Bioengineering Research of Chronic Wounds (eBook)

Preface 6
Contents 8
I Principles of ChronicWound Pathology, Pathomechanics and Healing Response 8
Fundamentals of Pressure, Shear and Friction and Their Effects on the Human Body at Supported Postures 11
Introduction 12
Terms and Definitions 12
Bursae 12
Mechanical Load 14
The Human Body 17
The Skeletal System 17
The Skin 17
Mechanical Properties of the Skin 19
Conclusion 21
The Effects of Mechanical Load on the Body 21
Contact with the Body 21
Reactions of the Body to Mechanical Load 23
Comfort, Discomfort and Pain 29
Pain 32
Conclusions 34
Body Support Surfaces 34
Solid 35
Liquid 35
Air 36
Conclusion 36
Conclusions 36
References 37
Mechanobiology of Cutaneous Wound Healing and Scarring 41
Introduction 41
Mechanobiology of Cutaneous Wound Healing 41
Conclusions 49
References 50
Cell Migration along the Basement Membrane during Wound Repair. The Corneal Endothelium as a Model System 53
Introduction 53
The Vertebrate Corneal Endothelium 55
Organ Cultured Corneal Endothelium as a Model System 58
Cell Proliferation Is a Component of Endothelial Wound Repair 62
Migratory Response of Corneal Endothelial Cells during Wound Repair 64
Eicosanoids and Injury-Induced Endothelial Cell Movement 70
Actin Cytoskeletal Changes Accompanying Cell Migration 71
Matrix Proteins and Endothelial Wound Repair 78
Summary and Conclusion 83
References 84
The Importance of the Microenvironment of Support Surfaces in the Prevalence of Pressure Ulcers 95
Introduction 95
Pressure Ulcer Prevalence and Incidence, Economic Cost 95
Current Definition of PU 96
Major Factors 96
Current Methods/Procedures to Prevent PUs 96
Relationship between the Prevalence of Pressure Ulcers and Interface Pressures 97
Microenvironment 99
What Constitutes Microenvironment? 99
Shear Stress 100
Pressure 101
Friction 105
Moisture 107
Summary and Conclusion 108
Areas for Future Research 108
References 108
II Mathematical Modeling of Chronic Wounds and Wound Healing 8
Partial Differential Equations for Modelling Wound Geometry 111
Introduction 111
Elliptic Partial Differential Equations for Shape Modelling 115
Classification of Partial Differential Equations 116
The Biharmonic Equation 117
The Solution of the Biharmonic Equation 118
Modelling Wound Geometry 119
Examples of PDE Geometry 123
Modelling Geometry of Wound Shapes 124
Measuring Properties of Wounds 128
Surface Area and Volume of the Wound Shape 128
Mass Properties of the Wound 129
An Example of Wound Modelling 130
Conclusions and Future Work 132
References 133
A Suite of Continuum Models for Different Aspects in Wound Healing 136
Introduction 136
Methodology 140
The Fisher-Kolmogorov Equation 140
A Diffusion-Reaction Equation for Chemotaxis 143
The Visco-elastic Equation 145
Wound Contraction 147
The Model Due to Tranquillo 147
The Model Due to Olsen $et al$ 151
Angiogenesis 153
The Model Due to Gaffney $et al$ 153
The Model Due to Maggelakis 156
Wound Closure 159
The Model Due to Sherratt and Murray 159
The Model Due to Adam 160
A Combination of Angiogenesis andWound Closure 165
Discussion and Conclusions 171
References 174
III Computer Methods for Studying Biomechanical Conditions at Chronic Wound Sites: From Tissue to Cellular Scales 9
MRI Integrated with Computational Methods for Determining Internal Soft Tissue Loads as Related to Chronic Wounds 178
Introduction 178
Coupled MRI-FE Linear Models 181
Coupled MRI-FE Non-linear Models 182
Hyperelastic Warping 186
Discussion 187
References 188
