Table of Contents

1. CLINICAL ISSUES IN WOUND MANAGEMENT…………………………………. 1-1
1.1 Physiology of Wound Closure ………………………………………………….. 1-1
1.1.1 Layers of the Skin and Supporting Structures ………………. 1-2
1.1.1.1 Epidermis …………………………………………………. 1-2
1.1.1.2 Dermis……………………………………………………… 1-5
1.1.1.3 Hypodermis ………………………………………………. 1-5
1.1.1.4 Fascia………………………………………………………. 1-6
1.1.1.5 Muscle……………………………………………………… 1-6
1.1.1.6 Bone………………………………………………………… 1-6
1.1.2 Wound Closure Process……………………………………………. 1-7
1.1.2.1 Hemostasis ………………………………………………. 1-7
1.1.2.2 Inflammation……………………………………………… 1-9
1.1.2.3 Proliferation …………………………………………….. 1-10
1.1.2.4 Remodeling Phase…………………………………… 1-11
1.2 Factors Affecting Wound Closure……………………………………………. 1-12
1.2.1 Intrinsic Factors……………………………………………………… 1-14
1.2.1.1 Age and Chronic Illness ……………………………. 1-14
1.2.1.2 Body Composition ……………………………………. 1-15
1.2.1.3 Nutritional Status……………………………………… 1-15
1.2.2 Extrinsic Factors…………………………………………………….. 1-16
1.2.2.1 Ambient Temperature……………………………….. 1-16
1.2.2.2 Desiccation/Hydration ………………………………. 1-16
1.2.2.3 Infection………………………………………………….. 1-17
1.2.2.4 Maceration ……………………………………………… 1-17
1.2.2.5 Medication and Other Treatment Modalities…. 1-17
1.2.2.6 Necrotic Tissue and Debris ……………………….. 1-18
1.2.2.7 Oxygen…………………………………………………… 1-18
1.2.2.8 Stress …………………………………………………….. 1-18
1.2.2.9 Wound Creation and Depth……………………….. 1-19
1.2.2.10 Wound Closure Techniques ………………………. 1-19
1.2.2.11 Other Extrinsic Factors……………………………… 1-20
1.2.3 Complications of Wound Healing ……………………………… 1-20
1.2.3.1 Scarring………………………………………………….. 1-20
1.2.3.2 Bleeding …………………………………………………. 1-21
1.3 Wound Types ………………………………………………………………………. 1-21
1.3.1 Illness-Related Wounds…………………………………………… 1-21
1.3.1.1 Etiology ………………………………………………….. 1-21
1.3.1.1.1 Arterial Ulcers ………………………. 1-23
1.3.1.1.2 Diabetic Ulcers……………………… 1-23
1.3.1.1.3 Venous Ulcers ……………………… 1-24
1.3.1.2 Epidemiology…………………………………………… 1-25
1.3.2 Pressure Ulcers……………………………………………………… 1-25
1.3.2.1 Etiology ………………………………………………….. 1-25
1.3.2.2 Epidemiology…………………………………………… 1-27
1.3.3 Surgical Wounds ……………………………………………………. 1-27
1.3.3.1 Etiology ………………………………………………….. 1-29
1.3.3.2 Epidemiology…………………………………………… 1-31
1.3.4 Traumatic Wounds …………………………………………………. 1-31
1.3.4.1 Etiology ………………………………………………….. 1-31
1.3.4.1.1 Abrasions, Contusions,
and Lacerations ……………………. 1-31
1.3.4.1.2 Amputations…………………………. 1-35
1.3.4.1.3 Burns ………………………………….. 1-35
1.3.4.2 Epidemiology…………………………………………… 1-39
Exhibit 1-1: The Skin’s Layers and Supporting Structures …………………………….. 1-3
Exhibit 1-2: Phases of the Wound Closure Process……………………………………… 1-8
Exhibit 1-3: Intrinsic and Extrinsic Factors Affecting Wound Closure …………….. 1-13
Exhibit 1-4: Illness-Related Wounds, Facts and Figures,
1996-2006, and 2009 ……………………………………………………………. 1-22
Exhibit 1-5: Pressure Ulcers, Facts and Figures, 1996-2006, and 2009 ………… 1-26
Exhibit 1-6: Stages of Pressure Ulcers……………………………………………………… 1-28
Exhibit 1-7: Surgical Wounds, Facts and Figures, 1996-2006, and 2009……….. 1-30
Exhibit 1-8: Lacerations and Other Types of Traumatic Wounds,
Facts and Figures, 1996-2006, and 2009…………………………………. 1-32
Exhibit 1-9: Amputations, Facts and Figures, 1996-2006, and 2009……………… 1-33
Exhibit 1-10: Burns, Facts and Figures, 1996-2006, and 2009 ………………………. 1-34
Exhibit 1-11: Classification of Burns, by Mechanism of Injury ………………………… 1-36
Exhibit 1-12: Classification of Burns, by Extent of Injury ……………………………….. 1-38
2. TISSUE-ENGINEERED SKIN REPLACEMENTS AND SUBSTITUTES….. 2-1
