<p>CONTRIBUTORS xix</p> <p>PREFACE xxix</p> <p><b>PART I 1 Collagen-Based Porous Scaffolds for Tissue Engineering 3<br /></b><i>Guoping Chen and Naoki Kawazoe</i></p> <p>1.1 Introduction, 3</p> <p>1.2 Collagen Sponges, 4</p> <p>1.3 Collagen Sponges with Micropatterned Pore Structures, 7</p> <p>1.4 Collagen Sponges with Controlled Bulk Structures, 10</p> <p>1.5 Hybrid Scaffolds, 12</p> <p>1.6 Conclusions, 13</p> <p>References, 14</p> <p><b>2 Marine Collagen Isolation and Processing Envisaging Biomedical Applications 16</b><br /><i>Joana Moreira-Silva, Gabriela S. Diogo, Ana L. P. Marques, Tiago H. Silva, and Rui L. Reis</i></p> <p>2.1 Introduction, 16</p> <p>2.2 Extraction of Collagen from Marine Sources, 18</p> <p>2.3 Collagen Characterization, 22</p> <p>2.4 Marine Collagen Wide Applications, 25</p> <p>2.5 Final Remarks, 32</p> <p>Acknowledgements, 34</p> <p>References, 34</p> <p><b>3 Gelatin-Based Biomaterials for Tissue Engineering and Stem Cell Bioengineering 37</b><br /><i>Mehdi Nikkhah, Mohsen Akbari, Arghya Paul, Adnan Memic, Alireza Dolatshahi-Pirouz, and Ali Khademhosseini</i></p> <p>3.1 Introduction, 37</p> <p>3.2 Crosslinking of Gelatin, 38</p> <p>3.3 Physical Properties of Gelatin, 39</p> <p>3.4 Application of Gelatin-Based Biomaterials in Tissue Engineering, 40</p> <p>3.5 Gelatin for Stem Cell Therapy, 45</p> <p>3.6 Application of Gelatin in Delivery Systems, 49</p> <p>3.7 Conclusion and Perspectives, 50</p> <p>Acknowledgements, 50</p> <p>Abbreviations, 50</p> <p>References, 51</p> <p><b>4 Hyaluronic Acid-Based Hydrogels on a Micro and Macro Scale 63</b><br /><i>A. Borzacchiello, L. Russo, and L. Ambrosio</i></p> <p>4.1 Classification and Structure of Hydrogels, 63</p> <p>4.2 Hyaluronic Acid, 65</p> <p>4.3 Hydrogel Mechanical Properties, 66</p> <p>4.4 HA-Based Hydrogel for Biomedical Applications, 70</p> <p>References, 75</p> <p><b>5 Chondroitin Sulfate as a Bioactive Macromolecule for Advanced Biological Applications and Therapies 79</b><br /><i>Nicola Volpi</i></p> <p>5.1 CS Structure, 81</p> <p>5.2 Biological Roles of CS, 81</p> <p>5.3 Osteoarthritis Treatment, 84</p> <p>5.4 Cardio-Cerebrovascular Disease, 84</p> <p>5.5 Tissue Regeneration and Engineering, 85</p> <p>5.6 Chondroitin Sulfate-Polymer Conjugates, 86</p> <p>5.7 Conclusions and Future Perspectives, 87</p> <p>References, 88</p> <p><b>6 Keratin 93</b><br /><i>Mark Van Dyke</i></p> <p>6.1 Introduction, 93</p> <p>6.2 Preparation of Keratoses, 98</p> <p>6.3 Preparation of Kerateines, 100</p> <p>6.4 Oxidative Sulfitolysis, 101</p> <p>6.5 Summary, 102</p> <p>References, 102</p> <p><b>7 Elastin-Like Polypeptides: Bio-Inspired Smart Polymers for Protein Purification, Drug Delivery and Tissue Engineering 106</b><br /><i>Jayanta Bhattacharyya, Joseph J. Bellucci, and Ashutosh Chilkoti</i></p> <p>7.1 Introduction, 106</p> <p>7.2 Recombinant Protein Production Using ELPs as Purification Tags, 107</p> <p>7.3 Delivery of