Polymers in Regenerative Medicine

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.

• Preface xiContributors xviiPart A Methods for Synthetic Extracellular Matrices and Scaffolds 11 Polymers as Materials for Tissue Engineering Scaffolds 3Ana Vallés Lluch Dunia Mercedes García Cruz Jorge Luis Escobar Ivirico Cristina Martínez Ramos and Manuel Monleón Pradas1.1 The Requirements Imposed by Application on Material Structures Intended as Tissue Engineering Scaffolds 31.2 Composition and Function 51.2.1 General Considerations 51.2.2 Some Families of Polymers for Tissue Engineering Scaffolds 81.2.3 Composite Scaffold Matrices 121.3 Structure and Function 141.3.1 General Considerations 141.3.2 Structuring Polymer Matrices 151.4 Properties of Scaffolds Relevant for Tissue Engineering Applications 241.4.1 Porous Architecture 241.4.2 Solid State Properties: Glass Transition Crystallinity 251.4.3 Mechanical and Structural Properties 261.4.4 Swelling Properties 281.4.5 Degradation Properties 291.4.6 Diffusion and Permeation 301.4.7 Surface Tension and Contact Angle 311.4.8 Biological Properties 311.5 Compound Multicomponent Constructs 321.5.1 Scaffold-Cum-Gel Constructs 321.5.2 Scaffolds and Membranes Containing Microparticles 341.5.3 Other Multicomponent Scaffold Constructs 341.6 Questions Arising from Manipulation and Final Use 351.6.1 Sterilization 351.6.2 Cell Seeding Cell Culture Analysis 361.6.3 In the Surgeon’s Hands 37References 372 Natural-Based and Stimuli-Responsive Polymers for Tissue Engineering and Regenerative Medicine 49Mariana B. Oliveira and João F. Mano2.1 Introduction 492.2 Natural Polymers and Their Application in TE & RM 522.2.1 Polysaccharides 522.2.2 Protein-Based Polymers 602.2.3 Polyesters 652.3 Natural Polymers in Stimuli-Responsive Systems 652.3.1 pH-Sensitive Natural Polymers 672.3.2 Temperature Sensitive Natural Polymers 672.3.3 Natural Polymers Modified to Show Thermoresponsive Behavior—Modifying Responsive Polymersand Agents 712.3.4 Light-Sensitive Polymers—Potential Use of Azobenzene/α-Cyclodextrin Inclusion Complexes 722.4 Conclusions 73References 743 Matrix Proteins Interactions with Synthetic Surfaces 91Patricia Rico Marco Cantini George Altankov and Manuel Salmerón-Sánchez3.1 Introduction 913.2 Protein Adsorption 923.2.1 Cell Adhesion Proteins 933.2.2 Experimental Techniques to Follow Protein Adsorption 943.2.3 Effect of Surface Properties on Protein Adsorption 973.3 Cell Adhesion 1093.3.1 Experimental Techniques to Characterize Cell Adhesion 1123.3.2 Cell Adhesion at Cell–Material Interface 1153.4 Remodeling of the Adsorbed Proteins 1223.4.1 Protein Reorganization and Secretion at the Cell–Material Interface 1223.4.2 Proteolytic Remodeling at Cell–Materials Interface 126References 1284 Focal Adhesion Kinase in Cell–Material Interactions 147Cristina González-García Manuel Salmerón-Sánchez and Andrés J. García4.1 Introduction 1474.2 Role of FAK in Cell Proliferation 1494.3 Role of FAK in Migratory and Mechanosensing Responses 1504.4 Role of FAK in the Generation of Adhesives Forces 1524.5 Influence of Material Surface Properties on FAK Signaling 1564.5.1 Effect of Mechanical Properties on FAK Signaling 1564.5.2 Effect of Surface Topography on FAK Signaling 1604.5.3 Effect of Surface Chemistry on FAK Signaling 1634.5.4 Effect of Surface Functionalization in FAK Expression 165References 1685 Complex Cell–Materials Microenvironments in Bioreactors 177Stergios C. Dermenoudis and Yannis F. Missirlis5.1 Introduction 1775.2 Cell–ECM Interactions 1785.2.1 ECM Chemistry 1795.2.2 ECM Topography 1815.2.3 ECM Mechanical Properties 1835.2.4 ECM 3D Structure 1845.2.5 ECM-Induced Mechanical