Microsystems for Enhanced Control of Cell Behavior (eBook)

Andrés Díaz Lantada is Associate Professor at Technical University of Madrid (UPM), Spain, teaching 'Design and manufacture with polymers', 'Computer-aided engineering', and 'Bioengineering. He carries out research at the UPM Product Development Laboratory linked to the development of biomedical devices based on smart/multifunctional materials, biomimetic fractal and non-Euclidean designs, and mechanical metamaterials for enhanced performance and adequate tissue interaction.

Preface 8
Acknowledgements 10
Contents 12
About the Editor 15
Part I Fundamentals 18
1 Some Introductory Notes to Cell Behavior 19
Abstract 19
1.1 The Cell: A Complex Multi-scale and Multi-physical/Biochemical Living System 21
1.2 Cell Differentiation and Cell Types 23
1.3 Cell Structure and Mechanics 25
1.4 Cell Adhesion, Migration and Contraction 27
1.5 Cellular Mechanochemical Transduction 28
1.6 Main Conclusions and Future Research 29
References 30
2 Brief Introduction to the Field of Biomedical Microsystems 31
Abstract 31
2.1 A Historical Perspective of Microsystem Technologies 31
2.2 Main Applications for Biomedical Microsystems 32
2.3 Biomedical Microsystems for Diagnostic Purposes 33
2.4 Biomedical Microsystems for Surgical Purposes 34
2.5 Biomedical Microsystems for Therapeutic Purposes 36
2.6 Biomedical Microsystems for Interacting with Cells 37
2.7 Main Conclusions and Future Research 39
References 40
3 Brief Introduction to Biomedical Microsystems for Interacting with Cells 41
Abstract 41
3.1 The Challenge of Interacting at a Cellular Level 41
3.2 Microsystems for Disease Management 45
3.3 Microsystems for Understanding Cell Behavior 47
3.4 Scaffolds and Microsystems for Tissue Engineering 48
3.5 Cell-Based Sensors and Cell-Based Actuators 49
3.6 Microsystems for Modeling Life by Controlling Cells 50
3.7 Main Conclusions and Future Research 51
References 52
4 State-of-the-Art Bioengineering Resources for Interacting with Cells 53
Abstract 53
4.1 Interacting at the Micro- and Nano-scale 53
4.2 Technologies for Mechanical Interaction with Cells 54
4.3 Technologies for Electromagnetical Interaction with Cells 55
4.4 Technologies for Culturing Cells and Obtaining Tissues 56
4.5 Main Microscopy Resources and Cell-Imaging Processes 58
4.6 Main Conclusions and Future Research 60
References 60
Part II Design and Manufacturing Technologies and Strategies 62
5 Systematic Methodologies for the Development of Biomedical Microdevices 63
Abstract 63
5.1 The Relevance of Systematic Development Strategies 64
5.2 Typical Stages Involved in Systematic Development Strategies 67
5.3 State-of-the-Art Design Technologies for Microsystems 72
5.4 State-of-the-Art Manufacturing Technologies for Biomedical Microsystems 73
5.5 State-of-the-Art Technologies for Functionalizing Biomedical Microsystems 74
5.6 State-of-the-Art Resources for Operating Biomedical Microsystems 75
5.7 Main Conclusions and Future Research 78
References 79
6 Addressing the Complexity of Biomaterials by Means of Biomimetic Computer Aided Design 80
Abstract 80
6.1 Biomaterials and Conventional Man-made Materials 81
6.2 Medical Images as Source for Inspiration 84
6.3 Digitalizing Biological Materials for Design Purposes 88
6.4 Computer-Aided Design for Controlling the Structure and Density Distribution of Materials 94
6.5 Computer-Aided Design for Controlling the Textures and Topographies of Materials 96
6.6 Main Conclusions and Future Research 102
References 102
Some Interesting Related Websites 105
7 Multi-scale and Multi-physical/Biochemical Modeling in Bio-MEMS 106
Abstract 106
7.1 The Relevance of Multi-scale and Multi-physical/Biochemical Modeling 107
7.2 Multi-scale Modeling of Cell Behavior 108
7.3 FEM-Based Simulations for Multi-physical Modeling of Cell Behavior and of Biomedical Microsystems (Bio-MEMS) 111
7.3.1 Multi-physical Modeling of Tissue Engineering Scaffolds 114
7.4 Resources for Multi-biochemical Modeling of Cells and Biomedical Microsystems (Bio-MEMS) 120
7.5 Modeling Cell Dynamics and Tissue Formation 122
7.6 Main Conclusions and Future Research 124
References 125
Some Interesting Related Websites 126
8 Rapid Prototyping of Biomedical Microsystems for Interacting at a Cellular Level 128
Abstract 128
8.1 Overview of Micromanufacturing Technologies 129
8.2 Rapid Prototyping by Means of Micromanufacturing Technologies Derived from the Electronic Industry 131
8.3 Rapid Prototyping and Solid Free-Form Fabrication Strategies for Biomedical Microsystems 139