Therapeutics with ELPs, 113</p> <p>7.4 Tissue Engineering with ELPs, 119</p> <p>7.5 Conclusions, 122</p> <p>Acknowledgements, 122</p> <p>Abbreviations, 122</p> <p>References, 123</p> <p><b>8 Silk: A Unique Family of Biopolymers 127</b><br /><i>A. Motta, M. Floren, and C. Migliaresi</i></p> <p>8.1 Introduction, 127</p> <p>8.2 Main Silk Polymers, 129</p> <p>8.3 Fibroin Basic Processing: Regenerated Silk Fibroin, 131</p> <p>8.4 Materials Fabrication of Silk Proteins, 131</p> <p>8.5 Advanced Material Applications of Silks, 135</p> <p>8.6 Conclusion, 136</p> <p>References, 137</p> <p><b>9 Silk Protein Sericin: Promising Biopolymer for Biological and Biomedical Applications 142</b><br /><i>Sunita Nayak and Subhas C. Kundu</i></p> <p>9.1 Introduction, 142</p> <p>9.2 Sericin Extraction and Processing, 146</p> <p>9.3 Potential Applications of Sericin, 147</p> <p>9.4 Immunogenicity and Toxicity of Sericin, 152</p> <p>9.5 Conclusion, 153</p> <p>Acknowledgements, 154</p> <p>References, 154</p> <p><b>10 Fibrin 159</b><br /><i>Markus Kerbl, Philipp Heher, James Ferguson, and Heinz Redl</i></p> <p>10.1 Introduction, 159</p> <p>10.2 Fibrin Clotting, 160</p> <p>10.3 Fibrin Degradation, 160</p> <p>10.4 Fibrin Glue, 163</p> <p>10.5 Conclusion, 170</p> <p>Acknowledgement, 171</p> <p>References, 171</p> <p><b>11 Casein Proteins 176</b><br /><i>Pranav K. Singh and Harjinder Singh</i></p> <p>11.1 Introduction, 176</p> <p>11.2 Structures and Properties of Casein, 178</p> <p>11.3 Interaction of Caseins with Metal Ions, 184</p> <p>11.4 Conclusions, 185</p> <p>References, 186</p> <p><b>12 Biomaterials from Decellularized Tissues 190</b><br /><i>Ricardo Londono and Stephen F. Badylak</i></p> <p>12.1 Introduction, 190</p> <p>12.2 Host Response to Implanted ECM-Derived Biomaterials, 196</p> <p>References, 199</p> <p><b>13 Demineralized Bone Matrix: A Morphogenetic Extracellular Matrix 211</b><br /><i>A. Hari Reddi and Ryosuke Sakata</i></p> <p>13.1 Introduction, 211</p> <p>13.2 Demineralized Bone Matrix (DBM), 211</p> <p>13.3 From DBM to Bone Morphogenetic Proteins (BMPs), 213</p> <p>13.4 BMPs Bind to Extracellular Matrix, 216</p> <p>13.5 BMP Receptors, 216</p> <p>13.6 Future Perspectives, 218</p> <p>Acknowledgements, 218</p> <p>References, 218</p> <p>PART II</p> <p><b>14 Recent Developments on Chitosan Applications in Regenerative Medicine 223</b><br /><i>Ana Rita C. Duarte, Vitor M. Correlo, Joaquim M. Oliveira, and Rui L. Reis</i></p> <p>14.1 Introduction, 223</p> <p>14.2 Chitosan and Derivatives, 224</p> <p>14.3 Regenerative Medicine Applications of Chitosan, 227</p> <p>14.4 Processing Methodologies, 231</p> <p>14.5 Final Remarks, 236</p> <p>Acknowledgments, 237</p> <p>References, 237</p> <p><b>15 Starch-Based Blends in Tissue Engineering 244</b><br /><i>P.P. Carvalho, M.T. Rodrigues, R.L. Reis, and M.E. Gomes</i></p> <p>15.1 Introduction, 244</p> <p>15.2 Starch, 245</p> <p>15.3 Modification of Starch for