TISSUE ENGINEERING AND REGENERATION: TECHNOLOGIES AND GLOBAL MARKETS

Transcription

1 TISSUE ENGINEERING AND REGENERATION: TECHNOLOGIES AND GLOBAL MARKETS HLC101B August 2014 Yojana Jeevane Project Analyst ISBN: BCC Research 49 Walnut Park, Building 2 Wellesley, MA USA (toll-free within the USA), or (+1) information@bccresearch.com

2 TABLE OF CONTENTS CHAPTER 1 INTRODUCTION 2 STUDY AND OBJECTIVE 2 SCOPE OF THE REPORT 2 INTENDED AUDIENCE 3 INFORMATION AND METHODOLOGY SOURCES 3 ANALYST'S CREDENTIALS 3 RELATED BCC RESEARCH REPORTS 4 BCC RESEARCH WEBSITE 4 DISCLAIMER 4 CHAPTER 2 EXECUTIVE SUMMARY 6 SUMMARY TABLE GLOBAL TISSUE ENGINEERING AND REGENERATION MARKET BY SUMMARY FIGURE GLOBAL TISSUE ENGINEERING AND REGENERATION MARKET BY REGION, ($ 7 7 CHAPTER 3 TISSUE ENGINEERING AND REGENERATION 10 MARKET OVERVIEW 10 PROGRESS AND PROMISES FOR THE TISSUE ENGINEERING INDUSTRY 11 FIGURE 1 TISSUE-ENGINEERING STRATEGIES 12 REPLACING BODY PARTS THROUGH TISSUE ENGINEERING 13 NANOTECHNOLOGY FOR TISSUE REGENERATION 13 FIGURE 2 POTENTIAL NANOTECHNOLOGY APPLICATIONS 14 EFFECTS OF NANOTECHNOLOGY ON STEM CELL BEHAVIOUR FOR TISSUE REGENERATION Nanoparticles 14 Nanoscaffolds 15 NANOTECHNOLOGY IN TISSUE REGENERATION APPLICATIONS 15 Bone and Cartilage Regeneration 15 Vascular Tissue Regeneration 15 Neural Tissue Regeneration 15 GENE THERAPIES AS PART OF THE FUTURE OF TISSUE ENGINEERING 16 PROGRESS 16 PROSPECTS 17 STEM CELL TECHNOLOGIES BOON TO TISSUE ENGINEERING 17 GOVERNMENT REGULATIONS AND LEGISLATIONS 18 U.S. AND EUROPEAN REGULATION FOR TISSUE ENGINEERING PRODUCTS 18 CHINESE REGULATION FOR TISSUE ENGINEERING 19 REGULATORY DIFFERENCES 20 TABLE 1 REGULATORY APPROVAL DIFFERENCES BETWEEN THE U.S. AND EUROPE 21 ETHICAL ISSUES REGARDING STEM CELL THERAPIES AND CORD BLOOD BANKING Ethical Issues Regarding Cord Blood Banking 21 Ethical Issues in Cord Blood Stem Cell Therapies 22 IMPACT OF THE HEALTHCARE SYSTEM ON TISSUE ENGINEERING MARKET DEVELOPMENT

3 TABLE 2 HEALTHCARE PROVISIONS BY COUNTRY, PORTER'S FIVE FORCE ANALYSIS OF THE TISSUE ENGINEERING AND REGENERATION MARKET FIGURE 3 PORTER S FIVE FORCE MODEL FOR TISSUE ENGINEERING PRODUCTS 24 SUPPLIER BARGAINING POWER: MODERATE 24 BUYER BARGAINING POWER: LOW 25 THREATS FROM SUBSTITUTE PRODUCTS: LOW 25 THREATS FROM NEW ENTRANTS: HIGH 25 COMPETETION FROM INDUSTRY PLAYERS: HIGH 25 CLINICAL TRIALS 26 U.S. TISSUE ENGINEERING CLINICAL TRIALS 26 TABLE 3 U.S. CLINICAL TRIALS FOR TISSUE ENGINEERING 26 Completed Clinical Trials for Tissue Engineering 27 TABLE 4 U.S. CLINICAL TRIALS FOR TISSUE ENGINEERING 27 Conclusion 28 Terminated Clinical Trials for Tissue Engineering 29 TABLE 5 U.S. TERMINATED CLINICAL TRIALS 29 Conclusion 29 EUROPEAN CLINICAL TRIALS FOR TISSUE ENGINEERING 29 TABLE 6 EUROPEAN CLINICAL TRIALS FOR TISSUE ENGINEERING 30 Conclusion 30 MARKET DYNAMICS 31 DRIVERS 31 Emergence of Stem Cell Technology 31 FIGURE 4 GROWTH IN DISEASE TREATED VERSUS CLINICAL TRIALS, (NO. OF TRIALS AND TREATMENTS) Prominent Potential of Nanotechnology 32 Rise in Prevalence of Trauma Emergencies and Chronic Diseases 33 TABLE 7 U.S. UNINTENTIONAL INJURIES FACTS, 2013 (NO./%) 33 Advancement in Surgical Technologies and Monitoring Devices 33 TABLE 8 REGENERATIVE MEDICINE INDUSTRY TRENDS, RESTRAINTS 34 Operational Inefficiency 34 Stringent Regulatory Policies and Ethical Issues 35 High Treatment Cost 35 STEM CELL APPLICATION OPPORTUNITIES 35 Classification of Stem Cells According to Their Ability to Differentiate 36 Getting Core Competency in Emerging Economies CHAPTER 4 TISSUE ENGINEERING AND REGENERATION MARKET ANALYSIS BY TECHNOLOGY TABLE 9 GLOBAL TISSUE ENGINEERING AND REGENERATION MARKET BY TECHNOLOGY, STEM CELL TECHNOLOGIES 38 TABLE 10 GLOBAL STEM CELL TISSUE ENGINEERING AND REGENERATION MARKET BY STEM CELL SOURCES 40 STEM CELL EXTRACTION TECHNIQUES

