portugal

ICVS/3B’s – PT Government Associate Laboratory, Braga/Guimaraes,Portugal

Matilde Alonso, G.I.R. BIOFORGE (Group for Advanced Materials andNanobiotechnology), Universidad de Valladolid – CIBER-BBN, Spain

Luigi Ambrosio, Institute for Composite and Biomedical Materials IMCB-CNR,Italy

Department of Chemical Science and Materials Technology DCSMT – CNR,Italy

Muge Andac, Department of Environmental Engineering, Hacettepe University,Ankara, Turkey

Gerard A. Ateshian, Department of Biomedical Engineering, Columbia University,New York, NY, USA

xix

xx CONTRIBUTORS

Department of Mechanical Engineering, Columbia University, New York, NY,USA

Stephen F. Badylak, University of Pittsburgh School of MedicineMcGowan Institute for Regenerative Medicine

Elizabeth Rosado Balmayor, Experimental Trauma Surgery, Klinikum rechts derIsar, Technical University of Munich, Ismaninger Strasse 22, D-81675 Munich,Germany

Hernane S. Barud, Institute of Chemistry, Sao Paulo State University – UNESP, CP355 Araraquara-SP, 14801-970 – Brazil

Joseph J. Bellucci Department of Biomedical Engineering, Duke University,Durham, North Carolina, USA

Jayanta Bhattacharyya, Center for Biologically Inspired Materials and MaterialSystems, Duke University, Durham, North Carolina, USA

Aldo R. Boccaccini, Institute for Biomaterials, University of Erlangen-Nuremberg,91058 Erlangen, Germany

Assunta Borza Borzacchiello, Institute for Composite and Biomedical MaterialsIMCB-CNR, Italy

Jose Carlos Rodrıguez-Cabello, G.I.R. BIOFORGE (Group for Advanced Materi-als and Nanobiotechnology), Universidad de Valladolid – CIBER-BBN, Spain

Gabriela D. Carlos, 3B’s Research Group – University of Minho, PortugalICVS/3B’s – PT Government Associate Laboratory, Portugal

Pedro Pires Carvalho, 3B’s Research Group – University of Minho; Headquartersof the European Institute of Excellence on Tissue Engineering and RegenerativeMedicine, AvePark, Parque de Ciencia e Tecnologia, Zona Industrial da Gandra,4805-017 Barco GMR – Portuga

ICVS/3B’s PT Government Associated Lab, Braga/Guimaraes, Portugal

Guoping Chen, Tissue Regeneration Materials Group, International Center forMaterials Nanoarchitectonics, National Institute for Materials Science, 1-1Namiki, Tsukuba, Ibaraki 305-0044, Japan

Ashutosh Chilkoti, Center for Biologically Inspired Materials and Material Sys-tems, Duke University, Durham, North Carolina, USA

Department of Biomedical Engineering, Duke University, Durham, NorthCarolina, USA

Smadar Cohen, The Avram and Stella Goldstein-Goren Department of Biotechnol-ogy Engineering, Ben-Gurion University of the Negev, Beer-Sheva, Israel

The Center for Regenerative Medicine and Stem Cell (RMSC) Research, Ben-Gurion University of the Negev, Beer-Sheva, Israel

CONTRIBUTORS xxi

The Ilse Katz Institute for Nanoscale Science and Technology, Ben-GurionUniversity of the Negev, Beer-Sheva, Israel

Vitor M. Correlo, 3B’s Research Group – University of Minho; Headquarters ofthe European Institute of Excellence on Tissue Engineering and RegenerativeMedicine, AvePark, Parque de Ciencia e Tecnologia, Zona Industrial da Gandra,4805-017 Barco GMR – Portugal


Ana Costa-Pinto, 3B’s Research Group – University of Minho; Headquarters ofthe European Institute of Excellence on Tissue Engineering and RegenerativeMedicine, AvePark, Parque de Ciencia e Tecnologia, Zona Industrial da Gandra,4805-017 Barco GMR – Portugal


Marta L. Alves da Silva, 3B’s Research Group – University of Minho; Headquartersof the European Institute of Excellence on Tissue Engineering and RegenerativeMedicine, AvePark, Parque de Ciencia e Tecnologia, Zona Industrial da Gandra,4805-017 Barco GMR – Portugal

ICVS/3B’s PT Government Associate Laboratory

Israel Gonzalez de Torre, G.I.R. BIOFORGE (Group for Advanced Materials andNanobiotechnology), Universidad de Valladolid – CIBER-BBN

