Regenerative Medicines: Bone and Joint Applications

Table of Contents

Chapter- 1: INTRODUCTION -- Complimentary 4

• OBJECTIVES AND GOALS OF STUDY 1
• INTENDED AUDIENCE 2
• SCOPE OF REPORT 2
• METHODOLOGY 3
• INFORMATION SOURCES 3
• ANALYST CREDENTIALS 3
• RELATED BCC REPORTS 3
• BCC ONLINE SERVICES 4
• DISCLAIMER 4

Chapter-2: SUMMARY 2

• SUMMARY (CONTINUED) 5
• SUMMARY TABLE U.S. MARKET FOR REGENERATIVE MEDICINE PRODUCTS USED IN BONE AND JOINT APPLICATIONS, THROUGH 2014 ($ MILLIONS) 6
• SUMMARY FIGURE U.S. MARKET FOR REGENERATIVE MEDICINE PRODUCTS USED IN BONE AND JOINT APPLICATIONS, 2007-2014 ($ MILLIONS) 6

Chapter-3: OVERVIEW AND OVERALL STATUS OF THE INDUSTRY 11

• TOTAL SCOPE OF REGENERATIVE MEDICINE MARKET 7
• TABLE 1 FUNCTIONAL ACTIVITIES WITH REGENERATIVE MEDICINE SECTOR 8
• HOW REGENERATIVE MEDICINE WORKS 8
• TISSUES AND ORGANS ON DEMAND 9
• ORGAN REPLACEMENT IS A $100 BILLION PER YEAR BUSINESS 10
• EXAMPLES OF IMPACT ON EXISTING CONDITIONS AND DISEASES 10
• BARRIERS TO REGENERATIVE MEDICINE 11
• CURRENT R&D PRIORITIES 12
• TABLE 2 PRINCIPAL REGENERATIVE MEDICINE BUSINESS R&D FOCUSES 13
• TABLE 3 20-YEAR PLANNING HORIZON FOR REGENERATIVE MEDICINE BUSINESS: LIKELY DEVELOPMENTS, 2015-2030 14
• TOTAL OUTPUT OF THE SECTOR 15
• REGENERATIVE MEDICINE AND HEALTHCARE ECONOMICS 15
• POPULATION TRENDS 16
• MARKET TIMING 16
• OVERSEAS INITIATIVES 17

Chapter-4: PRINCIPLE APPROACHES TO REGENERATIVE MEDICINE 13

• GENE- AND PROTEIN-BASED APPROACHES 31
• ANTIBODIES 31
• The Importance of Antibody Drugs 32
• Advantages of Monoclonal Antibody Drugs 33
• Antibodies and Osteoarthritis 34
• GROWTH FACTORS 35
• GROWTH FACTORS (CONTINUED) 36
• HOW BMPS FUNCTION 37
• TABLE 6 BONE MORPHOGENETIC PROTEINS 38
• Clinical Uses 38
• Companies 39
• CELLS AND TISSUES 40
• TISSUE ENGINEERING 40
• ARTIFICIAL SKIN 41
• CARTILAGE 42
• OTHER APPROACHES TO CARTILAGE 43
• BIOSYNTHETIC COMPOSITES FOR CARTILAGE REPAIR 44
• THE MARKET FOR TISSUE-ENGINEERED CARTILAGE PRODUCTS 44
• TABLE 7 U.S. MARKET FOR TISSUE-ENGINEERED CARTILAGE PRODUCTS, THROUGH 2014 ($ MILLIONS) 45
• OTHER PRODUCTS 45
• CREATION OF ENTIRE ORGANS 45
• CREATION OF ENTIRE ORGANS (CONTINUED) 46
• EMBRYONIC STEM CELLS 47
• NOVEL MATERIALS AND BIOMATERIALS 48