4 ALTERED NUCLEAR TRANSFER 42 BLASTOMERE EXTRACTION 42 STEM CELL EXPANSION 42 STEM CELL DELIVERY 43 TABLE 11 COMMONLY USED VEHICLES FOR STEM CELL DELIVERY 44 Direct Surgical Intramyocardial Injection 44 EXISTING AND DEVELOPMENT-STAGE STEM CELL PRODUCTS 44 TABLE 12 COMMERCIALIZED TISSUE ENGINEERING PRODUCT SALES, 2011 ($ Clinical Application of Stem Cell Technologies in the Commercial Market Cardiovascular Repair 45 Neural Repair 45 Bone Repair 46 Skeletal Muscle Repair 46 Urologic Repair 46 CELL CULTURE TECHNOLOGIES 46 PROJECT NO Project Description 48 PROJECT NO Project Description 48 PROJECT NO Project Description 49 PROJECT NO Project Description 49 PROJECT NO Project Description 49 PROJECT NO Project Description 50 PROJECT NO Project Description 50 TABLE 13 GLOBAL CELL CULTURE TISSUE ENGINEERING AND REGENERATION MARKET BY IMMUNOPASSIVATION AND IMMUNOMODULATION 51 IMMUNOMODULATION 51 CELL ENCAPSULATION 52 TABLE 14 GLOBAL IMMUNOPASSIVATION AND IMMUNOMODULATION TISSUE ENGINEERING AND REGENERATION MARKET BY REGION, THROUGH 2019 ($ CHAPTER 5 TISSUE ENGINEERING AND REGENERATION MARKET ANALYSIS BY MATERIALS TABLE 15 GLOBAL TISSUE ENGINEERING AND REGENERATION MARKET BY MATERIAL, SYNTHETIC MATERIALS 55 TABLE 16 GLOBAL SYNTHETIC TISSUE ENGINEERING AND REGENERATION MATERIAL MARKET BY TYPE, TABLE 17 GLOBAL SYNTHETIC TISSUE ENGINEERING AND REGENERATION MATERIAL MARKET BY

5 BIODEGRADABLE SYNTHETIC POLYMERS 56 TABLE 18 BIODEGRADABLE POLYMER CLASSIFICATION 57 TABLE 19 GLOBAL BIODEGRADABLE SYNTHETIC POLYMER MATERIAL MARKET BY MEDICAL POLY LACTIC ACID SCAFFOLD 58 TABLE 20 COMMERCIAL POLYMERIC SCAFFOLD PRODUCTS 59 TABLE 21 GLOBAL SCAFFOLD MATERIAL MARKET BY REGION, THROUGH 2019 ($ ARTIFICIAL VASCULAR GRAFT MATERIALS 60 Stem Cell Integration in Vascular Tissue Engineering 60 Extracellular Matrix ECM-Based Vascular Grafts 60 Cell Sheets without Scaffold Support 61 TABLE 22 GLOBAL ARTIFICIAL VASCULAR GRAFT MATERIAL MARKET BY REGION, HYDROGEL TECHNOLOGY 61 TABLE 23 GLOBAL HYDROGEL TECHNOLOGY MARKET BY REGION, THROUGH 2019 ($ BIOLOGICALLY DERIVED MATERIALS 62 TABLE 24 GLOBAL BIOLOGICALLY DERIVED TISSUE ENGINEERING AND REGENERATION MATERIAL MARKET BY TYPE, TABLE 25 GLOBAL BIOLOGICALLY DERIVED TISSUE ENGINEERING AND REGENERATION MATERIAL MARKET BY COLLAGEN 63 TABLE 26 GLOBAL BIOLOGICALLY DERIVED COLLAGEN MATERIAL MARKET BY TABLE 27 GLOBAL BIOLOGICALLY DERIVED COLLAGEN MATERIAL MARKET BY Animal-Derived 65 Recombinant 65 XENOGENIC TISSUE 65 TABLE 28 GLOBAL BIOLOGICALLY DERIVED XENOGENIC TISSUE MATERIAL MARKET BY GENETICALLY ENGINEERED MATERIALS 66 TABLE 29 GLOBAL GENETICALLY ENGINEERED MATERIAL MARKET BY TYPE, TABLE 30 GLOBAL GENETICALLY ENGINEERED MATERIAL MARKET BY REGION, DEOXYRIBONUCLEIC ACID TRANSFECTION VECTORS 67 TABLE 31 GLOBAL DEOXYRIBONUCLEIC ACID TRANSFECTION VECTOR MARKET BY GENETICALLY MANIPULATED CELLS 68 TABLE 32 GLOBAL GENETICALLY MANIPULATED CELL MARKET BY REGION, THREE-DIMENSIONAL POLYMER TECHNOLOGY 69 TABLE 33 GLOBAL THREE-DIMENSIONAL POLYMER TECHNOLOGY MARKET BY TRANGENICS 70 TABLE 34 GLOBAL TRANSGENIC TECHNOLOGY MARKET BY REGION, THROUGH 2019 ($ FIBROBLASTS

