Gefen Bioengineering Research of Chronic Wounds

A Multidisciplinary Study Approach
1. Auflage 2009
ISBN: 978-3-642-00534-3
Verlag: Springer
Format: PDF
Kopierschutz: Adobe DRM (»Systemvoraussetzungen)

E-Book, Englisch, 449 Seiten

Pressure-related chronic wounds are an important health concern that affects millions of patients and accumulates billions in annual costs. These wounds may occur when soft tissues are mechanically compressed between bony prominences and a supporting surface. This book gives a complete and quantitative explanation of the mechanobiology which causes chronic wounds. The reviews give an overall picture on all length scales of the phenomenon, starting from musculoskeletal biomechanics to the modeling of soft tissues and their interaction with bones. At the microscopic levels, it thoroughly reviews experiments and modeling of cellular forces and molecular processes that occur during injury and healing, including the integrity of living cells subjected to sustained mechanical forces and deformations. The results allow a complete picture of the tolerance of human tissues to sustained loads, and an understanding of the risk for onset of chronic wounds. Hence, this book is also valuable for all professionals involved in the prevention and treatment of chronic wounds.

Autoren/Hrsg.

Gefen, Amit

Inhaltsverzeichnis

1;Preface;6
2;Contents;8
3;I Principles of ChronicWound Pathology, Pathomechanics and Healing Response;8
3.1;Fundamentals of Pressure, Shear and Friction and Their Effects on the Human Body at Supported Postures;11
3.1.1;Introduction;12
3.1.2;Terms and Definitions;12
3.1.2.1;Bursae;12
3.1.2.2;Mechanical Load;14
3.1.3;The Human Body;17
3.1.3.1;The Skeletal System;17
3.1.3.2;The Skin;17
3.1.3.3;Mechanical Properties of the Skin;19
3.1.3.4;Conclusion;21
3.1.4;The Effects of Mechanical Load on the Body;21
3.1.4.1;Contact with the Body;21
3.1.4.2;Reactions of the Body to Mechanical Load;23
3.1.4.3;Comfort, Discomfort and Pain;29
3.1.4.4;Pain;32
3.1.4.5;Conclusions;34
3.1.5;Body Support Surfaces;34
3.1.5.1;Solid;35
3.1.5.2;Liquid;35
3.1.5.3;Air;36
3.1.5.4;Conclusion;36
3.1.6;Conclusions;36
3.1.7;References;37
3.2;Mechanobiology of Cutaneous Wound Healing and Scarring;41
3.2.1;Introduction;41
3.2.2;Mechanobiology of Cutaneous Wound Healing;41
3.2.3;Conclusions;49
3.2.4;References;50
3.3;Cell Migration along the Basement Membrane during Wound Repair. The Corneal Endothelium as a Model System;53
3.3.1;Introduction;53
3.3.2;The Vertebrate Corneal Endothelium;55
3.3.3;Organ Cultured Corneal Endothelium as a Model System;58
3.3.4;Cell Proliferation Is a Component of Endothelial Wound Repair;62
3.3.5;Migratory Response of Corneal Endothelial Cells during Wound Repair;64
3.3.6;Eicosanoids and Injury-Induced Endothelial Cell Movement;70
3.3.7;Actin Cytoskeletal Changes Accompanying Cell Migration;71
3.3.8;Matrix Proteins and Endothelial Wound Repair;78
3.3.9;Summary and Conclusion;83
3.3.10;References;84
3.4;The Importance of the Microenvironment of Support Surfaces in the Prevalence of Pressure Ulcers;95
3.4.1;Introduction;95
3.4.1.1;Pressure Ulcer Prevalence and Incidence, Economic Cost;95
3.4.1.2;Current Definition of PU;96
3.4.1.3;Major Factors;96
3.4.1.4;Current Methods/Procedures to Prevent PUs;96
3.4.2;Relationship between the Prevalence of Pressure Ulcers and Interface Pressures;97
3.4.3;Microenvironment;99
3.4.3.1;What Constitutes Microenvironment?;99
3.4.3.2;Shear Stress;100