Chapter-5: PRODUCTS AND TECHNOLOGIES: CATEGORIES OF REGENERATIVE MEDICINE 18

Chapter-6: STEM CELL THERAPIES AND REGENERATIVE MEDICINE 18

• STEM CELLS AS POTENTIAL REPLACEMENT CELLS 49
• TECHNICAL IMPEDIMENTS 50
• OVERVIEW OF FUNDING 51
• TABLE 8 FEDERAL FUNDING FOR STEM CELL RESEARCH, THROUGH 2008 ($ MILLIONS) 52
• STATE-LEVEL INITIATIVES FOR STEM CELL RESEARCH 52
• TABLE 9 STATE LEVEL PROGRAMS FOCUSED ON STEM CELL RESEARCH 53
• POTENTIAL APPLICATIONS: CURRENT STATUS 53
• IN VIVO REPROGRAMMING 54
• UMBILICAL CORD BLOOD STEM CELLS 55
• Recent Research Developments 55
• INDUCED PLURIPOTENT STEM CELLS 56
• Recent Research Developments 56
• Adult Multipotent Stem Cells 57
• Embryonic Stem Cells 57
• Embryonic Stem Cells (Continued) 58
• GERON AND THE FIRST HUMAN TRIALS 59
• GERON AND THE FIRST HUMAN TRIALS (CONTINUED) 60
• OTHER STEM CELL RESEARCH 61
• STATUS OF OTHER CLINICAL TRIALS 62
• STEM CELL THERAPY FOR ALS 63
• STEM CELL THERAPY FOR DUCHENNE MUSCULAR DYSTROPHY 64
• STEM CELL THERAPY AND BONE MARROW TRANSPLANTS 65
• Stem Cell Therapy and ... (Continued) 66

