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
2013 Elsevier Business Intelligence ii #A321
U.S. Markets for Orthopedic Biomaterials for
Bone Repair and Regeneration Table of Contents
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
2.3.1 Potential Market for Bioresorbable Fixation Devices ……. 2-20
2.3.1.1 Meniscal Repair……………………………………….. 2-20
2.3.1.2 Cruciate Ligament Fixation………………………… 2-21
2.3.1.3 Shoulder Reconstruction …………………………… 2-21
2.3.1.4 Small Joint/Bone Fragment Fixation……………. 2-21
2.4 Competitive Analysis …………………………………………………………….. 2-21
Exhibit 2-1: Advantages of Bioresorbable Fixation Devices …………………………… 2-2
Exhibit 2-2: Factors Affecting the Properties of Bioresorbable Polymers …………. 2-4
Bone Repair and Regeneration Table of Contents
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: 2012, Bioresorbable Fixation Devices Market,
By Procedure Type……………………………………………………………….. 2-18
Exhibit 2-10: Bioresorbable Fixation Devices, Market Forecast,
2012-2017 …………………………………………………………………………… 2-19
Exhibit 2-11: 2012, Bioresorbable Fixation Devices Market,
Share by Supplier…………………………………………………………………. 2-23
3. BONE ALLOGRAFT AND SYNTHETIC BONE GRAFT PRODUCTS …….. 3-1
3.1 Bone Graft Materials……………………………………………………………….. 3-1
3.1.1 Autograft…………………………………………………………………. 3-2
3.1.2 Allograft ………………………………………………………………….. 3-2
3.1.2.1 Regulations Governing Allograft Providers…….. 3-4
3.1.2.1.1 National Organ Transplant Act….. 3-4
3.1.2.1.2 United States Food and Drug Administration Requirements……. 3-4
3.1.2.2 Donor Screening ……………………………………….. 3-5
3.1.2.3 Recovering Tissue……………………………………… 3-5
3.1.2.4 Processing Tissue……………………………………… 3-6
3.1.2.5 Tissue Banking Industry ……………………………… 3-7
3.1.2.6 Base Tissue………………………………………………. 3-7
3.1.2.7 Demineralized Bone Matrix Products ……………. 3-8
3.1.2.8 Machined Bone ……………………………………….. 3-15
3.2 Synthetic Bone Grafts……………………………………………………………. 3-16
3.2.1 Products ……………………………………………………………….. 3-18
3.3 Bone Graft Applications…………………………………………………………. 3-18
3.3.1 Fracture Repair ……………………………………………………… 3-26
3.3.2 Revision Total Joint Surgery…………………………………….. 3-26
3.3.3 Tumors …………………………………………………………………. 3-26
3.3.4 Spine ……………………………………………………………………. 3-27
3.4 Market Analysis ……………………………………………………………………. 3-28
3.5 Competitive Analysis …………………………………………………………….. 3-29
3.5.1 Demineralized Bone Matrix ……………………………………… 3-29
3.5.2 Machined Bone Allografts………………………………………… 3-35
3.5.3 Synthetic Bone Graft Substitutes………………………………. 3-36
Exhibit 3-1: Selected Categories of Bone Grafts ………………………………………….. 3-3
Exhibit 3-2: Base Tissue Bone Allograft Applications in Orthopedic Surgery……………………………………………………………… 3-9
Exhibit 3-3: Base Tissue Bone Allograft Applications in Spine Surgery………….. 3-10
Exhibit 3-4: 2013, Description and Representative Pricing of Base Allografts Used in Spine Surgery…………………………………. 3-11
Exhibit 3-5: 2013, Selected Demineralized Bone Matrix Products…………………. 3-12
Exhibit 3-6: 2013, Selected Machined Bone Allografts………………………………… 3-17
Exhibit 3-7: Materials Used in Bone Graft Substitutes…………………………………. 3-19
Exhibit 3-8: 2013, Selected Synthetic Bone Grafts……………………………………… 3-20
Exhibit 3-9: Applications for Bone Grafts…………………………………………………… 3-25
Exhibit 3-10: Bone Allografts and Synthetic Bone Graft Substitutes,
Market Forecast, 2012-2017 ………………………………………………….. 3-30
Exhibit 3-11: 2012, Bone Allografts and Synthetic Bone Graft
Substitutes Market, Share by Tissue Type……………………………….. 3-32
Exhibit 3-12: 2012, Demineralized Bone Matrix Products Market,
Share by Supplier…………………………………………………………………. 3-34
Exhibit 3-13: 2012, Machined Bone Allografts Market, Share by Supplier ……….. 3-37
