Table of Contents

1. MUSCULOSKELETAL SYSTEM OVERVIEW …………………………………….. 1-1
1.1 Bone Structure and Function……………………………………………………. 1-1
1.1.1 Cellular Framework ………………………………………………….. 1-1
1.1.1.1 Osteoblasts ………………………………………………. 1-2
1.1.1.2 Osteocytes ……………………………………………….. 1-2
1.1.1.3 Osteoclasts ………………………………………………. 1-3
1.1.1.4 Osteogenesis ……………………………………………. 1-3
1.1.2 Bone Tissue ……………………………………………………………. 1-4
1.1.2.1 Cancellous and Cortical Bone Tissue……………. 1-4
1.1.2.2 Bone Marrow…………………………………………….. 1-6
1.1.3 Bone Anatomy…………………………………………………………. 1-6
1.1.3.1 Diaphysis and Epiphysis …………………………….. 1-6
1.1.3.2 Endosteum ……………………………………………….. 1-7
1.1.3.3 Periosteum ……………………………………………….. 1-7
1.1.4 Joint Components ……………………………………………………. 1-7
1.1.4.1 Cartilage…………………………………………………… 1-7
1.1.4.1.1 Elastic Cartilage……………………… 1-8
1.1.4.1.2 Fibrocartilage …………………………. 1-8
1.1.4.1.3 Hyaline Cartilage…………………….. 1-8
1.1.4.2 Bursae……………………………………………………. 1-10
1.1.4.3 Joint Cavity……………………………………………… 1-10
1.1.4.4 Menisci …………………………………………………… 1-10
1.1.4.5 Synovial Membrane and Fluid……………………. 1-10
1.1.4.6 Ligaments and Tendons……………………………. 1-11
1.1.4.7 Muscles ………………………………………………….. 1-11
1.1.5 Joint Structures ……………………………………………………… 1-12
1.1.5.1 Ankle ……………………………………………………… 1-13
1.1.5.2 Digits ……………………………………………………… 1-13
1.1.5.3 Elbow …………………………………………………….. 1-14
1.1.5.4 Hip…………………………………………………………. 1-14
1.1.5.5 Knee………………………………………………………. 1-14
1.1.5.6 Shoulder…………………………………………………. 1-14
1.1.5.7 Wrist ………………………………………………………. 1-15
1.1.6 Bone Formation and Remodeling……………………………… 1-15
1.1.6.1 In the Fetus …………………………………………….. 1-15
1.1.6.2 In Childhood ……………………………………………. 1-17
1.1.6.3 In Adulthood ……………………………………………. 1-17
1.1.6.4 In Old Age ………………………………………………. 1-17
1.1.6.5 Mechanical Stress and Wolff’s Law…………….. 1-18
1.1.7 Factors Affecting Bone Physiology……………………………. 1-18
1.1.7.1 Age………………………………………………………… 1-18
1.1.7.2 Gender …………………………………………………… 1-18
1.1.7.3 Genetic Disposition ………………………………….. 1-19
1.1.7.4 Hormonal Activity …………………………………….. 1-19
1.1.7.5 Physical Activity……………………………………….. 1-20
1.1.7.6 Cigarette Smoking……………………………………. 1-20
1.1.7.7 Alcohol and Caffeine Intake ………………………. 1-20
1.1.7.8 Nutritional Deficiencies……………………………… 1-21
1.2 Joint Structure and Function…………………………………………………… 1-22
1.2.1 Types of Joints ………………………………………………………. 1-22
1.2.1.1 Synarthroses …………………………………………… 1-22
1.2.1.2 Amphiarthroses ……………………………………….. 1-22
1.2.1.3 Diarthroses……………………………………………… 1-22
1.2.1.3.1 Ball-and-Socket…………………….. 1-23
1.2.1.3.2 Condyloid…………………………….. 1-23
1.2.1.3.3 Hinge ………………………………….. 1-23
1.2.1.3.4 Gliding…………………………………. 1-23
1.2.1.3.5 Pivot……………………………………. 1-23
1.2.2 Arthritis …………………………………………………………………. 1-23
1.2.2.1 Osteoarthritis…………………………………………… 1-24
1.2.2.2 Rheumatoid Arthritis…………………………………. 1-25
1.3 Management of Joint Disorders………………………………………………. 1-26
1.3.1 Joint Replacement………………………………………………….. 1-26
1.3.1.1 Dislocation………………………………………………. 1-27
1.3.1.2 Ligament and Tendon Injuries……………………. 1-27