Chapter-7: REGENERATIVE PRODUCTS TO TREAT BONE DISEASES 33

• MATERIALS FOR BONE TISSUE REPAIR 100
• INHERENT REGENERATION OF BONE 100
• OVERALL SIZE OF BONE GRAFT BUSINESS 101
• BONE GRAFT SUBSTITUTES 102
• ALLOGRAFT TISSUE 103
• OTHER OSTEOCONDUCTIVE BONE GRAFT SUBSTITUTES 104
• HYDROGELS AND REGENERATION 105
• COMPOSITION AND METHOD FOR SELF-ASSEMBLY AND MINERALIZATION OF PEPTIDE AMPHIPHILES 106
• CHONDROITINASE ABC I POLYNUCLEOTIDES 107
• Abstract 107
• TRANSDISCAL ADMINISTRATION OF CYCLINE COMPOUNDS 107
• Abstract 107
• COMPOSITION AND METHOD FOR PREPARING BIOCOMPATIBLE SURFACES 108
• Abstract 108
• SPINAL MOBILITY PRESERVATION APPARATUS HAVING AN EXPANDABLE MEMBRANE 108
• Abstract 108
• MAJOR DISEASES AND CONDITIONS AFFECTING BONES 109
• OSTEOPOROSIS 110
• Currently Available Products to Treat Osteoporosis 111
• Bisphosphonates 111
• Fosamax 112
• Boniva 113
• TABLE 19 DRUGS USED TO TREAT OSTEOPOROSIS 113
• Hormones 114
• Evista 114
• Forteo 114
• Forteo (Continued) 115
• Forteo (Continued) 116
• Miacalcin 117
• STEROIDS AND OSTEOPOROSIS 117
• Glucocorticoids 118
• THE MARKET FOR PRODUCTS TO TREAT OSTEOPOROSIS. 118
• TABLE 20 WORLDWIDE MARKET FOR DRUGS TO TREAT OSTEOPOROSIS, THROUGH 2014 ($ MILLIONS) 119
• FIGURE 4 WORLDWIDE MARKET FOR DRUGS TO TREAT OSTEOPOROSIS, 2007-2014 ($ MILLIONS) 119
• PAGET' S DISEASE 119
• DRUGS CURRENTLY AVAILABLE TO TREAT PAGET' S DISEASE 120
• Actonel 120
• Aredia 120
• Skelid 121
• Zometa 121
• THE MARKET FOR PRODUCTS TO TREAT PAGET' S DISEASE 121
• TABLE 21 WORLDWIDE MARKET FOR DRUGS TO TREAT PAGET' S DISEASE, THROUGH 2014 ($ MILLIONS) 121
• FIGURE 5 WORLDWIDE MARKET FOR DRUGS TO TREAT PAGET' S DISEASE, 2007-2014 ($ MILLIONS) 122
• INJURIES AND DEGENERATIVE CONDITIONS 122
• HIP FRACTURES 123
• TABLE 22 WORLDWIDE HIP FRACTURE VOLUMES, THROUGH 2014 124
• TABLE 23 U.S. HIP FRACTURE VOLUMES, THROUGH 2014 124
• TRADITIONAL TREATMENTS FOR BONE AND JOINT DISORDERS 124
• TABLE 24 U.S. MARKET SHARES FOR MUSCULOSKELETAL PRODUCTS, 2008 (%) 125
• TABLE 25 U.S. RECONSTRUCTIVE DEVICE MARKET, 2008 (%) 125
• MARKET LEADERS 125
• JOINT-REPLACEMENT SURGERY 126
• TABLE 26 HIP REPLACEMENT PROCEDURE VOLUMES, U.S., THROUGH 2014 126
• TABLE 27 HISTORICAL RATES OF HIP REPLACEMEN IN SIX MAJOR STATES, 2001 126
• TABLE 28 WORLDWIDE HIP REPLACEMENT MARKET, THROUGH 2014 ($ MILLIONS) 127
• FIGURE 6 WORLDWIDE HIP REPLACEMENT MARKET, 2007-2014 ($ MILLIONS) 127
• TABLE 29 U.S. HIP REPLACEMENT MARKET, THROUGH 2014 ($ MILLIONS) 127
• FIGURE 7 U.S. HIP REPLACEMENT MARKET, 2007-2014 ($ MILLIONS) 128
• KNEE REPLACEMENTS 128
• TABLE 30 WORLDWIDE KNEE-REPLACEMENT PROCEDURE VOLUMES, THROUGH 2014 129
• TABLE 31 U.S. KNEE REPLACEMENT PROCEDURE VOLUMES, THROUGH 2014 129
• TABLE 32 WORLDWIDE KNEE REPLACEMENT MARKET, THROUGH 2014 ($ MILLIONS) 129
• FIGURE 8 WORLDWIDE KNEE REPLACEMENT MARKET, 2007-2014 ($ MILLIONS) 130
• TABLE 33 U.S. KNEE REPLACEMENT MARKET, THROUGH 2014 ($ MILLIONS) 130
• FIGURE 9 U.S. KNEE REPLACEMENT MARKET, 2007-2014 ($ MILLIONS) 131
• TABLE 34 U.S. MARKET FOR UNICONDYLAR KNEE REPLACEMENT, THROUGH 2014 ($ MILLIONS) 131
• FIGURE 10 U.S. MARKET FOR UNICONDYLAR KNEE REPLACEMENT, 2007-2014 ($ MILLIONS) 132
• NATURAL THERAPEUTIC TREATMENTS FOR ARTHRITIS 132
• IMAGING AND REGENERATION 133
• IMAGING AND REGENERATION (CONTINUED) 134

Chapter-8: REGENERATIVE APPLICATIONS FOR BONES AND JOINTS 35

Chapter-9: ELECTRICAL BONE GROWTH STIMULATOR MARKET 8

• OVERVIEW 135
• SCIENTIFIC BASIS 136
• ULTRASONIC OSTEOGENESIS STIMULATORS FOR BONE HEALING 137
• MARKETERS OF INVASIVE AND NONINVASIVE ELECTRICAL BONE GROWTH STIMULATORS 138
• BIOMET 138
• ORTHOFIX 139
• DJO, INC. 140
• SMITH & NEPHEW 141
• MARKET SIZE 141
• TABLE 35 WORLDWIDE MARKET FOR NONINVASIVE BONE GROWTH STIMULATORS, THROUGH 2014 ($ MILLIONS) 141
• TABLE 36 U.S. MARKET FOR NONINVASIVE BONE GROWTH STIMULATORS, THROUGH 2007 ($ MILLIONS) 142