8.4 Rapid Form-Copying and Rapid-Tooling for Biomedical Microsystems 144
8.5 Combining Technologies for Multi-scale Biomedical Microdevices 153
8.6 Main Conclusions and Future Research 156
Acknowledgements 156
References 157
9 Nanomanufacturing Technologies for Biomedical Microsystems Interacting at a Molecular Scale 159
Abstract 159
9.1 Overview of Nanomanufacturing Technologies 160
9.2 Physical Vapor Deposition Processes for Biomedical Microsystems 163
9.3 Chemical Vapor Deposition Processes for Biomedical Microsystems 165
9.4 Solution Deposition Processes for Biomedical Microsystems 166
9.5 Self-assembly and Related Processes for Biomedical Microsystems 170
9.6 Main Conclusions and Future Research 172
References 173
10 Issues Linked to the Mass-Production of Biomedical Microsystems 175
Abstract 175
10.1 The Relevance of Mass-Production 176
10.2 Conventional Technologies for the Mass-Production of Biomedical Microsystems 177
10.3 Micro-Injection Molding for the Mass-Production of Biomedical Microsystems 178
10.4 Mass-Production of Additively Manufactured Biomedical Microsystems 181
10.5 Mass-Production of Biomedical Microsystems by Combination of Subtractive and Additive Processes 183
10.6 Main Conclusions and Future Research 184
Acknowledgments 185
References 185
Part III Applications 187
11 Biomedical Microsystems for Disease Management 188
Abstract 188
11.1 Introduction to Modern Disease Management 189
11.2 Microfluidic Devices for in vitro Drug Screening 189
11.3 Microfluidic Devices for Enhanced Disease Modeling 190
11.4 Microfluidic Devices for Enhanced Disease Diagnosis 191
11.5 Case Study: Capillary Microfluidic Platform for Point-of-Care Testing 192
11.6 Main Conclusions and Future Research 199
Acknowledgements 200
References 200
12 Overview of Microsystems for Studying Cell Behavior Under Culture 201
Abstract 201
12.1 Introduction to Microsystems for Cell Culture Aimed at Studying Cell Behavior 202
12.2 Petri Dishes and the Limitations of 2D Cell Culture 203
12.3 Microsystems for the Study of Cell Behavior Under Gradients of Biochemicals 205
12.4 Electrophoretic Medical Microsystems for Studying Cell Behavior 207
12.5 Multi-culture Platforms for Studying the Interactions Between Different Cell Types 212
12.6 Case Study: Dynamic Cell Culture Platform 215
12.7 Main Conclusions and Future Research 217
References 217
13 Microstructured Devices for Studying Cell Adhesion, Dynamics and Overall Mechanobiology 219
Abstract 219
13.1 Introduction to Mechanobiology and Its Connections with Tribology 220
13.2 Microstructured and Microtextured Systems for Studying Cell Mechanobiology 221
13.3 Microtopographies and Their Impact on Cell Behavior 223
13.4 Case Study: Microsystem for Studying the Impact of Microtextures on Cell Behavior 226
13.5 Case Study: Microtextured Platforms for Studying and Controlling Cell Behavior and Fate 231
13.6 Main Conclusions and Future Research 234
Acknowledgements 234
References 234
14 Smart Microsystems for Active Cell Culture, Growth and Gene Expression Toward Relevant Tissues 236
Abstract 236
14.1 From Cells to Tissues: Passive Versus Active Cell Culture 237
14.2 State-of-the-Art Devices for Active Cell Culture 238
14.3 Case Study: Resonant Cantilevers and Bridges for Cell Culture Promotion and Monitoring 239
14.4 Case Study: Resonant 2D Lattices for Cell Culture Promotion and Monitoring 242
14.5 Case Study: Resonant 3D Lattices for Cell Culture 249
14.6 Main Conclusions and Future Research 254
Acknowledgements 254
References 254
15 Tissue Engineering Scaffolds for 3D Cell Culture 257
Abstract 257
15.1 Introduction: From 2D to 3D Cell Culture 258
15.2 Design Strategies for Tissue Engineering Scaffolds 260
15.3 Manufacturing Strategies and Resources for Tissue Engineering Scaffolds 263
15.4 Case Study: Low Cost Rapid Prototyped Scaffolds 269
15.5 Case Study: Low Cost Models for Studying Tumor Growth 272
15.6 Main Conclusions and Future Research 274
Acknowledgements 274
References 274
16 Tissue Engineering Scaffolds for Bone Repair: General Aspects 277
Abstract 277
16.1 Introduction: Passive Prostheses versus Active Scaffolds 278
16.2 Mimicking Bone Properties with Synthetic Materials 281
16.3 Design of Lattice Structures and Functionally Graded Materials 282
16.4 Manufacture of Lattice Structures and Functionally Graded Materials 285
16.5 Case Study: Design of a Scaffold for Tibial Repair 288
16.6 Main Conclusions and Future Research 290
Acknowledgments 291