Adil Denizli, Department of Chemistry, Biochemistry Division, Hacettepe Univer-sity, Ankara, Turkey

Pieter J. Dijkstra, MIRA – Institute for Biomedical Technology and TechnicalMedicine, Department of Developmental Bioengineering, Faculty of Scienceand Technology, University of Twente, P.O. Box 217, 7500 AE Enschede, TheNetherlands

Alireza Dolatshahi-Pirouz, Center for Biomedical Engineering, Department ofMedicine, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA,02139, USA



Ana R. Duarte, 3B’s Research Group – University of Minho; Headquarters ofthe European Institute of Excellence on Tissue Engineering and RegenerativeMedicine, AvePark, Parque de Ciencia e Tecnologia, Zona Industrial da Gandra,4805-017 Barco GMR – Portugal


xxii CONTRIBUTORS

James Ferguson, Ludwig Boltzmann Institute for Experimental and Clinical Trau-matology, Donaueschingenstrasse 13, 1200 Vienna, Austria

Helena Ferreira, 3B’s Research Group – University of Minho; Headquarters ofthe European Institute of Excellence on Tissue Engineering and RegenerativeMedicine, AvePark, Parque de Ciencia e Tecnologia, Zona Industrial da Gandra,4805-017 Barco GMR – Portugal


Michael Floren, Department of Mechanical Engineering, University of Colorado atBoulder, Boulder, Colorado 80309

Igor Yu Galaev, DSM Biotechnology Center, Netherlands

Manuela E. Gomes, 3B’s Research Group – University of Minho; Headquartersof the European Institute of Excellence on Tissue Engineering and RegenerativeMedicine, AvePark, Parque de Ciencia e Tecnologia, Zona Industrial da Gandra,4805-017 Barco GMR – Portugal


Junkal Gutierrez, Depto. Ingenieria Quimica y del Medio Ambiente, EscuelaPolitecnica Donostia, Pza. Europa 1, 20018, Donostia-San Sebastian, Spain

M. David Harmon, Institute for Regenerative Engineering, University of Connecti-cut Health Center, Connecticut 06030, USA

The Raymond and Beverly Sackler Center for Biomedical, Biological, Physicaland Engineering Sciences, Connecticut 06030, USA

Department of Orthopaedic Surgery, University of Connecticut Health Center,Connecticut 06030, USA

Departments of Materials Science and Biomedical Engineering, University ofConnecticut, Connecticut 06269, USA

Philipp Heher, Ludwig Boltzmann Institute for Experimental and Clinical Trauma-tology, Donaueschingenstrasse 13, 1200 Vienna

Trauma Care Consult, Gonzagagasse 11/25, 1010 Vienna

Clark T. Hung, Department of Biomedical Engineering, Columbia University, NewYork, NY, USA

Courtney L. Jenkins, Department of Chemistry, Purdue University, West Lafayette,IN

Marcel Karperien, MIRA – Institute for Biomedical Technology and TechnicalMedicine, Department of Developmental Bioengineering, Faculty of Science andTechnology, University of Twente, P.O. Box 217, 7500 AE Enschede, The Nether-lands

Naoki Kawazoe, Tissue Regeneration Materials Unit, International Center for Mate-rials Nanoarchitectonics, National Institute for Materials Science, 1-1 Namiki,Tsukuba, Ibaraki 305-0044, Japan

CONTRIBUTORS xxiii

Markus Kerbl, Ludwig Boltzmann Institute for Experimental and Clinical Trauma-tology, Donaueschingenstrasse 13, 1200 Vienna

Ali Khademhosseini, Center for Biomedical Engineering, Department of Medicine,Brigham and Women’s Hospital, Harvard Medical School, Boston, MA, 02139,USA



Sangamesh G. Kumbar, Institute for Regenerative Engineering, University of Con-necticut Health Center, Connecticut 06030, USA




Subhas C. Kundu, Department of Biotechnology Indian Institute of Technology,Kharagpur-721301, India

Cato T. Laurencin, Institute for Regenerative Engineering, University of Connecti-cut Health Center, Connecticut 06030, USA




Lorena del Rosario Lizarraga-Valderrama, Applied Biotechnology ResearchGroup, Faculty of Science and Technology, University of Westminster, LondonW1W 6UW, UK

Ricardo Londono, University of Pittsburgh School of MedicineMcGowan Institute for Regenerative Medicine