3.4.3.3;Pressure;101
3.4.3.4;Friction;105
3.4.3.5;Moisture;107
3.4.4;Summary and Conclusion;108
3.4.4.1;Areas for Future Research;108
3.4.5;References;108
4;II Mathematical Modeling of Chronic Wounds and Wound Healing;8
4.1;Partial Differential Equations for Modelling Wound Geometry;111
4.1.1;Introduction;111
4.1.2;Elliptic Partial Differential Equations for Shape Modelling;115
4.1.2.1;Classification of Partial Differential Equations;116
4.1.2.2;The Biharmonic Equation;117
4.1.2.3;The Solution of the Biharmonic Equation;118
4.1.3;Modelling Wound Geometry;119
4.1.3.1;Examples of PDE Geometry;123
4.1.3.2;Modelling Geometry of Wound Shapes;124
4.1.4;Measuring Properties of Wounds;128
4.1.4.1;Surface Area and Volume of the Wound Shape;128
4.1.4.2;Mass Properties of the Wound;129
4.1.5;An Example of Wound Modelling;130
4.1.6;Conclusions and Future Work;132
4.1.7;References;133
4.2;A Suite of Continuum Models for Different Aspects in Wound Healing;136
4.2.1;Introduction;136
4.2.2;Methodology;140
4.2.2.1;The Fisher-Kolmogorov Equation;140
4.2.2.2;A Diffusion-Reaction Equation for Chemotaxis;143
4.2.2.3;The Visco-elastic Equation;145
4.2.3;Wound Contraction;147
4.2.3.1;The Model Due to Tranquillo;147
4.2.3.2;The Model Due to Olsen $et al$;151
4.2.4;Angiogenesis;153
4.2.4.1;The Model Due to Gaffney $et al$;153
4.2.4.2;The Model Due to Maggelakis;156
4.2.5;Wound Closure;159
4.2.5.1;The Model Due to Sherratt and Murray;159
4.2.5.2;The Model Due to Adam;160
4.2.5.3;A Combination of Angiogenesis andWound Closure;165
4.2.6;Discussion and Conclusions;171
4.2.7;References;174
5;III Computer Methods for Studying Biomechanical Conditions at Chronic Wound Sites: From Tissue to Cellular Scales;9
5.1;MRI Integrated with Computational Methods for Determining Internal Soft Tissue Loads as Related to Chronic Wounds;178
5.1.1;Introduction;178
5.1.2;Coupled MRI-FE Linear Models;181
5.1.3;Coupled MRI-FE Non-linear Models;182
5.1.4;Hyperelastic Warping;186
5.1.5;Discussion;187
5.1.6;References;188
5.2;A Finite-Element Biomechanical Model for Evaluating Buttock Tissue Loads in Seated Individuals with Spinal Cord Injury;190
5.2.1;Introduction;190
5.2.1.1;Unsolved Questions and Gaps in Pressure Ulcer Research Call for Mathematical Simulation;190
5.2.1.2;Why Finite Element Modeling in PU Research;191
5.2.1.3;History of FE Modeling Related to PU Research;191
5.2.2;Methodology on Building an FE Model for Buttocks for a Seated Individual;194
5.2.2.1;The Importance of Building the Model in a Seated Configuration;194
5.2.2.2;Building the Geometry of the Model;195
5.2.2.3;Mesh Generation of the Final Geometry;198
5.2.2.4;Selecting Material Model for Buttock FE Models;199
5.2.2.5;Assigning Boundary Conditions for Buttock FE Models;200
5.2.2.6;Assigning General Loading Conditions for Buttock FE Models;201
5.2.3;Results;202
5.2.3.1;FE Model Solution;202
5.2.3.2;Outputs of the FE Model Simulation;202
5.2.3.3;Methodology on Validating an FE Buttock Model for a Sitting Posture;203
5.2.3.4;Application of FE Models for Evaluating Buttock Loading in Sitting;205
5.2.4;Future Direction for FE Models in Pressure Ulcer Research for SCI Population;208
5.2.4.1;Improving Material Properties;208
5.2.4.2;Subject-Specific Model;209
5.2.4.3;Using Combination of MRI/Open MRI;210
5.2.4.4;Apply More Realistic Loading to the Model;210
5.2.4.5;Develop FE Models for Clinical Use;210
5.2.5;References;211
5.3;Finite Element and Animal Studies of Scar Contractions Leading to Chronic Wounds;215