Biomedical Applications, 247</p> <p>15.4 Starch-Based Blends, 248</p> <p>15.5 Conclusions and Future Perspectives, 254</p> <p>References, 255</p> <p><b>16 Agarose Hydrogel Characterization for Regenerative Medicine Applications: Focus on Engineering Cartilage 258</b><br /><i>Brendan L. Roach, Adam B. Nover, Gerard A. Ateshian, and Clark T. Hung</i></p> <p>16.1 The Foundations of Agarose, 258</p> <p>16.2 Structure-Function Relationships of Agarose Hydrogels, 259</p> <p>16.3 Agarose as a Tissue Engineering Scaffold, 261</p> <p>16.4 Agarose in the Clinic, 266</p> <p>16.5 A Scaffold to Build On, 267</p> <p>Acknowledgements, 268</p> <p>References, 268</p> <p><b>17 Bioengineering Alginate for Regenerative Medicine Applications 274</b><br /><i>Emil Ruvinov and Smadar Cohen</i></p> <p>17.1 Introduction, 274</p> <p>17.2 Regenerative Medicine: Definition and Strategies, 275</p> <p>17.3 Alginate Biomaterial, 277</p> <p>17.4 Alginate Implant: First in Man Trial for Prevention of Heart Failure, 281</p> <p>17.5 Alginate Hydrogel as a Vehicle for Stem Cell Delivery and Retention, 284</p> <p>17.6 Engineering Alginate-Based Cell Microenvironments, 287</p> <p>17.7 Alginate Hydrogel Carrier for Growth Factor Delivery, 289</p> <p>17.8 Engineering Alginate for Affinity Binding and Presentation of Heparin-Binding Growth Factors, 292</p> <p>References, 300</p> <p><b>18 Dextran 307</b><br /><i>Rong Wang, Pieter J. Dijkstra, and Marcel Karperien</i></p> <p>18.1 Introduction, 307</p> <p>18.2 Structure and Properties, 308</p> <p>18.3 Dextran Derivatives, 310</p> <p>18.4 Dextran Copolymers, 314</p> <p>18.5 Degradation, 316</p> <p>18.6 Outlook, 316</p> <p>References, 316</p> <p><b>19 Gellan Gum-based Hydrogels for Tissue Engineering Applications 320</b><br /><i>Joana Silva-Correia, Joaquim Miguel Oliveira, and Rui Lu´ys Reis</i></p> <p>19.1 Introduction, 320</p> <p>19.2 Gellan Gum and its Derivatives, 322</p> <p>19.3 Tissue Engineering Applications, 325</p> <p>19.4 Final Remarks, 331</p> <p>Acknowledgments, 332</p> <p>References, 332</p> <p>PART III</p> <p><b>20 Biomedical Applications of Polyhydroxyalkanoates 339</b><br /><i>L.R. Lizarraga-Valderrama, B. Panchal, C. Thomas, A.R. Boccaccini, and I. Roy</i></p> <p>20.1 Introduction, 339</p> <p>20.2 Skin Tissue Engineering, 341</p> <p>20.3 Nerve Tissue Engineering, 344</p> <p>20.4 Cardiac Tissue Engineering, 348</p> <p>20.5 Dental Tissue Engineering, 356</p> <p>20.6 Bone Tissue Engineering, 358</p> <p>20.7 Cartilage Tissue Engineering, 366</p> <p>20.8 Osteochondral Tissue Engineering, 368</p> <p>20.9 Drug Delivery, 370</p> <p>20.10 Conclusions and the Future Potential of PHAs in Biomedical Applications, 373</p> <p>References, 373</p> <p><b>21 Bacterial Cellulose 384</b><br /><i>Hernane S. Barud, Junkal Gutierrez, Wilton R. Lustri, Maristela F.S. Peres, Sidney J.L. Ribeiro, Sybele Saska, and Agniezska Tercjak</i></p> <p>21.1 Introduction, 384</p> <p>21.2 BC Dressings, 