Wilton R. Lustri, University Center of Araraquara- UNIARA, Araraquara-SP,Brazil

Joao F. Mano, 3B’s Research Group – University of Minho; Headquarters ofthe European Institute of Excellence on Tissue Engineering and RegenerativeMedicine, AvePark, Parque de Ciencia e Tecnologia, Zona Industrial da Gandra,4805-017 Barco GMR – Portugal


xxiv CONTRIBUTORS

Ana L. Marques, 3B’s Research Group – University of Minho; Headquarters ofthe European Institute of Excellence on Tissue Engineering and RegenerativeMedicine, AvePark, Parque de Ciencia e Tecnologia, Zona Industrial da Gandra,4805-017 Barco GMR – Portugal

ICVS/3B’s – PT Government Associate Laboratory, Portugal

Albino Martins, 3B’s Research Group – University of Minho; Headquarters ofthe European Institute of Excellence on Tissue Engineering and RegenerativeMedicine, AvePark, Parque de Ciencia e Tecnologia, Zona Industrial da Gandra,4805-017 Barco GMR – Portugal


Adnan Memic, Center for Biomedical Engineering, Department of Medicine,Brigham and Women’s Hospital, Harvard Medical School, Boston, MA, 02139,USA


Center of Nanotechnology, King Abdulaziz University, Jeddah, 21589, SaudiArabia

Heather J. Meredith, School of Materials Engineering, Purdue University, WestLafayette, IN

Claudio Migliaresi, Department of Industrial Engineering and BIOtech ResearchCentre, University of Trento, Italy

European Institute of Excellence on Tissue Engineering and RegenerativeMedicine, Trento, Italy

Joana Moreira-Silva, 3B’s Research Group – University of Minho; Headquartersof the European Institute of Excellence on Tissue Engineering and RegenerativeMedicine, AvePark, Parque de Ciencia e Tecnologia, Zona Industrial da Gandra,4805-017 Barco GMR – Portugal


Antonella Motta, Department of Industrial Engineering and BIOtech Research Cen-tre, University of Trento, Italy

European Institute of Excellence on Tissue Engineering and RegenerativeMedicine, Trento, Italy

Sunita Nayak, Department of Biotechnology Indian Institute of Technology,Kharagpur – 721301, India

Nuno M. Neves, 3B’s Research Group – University of Minho; Headquarters ofthe European Institute of Excellence on Tissue Engineering and RegenerativeMedicine, AvePark, Parque de Ciencia e Tecnologia, Zona Industrial da Gandra,4805-017 Barco GMR – Portugal


CONTRIBUTORS xxv

Mehdi Nikkhah, Center for Biomedical Engineering, Department of Medicine,Brigham and Women’s Hospital, Harvard Medical School, Boston, MA, 02139,USA


School of Biological and Health Systems Engineering (SBHSE), Arizona StateUniversity, Tempe, AZ 85287, USA

Adam B. Nover, Department of Biomedical Engineering, Columbia University, NewYork, NY, USA

Joaquim Miguel Oliveira, 3B’s Research Group – University of Minho; Headquar-ters of the European Institute of Excellence on Tissue Engineering and Regen-erative Medicine, AvePark, Parque de Ciencia e Tecnologia, Zona Industrial daGandra, 4805-017 Barco GMR – Portugal


Bijal Panchal, Applied Biotechnology Research Group, Faculty of Science andTechnology, University of Westminster, London W1W 6UW, UK

Arghya Paul, Center for Biomedical Engineering, Department of Medicine,Brigham and Women’s Hospital, Harvard Medical School, Boston, MA, 02139,USA



Department of Chemical and Petroleum Engineering, Bioengineering Program,University of Kansas, KS, USA.

Maristela F.S. Peres, Institute of Chemistry, Sao Paulo State University – UNESP,CP 355 Araraquara-SP, 14801-970, Brazil

A. Hari Reddi, Ellison Center for Tissue Regeneration, Department of OrthopaedicSurgery, University of California Davis, School of Medicine, Sacramento, Cali-fornia 95817, USA

Heinz Redl, Ludwig Boltzmann Institute for Experimental and Clinical Traumatol-ogy, Donaueschingenstrasse 13, 1200 Vienna, Austria

Trauma Care Consult, Gonzagagasse 11/25, 1010 Vienna, Austria

Rui L. Reis, 3B’s Research Group – University of Minho; Headquarters of the Euro-pean Institute of Excellence on Tissue Engineering and Regenerative Medicine,AvePark, Parque de Ciencia e Tecnologia, Zona Industrial da Gandra, 4805-017Barco GMR – Portugal