Chapter-10: ORTHOPEDICS - FDA CLEARANCES AND NEW PRODUCT DEVELOPMENT 16

• SUPPLIERS OF REGENERATIVE BONE AND JOINT PRODUCTS 143
• TABLE 37 RECENTLY APPROVED ORTHOPEDIC BONE AND JOINT DEVICES BY PRODUCT, COMPANY, AND APPROVAL DATE, 2008 - 2009 144
• TABLE 37 (CONTINUED) 145
• TABLE 37 (CONTINUED) 146
• TABLE 37 (CONTINUED) 147
• TABLE 37 (CONTINUED) 148
• TABLE 37 (CONTINUED) 149
• TABLE 37 (CONTINUED) 150
• TABLE 37 (CONTINUED) 151
• TABLE 37 (CONTINUED) 152
• TABLE 37 (CONTINUED) 153
• TABLE 37 (CONTINUED) 154
• TABLE 37 (CONTINUED) 155
• TABLE 37 (CONTINUED) 156
• TABLE 37 (CONTINUED) 157
• TABLE 37 (CONTINUED) 158

Chapter-11: MARKET FOR TISSUE ENGINEERING PRODUCTS 4

• TISSUE ENGINEERING AND CELL THERAPY 159
• RESEARCH INITIATIVES 160
• RESEARCH INITIATIVES (CONTINUED) 161
• RESEARCH INITIATIVES (CONTINUED) 162

Chapter-12: REGENERATIVE CONCEPTS AND PRODUCTS IN DENTISTRY 3

• OVERVIEW 163
• INDICATIONS AND HISTORY 163
• CHARACTERTISTICS AND MATERIALS 164
• BARRIER MEMBRANES 164
• NON-RESORBABLE 164
• RESORBABLE 164
• COLLAGEN RESORBABLE MEMBRANES 165
• SYNTHETIC RESORBABLE MEMBRANES 165

Chapter-13: SKIN TECHNOLOGIES 3

• SKIN TECHNOLOGIES (CONTINUED) 166
• SKIN-LIKE TISSUE DEVELOPED FROM HUMAN EMBRYONIC STEM CELLS 167
• TABLE 38 SALES OF ENGINEERED SKIN GRAFTS AND REPLACEMENTS, THROUGH 2014 ($ MILLIONS) 168

Chapter-14: NEUROLOGICAL APPLICATIONS IN REGENERATIVE MEDICINE 4

• OVERVIEW 169
• NEURODEGENERATIVE DISEASES 169
• CURRENT CONVENTIONAL THERAPIES FOR THE TREATMENT OF NEURODEGENERATIVE DISEASE SYMPTOMS 169
• SPINAL CORD INJURY, NEURODEGENERATIVE DISEASES, AND REGENERATIVE POTENTIAL 170
• SPINAL CORD INJURY, ... (CONTINUED) 171
• UNIVERSITY OF SOUTHERN CALIFORNIA (USC) 172

Chapter-15: REGENERATIVE MEDICINE AND APPLICATIONS IN CARDIAC CARE 6

• OVERVIEW 173
• STEM CELLS FOR THE FUTURE TREATMENT OF HEART DISEASE 173
• PARTICULAR R&D PRIORITIES 174
• PARTICULAR R&D PRIORITIES (CONTINUED) 175
• STEM CELLS AND BIOLOGICAL PACEMAKERS 176
• HEART PROGENITOR CELLS DEVELOPED FROM EMBRYONIC STEM CELLS 176
• OTHER CURRENT REGENERATIVE MEDICINE AS IT RELATES TO THE HEART 177
• OTHER CURRENT REGENERATIVE ...(CONTINUED) 178