Exhibit 3-14: 2012, Synthetic Bone Grafts Market, Share by Supplier …………….. 3-40
4. OSTEOBIOLOGICS ………………………………………………………………………… 4-1
4.1 Bone Growth Factors………………………………………………………………. 4-1
4.1.1 Bone Morphogenetic Proteins ……………………………………. 4-1
4.1.1.1 Products …………………………………………………… 4-2
4.1.1.1.1 Infuse Bone Graft……………………. 4-2
4.1.1.1.2 Osteogenic Protein-1 ………………. 4-6
4.1.1.2 Emerging Products…………………………………….. 4-7
4.1.1.3 Clinical Trials…………………………………………….. 4-9
4.1.2 Fibroblast Growth Factors …………………………………………. 4-9
4.1.3 Recombinant Platelet-Derived Growth Factor …………….. 4-11
4.1.3.1 Products …………………………………………………. 4-11
4.1.4 Autologous (Blood-Derived) Growth Factors………………. 4-12
4.1.4.1 Products …………………………………………………. 4-13
4.2 Small Molecules …………………………………………………………………… 4-15
4.3 Stem Cell Therapy………………………………………………………………… 4-17
4.3.1 Products ……………………………………………………………….. 4-17
4.3.2 Emerging Products…………………………………………………. 4-19
4.4 Gene Therapy ……………………………………………………………………… 4-22
4.4.1 Gene Therapy versus Growth Factors ………………………. 4-22
4.4.2 Systemic Gene Therapy………………………………………….. 4-24
4.4.3 Regional Gene Therapy ………………………………………….. 4-27
4.5 Other Osteobiologics …………………………………………………………….. 4-27
4.6 Market Analysis ……………………………………………………………………. 4-27
4.6.1 Bone Morphogenetic Proteins ………………………………….. 4-28
4.6.2 Other Osteobiologics………………………………………………. 4-29
4.7 Competitive Analysis …………………………………………………………….. 4-36
Exhibit 4-1: Selected Bone Morphogenetic Proteins …………………………………….. 4-3
Exhibit 4-2: Selected Recombinant Human Bone Morphogenetic
Protein Products…………………………………………………………………….. 4-8
Exhibit 4-3: Selected Recombinant Human Bone Morphogenetic
Proteins Under Development …………………………………………………. 4-10
Exhibit 4-4: 2013, Selected Autologous Therapy/
Platelet Concentrate Systems ………………………………………………… 4-14
Exhibit 4-5: 2013, Selected Growth Factor and Small Molecule Therapies
Under Development for Bone Healing and
Spinal Fusion Applications …………………………………………………….. 4-16
Exhibit 4-6: 2013, Selected Stem Cell Products for Bone Healing
and Enhancement of Spinal Fusion…………………………………………. 4-20
Exhibit 4-7: 2013, Selected Stem Cell Products Under Development
for Orthopedic and Spinal Fusion Applications………………………….. 4-23
Exhibit 4-8: Comparison of Growth Factors with Gene Therapy
for Bone Repair ……………………………………………………………………. 4-25
Exhibit 4-9: Gene Therapy Delivery Methods for Bone Repair……………………… 4-26
Exhibit 4-10: Recombinant Human Bone Morphogenetic Protein Products,
Market Forecast, 2012-2017 ………………………………………………….. 4-30
Exhibit 4-11: Stem Cells and Other Osteobiologic Agents for Bone Healing
and Enhancement of Spinal Fusion,
Market Forecast, 2012-2017 ………………………………………………….. 4-33
Exhibit 4-12: 2012, Market Shares of Stem Cell Applications for
Bone Healing and Spinal Fusion …………………………………………….. 4-35
Exhibit 4-13: 2012, Stem Cell Products Market for Bone Healing
and Spinal Fusion, Share by Supplier ……………………………………… 4-38
5. COMPANY PROFILES…………………………………………………………………….. 5-1
5.1 Arthrex, Inc. …………………………………………………………………………… 5-1
5.2 Baxter International, Inc…………………………………………………………… 5-2
5.3 Johnson & Johnson………………………………………………………………… 5-3
5.4 LifeNet Health, Inc………………………………………………………………….. 5-5
5.5 Medtronic, Inc………………………………………………………………………… 5-6
5.6 Musculoskeletal Transplant Foundation, Inc. ……………………………… 5-8
5.7 NuVasive, Inc. ……………………………………………………………………… 5-10
5.8 Orthofix International NV ……………………………………………………….. 5-11
5.9 RTI Biologics, Inc………………………………………………………………….. 5-12
5.10 Smith & Nephew PLC……………………………………………………………. 5-13
5.11 Stryker Corporation ………………………………………………………………. 5-14
APPENDIX: COMPANY LISTING……………………………………………………………… A-1