Sidney J.L. Ribeiro, Institute of Chemistry, Sao Paulo State University – UNESP,CP 355 Araraquara-SP, 14801-970, Brazil

xxvi CONTRIBUTORS

Brendan L. Roach, Department of Biomedical Engineering, Columbia University,New York, NY, USA

Marcia Rodrigues, 3B’s Research Group – University of Minho; Headquarters ofthe European Institute of Excellence on Tissue Engineering and RegenerativeMedicine, AvePark, Parque de Ciencia e Tecnologia, Zona Industrial da Gandra,4805-017 Barco GMR – Portugal


Ipsita Roy, Applied Biotechnology Research Group, Faculty of Science and Tech-nology, University of Westminster, London W1W 6UW, UK

Luisa Russo, Institute for Composite and Biomedical Materials IMCB-CNR, Italy

Emil Ruvinov, The Avram and Stella Goldstein-Goren Department of Biotechnol-ogy Engineering, Ben-Gurion University of the Negev, Beer-Sheva, Israel

Ryosuke Sakata, Ellison Center for Tissue Regeneration, Department ofOrthopaedic Surgery, University of California Davis, School of Medicine,Sacramento, California 95817, USA

Mercedes Santos, G.I.R. BIOFORGE (Group for Advanced Materials andNanobiotechnology), Universidad de Valladolid – CIBER-BBN, Spain

Tircia C. Santos, 3B’s Research Group – University of Minho; Headquarters ofthe European Institute of Excellence on Tissue Engineering and RegenerativeMedicine, AvePark, Parque de Ciencia e Tecnologia, Zona Industrial da Gandra,4805-017 Barco GMR – Portugal


Sybele Saska, Institute of Chemistry, Sao Paulo State University – UNESP, CP 355Araraquara-SP, 14801-970, Brazil

Tiago H. Silva 3B’s Research Group – University of Minho; Headquarters ofthe European Institute of Excellence on Tissue Engineering and RegenerativeMedicine, AvePark, Parque de Ciencia e Tecnologia, Zona Industrial da Gandra,4805-017 Barco GMR – Portugal


Joana Silva-Correia, 3B’s Research Group – University of Minho; Headquartersof the European Institute of Excellence on Tissue Engineering and RegenerativeMedicine, AvePark, Parque de Ciencia e Tecnologia, Zona Industrial da Gandra,4805-017 Barco GMR – Portugal


Pranav K. Singh, College of Dairy Science & Technology, GADVASU, Ludhiana,India

Harjinder Singh, Riddet Institute, Massey University, Palmerston North, NewZealand

CONTRIBUTORS xxvii

Ana Maria Testera, G.I.R. BIOFORGE (Group for Advanced Materials andNanobiotechnology), Universidad de Valladolid – CIBER-BBN, Spain

Agniezska Tercjak, Depto. Ingenieria Quimica y del Medio Ambiente, EscuelaPolitecnica Donostia, Pza. Europa 1, 20018, Donostia-San Sebastian, Spain

Christy Thomas, Applied Biotechnology Research Group, Faculty of Science andTechnology, University of Westminster, London W1W 6UW, UK

Mark Van Dyke, Associate Professor, Virginia Tech – Wake Forest School ofBiomedical Engineering and Sciences, Virginia Polytechnic Institute and StateUniversity, 323 Kelly Hall (0298), Blacksburg, VA 24061, USA

Martijn van Griensven, Experimental Trauma Surgery, Klinikum rechts der Isar,Technical University of Munich, Ismaninger Strasse 22, D-81675 Munich,Germany

Nicola Volpi, Department of Life Sciences, University of Modena and ReggioEmilia, Italy

Rong Wang, MIRA – Institute for Biomedical Technology and Technical Medicine,Department of Developmental Bioengineering, Faculty of Science and Technol-ogy, University of Twente, P.O. Box 217, 7500 AE Enschede, The Netherlands

Jonathan J. Wilker, Department of Chemistry, Purdue University, West Lafayette,IN, USA

School of Materials Engineering, Purdue University, West Lafayette, IN, USA

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BIOMATERIALS FROM NATURE FOR ADVANCED DEVICES AND … · biomaterials from nature for advanced devices and therapies edited by nuno m. neves and rui l. reis