Clarisse Ribeiro is Assistant Professor at the Department of Physics of the University of Minho, Portugal. Unai Silván is Research Associate at the Basque Center for Materials, Applications and Nanostructures in Leioa, Spain. Senentxu Lanceros-Méndez is Research Professor and Scientific Director of the Basque Center for Materials, Applications and Nanostructures in Leioa, Spain. His work is focused in the area of polymer-based smart materials for sensors and actuators, energy, and biomedical applications.

• Preface xiPart ISmart and Multifunctional Materials for Tissue Engineering 11 Electroactive Materials for Tissue Engineering 3Teresa Marques-Almeida, Estela O. Carvalho, Unai Silvan, Senentxu Lanceros-Méndez, and Clarisse Ribeiro1.1 Introduction 31.2 Relevance of the Electrical Signals in the Human Body 41.3 Relevance of the Electrical Signals in Cell Processes 71.4 Types of Electroactive Materials 101.4.1 Conductive Materials 101.4.2 Piezoelectric Materials 121.4.3 Magnetoelectric Materials 141.4.4 Thermoelectric Materials 151.5 Relevance of the Material’s Architecture 171.5.1 Films 171.5.2 Electrospun fibers 191.5.3 3D Porous Scaffolds 201.5.4 Hydrogels 211.6 Final Remarks 22Acknowledgments 22References 222 Piezoelectric, Triboelectric and Magnetoactive materials for Tissue Engineering 35Pratap N. Soni and Dipankar Mandal2.1 Introduction 352.1.1 Working Principle 362.1.1.1 Piezoelectric 362.1.1.2 Triboelectric 392.1.1.3 Magnetoactive 422.2 Piezoelectric, Triboelectric, and Magnetoactive Materials in Tissue Engineering 432.2.1 Piezoelectric Materials in Tissue Engineering 452.2.2 Triboelectric Materials in Tissue Engineering 602.2.3 Magnetoactive Materials in Tissue Engineering 692.3 Summary and Conclusion 74References 763 Shape-memory Polymers for Tissue Engineering Applications 91Fangyuan Zheng, Ane García-García, Isabel Moreno-Benítez, Leire Ruiz-Rubio, Leyre Pérez-Álvarez, and José L. Vilas-Vilela3.1 Introduction 913.2 Shape-memory Effect in Polymers 933.3 Shape-memory Mechanism and Molecular Structure 953.3.1 SMPs Based on Phase Transitions 973.3.2 SMPs Based on Supramolecular Interactions 983.3.3 SMPs Based on Dynamic Interactions 993.4 SMP Triggered by Stimuli Different to Temperature 1003.4.1 Photo-triggered SMPs 1013.4.2 Solvent and Other Triggers of SMPs 1023.5 Requirements of SMPs as Scaffolds 1043.5.1 Biocompatibility 1053.5.2 Mechanical Properties 1053.5.3 Biodegradability 1063.5.4 Porosity 1073.5.5 Sterilizability 1083.5.6 Motion Requirement 1093.6 Tissues-Specific Requirements 1103.6.1 Bone Tissues 1103.6.2 Cardiovascular Tissues 1113.6.3 Cartilage Tissues 1123.6.4 Neural Tissue 1123.7 Shape-memory Homopolymers and Copolymers for Tissue Engineering 1133.8 Shape-memory Composites for Tissue Engineering 1213.9 Shape-memory Hydrogels for Tissue Engineering Applications 1293.10 Conclusions and Future Trends 133References 1354 Photoresponsive Materials for Tissue Engineering 149Mikel Rincón-Iglesias, Cristian Mendes-Felipe, Senentxu Lanceros-Mendez, and Javier Reguera4.1 Introduction 1494.2 Photoisomerizable Materials 1514.3 Photopolymerizable Materials 1544.4 Photocleavable Materials 1584.5 Photothermal Materials 1634.6 Conclusions and Outlook 167Acknowledgments 168References 1685 Controlled Degradation of Stimuli-Responsive Materials