5.3.1;Introduction;215
5.3.2;Methods;217
5.3.2.1;Laboratory Experiment;217
5.3.2.2;Constitutive Model of Skin;219
5.3.2.3;Finite Element Study;224
5.3.3;Results;225
5.3.3.1;Orientation and Distribution of Wrinkles;225
5.3.3.2;Dependence of Wrinkles on Skin Tension;228
5.3.3.3;Dependence of Wrinkles on Degree of Contraction;229
5.3.3.4;Stress Fields in Vicinity of Wrinkles;231
5.3.3.5;Investigating the Assumption of a Homogeneous Stress Field;233
5.3.4;Discussion;234
5.3.5;References;239
5.4;Cellular Deformations under Compression in Cells Involved in Deep Tissue Injury;242
5.4.1;Introduction;242
5.4.2;Two-Dimensional Finite Element Analyses of a Compressed Cell;244
5.4.3;Three-Dimensional Finite Element Analyses of Compressed Myoblast and Fibroblast Cells;247
5.4.4;Finite Element Analysis of a Compressed Cell/Extracellular Matrix Construct;250
5.4.5;Summary and Conclusions;253
5.4.6;References;253
6;IV Tissue-Engineered Constructs for Studying and Repairing Chronic Wounds;9
6.1;Tissue Engineered Models: A Valuable Tool in Pressure Ulcer Research;256
6.1.1;Introduction;256
6.1.2;Single Cell Studies;258
6.1.3;Tissue Engineered Skeletal Muscle Studies;260
6.1.4;Closing Remarks;266
6.1.5;References;267
6.2;Tissue-Engineered Models for the Study of Cutaneous Wound-Healing;270
6.2.1;Introduction;270
6.2.2;Tailoring 3D Tissue Models for Specific Wound Healing Applications;272
6.2.3;Limitations and Future Directions of 3D Wound Healing Models;276
6.2.4;Construction of 3D Human Skin;277
6.2.5;Wound Healing Protocol;277
6.2.5.1;Fabrication of Collagen Matrix with Dermal Fibroblasts;279
6.2.5.2;Addition of Keratinocytes to the Surface of Contracted Collagen Gels;280
6.2.5.3;Fabrication of Three-Dimensional Wound Healing Model of Human Skin;281
6.2.5.4;Anticipated results;282
6.2.5.5;Time Considerations;283
6.2.6;Notes;283
6.2.7;Materials;284
6.2.7.1;Medium Components;284
6.2.8;References;286
6.3;Tissue-Derived Materials for Adipose Regeneration;288
6.3.1;Introduction;288
6.3.2;Etiology and Clinical Treatment Options;289
6.3.3;Biomaterials as Models of Disease;291
6.3.4;Cell-ECM Interactions in Adipogenesis;291
6.3.5;Vascularization and Adipogenesis;292
6.3.6;Materials for Adipose Tissue Engineering;293
6.3.6.1;Matrigel$^{TM}$;293
6.3.6.2;Collagen;294
6.3.6.3;Fibrin;295
6.3.6.4;Poly(ethylene glycol);295
6.3.6.5;Other Materials;295
6.3.7;Tissue-Derived Hydrogels;296
6.3.7.1;Extraction and Gelation of Tissue-Derived Hydrogels;296
6.3.7.2;Composition of Tissue-Derived Hydrogels;298
6.3.7.3;Physical and Mechanical Properties of Tissue Derived Hydrogels;299
6.3.8;Cell Differentiation on Tissue-Derived Hydrogels;300
6.3.9;Tissue-Derived Hydrogels Promote Vascularized Adipose Formation $in vivo$;300
6.3.10;Synthetic Mimics of Tissue Derived Materials;303
6.3.11;Summary and Conclusions;303
6.3.12;References;304
7;V Biochemical Markers for Early Identification and for Monitoring the Healing of Chronic Wounds;9
7.1;Clinical and Molecular Perspectives of Deep Tissue Injury: Changes in Molecular Markers in a Rat Model;307
7.1.1;Deep Tissue Injury (DTI)—Clinical Spectrum and Controversies;307
7.1.1.1;Novel Concept of DTI and Its Classification;307
7.1.1.2;Clinical Confusion and Controversies of DTI: Is This a New Way of Understanding the Pathophysiology of Deep PUs, Or a Novel Clinical Entity?;309
7.1.2;Pathways Involved in Deep Tissue Breakdown in Response to Mechanical Stress;318