Chapter-16: REGENERATIVE MEDICINE AND DIABETES 2

• BACKGROUND 179
• POSSIBLE APPLICATIONS FOR REGENERATIVE MEDICINE 179
• POSSIBLE APPLICATIONS FOR ... (CONTINUED) 180

Chapter-17: FDA APPROVED CLINICAL TRIALS INVOLVING REGENERATIVE MEDICINE 29

• CURRENT STATUS OF THE REGENERATIVE MEDICINE BUSINESS 181
• REGULATORY ENVIRONMENT 181
• REGULATORY ENVIRONMENT (CONTINUED) 182
• STATUS OF RESEARCH AND CLINICAL TRIALS 183
• ANALYSIS OF CLINICAL TRIALS 184
• TABLE 39 REGENERATIVE MEDICINE CLINICAL TRIALS BY MAJOR CATEGORY 185
• TABLE 40 CURRENT CLINICAL TRIALS IN THE FIELD OF REGENERATIVE MEDICINE STATUS, CONDITIONS, INTERVENTION, AND SPONSOR 185

• TABLE 40 (CONTINUED) 186
• TABLE 40 (CONTINUED) 187
• TABLE 40 (CONTINUED) 188
• TABLE 40 (CONTINUED) 189
• TABLE 40 (CONTINUED) 190
• TABLE 40 (CONTINUED) 191
• TABLE 40 (CONTINUED) 192
• TABLE 40 (CONTINUED) 193
• TABLE 40 (CONTINUED) 194
• TABLE 40 (CONTINUED) 195
• TABLE 40 (CONTINUED) 196
• TABLE 40 (CONTINUED) 197
• TABLE 40 (CONTINUED) 198
• TABLE 40 (CONTINUED) 199
• TABLE 40 (CONTINUED) 200
• TABLE 40 (CONTINUED) 201
• TABLE 40 (CONTINUED) 202
• TABLE 40 (CONTINUED) 203
• TABLE 40 (CONTINUED) 204
• TABLE 40 (CONTINUED) 205
• TABLE 40 (CONTINUED) 206
• TABLE 40 (CONTINUED) 207
• TABLE 40 (CONTINUED) 208
• TABLE 40 (CONTINUED) 209

Chapter-18: OVERSEAS ACTIVITIES 3

• DOMESTIC VERSUS OVERSEAS REGENERATIVE MEDICINE COMPANIES 210
• JAPAN 210
• EUROPE 211
• AUSTRALIA AND CHINA 212

Chapter-19: PATENT ANALYSIS 5

• ANALYSIS 213
• TISSUE ENGINEERING PATENTS 213
• TABLE 41 MOST FREQUENTLY CITED PATENT ASSIGNEES IN TISSUE ENGINEERING FIELD 214
• GEOGRAPHIC DISTRIBUTION 214
• TABLE 42 WORLD DISTRIBUTION OF REGENERATIVE MEDICINE PATENTS ISSUED, 1985 - 2009 (%) 215
• RECENT PATENTS 215
• DIRECT DIFFERENTIATION METHOD FOR MAKING CARDIOMYOCYTES FROM HUMAN EMBRYONIC STEM CELLS 215
• Abstract 215
• METHOD FOR PREPARING NOVEL TRANSCRIPTION FACTORS AND USE 216
• Abstract 216
• ENDODERM CELLS FROM HUMAN EMBRYONIC STEM CELLS 216
• Abstract 216
• GENES WITH ES CELL-SPECIFIC EXPRESSION 217
• Abstract 217
• MARKER SYSTEM FOR PREPARING AND CHARACTERIZING HIGH-QUALITY HUMAN EMBRYONIC STEM CELLS 217
• Abstract 217