6 TABLE 35 GLOBAL FIBROBLAST MARKET BY 71 NEURAL STEM CELLS 71 TABLE 36 GLOBAL NEURAL STEM CELL MARKET BY REGION, THROUGH 2019 ($ GENE-ACTIVATED MATRICES 72 TABLE 37 GLOBAL GENE-ACTIVATED MATRIX MARKET BY REGION, THROUGH 2019 ($ CHAPTER 6 TISSUE ENGINEERING AND REGENERATION MARKET BY APPLICATION 75 TABLE 38 GLOBAL TISSUE ENGINEERING AND REGENERATION APPLICATION MARKET BY TYPE, INTERNAL ORGAN REGENERATION 75 TABLE 39 GLOBAL INTERNAL ORGAN REGENERATION APPLICATION MARKET BY LIVER REGENERATION 76 TABLE 40 U.S. LIVER FAILURE STATISTICS, TABLE 41 ARTIFICIAL LIVER SUPPORT SYSTEMS 78 PANCREAS AND ISLET CELL REGENERATION 79 TABLE 42 U.S. PANCREATIC CANCER AND DIABETES STATISTICS, KIDNEY AND RENAL TUBULE REGENERATION 81 TABLE 43 U.S. KIDNEY DISEASE STATISTICS, ORTHOPEDIC APPLICATIONS 82 TABLE 44 KEY FACTS REGARDING ORTHOPEDIC DISEASES, BY REGION 82 TABLE 45 GLOBAL ORTHOPEDIC APPLICATION MARKET BY REGION, THROUGH 2019 ($ BONE REPAIR AND REPLACEMENT 83 TABLE 46 BONE DAMAGE AND RELATED DISEASES, 2011 ( 84 CARTILAGE AND CONNECTIVE TISSUE DAMAGE TREATMENT 84 TISSUE-ENGINEERED PRODUCTS FOR BONE DEFECTS 85 CARTILAGE REPAIR AND REPLACEMENT 87 TABLE 47 GLOBAL CARTILAGE DAMAGE STATISTICS, MENISCUS REPAIR AND REPLACEMENT 88 TENDON AND LIGAMENT REPAIR AND REPLACEMENT 88 TISSUE ENGINEERING FOR THE CENTRAL NERVOUS SYSTEM 89 TISSUE ENGINEERING FOR CENTRAL NERVOUS SYSTEM DISEASES 90 TABLE 48 GLOBAL TISSUE ENGINEERING FOR CENTRAL NERVOUS SYSTEM APPLICATION MARKET BY NEUROSURGICAL 91 Cell Implants for Parkinson's Diseases 92 TABLE 49 GLOBAL NEURODEGENERATIVE DISEASE STATISTICS, Cell Transplants for Epilepsy Treatment 93 Stem Cell Therapy for Multiple Sclerosis 93 SPINAL CORD INJURY AND SPINAL DISC REPAIR AND REPLACEMENT 94 TABLE 50 GLOBAL SPINAL CORD INJURY STATISTICS, Spinal Cord Injury Treatments 94 Tissue Engineering for Spinal Cord Injury 95 Cell Therapy for Spinal Cord Injury 95 Scaffold Approach for Spinal Cord Injury Treatment 96 TISSUE ENGINEERING FOR CARDIOVASCULAR DISORDERS

7 TABLE 51 GLOBAL CARDIOVASCULAR DISORDERS APPLICATION MARKET BY PERIPHERAL VASCULAR DISEASE APPLICATIONS 98 CORONARY ARTERY DISEASE APPLICATIONS 99 Heart Valves and Tissue Engineering 100 Mechanical Heart Valves 100 Biological Heart Valves 100 TABLE 52 COMPANIES DEVELOPING CELL THERAPIES FOR CARDIO VASCULAR DISORDERS, 2013 DENTAL TISSUE ENGINEERING 102 TABLE 53 GLOBAL DENTAL TISSUE ENGINEERING APPLICATION MARKET BY DERMATOLOGY TISSUE ENGINEERING 103 TABLE 54 U.S. AND GLOBAL SKIN DAMAGE MEDICAL CONDITION STATISTICS, TABLE 55 COMMERCIALIZED ACELLULAR SKIN TISSUE-ENGINEERED, TABLE 56 COMMERCIALIZED CELLULAR SKIN TISSUE ENGINEERED PRODUCTS 105 TABLE 57 GLOBAL DERMATOLOGY TISSUE ENGINEERING APPLICATION MARKET BY WOUND MANAGEMENT 107 TABLE 58 WOUND CARE MARKET BY CATEGORY (%) 107 Burn Treatment 108 Ulcer Treatment 109 ANTI-AGING THERAPIES 110 OTHERS 110 TABLE 59 GLOBAL OTHER APPLICATION MARKET BY REGION, THROUGH 2019 ($ MUSCLE REGENERATION 110 TABLE 60 IN VITRO VERSUS IN VIVO SKELETAL MUSCLE TISSUE ENGINEERING 111 PERIPHERAL NERVE REPAIR 112 HERNIA AND SOFT TISSUE REPAIR CHAPTER 7 TISSUE ENGINEERING AND REGENERATION MARKET BY REGION 114 TABLE 61 COMPANIES OPERATING IN REGENERATIVE MEDICINES MARKET BY CONTINENT, 2011 ($ TABLE 62 GLOBAL TISSUE ENGINEERING AND REGENERATION MARKET BY REGION, NORTH AMERICA 115 TABLE 63 NORTH AMERICAN COMMERCIALIZED TISSUE ENGINEERING PRODUCTS, 2013 TABLE 64 NORTH AMERICAN TISSUE ENGINEERING AND REGENERATION APPLICATION MARKET, U.S. SKIN TISSUE ENGINEERING PRODUCT MARKET 119 TABLE 65 U.S. SKIN DAMAGE CONDITIONS REQUIRING WOUND CARE, U.S. CARTILAGE AND BONE TISSUE ENGINEERING PRODUCT MARKET 120 TABLE 66 U.S. BONE DAMAGE AND RELATED DISEASE STATISTICS, U.S. TISSUE ENGINEERING PRODUCTS FOR CARDION VASCULAR DISORDERS MARKET TABLE 67 U.S. CARDIOVASCULAR DISORDER STATISTICS, 2010 AND EUROPE