385</p> <p>21.3 Bacterial Cellulose for Tissue Engineering and Regenerative Medicine, 388</p> <p>21.4 Concluding Remarks, 393</p> <p>Acknowledgments, 394</p> <p>References, 394</p> <p>PART IV</p> <p><b>22 Molecularly Imprinted Cryogels for Protein Purification 403</b><br /><i>Müge Andac¸, Igor Yu Galaev, and Adil Denizli</i></p> <p>22.1 Introduction, 403</p> <p>22.2 Molecularly Imprinted Cryogels for Protein Purification, 405</p> <p>22.3 Some Selected Applications of Molecularly Imprinted Cryogels (MIC) for Macromolecules, 414</p> <p>22.4 Concluding Remarks and Future Perspectives, 421</p> <p>References, 423</p> <p><b>23 Immunogenic Reaction of Implanted Biomaterials from Nature 429</b><br /><i>Martijn Van Griensven and Elizabeth Rosado Balmayor</i></p> <p>23.1 Introduction, 429</p> <p>23.2 Implantation Leads to Tissue Injury, 430</p> <p>23.3 Inflammatory Responses, 431</p> <p>23.4 Foreign Body Reaction, 433</p> <p>23.5 Immunogenic Reactions Towards Natural Biomaterials, 435</p> <p>23.6 Final Remarks, 438</p> <p>References, 438</p> <p><b>24 Chemical Modification of Biomaterials from Nature 444</b><br /><i>J.C. Rodr´yguez Cabello, I. Gonz´alez De Torre, M. Santos, A.M. Testera, and M. Alonso</i></p> <p>24.1 Protein Modification, 444</p> <p>24.2 Lipid Modifications, 451</p> <p>24.3 Polysaccharide Chemical Modifications, 457</p> <p>References, 466</p> <p>PART V</p> <p><b>25 Processing of Biomedical Devices for Tissue Engineering and Regenerative Medicine Applications 477</b><br /><i>Vitor M. Correlo, Albino Martins, Nuno M. Neves, and Rui L. Reis</i></p> <p>25.1 Introduction, 477</p> <p>25.2 Processing Techniques of Naturally Derived Biomaterial, 478</p> <p>25.3 Processing Techniques of Natural-Based Polymeric Blends, 483</p> <p>References, 487</p> <p><b>26 General Characterization of Physical Properties of Natural-Based Biomaterials 494</b><br /><i>Manuel Alatorre-Meda and Joäo F. Mano</i></p> <p>26.1 Introduction, 494</p> <p>26.2 Bulk Properties, 495</p> <p>26.3 Surface Properties, 507</p> <p>26.4 Concluding Remarks, 512</p> <p>Acknowledgments, 512</p> <p>References, 512</p> <p><b>27 General Characterization of Chemical Properties of Natural-Based Biomaterials 517</b><br /><i>Manuel Alatorre-Meda and Joäo F. Mano</i></p> <p>27.1 Introduction, 517</p> <p>27.2 Molecular Weight and Elemental Composition, 518</p> <p>27.3 Physiological Degradation, 524</p> <p>27.4 Concluding Remarks, 527</p> <p>Acknowledgments, 529</p> <p>References, 529</p> <p><b>28 In Vitro Biological Testing in the Development of New Devices 532</b><br /><i>Marta L. Alves Da Silva, Albino Martins, Ana Costa-Pinto, Rui L. Reis, and Nuno M. Neves</i></p> <p>28.1 Introduction, 532</p> <p>28.2 Cytotoxicity Assays, 533</p> <p>28.3 Evaluation of Cell Morphology and Distribution, 533</p> <p>28.4 Cell Viability Assays, 535</p> <p>28.5 Cell Proliferation Assays, 536</p> <p>28.6 Biochemical Analysis, 537</p> <p>28.7 Genotypic