Disclosures. New therapies for spinal fusions. Cells, Molecules and Surfaces" Hyun Bae, MD

Transcription

1 Hyun Bae, MD Professor of Surgery Department of Surgery Director of Education Cedars Spine Center Medical Director Disclosures Depuy- Consultant Stryker- Consultant Nuvasive- Consultant Prosidyan- SAB and CMO, Royalties New therapies for spinal fusions Cells, Molecules and Surfaces" 1

2 Stem Cell Enhanced Allograft Osteocell Plus-- Nuvasive Trinity Evolution-- Orthofix Cellentra BioMet SEM Analysis of Osteocel Plus 100 X and 4000 X Selective Immunodepletion NuVasive, Inc

3 DePuy Synthes All rights reserved. ViviGen is a registered trademark of LifeNet Health DSUS/SPN/0715/ /15 Paradigm Shift Bone Cells (Osteoblasts and Osteocytes) are the preferred cell types for bone repair 2,3,4,5,6 8 DSUS/SPN/0715/ /15 9 DSUS/SPN/0715/ /15 A surgeon must always rely on his or her own professional clinical judgment when deciding whether to use a particular product when treating a particular patient. Stryker does not dispense medical advice and recommends that surgeons be trained in the use of any particular product before using it in surgery. The information presented is intended to demonstrate the breadth of Stryker product offerings. A surgeon must always refer to the package insert, product label and/or instructions for use before using any Stryker product. Products may not be available in allmarkets because product availability is subject to the regulatory and/or medical practices in individual markets. Please contact your Stryker representative if you have questions about the availability of Stryker products in your area. 3

4 BIO 4 _ Next Generation BIO 4 is processed from allograft donor bone using proprietary methods BIO 4 includes all components of natural bone: cancellous bone containing endogenous cells and cortical bone, and periosteum Cancellous bone Scaffold Cancellous bone Cells Cortical bone Signals Periosteum Signals 10 DSUS/SPN/0715/ /15 Osiris Data on File Cellular Allograft in Anterior Cervical Discectomy and Fusion (ACDF) Evaluation of Clinical and Radiographic Outcomes from a Prospective Multi-center Study Robert Eastlack 1, Christopher R. Brown 2, Craig Meyer 3. IMAST, July Scripps Clinic, La Jolla, CA 2 Duke University Medical Center, Durham, NC 3 Columbia Orthopaedic Group, Columbia, MO BACKGROUND Prospective, multicenter trial (17 sites) 249 levels (182 patients) 1- (63%) or 2- (37%) level ACDF (C3-T1) 2 year follow-up with radiograph and CT data Data reviewed by 3 independent spine surgeon reviewers SUMMARY OF RESULTS Single Level: 95% fusion (<3 ROM on F/E); 92% fusion (CT) Two Level: 89% fusion (<3 ROM on F/E); 83% fusion (CT) All Levels: 92% fusion (<3 ROM on F/E); 87% fusion (CT) 93% patient satisfaction scores 11 DSUS/SPN/0715/ /15 4

5 MSC Allograft vs DBM Advantages It s a good source of allograft Good Safety Profile 5

6 PEEK vs. Titanium Titanium Widely used across all many Bone applications Bio-compatible Compatible with MRI and CT Bone ingrowth directly onto surface of some Implants (surface dependent) (Re-) Emerging as a reliable material for spine fusion Ti Surface 6

7 Nanotechnology How small is nano One nanometer is a billionth of a meter, or 10-9 of a meter. Here are a few illustrative examples: A sheet of newspaper is about 100,000 nanometers thick On a comparative scale, if a marble were a nanometer, then one meter would be the size of the Earth Power of Nano: Surface-to-Volume Comparisons Single Box Ratio 6 m 2 1 m 3 = 6 m 2 /m 3 1cm Smaller Boxes Ratio Volume is constant 1 cm x 1 cm x 1 cm = 1 cm 3 Area = 6 x 1 cm 2 = 6 cm 2 Area = 6 x (1/2 cm)2 x 8= 12 cm 2 Neglecting spaces between the smaller boxes, the volumes of the box on the left and the boxes on the right are the same but the surface area of the smaller boxes added together is much greater than the single box. Power of Nano 1cm Area = 6 x 1 cm 2 = 6 cm 2 Area = 6 x (1/2 cm)2 x 8= 12 cm 2 10 nm Constant Volume 1 cm 3 Area = 6 x (10 nm) 2 x 1,000,000 3 = 600,000,000 cm 2 or 6000 km 2 7

8 Surface area 6000 km 2 1 cm 3 Great Salt Lake 3000 to 6000 km 2 Manhattan 58 km 2 Los Angeles 1200 km 2 Human Stem Cell on nanolock TM surface Confidential Titan Spine, LLC lup regulate Osteoblasts TGF B1, BMP 2,4,7 Physiologic BMP production TCPS = Tissue Culture Polystyrene sti = Smooth Titanium rti = Roughened Titanium (Micro scale) Confidential Titan Spine, LLC 8