1.3.1.3 Meniscal Injuries………………………………………. 1-28
Exhibit 1-1: Illustration of Bone Tissue ……………………………………………………….. 1-5
Exhibit 1-2: Types of Cartilage ………………………………………………………………….. 1-9
Exhibit 1-3: Stages of Bone Remodeling…………………………………………………… 1-16
2. BIORESORBABLE FIXATION DEVICES …………………………………………… 2-1
2.1 Materials……………………………………………………………………………….. 2-1
2.2 Products ……………………………………………………………………………….. 2-3
2.2.1 Bioresorbable Pins …………………………………………………… 2-3
2.2.2 Bioresorbable Screws, Nails, and Tacks ……………………… 2-8
2.2.3 Bioresorbable Interference Screws …………………………….. 2-8
2.2.4 Bioresorbable Suture Anchors……………………………………. 2-8
2.2.5 Bioresorbable Meniscal Repair Devices…………………….. 2-13
2.3 Market Analysis ……………………………………………………………………. 2-16
2.4 Competitive Analysis …………………………………………………………….. 2-19
Exhibit 2-1: Advantages of Bioresorbable Fixation Devices …………………………… 2-2
Exhibit 2-2: Factors Affecting the Properties of Bioresorbable Polymers …………. 2-4
Exhibit 2-3: Types of Bioresorbable Fixation Devices …………………………………… 2-5
Exhibit 2-4: 2013, Selected Bioresorbable Pins……………………………………………. 2-6
Exhibit 2-5: 2013, Selected Bioresorbable Nails, Screws, and Tacks ……………… 2-9
Exhibit 2-6: 2013, Selected Bioresorbable Interference Screws……………………. 2-11
Exhibit 2-7: 2013, Selected Bioresorbable Suture Anchors………………………….. 2-14
Exhibit 2-8: 2013, Selected Bioresorbable Meniscal Repair Devices …………….. 2-17
Exhibit 2-9: Bioresorbable Fixation Devices, Market Forecast, 2012-2017 ……. 2-18
Exhibit 2-10: 2012, Bioresorbable Fixation Devices Market, Share by Supplier… 2-21
3. VISCOSUPPLEMENTATION ……………………………………………………………. 3-1
3.1 Osteoarthritis Clinical Overview………………………………………………… 3-1
3.2 Viscosupplementation Therapy ………………………………………………… 3-1
3.3 Products ……………………………………………………………………………….. 3-4
3.3.1 Anika Therapeutics…………………………………………………… 3-6
3.3.2 Ferring Pharmaceuticals……………………………………………. 3-7
3.3.3 Fidia Pharma USA/Fidia Farmaceutici ………………………… 3-7
3.3.4 Genzyme/Sanofi………………………………………………………. 3-8
3.3.5 Seikagaku……………………………………………………………….. 3-8
3.3.6 Smith & Nephew………………………………………………………. 3-9
3.4 Emerging Products……………………………………………………………….. 3-13
3.5 Potential Viscosupplementation Patients………………………………….. 3-14
3.6 Product Reimbursement………………………………………………………… 3-18
3.7 Market Analysis ……………………………………………………………………. 3-18
3.8 Competitive Analysis …………………………………………………………….. 3-23
Exhibit 3-1: 2013, Administerers of Hyaluronic Acid Injection Therapy,
by Specialty …………………………………………………………………………… 3-3
Exhibit 3-2: 2013, Selected Viscosupplementation Products ……………………….. 3-10
Exhibit 3-3: 2013, Selected Emerging Viscosupplementation Therapies ……….. 3-15
Exhibit 3-4: 2012, Patients with Knee Osteoarthritis……………………………………. 3-17
Exhibit 3-5: Projected Incidence of Symptomatic Knee Osteoarthritis,
by 10-Year Age Group…………………………………………………………… 3-19
Exhibit 3-6: Historical and Future Annual Growth Rates
in the Elderly Population………………………………………………………… 3-22