References 291
17 Tissue Engineering Scaffolds for Bone Repair: Application to Dental Repair 294
Abstract 294
17.1 Introduction to Dental Implants and Prostheses 295
17.2 Novel Concepts in the Field of Dental Implants 296
17.3 Case Study: Development of a Scaffold Library for Dental Applications 299
17.4 Case Study: Modeling the Interaction Between Dental Implants and Jaw Bone 301
17.5 Manufacturing Strategies for Dental Scaffolds and Trabecular Dental Implants 303
17.6 Main Conclusions and Future Research 304
Acknowledgements 305
References 305
18 Tissue Engineering Scaffolds for Repairing Soft Tissues 307
Abstract 307
18.1 Introduction: Tissue Engineering Soft Tissues 308
18.2 Mimicking Soft Tissues with Synthetic Materials 311
18.3 Case Study: Scaffolds for Cartilage Repair 312
18.4 Case Study: Scaffolds for Muscle Repair 315
18.5 Case Study: 1D and 3D Scaffolds for Ligament and Tendon Repair 319
18.5.1 Materials, Design, Manufacturing and Testing Methods 321
18.5.2 Main Results Regarding the Developed Library of Tendon Repair Scaffolds 329
18.6 Main Conclusions and Future Research 333
References 334
19 Tissue Engineering Scaffolds for Osteochondral Repair 337
Abstract 337
19.1 Introduction: Complex Needs in Articular Repair 338
19.2 Design Strategies for Scaffolds with Radical Variations of Mechanical Properties 339
19.3 Manufacture of Scaffolds with Radical Variations of Mechanical Properties 341
19.4 Case Study: Composite Ti-PDMS Scaffold for Osteochondral Repair 341
19.5 Case Study: Scaffolds for Repairing Vertebrae and Spinal Discs 347
19.6 Main Conclusions and Future Research 352
References 354
20 Fluidic Microsystems: From Labs-on-Chips to Microfluidic Cell Culture 356
Abstract 356
20.1 Introduction: Labs-on-Chips and Enhanced Microfluidic Cell Culture 357
20.2 Overview of Existing and Commercial Devices 359
20.3 Design Strategies for Microfluidic Devices Aimed at Interacting with Cells 362
20.4 Manufacture Strategies for Microfluidic Devices Aimed at Interacting with Cells 366
20.5 Case Study: Development of a Microfluidic Device with Several Cell Culture Chambers 368
20.6 Main Conclusions and Future Research 375
References 376
21 Cell-Based Sensors and Cell-Based Actuators 378
Abstract 378
21.1 Introduction: Bio-hybrid Systems and the Future of Engineering 379
21.2 Main Accomplishments and Current Challenges 381
21.3 Developing Cell-Based Sensors 382
21.4 Developing Cell-Based Actuators 383
21.5 Case Study: Design Library of Conceptual Cell-Based Actuators 387
21.6 Main Conclusions and Future Research 389
Part IV Present Challenges and Future Proposals 392
22 Towards Reliable Organs-on-Chips and Humans-on-Chips 393
Abstract 393
22.1 Introduction to Organs-on-Chips and Related Design and Manufacturing Technologies 394
22.2 Case Study: Development of a Blood-Brain Barrier Platform 396
22.3 Case Study: Development of a Lung-on-Chip Platform 400
22.4 Case Study: Development of a Liver-on-Chip Platform 403
22.5 From Organs-on-Chips to Reliable Humans-on-Chips 410
22.6 Main Conclusions and Future Research 411
Acknowledgements 411
References 411
23 Towards Effective and Efficient Biofabrication Technologies 413
Abstract 413
23.1 Introduction: The Manufacture of Biological Systems 414
23.2 The Potential of Biofabrication and Its Application Fields 415
23.3 Advances and Challenges Linked to Biomaterials 416
23.4 Advances and Challenges Linked to Biodesign Tools 417
23.5 Advances and Challenges Linked to Biomanufacturing Resources 418
23.6 Main Conclusions and Future Research 420
Some Interesting Related Websites 422
24 Project-Based Learning in the Field of Biomedical Microdevices: The CDIO Approach 423
Abstract 423
24.1 Introduction 424
24.2 The “Biomedical Devices” Course of the “Biomedical Engineering” Degree at TU Madrid 425
24.3 Learning Objectives, Desired Outcomes and Teaching Methodology: The “CDIO” Approach 427
24.4 Results Obtained: Designs, Prototypes, Trials 428
24.5 Assessment of the Experience: Personal Views 432
24.6 Main Conclusions 433
References 434
Appendix 436
A.I Summary of Especially Relevant References Linked to the Contents 436
A.II Summary of Especially Relevant Websites 438
A.III Summary of Relevant Standards and Associations 440
A.IV Relevant Scientific Journals Linked to Medical Microdevices and Related Topics of Interest 441
A.V Relevant Enterprises Linked to Medical Microdevices 443
A.VI Relevant Enterprises Linked to Labs-on-Chips 444
A.VII Some Matlab Programs for Helping Designers 446