A Finite-Element Biomechanical Model for Evaluating Buttock Tissue Loads in Seated Individuals with Spinal Cord Injury 190
Introduction 190
Unsolved Questions and Gaps in Pressure Ulcer Research Call for Mathematical Simulation 190
Why Finite Element Modeling in PU Research 191
History of FE Modeling Related to PU Research 191
Methodology on Building an FE Model for Buttocks for a Seated Individual 194
The Importance of Building the Model in a Seated Configuration 194
Building the Geometry of the Model 195
Mesh Generation of the Final Geometry 198
Selecting Material Model for Buttock FE Models 199
Assigning Boundary Conditions for Buttock FE Models 200
Assigning General Loading Conditions for Buttock FE Models 201
Results 202
FE Model Solution 202
Outputs of the FE Model Simulation 202
Methodology on Validating an FE Buttock Model for a Sitting Posture 203
Application of FE Models for Evaluating Buttock Loading in Sitting 205
Future Direction for FE Models in Pressure Ulcer Research for SCI Population 208
Improving Material Properties 208
Subject-Specific Model 209
Using Combination of MRI/Open MRI 210
Apply More Realistic Loading to the Model 210
Develop FE Models for Clinical Use 210
References 211
Finite Element and Animal Studies of Scar Contractions Leading to Chronic Wounds 215
Introduction 215
Methods 217
Laboratory Experiment 217
Constitutive Model of Skin 219
Finite Element Study 224
Results 225
Orientation and Distribution of Wrinkles 225
Dependence of Wrinkles on Skin Tension 228
Dependence of Wrinkles on Degree of Contraction 229
Stress Fields in Vicinity of Wrinkles 231
Investigating the Assumption of a Homogeneous Stress Field 233
Discussion 234
References 239
Cellular Deformations under Compression in Cells Involved in Deep Tissue Injury 242
Introduction 242
Two-Dimensional Finite Element Analyses of a Compressed Cell 244
Three-Dimensional Finite Element Analyses of Compressed Myoblast and Fibroblast Cells 247
Finite Element Analysis of a Compressed Cell/Extracellular Matrix Construct 250
Summary and Conclusions 253
References 253
IV Tissue-Engineered Constructs for Studying and Repairing Chronic Wounds 9
Tissue Engineered Models: A Valuable Tool in Pressure Ulcer Research 256
Introduction 256
Single Cell Studies 258
Tissue Engineered Skeletal Muscle Studies 260
Closing Remarks 266
References 267
Tissue-Engineered Models for the Study of Cutaneous Wound-Healing 270
Introduction 270
Tailoring 3D Tissue Models for Specific Wound Healing Applications 272
Limitations and Future Directions of 3D Wound Healing Models 276
Construction of 3D Human Skin 277
Wound Healing Protocol 277
Fabrication of Collagen Matrix with Dermal Fibroblasts 279
Addition of Keratinocytes to the Surface of Contracted Collagen Gels 280
Fabrication of Three-Dimensional Wound Healing Model of Human Skin 281
Anticipated results 282
Time Considerations 283
Notes 283
Materials 284
Medium Components 284
References 286
Tissue-Derived Materials for Adipose Regeneration 288
Introduction 288
Etiology and Clinical Treatment Options 289
Biomaterials as Models of Disease 291
Cell-ECM Interactions in Adipogenesis 291
Vascularization and Adipogenesis 292
Materials for Adipose Tissue Engineering 293
Matrigel$^{TM}$ 293
Collagen 294
Fibrin 295
Poly(ethylene glycol) 295
Other Materials 295
Tissue-Derived Hydrogels 296
Extraction and Gelation of Tissue-Derived Hydrogels 296
Composition of Tissue-Derived Hydrogels 298
Physical and Mechanical Properties of Tissue Derived Hydrogels 299
Cell Differentiation on Tissue-Derived Hydrogels 300
Tissue-Derived Hydrogels Promote Vascularized Adipose Formation $in vivo$ 300