Exhibit 3-7: Viscosupplementation Products, Market Forecast, 2012-2017 ……. 3-24
Exhibit 3-8: 2012, Viscosupplementation Products Market,
Share by Supplier…………………………………………………………………. 3-28
4. CARTILAGE REPAIR AND REGENERATION ……………………………………. 4-1
4.1 Clinical Overview……………………………………………………………………. 4-1
4.2 Products ……………………………………………………………………………….. 4-5
4.2.1 Cell-Based Approaches…………………………………………….. 4-7
4.2.1.1 Chondrocyte Transplantation ………………………. 4-7
4.2.1.1.1 Anika Therapeutics …………………. 4-7
4.2.1.1.2 BioTissue Technologies…………. 4-12
4.2.1.1.3 DePuy Mitek/
Johnson & Johnson ………………. 4-12
4.2.1.1.4 Geistlich Pharma…………………… 4-12
4.2.1.1.5 Genzyme/Sanofi …………………… 4-12
4.2.1.1.6 ProChon Biotech/Histogenics …. 4-13
4.2.1.1.7 Sanofi………………………………….. 4-14
4.2.1.1.8 TETEC/B. Braun Melsungen…… 4-14
4.2.1.1.9 TiGenix ……………………………….. 4-14
4.2.1.1.10 Allogeneic Juvenile
Chondrocytes……………………….. 4-14
4.2.1.2 Stem Cells………………………………………………. 4-15
4.2.1.2.1 Geron………………………………….. 4-16
4.2.1.2.2 Medipost ……………………………… 4-16
4.2.1.2.3 Mesoblast ……………………………. 4-17
4.2.1.2.4 Smith & Nephew …………………… 4-17
4.2.1.3 Growth Factor Technology ………………………… 4-17
4.2.1.3.1 BioMimetic Therapeutics/
Wright Medical Group ……………. 4-19
4.2.1.3.2 EMD Serono/Merck……………….. 4-19
4.2.1.3.3 Sanofi………………………………….. 4-19
4.2.1.3.4 TissueGene …………………………. 4-22
4.2.2 Cell-Free Composites and Scaffolds …………………………. 4-22
4.2.2.1 Anika Therapeutics…………………………………… 4-23
4.2.2.2 Arthro Kinetics…………………………………………. 4-27
4.2.2.3 Biomet ……………………………………………………. 4-27
4.2.2.4 BioTissue ……………………………………………….. 4-27
4.2.2.5 Cartiva……………………………………………………. 4-27
4.2.2.6 Cytex ……………………………………………………… 4-28
4.2.2.7 Histogenics……………………………………………… 4-28
4.2.2.8 Kensey Nash/Royal DSM………………………….. 4-28
4.2.2.9 Piramal Healthcare…………………………………… 4-29
4.2.2.10 Regentis Biomaterials ………………………………. 4-29
4.2.2.11 Smith & Nephew………………………………………. 4-29
4.3 Reimbursement ……………………………………………………………………. 4-30
4.4 Market Analysis ……………………………………………………………………. 4-31
4.5 Competitive Analysis …………………………………………………………….. 4-35
Exhibit 4-1: The Outerbridge Classification System for Chondral Defects………… 4-3
Exhibit 4-2: Arthroscopic Knee Surgery, Procedure Volumes Forecast,
2012-2017 …………………………………………………………………………….. 4-4
Exhibit 4-3: 2012, Cartilage Repair Procedures …………………………………………… 4-6
Exhibit 4-4: Genzyme’s Carticel Autologous Chondrocyte
Implantation Device………………………………………………………………… 4-8
Exhibit 4-5: 2013, Selected Chondrocyte Graft Products and Technologies …….. 4-9
Exhibit 4-6: 2013, Selected Emerging Stem Cell-Based Products for
Cartilage Repair …………………………………………………………………… 4-18
Exhibit 4-7: 2013, Selected Emerging Recombinant Human Growth
Factor Products ……………………………………………………………………. 4-20
Exhibit 4-8: 2013, Selected Cell-Free Scaffolds for Cartilage Repair
and Regeneration…………………………………………………………………. 4-24
Exhibit 4-9: Cartilage Repair and Regeneration Products,
Market Forecast, 2012-2017 ………………………………………………….. 4-32
Exhibit 4-10: Cartilage Regeneration, Potential Procedure