Expression Analysis, 541</p> <p>28.8 Histological Assessment, 542</p> <p>28.9 In Vitro Engineered Tissues, 543</p> <p>28.10 Concluding Remarks, 548</p> <p>References, 548</p> <p><b>29 Advanced In-Vitro Cell Culture Methods Using Natural Biomaterials 551</b><br /><i>Marta L. Alves Da Silva, Rui L. Reis, and Nuno M. Neves</i></p> <p>29.1 Introduction, 551</p> <p>29.2 Bioreactors, 552</p> <p>29.3 Hypoxia, 553</p> <p>29.4 Co-Cultures, 555</p> <p>29.5 Transfection, 555</p> <p>29.6 Nanoparticles and Related Systems, 558</p> <p>29.7 Concluding Remarks, 559</p> <p>References, 559</p> <p><b>30 Testing Natural Biomaterials in Animal Models 562</b><br /><i>Ana Costa-Pinto, Tírcia C. Santos, Nuno M. Neves, and Rui L. Reis</i></p> <p>30.1 Laboratory Animals as Tools in Biomaterials Testing, 562</p> <p>30.2 Inflammation and Host Reaction, 564</p> <p>30.3 Animal Models for Tissue Engineering, 568</p> <p>30.4 Final Remarks, 574</p> <p>References, 575</p> <p>PART VI</p> <p><b>31 Delivery Systems Made of Natural-Origin Polymers for Tissue Engineering and Regenerative Medicine Applications 583</b><br /><i>Albino Martins, Helena Ferreira, Rui L. Reis, and Nuno M. Neves</i></p> <p>31.1 Introduction, 583</p> <p>31.2 Advantages and Disadvantages of Natural Polymers-Based Delivery Systems, 585</p> <p>31.3 Fundamentals of Drug Delivery, 586</p> <p>31.4 In Vitro and In Vivo Applications of Natural-Based Delivery Systems, 591</p> <p>31.5 Concluding Remarks, 601</p> <p>References, 602</p> <p><b>32 Translational Research into New Clinical Applications 612</b><br /><i>M. David Harmon and Sangamesh G. Kumbar</i></p> <p>32.1 Introduction, 612</p> <p>32.2 Cardiovascular System Applications, 613</p> <p>32.3 Integumentary System Applications, 616</p> <p>32.4 Musculoskeletal System Applications, 618</p> <p>32.5 Nervous System Applications, 619</p> <p>32.6 Respiratory System Applications, 621</p> <p>32.7 Gastrointestinal System Applications, 622</p> <p>32.8 From Idea to Product, 624</p> <p>Acknowledgements, 626</p> <p>References, 626</p> <p><b>33 Challenges and Opportunities of Natural Biomaterials for Advanced Devices and Therapies 629</b><br /><i>R.L. Reis and N.M. Neves</i></p> <p>33.1 Introduction, 629</p> <p>33.2 Challenges of Natural Biomaterials, 630</p> <p>33.3 Opportunities of Natural Biomaterials, 631</p> <p>33.4 Final Remarks, 631</p> <p>References, 632</p> <p><b>34 Adhesives Inspired by Marine Mussels 634</b><br /><i>Courtney L. Jenkins, Heather J. Meredith, and Jonathan J. Wilker</i></p> <p>34.1 Introduction, 634</p> <p>34.2 Requirements for a Bioadhesive, 635</p> <p>34.3 Marine Mussels, 636</p> <p>34.4 Bulk Adhesion Testing, 638</p> <p>34.5 Extracted Mussel Adhesive Proteins, 640</p> <p>34.6 Mimics of Mussel Adhesive, 641</p> <p>34.7 Conclusions, 645</p> <p>Acknowledgement, 645</p> <p>References, 645</p> <p><b>35 Final Comments and Remarks 649</b><br /><i>R.L. Reis and N.M. Neves</i></p> <p>INDEX 651</p>