8 TABLE 68 TISSUE ENGINEERING FIRMS BY TYPE, 2012 (%) 122 TABLE 69 EUROPEAN TISSUE ENGINEERING FIRMS BY REGION, 2012 (%) 123 TABLE 70 EUROPEAN SKIN DAMAGE CONDITIONS REQUIRING WOUND CARE STATISTICS, 2011 TABLE 71 EUROPEAN COMPANIES SELLING OR DEVELOPING SKIN TISSUE-ENGINEERED PRODUCTS, 2013 TABLE 72 EUROPEAN TISSUE ENGINEERING AND REGENERATION APPLICATION MARKET, EUROPEAN AND BONE TISSUE ENGINEERING PRODUCT MARKET 126 TABLE 73 EUROPEAN BONE DAMAGE AND RELATED DISEASE MARKET BY COUNTRY EUROPEAN TISSUE ENGINEERING PRODUCTS FOR CARDIOVASCULAR DISORDERS MARKET TABLE 74 EUROPEAN CARDIOVASCULAR DISORDER STATISTICS, TABLE 75 EUROPEAN RATE OF DEATH FROM HEART DISEASE BY COUNTRY, 2011 (DEATHS PER 100,000 CASES) EUROPEAN TISSUE ENGINEERING PRODUCTS FOR CENTRAL NERVOUS SYSTEM-RELATED INJURIES AND DISORDERS MARKET TABLE 76 EUROPEAN CENTRAL NERVOUS SYSTEM DISORDERS AND INJURIES, TABLE 77 EUROPEAN SPINAL CORD INJURY AND PARKINSON'S DISEASE BY COUNTRY, 2011 TABLE 78 EUROPEAN STEM CELL POLICIES BY COUNTRY, 130 TABLE 79 EUROPEAN COMPANIES DEVELOPING PRODUCTS IN TISSUE ENGINEERING AND REGENERATION FOR CENTRAL NERVOUS SYSTEM DISORDERS AND INJURIES EUROPEAN TISSUE ENGINEERING FOR INTERNAL ORGANS MARKET 131 ASIA-PACIFIC 132 FIGURE 5 PATHWAY FOR DISSEMINATION OF REGENERATIVE MEDICINE 133 TABLE 80 ASIA-PACIFIC TISSUE ENGINEERING AND REGENERATION APPLICATION MARKET, ASIA-PACIFIC CARTILAGE AND BONE TISSUE ENGINEERING PRODUCT MARKET ASIA-PACIFIC MARKET FOR CARDIOVASCULAR TISSUE ENGINEERING PRODUCTS ASIA-PACIFIC SKIN TISSUE ENGINEERING PRODUCT MARKET 134 REST OF THE WORLD 135 TABLE 81 GLOBAL SKIN-RELATED MEDICAL CONDITION STATISTICS, TABLE 82 REST OF WORLD TISSUE ENGINEERING AND REGENERATION APPLICATION MARKET, REST OF THE WORLD CARTILAGE AND BONE TISSUE ENGINEERING PRODUCT MARKET REST OF WORLD TISSUE ENGINEERING PRODUCTS FOR CARDIOVASCULAR DISORDERS MARKET TABLE 83 GLOBAL CARDIOVASCULAR DISORDER STATISTICS, TABLE 84 REST OF THE WORLD COMPANIES THAT MANUFACTURE AND DEVELOP TISSUE-ENGINEERED PRODUCTS FOR CARDIOVASCULAR DISORDER, BY COUNTRY REST OF THE WORLD TISSUE ENGINEERING PRODUCTS FOR CENTRAL NERVOUS SYSTEM-RELATED INJURIES AND DISEASES MARKET TABLE 85 GLOBAL CENTRAL NERVOUS SYSTEM DISORDER AND INJURY STATISTICS,