Synthetic Mimics of Tissue Derived Materials 303
Summary and Conclusions 303
References 304
V Biochemical Markers for Early Identification and for Monitoring the Healing of Chronic Wounds 9
Clinical and Molecular Perspectives of Deep Tissue Injury: Changes in Molecular Markers in a Rat Model 307
Deep Tissue Injury (DTI)—Clinical Spectrum and Controversies 307
Novel Concept of DTI and Its Classification 307
Clinical Confusion and Controversies of DTI: Is This a New Way of Understanding the Pathophysiology of Deep PUs, Or a Novel Clinical Entity? 309
Pathways Involved in Deep Tissue Breakdown in Response to Mechanical Stress 318
Wound Healing Versus Regeneration in the Deep Tissues: The Role of Somatic Stem/Progenitor Cells 319
Regeneration of Muscle Tissue: Satellite Cells 320
Regeneration of Adipose Tissue?: Adipose-Derived Stromal Cells 322
Regeneration of Vessels: Endothelial Progenitor Cells? 325
Biochemical and Molecular Markers for Detecting DTI 327
Candidate Molecular Markers for DTI 327
Upregulation of Markers in Our Own Rat DTI Model 332
Conclusion 337
References 339
Proteomic Approaches for Studying the Phases of Wound Healing 348
Introduction 348
Sample Handling and Storage 349
Protein Concentration Measurement 350
Separation of Proteins 350
SDS-PAGE 350
Western Blot 351
2D-PAGE 353
Mass Spectrometry 355
2D-DIGE 356
Protein Quantification 357
iTRAQ 357
ELISA 357
Immunohistochemistry 361
Bioassay and Enzyme Assays 361
Antibody Arrays/Protein Expression Microarrays 363
Conclusion 364
References 364
VI Innovative Technologies and Devices in the Diagnosis and Treatment of Chronic Wounds 10
Bioengineering Techniques in Wound Assessment 368
Introduction 368
Wound Video Image Analysis 369
Shape Characterization 371
Chromatic Assessment 374
Ultrasonography 375
Laser Doppler Systems 377
Laser Doppler Flowmetry 377
Laser Doppler Perfusion Imaging 378
Transcutaneous Oxymetry 378
pH Measurement 379
Confocal Microscopy 379
Magnetic Resonance Imaging 380
TEWL 381
Conclusions 382
References 383
Optical Non-invasive Characterization of Chronic Wounds 386
Introduction 387
Optical Coherence Tomography 388
Laser Doppler Perfusion Monitoring and Imaging 390
Diffuse Reflectance Spectroscopy 393
Deep Tissue Spectroscopy 397
Near Infrared Diffuse Photon Density Wave Methodology 398
Hyperspectral Imaging 399
Orthogonal Polarization Spectral Imaging 402
Thermal Imaging 404
Conclusions 406
References 406
Regenerative Wound Healing via Biomaterials 410
Introduction 410
Evolution of Biomaterials 411
Development of Biologics for Regenerative Wound Healing 412
Regeneraive Capacity of Engineered Biologics 414
Importance of Nanostructures in Nature 417
Structure of the ECM 417
Cellular Interface with ECM 418
Balancing Forces: Cell-Biomaterial “Responsive” System 422
Engineered Fibrous Scaffolds for Regenerative Repair 425
References 426
Abdominal Wall Hernias and Biomaterials 430
Introduction 430
Anatomy of the Anterior Abdominal Wall 431
Ventral Hernias 431
Evaluation for Ventral Hernia 431
Umbilical Hernia 432
Epigastric Hernia 433
Spigelian Hernia 434
Inguinal Hernia 434
Incisional Hernia 435
History of Prosthetic Hernia Repair 437
Synthetic Prosthetic Meshes 437
Polypropylene (PP) 440
Polytetrafluoroethylene (PTFE) 440
Polyester 441
Combination Prostheses 442
Absorbable Combination Prostheses 442
Permanent Combination Prostheses 443
Absorbable Prostheses 443
Lightweight Or Heavyweight Prostheses 444
Biologic Grafts 445
Appropriate Prosthetic Choice 446
References 448
Author Index 453