Chapter-20: COMPANY PROFILES 45

• TABLE 43 PUBLICALLY TRADED COMPANIES IN THE REGENERATIVE MEDICINE INDUSTRY, AS OF JULY 1, 2009 218
• AASTROM BIOSCIENCES, INC. 219
• ADVANCED BIOHEALING, INC. 219
• ADVANCED CELL TECHNOLOGY, INC. 220
• AESCULAP, INC. 221
• ALDAGEN, INC. 221
• ALPHATEC SPINE, INC. 222
• ANGIOTECH PHARMACEUTICALS, INC. 222
• ARTERIOCYTE MEDICAL SYSTEMS, INC. 223
• ARTHREX, INC. 223
• ARTHROCARE CORPORATION 223
• BIOMET, INC. 224
• BIOMIMETIC THERAPEUTICS, INC. 224
• BIOTISSUE TECHNOLOGIES GMBH 224
• CAPSTONE THERAPEUTICS 225
• CENTERPULSE ORTHOPAEDICS, INC. 226
• CERAPEDICS, INC. 226
• CITAGENIX, INC. 226
• CONMED CORPORATION 227
• CROSSCART INC. 228
• CRYOLIFE, INC. 229
• CURIS 230
• CYTORI THERAPEUTICS, INC. 231
• DEPUY ORTHOPAEDICS, INC. (UNIT OF THE DEPUY COMPANIES) 231
• DJO SURGICAL 232
• ESBATECH AG 232
• ETEX CORPORATION 233
• EXACTECH, INC. 234
• FATE THERAPEUTICS, INC. 234
• GARNET BIOTHERAPEUTICS 234
• GENZYME BIOSURGERY 235
• GERON CORPORATION 236
• INTEGRA LIFESCIENCES HOLDING CORP. 236
• ISOTIS ORTHOBIOLOGICS, INC. (INTEGRA ORTHOBIOLOGICS) 237
• INTERNATIONAL STEM CELL 237
• INTERPORE CROSS INTERNATIONAL 238
• ISTO TECHNOLOGIES, INC. 239
• KENSEY NASH CORPORATION 240
• LIFECELL (A SUBSIDIARY OF KINETIC CONCEPTS, INC.) 241
• MCEWEN CENTRE FOR REGENERATIVE MEDICINE 241
• MCGOWAN INSTITUTE FOR REGENERATIVE MEDICINE 242
• MEDTRONIC, INC. 242
• MESOBLAST, LIMITED 243
• NATIONAL CENTER FOR REGENERATIVE MEDICINE 243
• NATIONAL TISSUE ENGINEERING CENTER (NTEC) 244
• NEURALSTEM 245
• NOVABONE PRODUCTS, LLC 246
• NOVARTIS CORPORATION 246
• NOVOCELL, INC. 246
• OPEXA THERAPEUTICS 246
• ORGANOGENESIS INC. 247
• ORTHOFIX INTERNATIONAL N.V. 248
• ORTHOPEUTICS, L.P. 248
• ORTHOVITA, INC. 249
• OSIRIS THERAPEUTICS, INC. 249
• OSTEOTECH, INC. 250
• PFIZER, INC. 250
• PLURISTEM THERAPEUTICS 250
• REGEN BIOLOGICS, INC. 251
• RENEURON 252
• RTI BIOLOGICS, INC. 252
• SCIL TECHNOLOGY GMBH 252
• SMITH AND NEPHEW 253
• STEMCELLS, INC. 253
• STEMCOR SYSTEMS, INC. 254
• STRAUMANN USA LLC 254
• STRYKER CORP. 255
• SYNTHES, INC. 255
• TENGION 256
• TEPHA 257
• THERMOGENESIS CORP. 257
• TIGENIX N.V. 258
• UCB S.A. (HEADQUARTERS) 259
• WAKE FOREST INSTITUTE FOR REGENERATIVE MEDICINE 259
• WRIGHT MEDICAL GROUP, INC. 260
• ZIMMER HOLDINGS, INC. 261
• OTHER ORGANIZATIONS INVOLVED IN REGENRERATIVE MEDICINE R&D 261
• ACADEMIC INSTITUTIONS 261
• U.S. GOVERNMENT 262
• OTHER SOCIETIES AND ORGANIZATIONS 262

Chapter-21: GLOSSARY OF KEY TERMS IN REGENERATIVE MEDICINE BUSINESS 7

• GLOSSARY OF KEY TERMS 263
• GLOSSARY OF KEY TERMS (CONTINUED) 264
• GLOSSARY OF KEY TERMS (CONTINUED) 265
• GLOSSARY OF KEY TERMS (CONTINUED) 266
• GLOSSARY OF KEY TERMS (CONTINUED) 267
• GLOSSARY OF KEY TERMS (CONTINUED) 268
• GLOSSARY OF KEY TERMS (CONTINUED) 269