9 CHAPTER 8 COMPETITIVE LANDSCAPE 142 FIGURE 6 KEY COMPETITIVE STRATEGIES*, (%) 142 TABLE 86 KEY COMPETITIVE STRATEGIES, (%) 143 APPROVAL 143 FIGURE 7 APPROVAL STRATEGY BY COMPANY, (%) 144 TABLE 87 APPROVAL STRATEGIES BY COMPANY, (NO./%) 145 TABLE 88 KEY APPROVALS, AGREEMENTS, MERGERS AND ACQUISITIONS 146 FIGURE 8 AGREEMENTS, MERGERS AND ACQUISITIONS, BY COMPANY, (%) TABLE 89 AGREEMENTS, MERGERS AND ACQUISITIONS BY COMPANY, (%) TABLE 90 KEY AGREEMENTS, MERGERS AND ACQUISITIONS, PRODUCT LAUNCHES AND CLINICAL TRIALS 149 FIGURE 9 PRODUCT LAUNCHES AND CLINICAL TRIALS BY COMPANY, (%) 150 TABLE 91 PRODUCT LAUNCHES AND CLINICAL TRIALS BY COMPANY, (%) 151 TABLE 92 KEY AGREEMENTS, MERGERS AND ACQUISITIONS, 2010 AND CHAPTER 9 PATENT ANALYSIS 153 TABLE 93 REGISTERED AND APPROVED PATENTS BY COUNTRY, (%) 153 FIGURE 10 REGISTERED AND APPROVED PATENTS BY COUNTRY, (%) 153 U.S. PATENT ANALYSIS BY MARKET PARTICIPANT 154 TABLE 94 U.S. PATENT ANALYSIS BY MARKET PARTICIPANT, (%) 154 FIGURE 11 U.S. PATENT ANALYSIS BY MARKET PARTICIPANT, (%) 154 U.S. PATENT ANALYSIS BY APPLICATIONS 155 TABLE 95 U.S. PATENT ANALYSIS BY APPLICATION, (%) 155 FIGURE 12 U.S. PATENT ANALYSIS BY APPLICATION, (%) 155 EUROPEAN PATENT ANALYSIS BY MARKET PARTICIPANT 156 TABLE 96 EUROPEAN PATENT ANALYSIS BY MARKET PARTICIPANT, (%) 156 FIGURE 13 EUROPEAN PATENT ANALYSIS BY MARKET PARTICIPANT, (%) 156 EUROPEAN PATENT ANALYSIS BY APPLICATIONS 157 TABLE 97 EUROPEAN PATENT ANALYSIS BY APPLICATION, (%) 158 FIGURE 14 EUROPEAN PATENT ANALYSIS BY APPLICATION, (%) 158 JAPANESE PATENT ANALYSIS BY APPLICATION 158 TABLE 98 JAPANESE PATENT ANALYSIS BY APPLICATION, (%) 159 FIGURE 15 JAPANESE PATENT ANALYSIS BY APPLICATION, (%) 159 CHAPTER 10 COMPANY PROFILES 161 ADVANCED BIOHEALING (A SHIRE PHARMACEUTICAL COMPANY) 161 TISSUE ENGINEERING PRODUCT PORTFOLIO 161 TABLE 99 ADVANCED BIOHEALING RECENT DEVELOPMENTS 162 TABLE 100 ADVANCED BIOHEALING FINANCIALS, ($ MILLIONS/%) 162 ADVANCED CELL TECHNOLOGY INC. 162 TISSUE ENGINEERING PRODUCT PORTFOLIO 163 TABLE 101 ADVANCED CELL TECHNOLOGY INC. RECENT DEVELOPMENTS 163 ARTERIOCYTE 163 TISSUE ENGINEERING PRODUCT PORTFOLIO 163 TABLE 102 ARTERIOCYTE RECENT DEVELOPMENTS 164

10 ATHERSYS INC. 164 TISSUE ENGINEERING PRODUCT PORTFOLIO 164 TABLE 103 ATHERSYS INC. RECENT DEVELOPMENTS 165 TABLE 104 ATHERSYS FINANCIALS, ($ MILLIONS/%) 165 BIOHEART INC. 165 TISSUE ENGINEERING PRODUCT PORTFOLIO 166 TABLE 105 BIOHEART INC. RECENT DEVELOPMENTS 166 CERAPEDICS INC. 166 TISSUE ENGINEERING PRODUCT PORTFOLIO 167 TABLE 106 CERAPEDICS INC. RECENT DEVELOPMENTS 167 CO.DON AG 167 TISSUE ENGINEERING PRODUCT PORTFOLIO 168 TABLE 107 CO.DON AG RECENT DEVELOPMENTS 168 COOK MEDICAL INC. 168 TISSUE ENGINEERING PRODUCT PORTFOLIO 169 TABLE 108 COOK MEDICAL INC. RECENT DEVELOPMENTS 169 CRYOLIFE INC 169 TISSUE ENGINEERING PRODUCT PORTFOLIO 169 TABLE 109 CRYO LIFE INC. RECENT DEVELOPMENTS 170 CYTOGRAFT TISSUE ENGINEERING 170 TISSUE ENGINEERING PRODUCT PORTFOLIO 170 TABLE 110 CYTOGRAFT TISSUE ENGINEERING RECENT DEVELOPMENTS 171 CYTOMEDIX INC. 171 TISSUE ENGINEERING PRODUCT PORTFOLIO 171 TABLE 111 CYTOMEDIX INC. RECENT DEVELOPMENTS 172 CYTORI THERAPEUTICS INC. 172 TISSUE ENGINEERING PRODUCT PORTFOLIO 172 TABLE 112 CYTORI THERAPEUTICS INC. RECENT DEVELOPMENTS 173 TABLE 113 CYTORI THERAPEUTICS FINANCIALS, ($ MILLIONS/%) 173 GENZYME (A SANOFI COMPANY) 173 TISSUE ENGINEERING PRODUCT PORTFOLIO 174 TABLE 114 GENZYME RECENT DEVELOPMENTS 174 TABLE 115 GENZYME FINANCIALS, ($ MILLIONS/%) 174 KINETIC CONCEPTS INC. 174 TISSUE ENGINEERING PRODUCT PORTFOLIO 175 TABLE 116 KINETIC CONCEPTS INC. RECENT DEVELOPMENTS 175 TABLE 117 KINETICS CONCEPTS FINANCIALS, ($ MILLIONS/%) 175 MESOBLAST LTD. 176 TISSUE ENGINEERING PRODUCT PORTFOLIO 176 ORGANOGENESIS INC. 176 TISSUE ENGINEERING PRODUCT PORTFOLIO 176 ORTHOPEUTICS 177 WRIGHT MEDICAL TECHNOLOGY INC. 177 TISSUE ENGINEERING PRODUCT PORTFOLIO 177 TABLE 118 WRIGHT MEDICAL TECHNOLOGY INC. RECENT DEVELOPMENTS 178 TABLE 119 WRIGHT MEDICAL TECHNOLOGY FINANCIALS, ($ MILLIONS/%) 178

