Therapeutic Nanomaterials

Mustafa O. Guler, PhD, is an Associate Professor at the Institute of Materials Science and Nanotechnology, National Nanotechnology Research Center at Bilkent University (Ankara, Turkey). His research interests involve synthesis and characterization of novel materials for applications in chemistry, biology, and materials science.Ayse B. Tekinay, PhD, is an Associate Professor and Principal Investigator at the Institute of Materials Science and Nanotechnology, National Nanotechnology Research Center at Bilkent University (Ankara, Turkey) as well as a member of the adjunct faculty at the Rockefeller University (New York, U.S.A.). Her research focuses on molecular interactions of the cells and environment and the utilization of these interactions for regenerative medicine and drug delivery.

• List of Contributors xiPreface xiii1 Nanomaterials for Medicine 1Mustafa O. Guler and Ayse B. Tekinay1.1 Introduction 11.2 Nanoscale Material Properties 21.3 Nanomaterials for Understanding Disease Pathways 21.4 Nanomaterials for Therapy 31.5 Challenges and Future Prospects 52 Nanosized Delivery Systems for Tissue Regeneration 7Goksu Cinar, Didem Mumcuoglu, Ayse B. Tekinay, and Mustafa O. Guler2.1 Introduction 72.2 Delivery of Protein Therapeutics with Nanocarriers for Tissue Regeneration 102.2.1 GFs and Cytokines 102.3 Gene and siRNA Delivery with Nanocarriers for Tissue Regeneration 132.3.1 Gene Delivery 132.3.2 siRNA Delivery 152.4 Systemic Targeting and Cellular Internalization Strategies for Tissue Regeneration 152.4.1 Targeted Delivery 152.4.2 Cellular Internalization Strategies 182.5 Future Perspectives 20References 223 Nanomaterials for Neural Regeneration 33Melike Sever, Busra Mammadov, Mevhibe Gecer, Mustafa O. Guler, and Ayse B. Tekinay3.1 Introduction 333.1.1 Extracellular Matrix of Central Nervous System 333.1.2 ECM of Peripheral Nervous System 373.1.3 Urgent Need for Materials to Induce Regeneration in Nervous Tissue 393.2 Nanomaterials for Neural Regeneration 403.2.1 Physical Functionalization of Nanomaterials to Induce Neural Differentiation 403.2.2 Effects of Mechanical Stiffness on Cellular Behavior 403.2.3 Effects of Dimensionality on Cellular Behavior 423.2.4 Effects of Substrate Topography on Cell Behavior 433.2.5 Effects of Electrical Conductivity on Cell Behavior 443.3 Chemical and Biological Functionalization of Nanomaterials for Neural Differentiation 453.3.1 Effects of Biologically Active Molecules on Cell Behavior 453.3.2 Effects of Chemical Groups on Cellular Behavior 463.3.3 Effects of Biofunctionalization on Cellular Behavior Through ECM‐Derived Short Peptides 483.4 Conclusion 50References 514 Therapeutic Nanomaterials for Cartilage Regeneration 59Elif Arslan, Seher Ustun Yaylacı, Mustafa O. Guler, and Ayse B. Tekinay4.1 Introduction 594.2 Current Treatment Methods for Cartilage Injuries 634.3 Tissue Engineering Efforts 664.3.1 Natural Polymers 674.3.2 Synthetic Polymers 694.3.3 Composite Materials 704.3.4 Physical Stimuli 714.4 Clinical Therapeutics for Cartilage Regeneration 724.5 Conclusions and Future Perspectives 73References 785 Wound Healing Applications of Nanomaterials 87Berna Senturk, Gozde Uzunalli, Rashad Mammadov, Mustafa O. Guler, and Ayse B. Tekinay5.1 Introduction 875.1.1 The Structure of Healthy Mammalian Skin 885.1.2 The Mechanisms of Wound Healing 895.1.3 Repair Process in Chronic Wounds 945.2 Applications of Nanomaterials for the Enhancement of Wound Healing Process 955.2.1 Artificial Skin 965.2.2 Natural Nanomaterials for Wound Healing 975.2.3 Synthetic Nanomaterials for Wound Healing 1005.2.4 Wound Dressings Containing Growth Factors 1015.2.5 Biomimetic Materials 1025.2.6 Current Challenges in the Design of Nanomaterials for Chronic Wound Management 1035.3 Peptide