for Tissue Engineering 181Teresa Carranza, Ainhoa Irastorza, Ander Izeta, Pedro Guerrero, Koro de la Caba, and Alaitz Etxabide5.1 Introduction 1815.2 Degradation Mechanisms 1835.2.1 Biological-Activity-Mediated Degradation 1835.2.2 Chemical Degradation 1865.2.3 Physical Degradation 1895.3 Degradation Measurement Techniques 1915.3.1 Characterization of the Degradation Process In Vitro 1915.3.2 Characterization of the Degradation Process In Vivo 1945.3.3 Characterization of Degradation Products 1965.3.3.1 Identification and Quantification of Degradation Products In Vitro 1965.3.3.2 Cytotoxicity Evaluation In Vitro 1975.3.3.3 Toxicokinetic Studies In Vivo 1985.3.3.4 Local Effects after Implantation 1995.4 Conclusions and Future Perceptions 200References 201Part II Tissue Regeneration Strategies Based on Smart and Active Biomaterials 2116 Active Biomaterials for Bone Tissue Regeneration 213Martina Marcotulli, Lucia Iafrate, Efsun Senturk, Andrada Pica, Franco Marinozzi, Fabiano Bini, Giancarlo Ruocco, Chiara Scognamiglio, and Gianluca Cidonio6.1 Introduction 2136.2 Ultrasound-Based Strategies for the Engineering of Biomaterials for Bone Regeneration 2146.2.1 Ultrasound in Regenerative Medicine 2146.2.2 Bioeffects Induced by US 2156.2.2.1 Differentiation 2156.2.2.2 Proliferation 2176.2.2.3 Migration 2176.2.3 US-stimulated Biomaterials for Tissue Engineering Applications 2176.2.3.1 Acoustofluidics 2186.2.3.2 US-triggered Release of Drugs 2196.2.3.3 US-triggered Piezoelectric Biomaterials 2206.2.3.4 US-assisted Synthesis 2206.2.4 Future Development for US-driven Bone Regeneration 2216.3 Magnetic Forces to Assist Biomaterials in Bone Formation 2216.3.1 Magnetic Materials in Regenerative Medicine 2216.3.1.1 Magnetic Fields 2226.3.1.2 Magnetic Materials 2226.3.1.3 Biosafety of Magnetic Forces 2226.3.2 Production and Activation of Magnetic Biomaterials 2236.3.3 Magnetic Stimulation of Biomaterials 2236.3.3.1 Magnetism and Electricity Correlation on Bone Healing 2236.3.3.2 Magnetic Hyperthermia 2246.3.4 Magnetically Induced Effects in Bone Tissues 2246.3.4.1 Magnetic to Mechanical Cell Stimulation 2246.3.4.2 Targeted Release of Growth Factors or Drugs 2256.3.5 Harnessing Magnetic Biomaterials to Tackle Bone Regeneration 2266.3.5.1 Bone Fractures Healing by Magnetic Biomaterials 2266.3.5.2 Magnetic Therapy for Osteoporosis 2266.3.5.3 Magnetic-based Treatments for Bone Cancer 2266.3.6 Future Perspectives for Magnetic Stimuli of Bone Repair 2276.4 Piezoelectric Materials as Biomimetic Substrate for Skeletal Engineering 2276.4.1 Bone is a Piezoelectric Material 2276.4.2 Collagen Fibrils and the Role in Bone Piezoelectric Behavior 2286.4.3 Biomimetic Bone Piezomaterials 2296.4.4 New Approaches Harnessing Piezoelectric Behavior of Skeletal Tissue 2316.4.5 Future Outlook of Piezoelectric Bioactive Skeletal Materials 232References 2337 Muscle and Heart Tissue Regeneration Based on Stimuli-Responsive Materials 247Sylvie Ribeiro, Clarisse Ribeiro, and Senentxu Lanceros Mendez7.1 Introduction 2477.2 Skeletal and Cardiac Muscle Organization 2487.2.1 Skeletal Muscle Tissue 2487.2.1.1 The Anatomy of the Vasculature in Skeletal Muscle 2507.2.1.2 Nerve Supply in Skeletal Muscle 2517.2.2 Cardiac Muscle Tissue 2527.2.2.1 Other Relevant Components of Cardiac Tissue 2537.3 