11 CHAPTER 11 PATENTS 180 TABLE 120 NORTH AMERICAN PATENTS 180 TABLE 121 EUROPEAN PATENTS 181 TABLE 122 JAPANESE PATENTS 182

12 LIST OF TABLES TABLE HEADING SUMMARY TABLE GLOBAL TISSUE ENGINEERING AND REGENERATION MARKET BY TABLE 1 REGULATORY APPROVAL DIFFERENCES BETWEEN THE U.S. AND EUROPE 21 TABLE 2 HEALTHCARE PROVISIONS BY COUNTRY, TABLE 3 U.S. CLINICAL TRIALS FOR TISSUE ENGINEERING 26 TABLE 4 U.S. CLINICAL TRIALS FOR TISSUE ENGINEERING 27 TABLE 5 U.S. TERMINATED CLINICAL TRIALS 29 TABLE 6 EUROPEAN CLINICAL TRIALS FOR TISSUE ENGINEERING 30 TABLE 7 U.S. UNINTENTIONAL INJURIES FACTS, 2013 (NO./%) 33 TABLE 8 REGENERATIVE MEDICINE INDUSTRY TRENDS, TABLE 9 GLOBAL TISSUE ENGINEERING AND REGENERATION MARKET BY TECHNOLOGY, TABLE 10 GLOBAL STEM CELL TISSUE ENGINEERING AND REGENERATION MARKET BY TABLE 11 COMMONLY USED VEHICLES FOR STEM CELL DELIVERY 44 TABLE 12 COMMERCIALIZED TISSUE ENGINEERING PRODUCT SALES, 2011 ($ TABLE 13 GLOBAL CELL CULTURE TISSUE ENGINEERING AND REGENERATION MARKET BY TABLE 14 GLOBAL IMMUNOPASSIVATION AND IMMUNOMODULATION TISSUE ENGINEERING AND REGENERATION MARKET BY REGION, THROUGH 2019 ($ TABLE 15 GLOBAL TISSUE ENGINEERING AND REGENERATION MARKET BY MATERIAL, TABLE 16 GLOBAL SYNTHETIC TISSUE ENGINEERING AND REGENERATION MATERIAL MARKET BY TYPE, TABLE 17 GLOBAL SYNTHETIC TISSUE ENGINEERING AND REGENERATION MATERIAL MARKET BY TABLE 18 BIODEGRADABLE POLYMER CLASSIFICATION 57 TABLE 19 GLOBAL BIODEGRADABLE SYNTHETIC POLYMER MATERIAL MARKET BY TABLE 20 COMMERCIAL POLYMERIC SCAFFOLD PRODUCTS 59 TABLE 21 GLOBAL SCAFFOLD MATERIAL MARKET BY REGION, THROUGH 2019 ($ TABLE 22 GLOBAL ARTIFICIAL VASCULAR GRAFT MATERIAL MARKET BY REGION, TABLE 23 GLOBAL HYDROGEL TECHNOLOGY MARKET BY REGION, THROUGH 2019 ($ TABLE 24 GLOBAL BIOLOGICALLY DERIVED TISSUE ENGINEERING AND REGENERATION MATERIAL MARKET BY TYPE, TABLE 25 GLOBAL BIOLOGICALLY DERIVED TISSUE ENGINEERING AND REGENERATION MATERIAL MARKET BY TABLE 26 GLOBAL BIOLOGICALLY DERIVED COLLAGEN MATERIAL MARKET BY TABLE 27 GLOBAL BIOLOGICALLY DERIVED COLLAGEN MATERIAL MARKET BY TABLE 28 GLOBAL BIOLOGICALLY DERIVED XENOGENIC TISSUE MATERIAL MARKET BY TABLE 29 GLOBAL GENETICALLY ENGINEERED MATERIAL MARKET BY TYPE,