9 Nanoscale Mimics Nanoscale Bone Nanoscale Bone Nanoscale Titanium Nanotubular Titanium Oxide Nanoscale PEEK 9

10 Acta Biomater (2014), Hierarchy of Implant Surface Topography Macro level (10 3 m) Biochemical Influence Barrier Micro level (10 6 m) Nano level (10 9 m) Macro Micro Sub Micro/ Nano 10 3 m 10 6 m 10 9 m Gittens RA et al. Implant osseointegration and the role of microroughness and nanostructures: Lessons for spine implants. Confidential - Titan Spine, LLC Nano Unlocks the Alpha 2 Beta 1 Integrins to start cellular transcription. Confidential - Titan Spine, Image LLC courtesy of Barbara D. Boyan, PhD 10

11 3-D Printing Tritanium PL Cage featuring Tritanium In-Growth Technology 1 Tritanium In Growth Technology 1 Tritanium PL Cage Designed for in growth 1 Created to allow visualization 5 Empowered by expertise Developed to minimize subsidence 2 Engineered for stability 3,4 1. PROJ PROJ PROJ PROJ Data on file The Stryker Spine Tritanium PL Cage is an intervertebral body fusion device indicated for use with autograft and/or allogenic bone graft comprised of cancellous and/or corticocancellous bone graft when used as an adjunct to fusion in patients with degenerative disc disease (DDD) at one level or two contiguous levels from L2 to S1. TRITA SO 2 Tritanium PL Cage specifications Material: Ti Alloy Ti6Al4V Porous Surface Parameters: Porosity: mean 60% 1,2, 4 Pore size: µm; mean 438µm 3,4 Sizing: Height: 7 14mm Width: 9 and 11mm Length: 23 and 28mm Lordosis: 0 and 6 (oblique for 28mm) TRITA SO 2 1 Bobyn, J.D. Characteristics of bone ingrowth and interface mechanics of a new porous tantalum biomaterial. Bone Joint Surgery [Br] 1999; 81 B: Bobyn, J.D. Next generation porous metals for biologic fixation. Hip and Knee Reconstruction. American Academy Orthopedic Surgery, Rosemont IL, 2011 pp Poggie, M. et. al. (2013). Novel Porous Titanium Implants Demonstrate Bone In growth In A Rabbit Model. Stryker Orthopaedics, Mahwah, NJ. 4 DHF Pre-Clinical Study 1 Histology* Sagittal View Cranial vertebra Cranial vertebra Cranial vertebra Caudal vertebra Caudal vertebra Caudal vertebra PEEK Cage Ti Plasma Sprayed PEEK Cage Tritanium PL Cage 16 weeks post op in an ovine model *Correlation to humans has not been established or demonstrated. TRITA SO 2 1 STL / Stryker

12 COHERE TM Cervical Cage Product Line Increased Cell Proliferation Increased Osteogenic Differentiation 34 Not all Porosities are the same 12

13 How Bones Heal Fibers provide connectivity for bones to heal Sentinel Healing-Fibrin Clot Fibrin Clot In situ catalytic conversion of fibrinogen to fibrin by thrombin to form cross-linked fibrin matrix Fiber mediated healing Basic mechanism for all connective tissue healing. FIBERGRAFT TM IN-VITRO BIOACTIVITY TEST 3 day FIBERGRAFT TM in SBF at 37C 13

14 Cell Proliferation Study Laboratory Tests Show Rapid Growth of Bone Forming Cells on Bioactive Glass Fibers 12M Follow up 12mont CT Follow up 14

15 i-factor Peptide Enhanced Bone Graft* Mechanism of Action: Attract - Attach - Activate i-factor Bone Graft will Attract anchorage dependent osteogenic cells that Attach to P-15, Activate and form bone Osteogenic Cell ABM is Anorganic Bone Mineral (Natural Hydroxyapatite) P-15 P-15 is a Fifteen Amino Acid Synthetic Analog of the Cell- Binding Domain of Human Type I Collagen ABM * Investigational Device, not approved for use in the United States 43 Primary Outcomes and Responder Analysis i-factor Bone Graft vs Autograft 100.0% 80.0% 60.0% 89.0% 85.8% p = % 74.1% p = % 93.0% p = % 95.4% p = * p = % 56.9% 40.0% 20.0% 0.0% Fusion Success NDI Success Neurological Success Safety Success Overall Success i-factor Bone Graft Autograft Black p values non-inferiority test Red p value superiority test * Safety: no difference in re-operations at index level Fisher s exact test for superiority 44 THANK YOU 15