Volumes Forecast, 2012-2017 ……………………………………………….. 4-34
5. MENISCAL REPAIR, REGENERATION, AND REPLACEMENT …………… 5-1
5.1 Clinical Overview……………………………………………………………………. 5-1
5.1.1 Meniscal Injuries………………………………………………………. 5-2
5.1.1.1 Traumatic Tears ………………………………………… 5-2
5.1.1.2 Degenerative Tears……………………………………. 5-5
5.2 Current Treatment ………………………………………………………………….. 5-5
5.2.1 Nonoperative Treatment……………………………………………. 5-8
5.2.2 Surgical Treatment …………………………………………………… 5-8
5.2.2.1 Arthroscopic Suturing …………………………………. 5-8
5.2.2.2 Bioresorbable Fixation………………………………… 5-9
5.2.2.3 Meniscectomy …………………………………………… 5-9
5.3 Procedure Volumes………………………………………………………………. 5-10
5.4 Meniscal Repair and Regeneration …………………………………………. 5-10
5.4.1 Bioresorbable Fixation Products……………………………….. 5-10
5.4.2 Market Analysis ……………………………………………………… 5-12
5.4.3 Competitive Analysis ………………………………………………. 5-14
5.5 Meniscal Replacement ………………………………………………………….. 5-16
5.5.1 Meniscal Allografts …………………………………………………. 5-18
5.5.2 Market Analysis ……………………………………………………… 5-19
5.5.3 Competitive Analysis ………………………………………………. 5-21
5.6 Meniscal Repair, Regeneration, and Replacement Technologies
Under Development………………………………………………………………. 5-21
5.6.1 Scaffolding Technologies ………………………………………… 5-21
5.6.1.1 Collagen …………………………………………………. 5-24
5.6.1.2 Fibrin ……………………………………………………… 5-24
5.6.1.3 Polymers ………………………………………………… 5-25
5.6.2 Cell Therapy………………………………………………………….. 5-26
5.7 Combined Market Forecast ……………………………………………………. 5-30
Exhibit 5-1: Anatomy of the Knee Joint ………………………………………………………. 5-3
Exhibit 5-2: Common Types of Meniscal Tears……………………………………………. 5-4
Exhibit 5-3: Illustration of a Meniscal Tear…………………………………………………… 5-6
Exhibit 5-4: Comparison of Treatment Options for Meniscal Injuries……………….. 5-7
Exhibit 5-5: Meniscectomy and Meniscal Repair,
Procedure Volumes Forecast, 2012-2017………………………………… 5-11
Exhibit 5-6: 2013, Selected Bioresorbable Fixation Devices
for Meniscal Repair……………………………………………………………….. 5-13
Exhibit 5-7: Bioresorbable Fixation Devices for Meniscal Repair,
Market Forecast, 2012-2017 ………………………………………………….. 5-15
Exhibit 5-8: 2012, Market for Bioresorbable Fixation Devices for
Meniscal Repair, Share by Supplier ………………………………………… 5-17
Exhibit 5-9: 2013, Selected Meniscal Allografts………………………………………….. 5-20
Exhibit 5-10: Meniscal Allografts, Market Forecast, 2012-2017 ……………………… 5-22
Exhibit 5-11: 2012, Meniscal Allografts Products Market, Share by Supplier ……. 5-23
Exhibit 5-12: 2013, Selected Meniscal Scaffolding Products
Under Development………………………………………………………………. 5-27
Exhibit 5-13: Chondrogen Phase I/II Clinical Trial Results …………………………….. 5-29
Exhibit 5-14: Meniscal Repair, Regeneration, and Replacement Products,
Combined Market Forecast, 2012-2017 …………………………………… 5-31
6. LIGAMENT AND TENDON REPAIR, REGENERATION,
AND REPLACEMENT ……………………………………………………………………… 6-1
6.1 Clinical Overview……………………………………………………………………. 6-1
6.1.1 The Knee………………………………………………………………… 6-1
6.1.2 The Achilles Tendon…………………………………………………. 6-5