13 TABLE HEADING TABLE 30 GLOBAL GENETICALLY ENGINEERED MATERIAL MARKET BY REGION, TABLE 31 GLOBAL DEOXYRIBONUCLEIC ACID TRANSFECTION VECTOR MARKET BY TABLE 32 GLOBAL GENETICALLY MANIPULATED CELL MARKET BY REGION, TABLE 33 GLOBAL THREE-DIMENSIONAL POLYMER TECHNOLOGY MARKET BY TABLE 34 GLOBAL TRANSGENIC TECHNOLOGY MARKET BY REGION, THROUGH 2019 ($ TABLE 35 GLOBAL FIBROBLAST MARKET BY 71 TABLE 36 GLOBAL NEURAL STEM CELL MARKET BY REGION, THROUGH 2019 ($ TABLE 37 GLOBAL GENE-ACTIVATED MATRIX MARKET BY REGION, THROUGH 2019 ($ TABLE 38 GLOBAL TISSUE ENGINEERING AND REGENERATION APPLICATION MARKET BY TYPE, TABLE 39 GLOBAL INTERNAL ORGAN REGENERATION APPLICATION MARKET BY TABLE 40 U.S. LIVER FAILURE STATISTICS, TABLE 41 ARTIFICIAL LIVER SUPPORT SYSTEMS 78 TABLE 42 U.S. PANCREATIC CANCER AND DIABETES STATISTICS, TABLE 43 U.S. KIDNEY DISEASE STATISTICS, TABLE 44 KEY FACTS REGARDING ORTHOPEDIC DISEASES, BY REGION 82 TABLE 45 GLOBAL ORTHOPEDIC APPLICATION MARKET BY REGION, THROUGH 2019 ($ TABLE 46 BONE DAMAGE AND RELATED DISEASES, 2011 ( 84 TABLE 47 GLOBAL CARTILAGE DAMAGE STATISTICS, TABLE 48 GLOBAL TISSUE ENGINEERING FOR CENTRAL NERVOUS SYSTEM APPLICATION MARKET BY TABLE 49 GLOBAL NEURODEGENERATIVE DISEASE STATISTICS, TABLE 50 GLOBAL SPINAL CORD INJURY STATISTICS, TABLE 51 GLOBAL CARDIOVASCULAR DISORDERS APPLICATION MARKET BY REGION, TABLE 52 COMPANIES DEVELOPING CELL THERAPIES FOR CARDIO VASCULAR DISORDERS, 2013 TABLE 53 GLOBAL DENTAL TISSUE ENGINEERING APPLICATION MARKET BY REGION, TABLE 54 U.S. AND GLOBAL SKIN DAMAGE MEDICAL CONDITION STATISTICS, TABLE 55 COMMERCIALIZED ACELLULAR SKIN TISSUE-ENGINEERED, TABLE 56 COMMERCIALIZED CELLULAR SKIN TISSUE ENGINEERED PRODUCTS 105 TABLE 57 GLOBAL DERMATOLOGY TISSUE ENGINEERING APPLICATION MARKET BY TABLE 58 WOUND CARE MARKET BY CATEGORY (%) 107 TABLE 59 GLOBAL OTHER APPLICATION MARKET BY REGION, THROUGH 2019 ($ TABLE 60 IN VITRO VERSUS IN VIVO SKELETAL MUSCLE TISSUE ENGINEERING 111 TABLE 61 COMPANIES OPERATING IN REGENERATIVE MEDICINES MARKET BY CONTINENT, 2011 ($ TABLE 62 GLOBAL TISSUE ENGINEERING AND REGENERATION MARKET BY REGION,

14 TABLE HEADING TABLE 63 NORTH AMERICAN COMMERCIALIZED TISSUE ENGINEERING PRODUCTS, 2013 TABLE 64 NORTH AMERICAN TISSUE ENGINEERING AND REGENERATION APPLICATION MARKET, TABLE 65 U.S. SKIN DAMAGE CONDITIONS REQUIRING WOUND CARE, TABLE 66 U.S. BONE DAMAGE AND RELATED DISEASE STATISTICS, TABLE 67 U.S. CARDIOVASCULAR DISORDER STATISTICS, 2010 AND TABLE 68 TISSUE ENGINEERING FIRMS BY TYPE, 2012 (%) 122 TABLE 69 EUROPEAN TISSUE ENGINEERING FIRMS BY REGION, 2012 (%) 123 TABLE 70 EUROPEAN SKIN DAMAGE CONDITIONS REQUIRING WOUND CARE STATISTICS, 2011 TABLE 71 EUROPEAN COMPANIES SELLING OR DEVELOPING SKIN TISSUE-ENGINEERED PRODUCTS, 2013 TABLE 72 EUROPEAN TISSUE ENGINEERING AND REGENERATION APPLICATION MARKET, TABLE 73 EUROPEAN BONE DAMAGE AND RELATED DISEASE MARKET BY COUNTRY 126 TABLE 74 EUROPEAN CARDIOVASCULAR DISORDER STATISTICS, TABLE 75 EUROPEAN RATE OF DEATH FROM HEART DISEASE BY COUNTRY, 2011 (DEATHS PER 100,000 CASES) TABLE 76 EUROPEAN CENTRAL NERVOUS SYSTEM DISORDERS AND INJURIES, TABLE 77 EUROPEAN SPINAL CORD INJURY AND PARKINSON'S DISEASE BY COUNTRY, 2011 TABLE 78 EUROPEAN STEM CELL POLICIES BY COUNTRY, 130 TABLE 79 EUROPEAN COMPANIES DEVELOPING PRODUCTS IN TISSUE ENGINEERING AND REGENERATION FOR CENTRAL NERVOUS SYSTEM DISORDERS AND INJURIES TABLE 80 ASIA-PACIFIC TISSUE ENGINEERING AND REGENERATION APPLICATION MARKET, TABLE 81 GLOBAL SKIN-RELATED MEDICAL CONDITION STATISTICS, TABLE 82 REST OF WORLD TISSUE ENGINEERING AND REGENERATION APPLICATION MARKET, TABLE 83 GLOBAL CARDIOVASCULAR DISORDER STATISTICS, TABLE 84 REST OF THE WORLD COMPANIES THAT MANUFACTURE AND DEVELOP TISSUE-ENGINEERED PRODUCTS FOR CARDIOVASCULAR DISORDER, BY COUNTRY TABLE 85 GLOBAL CENTRAL NERVOUS SYSTEM DISORDER AND INJURY STATISTICS, 2011 TABLE 86 KEY COMPETITIVE STRATEGIES, (%) 143 TABLE 87 APPROVAL STRATEGIES BY COMPANY, (NO./%) 145 TABLE 88 KEY APPROVALS, TABLE 89 AGREEMENTS, MERGERS AND ACQUISITIONS BY COMPANY, (%) 148 TABLE 90 KEY AGREEMENTS, MERGERS AND ACQUISITIONS, TABLE 91 PRODUCT LAUNCHES AND CLINICAL TRIALS BY COMPANY, (%) 151 TABLE 92 KEY AGREEMENTS, MERGERS AND ACQUISITIONS, 2010 AND TABLE 93 REGISTERED AND APPROVED PATENTS BY COUNTRY, (%) 153 TABLE 94 U.S. PATENT ANALYSIS BY MARKET PARTICIPANT, (%) 154 TABLE 95 U.S. PATENT ANALYSIS BY APPLICATION, (%) 155 TABLE 96 EUROPEAN PATENT ANALYSIS BY MARKET PARTICIPANT, (%) 156 TABLE 97 EUROPEAN PATENT ANALYSIS BY APPLICATION, (%) 158 TABLE 98 JAPANESE PATENT ANALYSIS BY APPLICATION, (%) 159 TABLE 99 ADVANCED BIOHEALING RECENT DEVELOPMENTS 162 TABLE 100 ADVANCED BIOHEALING FINANCIALS, ($ MILLIONS/%)

