What are the ideal Regenerative Medicine principles?

2. What are the ideal Regenerative Medicine principles?

3. What are the ideal Regenerative Medicine principles?

4. Plastic Surgery Commercially Available • Plastic & Orthopedic Surgery • Soft tissue repair indications • Acute trauma • Post surgery closure • Difficult to heal wounds • No donor site surgery required 91 y/o patient with Melanoma on top of right hand. One week post surgery, full thickness remodeling initiated. Patient exhibits minimal inflammation and pain. Two months post surgery, full thickness remodeling near completion. Patient has complete range of motion.

5. What is an Extracellular Matrix (ECM) • ECM occupies the space between cells • Is part every organ of every species • Xenogenic transferability • Universal among species • Complex infrastructure • Collagen types • Proteoglycans • Hyaluronic acid, laminin, fibronectin • Glycoproteins • Mediates cell-to-cell interactions • Proliferation and differentiation • Modulates biological activities of growth factors

6. MatriStem (UBM) Peer Reviewed Publications (39) • Thoracic Wall Reconstruction • Repair of thoracic wall, including ribs • Esophageal Remodeling • Esophageal Reconstruction • Reinforcement of esophagus • Cardiac Remodeling • Reconstruction of myocardium • Inductive scaffold for myocardium • Tunica Repair • Corporal tissue function maintained • Urinary Incontinence • Particulate for treatment of UI • Hybrid Design • Biodegradable elastomer and UBM • Technology Properties • Basement membrane components of UBM • Antibacterial properties of UBM • Material Properties of UBM • Cell migration and proliferation • Technology Forms • Gel form of UBM • Mechanical properties of Multi-laminante • Characterization of UBM Powder • Orthopedic • Chemoattraction of Progenitor Cells in Achilles tendon • UBM injectable in dogs with osteoarthritis, an RCT

7. Scientific Advisors • Anthony A. Atlala, M.D. • Director of the Wake Forest Institute for Regenerative Medicine and the William Boyce Professor and Chair of the Department of Urology at Wake Forest University School of Medicine • Thomas W. Gilbert, Ph.D. • Research Assistant Professor in the Department of Surgery at the University of Pittsburgh, McGowan Institute for Regenerative Medicine • Christopher D. Prevel, M.D. • Founder of the Plastic Surgery Institute of Florida • Clinical Associate Professor of Surgery at the University of South Florida School of Medicine • Alejandro Nieponice, M.D. • Research Assistant Professor of the department of surgery at University of Pittsburgh and faculty of the McGowan Institute for Regenerative Medicine • Surgical associate and director of the Clinical Translation Unit at the Austral University Hospital in Buenos Aires, Argentina. • Dr. Jeff Wood, Dr. William Rose, Dr. Rick Mitchell, Dr. Cooper Williams and Dr. Nicolai Jarlov are advisors of ACell and practicing veterinarians who have conducted pioneering research with various applications of UBM for animals such as horses and dogs.

8. FDA Clearances And Pathway • .

9. ACell Vet (UBM) • Basement membrane porcine urinary bladder • ACell Vetis ACellular • Non-crosslinked • Biphasic design • Basement membrane layer • Tunica propria layer • Promotes angiogenesis • Recruitment of progenitor (adult) stem cells • Gradual scaffold degradation • Antibacterial properties • Tissue remodeling instead of scarring • Returns body to normal state and function

10. Complex Structural Composition • Collagen • Types: I, II, III, IV, VII • Bioactive Components • GAGs • Proteoglycans • Growth Factors • VEGF, BMP4, PDGF-BB, KGF, TGFbeta1, IGF, bFGF, EGF, TGFalpha • Glycoproteins • Laminin, Elastin, Fibronectin • Anti-Infective Peptides • 18 AMP’s have been identified in porcine tissue • Porcine defensin pBD-1 Badylak, et. al. The basement membrane component of biologic scaffolds derived from extracellular matrix. Tissue Eng. 2006 Mar;12(3):519-26. Atala, et. al. Identification and Characterization of Bioactive Factors in Bladder Submucosa Matrix. Biomaterials. 2007 Oct;28(29):4251-6. Badylak, et. al. Antibacterial activity within degradation products of biological scaffolds composed of extracellular matrix. Tissue Eng. 2006 Oct;12(10):2949-55.

11. What is ACell Vet ? • Extracellular Matrix (ECM) • Scaffold to Promote Site Specific Host • Cells to Infiltrate • Naturally derived (porcine) • ACell-ular • No Immune System Rejection • Totally Resorbable • Completely Replaced By Healthy Host Tissue • Not Chemically Crosslinked • No Additional Chemicals to Promote Rejection

12. How ECMs Work • Site Specific Constructive Remodeling • of Host Tissue by recruitment of • Peripheral • and • Bone Marrow Derived Progenitor Cells.

13. ACell Vet Applications • Wound Care • Corneal Ulcers • Dental Applications • Tendon & Ligament Repair • Fracture Repair • Gastrointestinal Surgery • Osteoarthritis • Body wall, soft tissue repair • Cancer reconstruction • Urological procedures including Incontinence • Dura Repair • Cranial Cruciate Regeneration

14. Dudley – Degloving Injury • Classic degloving injury after HBC • Single layer ACell Vet applied 10/11/02

15. Dudley – Degloving Injury • Day 3 - initial formation of granulation bed apparent. ACell Vet reapplied. • Day 11 - excellent granulation bed and vascularization.

16. Dudley – Degloving Injury • Day 17 – progressing nicely • Day 30 – almost closed

17. Dudley – Degloving Injury • Day 66 – Wound barely visible and regrowth of hair proceeding nicely.

18. Classy • Wound was unresponsive to treatment for 2 years • Skin defect 12 x 14 cm. • Bone defect 10 x 7 cm. • Treated with ACell and surgery • 8 months later • Little scar

19. Bilateral CHDIntra-articular Injection

20. Study Abstract : Canine Joints • Jeff Wood, DVM • Arthritic Hip Controlled Study • 20 dogs • Study Length • 168 days • Single Injection • Effective for 6 months on treatment group • Effective up to 12 months in some dogs • No Adverse Effects

21. Regenerative Medicine • Cost Effective • Reduced Treatment Time • Easy to Use • Predictable Results • Better Healing…Naturally!