Nanofiber Gels for Wound Healing 1055.3.1 Relevance of Nanofibrous Structure of Peptide Gels for Wound Healing 1065.3.2 Engineered PA Nanofiber Gels for Wound Healing and Insights into Various Designs 107References 1106 Nanomaterials for Bone Tissue Regeneration and Orthopedic Implants 119Gulcihan Gulseren, Melis Goktas, Hakan Ceylan, Ayse B. Tekinay, and Mustafa O. Guler6.1 Introduction 1196.2 Bone Matrix 1206.2.1 Organic Matrix and Bioactivity 1206.3 Inorganic Matrix, Mineralization, and Bone Organization 1226.3.1 Mechanical Properties and Structural Hierarchy of Bone Tissue 1236.4 Regulation of Bone Matrix in Adult Tissue 1256.4.1 Angiogenic Factors in Bone Remodeling 1266.5 Strategies for Bone Tissue Regeneration 1276.5.1 Hard Grafts for Bone Regeneration 1276.6 Soft Grafts for Bone Regeneration 1316.6.1 Peptide‐Based Bone Grafts 1326.6.2 Polymer Nanocomposites as Bone Grafts 1346.7 Future Perspectives 138References 1387 Nanomaterials for the Repair and Regeneration of Dental Tissues 153Gulistan Tansık, Alper Devrim Ozkan, Mustafa O. Guler, and Ayse B. Tekinay7.1 Introduction 1537.2 Formation of Dental and Osseous Tissues 1557.3 Dental Implants 1567.3.1 Metallic Implants 1587.3.2 Ceramic Implants 1587.3.3 Polymeric Implants 1597.4 Osseointegration of Dental Implants 1597.5 Uses of Nanotechnology in the Development of Dental Implants 1607.5.1 Enhancement of the Osseointegration Process 1617.5.2 Pulp and Dentin Tissue Regeneration 1627.5.3 Whole Tooth Regeneration 1657.6 Conclusions and Future Perspectives 166References 1668 Nanomaterials as Tissue Adhesives 173I. Ceren Yasa, Hakan Ceylan, Ayse B. Tekinay, and Mustafa O. Guler8.1 Introduction 1738.2 Tissue Adhesives Based on Synthetic Polymers 1768.3 Naturally Derived Tissue Adhesives 1808.4 Bioinspired Strategies 1828.5 Nanoenabled Adhesives 1868.6 Conclusion and Future Prospects 186References 1899 Advances in Nanoparticle‐Based Medical Diagnostic and Therapeutic Techniques 197Melis Sardan, Alper Devrim Ozkan, Aygul Zengin, Ayse B. Tekinay, and Mustafa O. Guler9.1 Introduction 1979.2 NPs used in MRI 2009.2.1 T1 CAs 2019.2.2 T2 CAs 2059.2.3 Dual Modal Contrast Agents 2079.3 NPs used in Computed Tomography 2089.3.1 Noble Metal‐Based NPs 2099.3.2 Heavy Metal‐Based NPs 2119.4 NPs used in Optical and Fluorescence Imaging 2139.4.1 Quantum Dots 2149.4.2 AuNPs 2169.4.3 UCNPs 2179.5 Theranostic Approaches and Multimodal Systems 2189.6 Overlook and Future Directions 222References 22310 Biosensors for Early Disease Diagnosis 235Ahmet E. Topal, Alper Devrim Ozkan, Aykutlu Dana, Ayse B. Tekinay, and Mustafa O. Guler10.1 Introduction 23510.2 Biosensor Elements 23710.2.1 Recognition Elements 23710.2.2 Output Type and Detection Techniques 23910.2.3 Optical Biosensors 24810.2.4 Electrical and Electrochemical Biosensors 25010.2.5 Mechanical Biosensors 25110.2.6 Other Biosensor Types 25210.3 The Impact of Nanotechnology and Nanomaterials in Biosensor Design 25310.4 Early Diagnosis and Biosensor‐Based Disease Detection 25510.5 Conclusion and Future Directions 258References 25911 Safety of Nanomaterials 271Nuray Gunduz, Elif Arslan, Mustafa O. Guler, and Ayse B. Tekinay11.1 Introduction 27111.2 Characterization, Design, and Synthesis of Nanomaterials 27211.2.1 Chemical Identity and Physicochemical Properties 27211.2.2 Biological Identity 27511.3 Interactions at the Cell–Material Interface 27711.3.1 Intracellular Activity 27811.3.2 Cellular Uptake Mechanisms 28311.4 Assays for Cell Viability/Proliferation 28311.4.1 Assays for Oxidative Stress and Apoptosis Mechanisms 28411.4.2 E valuation of Uptake and Accumulation of ENMs 28411.4.3 Genotoxicity Assays 28511.5 Animal Models and Long‐Term Risk Assessment 28611.5.1 The Blood–Brain Barrier 28611.6 Conclusions and Future Perspectives 290References 291Index 299