Stimuli 1865.3 Cell–Nutrient Medium 1875.3.1 Composition and Volume-Related Phenomena 1885.3.2 Mechanical Stresses Induced by Nutrient Medium 1915.4 Other Aspects of Interaction 1945.4.1 Co-Culture Systems 1955.4.2 Material Interactions 1965.5 Conclusions 197References 197Part B N anostructures for Tissue Engineering 2076 Self-Curing Systems for Regenerative Medicine 209Julio San Román Blanca Vázquez and María Rosa Aguilar6.1 Introduction 2096.2 Self-Curing Systems for Hard Tissue Regeneration 2106.2.1 Antimicrobial Self-Curing Formulations 2116.2.2 Self-Curing Formulations for Osteoporotic Bone 2146.2.3 Antineoplastic Drug-Loaded Self-Curing Formulations 2166.2.4 Nonsteroidal Anti-Inflammatory Drug-Loaded Formulations 2176.2.5 Self-Curing Formulations with Biodegradable Components 2186.3 Self-Curing Hydrogels for Soft Tissue Regeneration 2196.3.1 Chemically Cross-Linked Hydrogels 2206.3.2 Chemically and Physically Cross-Linked Hydrogels 2256.4 Expectative and Future Directions 226References 2267 Self-Assembling Peptides as Synthetic Extracellular Matrices 235M.T. Fernandez Muiños and C.E. Semino7.1 Introduction 2357.2 In Vitro Applications 2387.3 In Vivo Applications 242References 2458 Polymer Therapeutics as Nano-Sized Medicines for Tissue Regeneration and Repair 249Ana Armiñán Pilar Sepúlveda and María J. Vicent8.1 Polymer Therapeutics as Nano-Sized Medicines 2498.1.1 The Concept and Biological Rationale behind Polymer Therapeutics 2498.1.2 Current Status and Future Trends 2528.2 Polymer Therapeutics for Tissue Regeneration and Repair 2548.2.1 Ischemia/Reperfusion Injuries 2558.2.2 Wound Healing/Repair 2608.2.3 Musculoskeletal Disorders 2638.2.4 Diseases of the Central Nervous System 2678.3 Conclusions and Future Perspectives 272References 2739 How Regenerative Medicine Can Benefit from Nucleic Acids Delivery Nanocarriers? 285Erea Borrajo Anxo Vidal Maria J. Alonso and Marcos Garcia-Fuentes9.1 Introduction 2859.1.1 Learning from Viruses: How to Overcome Cellular Barriers 2869.2 Nanotechnology in Gene Delivery 2929.2.1 Lipid Nanocarriers 2929.2.2 Polymeric Nanocarriers 2949.2.3 Inorganic Nanoparticles 3009.3 Nanotechnology in Regenerative Medicine 3029.3.1 Bone Regeneration 3039.3.2 Cartilage Regeneration 3059.3.3 Tendon Regeneration 3089.3.4 Myocardium Regeneration 3099.3.5 Neurological Tissue 3119.4 Conclusions 313References 31310 Functionalized Mesoporous Materials with Gate-Like Scaffoldings for Controlled Delivery 337Elena Aznar Estela Climent Laura Mondragon Félix Sancenón and Ramón Martínez-Máñez10.1 Introduction 33710.2 Mesoporous Silica Materials with Gate-Like Scaffoldings 33910.2.1 Controlled Delivery by pH Changes 33910.2.2 Controlled Delivery Using Redox Reactions 34510.2.3 Controlled Delivery Using Photochemical Reactions 34910.2.4 Controlled Delivery via Temperature Changes 35210.2.5 Controlled Delivery Using Small Molecules 35510.2.6 Controlled Delivery Using Biomolecules 35610.3 Concluding Remarks 360References 36111 Where Are We Going? Future Trends and Challenges 367Sang Jin Lee and Anthony Atala11.1 Introduction 36711.2 Classification of Biomaterials in Tissue Engineering and Regenerative Medicine 36811.2.1 N aturally Derived Materials 36811.2.2 Biodegradable Synthetic Polymers 37011.2.3 Tissue Matrices 37211.3 Basic Principles of Biomaterials in Tissue Engineering 37311.4 Development of Smart Biomaterials 37411.5 Scaffold Fabrication Technologies 37611.5.1 Injectable Hydrogels 37611.5.2 Electrospinning 37711.5.3 Computer-Aided Scaffold Fabrication 37811.5.4 Functionalization of Tissue-Engineered Biomaterial Scaffolds 37911.6 Summary and Future Directions 381References 384Index 391