7.1.3;Wound Healing Versus Regeneration in the Deep Tissues: The Role of Somatic Stem/Progenitor Cells;319
7.1.3.1;Regeneration of Muscle Tissue: Satellite Cells;320
7.1.3.2;Regeneration of Adipose Tissue?: Adipose-Derived Stromal Cells;322
7.1.3.3;Regeneration of Vessels: Endothelial Progenitor Cells?;325
7.1.4;Biochemical and Molecular Markers for Detecting DTI;327
7.1.4.1;Candidate Molecular Markers for DTI;327
7.1.4.2;Upregulation of Markers in Our Own Rat DTI Model;332
7.1.5;Conclusion;337
7.1.6;References;339
7.2;Proteomic Approaches for Studying the Phases of Wound Healing;348
7.2.1;Introduction;348
7.2.2;Sample Handling and Storage;349
7.2.3;Protein Concentration Measurement;350
7.2.4;Separation of Proteins;350
7.2.4.1;SDS-PAGE;350
7.2.4.2;Western Blot;351
7.2.4.3;2D-PAGE;353
7.2.4.4;Mass Spectrometry;355
7.2.4.5;2D-DIGE;356
7.2.5;Protein Quantification;357
7.2.5.1;iTRAQ;357
7.2.5.2;ELISA;357
7.2.5.3;Immunohistochemistry;361
7.2.5.4;Bioassay and Enzyme Assays;361
7.2.5.5;Antibody Arrays/Protein Expression Microarrays;363
7.2.6;Conclusion;364
7.2.7;References;364
8;VI Innovative Technologies and Devices in the Diagnosis and Treatment of Chronic Wounds;10
8.1;Bioengineering Techniques in Wound Assessment;368
8.1.1;Introduction;368
8.1.2;Wound Video Image Analysis;369
8.1.3;Shape Characterization;371
8.1.4;Chromatic Assessment;374
8.1.5;Ultrasonography;375
8.1.6;Laser Doppler Systems;377
8.1.6.1;Laser Doppler Flowmetry;377
8.1.6.2;Laser Doppler Perfusion Imaging;378
8.1.7;Transcutaneous Oxymetry;378
8.1.8;pH Measurement;379
8.1.9;Confocal Microscopy;379
8.1.10;Magnetic Resonance Imaging;380
8.1.11;TEWL;381
8.1.12;Conclusions;382
8.1.13;References;383
8.2;Optical Non-invasive Characterization of Chronic Wounds;386
8.2.1;Introduction;387
8.2.2;Optical Coherence Tomography;388
8.2.3;Laser Doppler Perfusion Monitoring and Imaging;390
8.2.4;Diffuse Reflectance Spectroscopy;393
8.2.5;Deep Tissue Spectroscopy;397
8.2.6;Near Infrared Diffuse Photon Density Wave Methodology;398
8.2.7;Hyperspectral Imaging;399
8.2.8;Orthogonal Polarization Spectral Imaging;402
8.2.9;Thermal Imaging;404
8.2.10;Conclusions;406
8.2.11;References;406
8.3;Regenerative Wound Healing via Biomaterials;410
8.3.1;Introduction;410
8.3.2;Evolution of Biomaterials;411
8.3.3;Development of Biologics for Regenerative Wound Healing;412
8.3.4;Regeneraive Capacity of Engineered Biologics;414
8.3.5;Importance of Nanostructures in Nature;417
8.3.5.1;Structure of the ECM;417
8.3.5.2;Cellular Interface with ECM;418
8.3.6;Balancing Forces: Cell-Biomaterial “Responsive” System;422
8.3.7;Engineered Fibrous Scaffolds for Regenerative Repair;425
8.3.8;References;426
8.4;Abdominal Wall Hernias and Biomaterials;430
8.4.1;Introduction;430
8.4.2;Anatomy of the Anterior Abdominal Wall;431
8.4.3;Ventral Hernias;431
8.4.3.1;Evaluation for Ventral Hernia;431
8.4.3.2;Umbilical Hernia;432
8.4.3.3;Epigastric Hernia;433
8.4.3.4;Spigelian Hernia;434
8.4.3.5;Inguinal Hernia;434
8.4.3.6;Incisional Hernia;435
8.4.4;History of Prosthetic Hernia Repair;437
8.4.5;Synthetic Prosthetic Meshes;437
8.4.5.1;Polypropylene (PP);440
8.4.5.2;Polytetrafluoroethylene (PTFE);440
8.4.5.3;Polyester;441
8.4.6;Combination Prostheses;442
8.4.6.1;Absorbable Combination Prostheses;442
8.4.6.2;Permanent Combination Prostheses;443
8.4.6.3;Absorbable Prostheses;443
8.4.6.4;Lightweight Or Heavyweight Prostheses;444
8.4.7;Biologic Grafts;445
8.4.8;Appropriate Prosthetic Choice;446
8.4.9;References;448
9;Author Index;453