2.1 Allografts ………………………………………………………………………………. 2-1
2.2 Autografts……………………………………………………………………………… 2-2
2.3 Xenografts …………………………………………………………………………….. 2-4
2.4 Autologous and Tissue-Engineered
Skin Replacements/Substitutes………………………………………………… 2-5
2.4.1 Epidermal Equivalent Products ………………………………….. 2-6
2.4.2 Dermal Equivalent Products………………………………………. 2-8
2.4.3 Multilayer Equivalent Products …………………………………… 2-9
2.5 Market Forecast …………………………………………………………………… 2-11
2.6 Competitive Analysis …………………………………………………………….. 2-17
Exhibit 2-1: 2013, Selected Current and Emerging Tissue-Engineered
Skin Replacements and Substitutes………………………………………… 2-12
Exhibit 2-2: Tissue-Engineered Skin Replacements and Substitutes,
Market Forecast, 2011-2016 ………………………………………………….. 2-18
Exhibit 2-3: 2011, Tissue-Engineered Skin Replacements and Substitutes
Market, Share by Supplier ……………………………………………………… 2-20
3. ACTIVE WOUND REPAIR MODULATORS………………………………………… 3-1
3.1 Growth Factors………………………………………………………………………. 3-1
3.1.1 Growth Factor Classification………………………………………. 3-3
3.1.1.1 Fibroblast Growth Factors …………………………… 3-4
3.1.1.2 Transforming Growth Factors………………………. 3-7
3.1.1.3 Epidermal Growth Factors…………………………… 3-7
3.1.1.4 Platelet-Derived Growth Factors ………………….. 3-8
3.1.1.5 Insulin-Like Growth Factors…………………………. 3-9
3.1.1.6 Keratinocyte Growth Factors……………………….. 3-9
3.1.1.7 Vascular Endothelial Growth Factors ………….. 3-10
3.1.1.8 Autologous Growth Factors……………………….. 3-10
3.1.1.8.1 Arteriocyte Medical Systems…… 3-11
3.1.1.8.2 Biomet…………………………………. 3-11
3.1.1.8.3 Cytomedix……………………………. 3-11
3.1.1.8.4 Harvest Technologies/Terumo… 3-11
3.1.1.9 Summary of Angiogenic Growth Factors……… 3-12
3.1.2 Competitors and Products……………………………………….. 3-12
3.1.3 Market Forecast …………………………………………………….. 3-15
3.2 Gene Therapy Agents …………………………………………………………… 3-18
3.3 Stem Cells …………………………………………………………………………… 3-20
3.3.1 Types of Stem Cells ……………………………………………….. 3-21
3.3.1.1 Embryonic Stem Cells ………………………………. 3-22
3.3.1.2 Adult Stem Cells………………………………………. 3-24
3.3.1.3 Cord Blood Stem Cells ……………………………… 3-26
3.3.2 The Role of Stem Cells in Wound Healing …………………. 3-27
3.3.3 Market Status ………………………………………………………… 3-28
3.4 Other Active Wound Repair Modulators and Pharmaceuticals…….. 3-28
3.4.1 Antibiotics and Anti-Infectives…………………………………… 3-28
3.4.2 Hormones……………………………………………………………… 3-29
3.4.3 Matrix Metalloproteinase Enzyme Inhibitors……………….. 3-29
3.4.4 Neuropeptides in Diabetic Wounds …………………………… 3-30
3.4.5 Other Products ………………………………………………………. 3-31
Exhibit 3-1: Selected Growth Factors in Development for
Wound Healing Applications…………………………………………………….. 3-5
Exhibit 3-2: The Angiogenesis Process…………………………………………………….. 3-13
Exhibit 3-3: 2012, Selected Angiogenic Growth Factors ……………………………… 3-14
Exhibit 3-4: Growth Factors, Market Forecast, 2011-2016 …………………………… 3-19
4. COMPANY PROFILES…………………………………………………………………….. 4-1
4.1 Biomet, Inc. …………………………………………………………………………… 4-1
4.2 Forticell Bioscience, Inc…………………………………………………………… 4-1
4.3 Genentech, Inc./F. Hoffmann-La Roche LTD ……………………………… 4-2
4.4 Genzyme Corporation/Sanofi SA ……………………………………………… 4-3
4.5 Integra LifeSciences, Inc./
Integra LifeSciences Holdings Corporation ………………………………… 4-3
4.6 LifeCell Corporation/Kinetic Concepts, Inc. ………………………………… 4-4
4.7 Organogenesis, Inc. ……………………………………………………………….. 4-6
4.8 Smith & Nephew PLC……………………………………………………………… 4-6
4.9 TEI Biosciences, Inc……………………………………………………………….. 4-9
APPENDIX: COMPANY LISTING……………………………………………………………… A-1