6.1.3 Hand Ligaments and Tendons …………………………………… 6-7
6.1.4 Shoulder Ligaments and Tendons………………………………. 6-8
6.2 Procedure Volumes………………………………………………………………. 6-10
6.3 Current Treatments ………………………………………………………………. 6-10
6.3.1 Anterior Cruciate Ligament Tears……………………………… 6-10
6.3.2 Rotator Cuff Tears………………………………………………….. 6-13
6.4 Allografts …………………………………………………………………………….. 6-14
6.5 Tissue Engineering……………………………………………………………….. 6-16
6.5.1 Biologic Scaffolds …………………………………………………… 6-16
6.5.2 Polymer-Based Scaffolds ………………………………………… 6-19
6.6 Growth Factors…………………………………………………………………….. 6-24
6.6.1 Platelet-Rich Plasma ………………………………………………. 6-24
6.6.2 Synthetic Growth Factors ………………………………………… 6-26
6.7 Cell and Gene Therapies……………………………………………………….. 6-27
6.7.1 Cell-Based Therapies Under Development ………………… 6-30
6.8 Market Analysis ……………………………………………………………………. 6-31
6.9 Competitive Analysis …………………………………………………………….. 6-36
6.10 Ligament and Tendon Replacement Market Status …………………… 6-36
6.11 Emerging Ligament and Tendon Regeneration Products Market…. 6-38
Exhibit 6-1: Anatomy of the Knee Joint ………………………………………………………. 6-3
Exhibit 6-2: Anterior Cruciate Ligament Injury ……………………………………………… 6-4
Exhibit 6-3: Achilles Tendon Rupture …………………………………………………………. 6-6
Exhibit 6-4: Ligaments of the Shoulder……………………………………………………….. 6-9
Exhibit 6-5: 2012, Ligament and Tendon Procedures, by Anatomic Location …. 6-11
Exhibit 6-6: 2013, Selected Allografts for Ligament and Tendon Replacement.. 6-15
Exhibit 6-7: 2013, Selected Tissue-Engineered Ligament and Tendon
Repair Products……………………………………………………………………. 6-21
Exhibit 6-8: 2013, Selected Collagen-Based Scaffolds Under Development
for Ligament and Tendon Repair…………………………………………….. 6-22
Exhibit 6-9: 2013, Selected Synthetic Scaffolds Under Development for
Ligament and Tendon Repair…………………………………………………. 6-23
Exhibit 6-10: Aperion Biologics’ Z-Lig Xenograft ………………………………………….. 6-25
Exhibit 6-11: 2013, Selected Growth Factor Products and Technologies
Under Development………………………………………………………………. 6-28
Exhibit 6-12: 2013, Selected Cell-Based Therapy Approaches Under
Development for Tendon Repair …………………………………………….. 6-32
Exhibit 6-13: Ligament and Tendon Allografts, Market Forecast, 2012-2017……. 6-33
Exhibit 6-14: 2012, Ligament and Tendon Allografts Market, Share by Supplier . 6-37
7. COMPANY PROFILES…………………………………………………………………….. 7-1
7.1 Arthrex, Inc. …………………………………………………………………………… 7-1
7.2 ConMed Linvatec/ConMed Corporation …………………………………….. 7-2
7.3 Fidia Pharma USA, Inc./Fidia Farmaceutici SpA …………………………. 7-4
7.4 Genzyme Corporation/Sanofi SA ……………………………………………… 7-4
7.5 Johnson & Johnson………………………………………………………………… 7-6
7.6 LifeNet Health, Inc………………………………………………………………….. 7-9
7.7 Medtronic, Inc………………………………………………………………………… 7-9
7.8 Musculoskeletal Transplant Foundation, Inc. ……………………………. 7-10
7.9 RTI Biologics, Inc………………………………………………………………….. 7-11
7.10 Smith & Nephew PLC……………………………………………………………. 7-12
APPENDIX: COMPANY LISTING……………………………………………………………… A-1