15 TABLE HEADING TABLE 101 ADVANCED CELL TECHNOLOGY INC. RECENT DEVELOPMENTS 163 TABLE 102 ARTERIOCYTE RECENT DEVELOPMENTS 164 TABLE 103 ATHERSYS INC. RECENT DEVELOPMENTS 165 TABLE 104 ATHERSYS FINANCIALS, ($ MILLIONS/%) 165 TABLE 105 BIOHEART INC. RECENT DEVELOPMENTS 166 TABLE 106 CERAPEDICS INC. RECENT DEVELOPMENTS 167 TABLE 107 CO.DON AG RECENT DEVELOPMENTS 168 TABLE 108 COOK MEDICAL INC. RECENT DEVELOPMENTS 169 TABLE 109 CRYO LIFE INC. RECENT DEVELOPMENTS 170 TABLE 110 CYTOGRAFT TISSUE ENGINEERING RECENT DEVELOPMENTS 171 TABLE 111 CYTOMEDIX INC. RECENT DEVELOPMENTS 172 TABLE 112 CYTORI THERAPEUTICS INC. RECENT DEVELOPMENTS 173 TABLE 113 CYTORI THERAPEUTICS FINANCIALS, ($ MILLIONS/%) 173 TABLE 114 GENZYME RECENT DEVELOPMENTS 174 TABLE 115 GENZYME FINANCIALS, ($ MILLIONS/%) 174 TABLE 116 KINETIC CONCEPTS INC. RECENT DEVELOPMENTS 175 TABLE 117 KINETICS CONCEPTS FINANCIALS, ($ MILLIONS/%) 175 TABLE 118 WRIGHT MEDICAL TECHNOLOGY INC. RECENT DEVELOPMENTS 178 TABLE 119 WRIGHT MEDICAL TECHNOLOGY FINANCIALS, ($ MILLIONS/%) 178 TABLE 120 NORTH AMERICAN PATENTS 180 TABLE 121 EUROPEAN PATENTS 181 TABLE 122 JAPANESE PATENTS 182

16 LIST OF FIGURES FIGURE TITLE SUMMARY FIGURE GLOBAL TISSUE ENGINEERING AND REGENERATION MARKET BY REGION, ($ FIGURE 1 TISSUE-ENGINEERING STRATEGIES 12 FIGURE 2 POTENTIAL NANOTECHNOLOGY APPLICATIONS 14 FIGURE 3 PORTER S FIVE FORCE MODEL FOR TISSUE ENGINEERING PRODUCTS 24 FIGURE 4 GROWTH IN DISEASE TREATED VERSUS CLINICAL TRIALS, (NO. OF TRIALS AND TREATMENTS) FIGURE 5 PATHWAY FOR DISSEMINATION OF REGENERATIVE MEDICINE 133 FIGURE 6 KEY COMPETITIVE STRATEGIES*, (%) 142 FIGURE 7 APPROVAL STRATEGY BY COMPANY, (%) 144 FIGURE 8 AGREEMENTS, MERGERS AND ACQUISITIONS, BY COMPANY, (%) 147 FIGURE 9 PRODUCT LAUNCHES AND CLINICAL TRIALS BY COMPANY, (%) 150 FIGURE 10 REGISTERED AND APPROVED PATENTS BY COUNTRY, (%) 153 FIGURE 11 U.S. PATENT ANALYSIS BY MARKET PARTICIPANT, (%) 154 FIGURE 12 U.S. PATENT ANALYSIS BY APPLICATION, (%) 155 FIGURE 13 EUROPEAN PATENT ANALYSIS BY MARKET PARTICIPANT, (%) 156 FIGURE 14 EUROPEAN PATENT ANALYSIS BY APPLICATION, (%) 158 FIGURE 15 JAPANESE PATENT ANALYSIS BY APPLICATION, (%)