Stimuli-Responsive Materials for Muscle Tissue Engineering 2547.3.1 External Regulated Stimuli-Responsive Materials in Muscle Tissue Regeneration 2567.3.1.1 Temperature-Responsive Materials 2567.3.1.2 Light-Responsive Materials 2577.3.1.3 Electro-Responsive Materials 2587.3.1.4 Ultrasound Stimuli-Responsive Materials 2617.3.1.5 Magnetic Stimuli-Responsive Materials 2627.3.2 Internally Regulated Stimuli-Responsive Materials for Muscle Tissue Regeneration 2647.3.2.1 Redox-Responsive Materials 2647.3.2.2 pH-Responsive Materials 2657.4 Conclusions and Future Perspectives 268Acknowledgments 268References 2698 Neural Tissue Regeneration Based on Stimuli-Responsive Materials 277Tiffany S. Pinho, Belém Sampaio-Marques, Clarisse Ribeiro, Cristiana B. Cunha, Senentxu Lanceros-Mendez, and António J. Salgado8.1 Introduction 2778.2 Electroactive Smart Polymers: An Overview 2798.3 Electroactive Smart Polymers for In Vitro Neuronal Outgrowth and Differentiation 2808.3.1 Electrically Conductive Materials 2808.3.2 Piezoelectric Polymers 2828.3.3 Ionic Conductive Polymers 2838.4 Electroactive Smart Polymers as a Regenerative Approach for Neural Regeneration In Vivo 2858.4.1 Spinal Cord Injury 2858.4.2 Brain Injury 2878.5 Major Challenges and Future Directions 2908.6 Final Remarks 290References 2919 Skin Tissue Regeneration Based on Stimuli-Responsive Materials 303Igor Irastorza, Beatriz Jiménez-Leiva, Gaskon Ibarretxe, Lucía Jiménez-Rojo, Clarisse Ribeiro, Senentxu Lanceros-Méndez, and Unai Silvan9.1 Introduction 3039.2 Structural Organization of the Skin 3039.3 Physiology of Wound Healing 3089.3.1 Hemostasis 3099.3.2 Inflammatory Phase 3099.3.3 Proliferation Phase 3109.3.4 Wound Remodeling and Contraction 3109.4 Biomaterials for Skin Regeneration 3119.4.1 Biomaterial Requirements for Skin Regeneration 3119.4.1.1 Biocompatibility 3119.4.1.2 Scaffold Architecture 3119.4.1.3 Biodegradability 3129.4.1.4 Porosity 3139.4.1.5 Functionalization with Bioactive Molecules 3139.4.1.6 Mechanical Properties 3139.4.1.7 Surface Wettability, Water Uptake, and Vapor Transmission 3149.5 Stimuli-responsive Materials 3149.5.1 Endogenous Triggers 3149.5.1.1 pH 3149.5.1.2 Temperature 3159.5.1.3 Redox Potential 3159.5.1.4 Mechanical Stress 3169.5.2 Exogenous Triggers 3179.5.2.1 Light 3179.5.2.2 Ultrasound 3179.5.2.3 Magnetic Fields 3189.6 Future Perspectives 319Acknowledgments 319References 31910 Cancer Therapies Based on Stimuli-Responsive Materials 329Giuliana Mosconi, Micaela A. Macchione, and Marcelo R. Romero10.1 A Brief Review 32910.2 Chemotherapy and the Role Played by Stimuli-Responsive Materials 33010.3 Stimuli Types and Targeting 33110.3.1 Stimuli Based on pH 33210.3.2 Redox Stimuli 33410.3.3 Enzyme-Responsive Materials 33410.3.4 UV–Visible—Photodynamic Therapy 33710.3.5 NIR and Microwave Radiation—Photothermal Therapy and Temperature/Light-Trigger Chemotherapy 33910.3.6 NIR and Microwave Radiation—Thermo-responsive Polymers 33910.3.7 Ultrasound Waves 34210.3.8 Magnetic Fields and Magnetic Materials 34410.3.9 Neutron Beams and Specific-responsive Materials 34410.3.10 Others: Multi-responsive Systems 34610.4 Concluding Remarks and Perspectives 346Acknowledgments 346References 347Summary and Outlook 351Clarisse Ribeiro, Unai Silvan, and Senentxu Lanceros-MéndezAcknowledgments 353Index 355