Cormatrix zagreb presentation by Anna Sucharska

CorMatrix速 Extracellular Matrix (ECM速)

Biomaterials Are Not Created Equal CorMatrix is an open, scaffold-like structure that is not cross-linked Has a complex composition that is kept intact

CorMatrix

Is remodeled, not simply re-absorbed, thus forming an organized, recapitulated tissue 

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Is NOT a long-term foreign body, unlike many synthetics or cross-linked tissues Is very Safe & remarkably Strong

CorMatrix

CorMatrix ECM - derived from Porcine Small Intestinal Submucosa (SIS) •

Submucosa is found between the mucosal and muscular layers of the small intestine.

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A complex matrix of collagen

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Provides strength to the intestine and also serves as a reservoir for cytokines that support the growth and differentiation of intestinal epithelial cells.

100 µm H&E; 200X

ECM Composition- components of different catageories which drive cells growth and function  Collagen: types I (predominant),III, IV, V, VI 92% of dry weight  Glycosaminoglycans (GAGs): chondroitin sulfate A and B, heparan, heparin, hyaluronic acid  Glycoproteins: fibronectin, entactin, laminin  Proteoglycans: decorin, perlecan  Growth factors: TGFb, FGF-2, VEGF, PDGF, HDGF

CorMatrix® ECM® Technology

CorMatrix technology... enables one’s own stem cells to regenerate an individual’s own tissue without requiring any harvesting of stem cells,

The material is remodeled, allowing for an individual to re-grow and restore functional tissue.

Unique CorMatrix Material Characteristics 

Acellular / no cells

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Not treated with glutaraldehyde (not “cross-linked”)

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Retains specific composition

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Enables patient’s own cells to effect repair

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Resistant to infection (consist of specific peptides with antiinfective properties)

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Rapid revascularization and neoangiogenesis

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Site specific tissue repair and remodeling

Angiogenesis is vastly different (Micro immunoflorescence at 21 days) Chemically stripped

ECM

Collagen

500X

SIS is resistant to infection Comparison of small-intestinal submucosa and expanded polytetrafluoroethylene as a vascular conduit in the presence of gram-positive contamination. Ann Surg. 2005 Jun;241(6):995-1001; discussion 1001-4 Shell DH 4th, Croce MA, Cagiannos C, Jernigan TW, Edwards N, Fabian TC.

“ All SIS grafts were incorporated. Histology demonstrated remodeling into host artery with smooth muscle and capillary ingrowth in all SIS groups. Scanning electron micrography illustrated smooth and complete endothelialization of all SIS grafts. CONCLUSIONS: Compared with ePTFE, SIS induces host tissue remodeling, exhibits a decreased neointimal response to infection, and is resistant to bacterial colonization”. © 2010 Cormatrix, Inc. All Rights Reserved. Contents are confidential

Comparison of small-intestinal submucosa and expanded ePTFE as a vascular conduit in the presence of gram-positive contamination. ePTFE

Pic. 1 Stained Gram positive bacteria in ePTFE material Pic. 2 Picture from scanning electon microscope showing hiperplasia of neointima around ePTFE material

SIS

Pic. 1 i 2. Trichrome staining demonstrating new capillary (arrow) and collagen ingrowth in contaminated SIS graft. Pic.3 Scanning electron micrographs demonstrating excessive neointimal hyperplasia in contaminated ePTFE and ÂŠ 2010 Cormatrix, Inc. All Rights Reserved. Contents are confidential tissue incorporation SIS.

CorMatrix Company Overview • Founded in 2001 • 3 FDA cleared products for distribution in the US with related CE Mark for distribution in the European Community     

CorMatrix ECM for Pericardial Closure: 1st Implant March 2006 CorMatrix ECM for Cardiac Tissue Repair: 1 st Implant August 2007 CorMatrix ECM for Carotid Repair: FDA Clearance received July 27, 2011 70,000+ human cardiovascular implants to-date Utilized in over 700 hospitals Worldwide.

• 50% increase in implant rates in 2011 vs. 2010 • Presently has 38 employees

CorMatrix for Pericardial Closure Clinical Experience

Running suture down left and right sides

Opening for chest tubes

CorMatrix

Reoperation in 4 month old infant ECM placed at 4 days of age

CorMatrix for Pericardial Closure Clinical Follow-Up: Pediatric Applications

New New Blood Blood Vessels Vessels

Original operation at 4 days of age and reoperation at 4 months. Protects underlying heart structures.

Histology on tissue sample taken during re-op on 6 month old patient shows neo-vascularity, cell infiltration, and collagen deposition ÂŠ 2011 CorMatrix, Inc. All Rights Reserved. Contents are confidential

ECM as vascular patches – porcine model ECM as patch on aorta and pulmonary artery – after 6 weeks

Smart Remodeling The CorMatrix ECM was implanted in the same animal in two different locations at the same time

Aorta

Pulmonary artery

Pulmonary artery cellular infiltration and ECM degradation, 6 weeks after implantation HE stain 10X

The ECM pulmonary artery patch has thickened up 3 fold to the level of normal PA with the infiltration of cells and deposition of new matrix

New matrix

Remaining Implanted ECM

Right Ventricle ECM-patch -GLP Study

RV ECM-patch GLP Study

ECM replaced by functioning myocardium at 10 weeks

Cardiomyocytes forming in the ECM ID

RV ECM-patch Histology Low Power

CorMatrix for Vascular Graft Applications Pre-Clinical Animal Testing

CorMatrix

Gluteraldehyde pericardium

This endothelial lining is important to avoid the clotting of blood that may cause any number of adverse effects such as heart attacks, stokes, etc.

Distal prior to hydrating

ECM Valve Conduit, Hydrated

ECM Valve Conduit at 3 months

CorMatrix for Heart Valve Repair & Replacement Animal Testing

Open PA and leaflets

TORONTO GENERAL HOSPITAL SUMMARY OF USE SEPTEMBER 27, 2012 Everyday use Patch Enlargement of Aortic Root 26 Aortic Annular Reconstruction 4 Mitral Annular Reconstruction 8 ASD Repair 7 Reconstruction following Cardiac Resection 7 Pericardial Closure (Redo) 2 Pulmonary Artery 7 Superior Vena Cava 2 Inferior Vena Cava 2 Innominate Vein 2 Femoral Vein 1 Aortic Leaflet Augmentation 2 Mitral Leaflet Augmentation 6 Tricuspid Leaflet Augmentation 4 LVA Repair 7 Special Situations Extensive Reconstruction of Fibrous Skeleton 2 Patch Repair in Acute Endocarditis +/- Abscess 7 Tricuspid Valve Restoration 1

IDEAL PATCH (Frank G. Scholl) 1.Pliable and easily handled 2.Accepts sutures without difficulty 3.Should be haemostatic 4.Quite strong, resists tearing 5.Able to conform to complex shapes

6. Suitable in intra and extracardiac repairs 7. Would not calcify or shrink over time 8. Not immunogenic 9. No scar tissue development 10. Encourages native tissue regeneration 11. Potential for growth ÂŠ 2011 CorMatrix, Inc. All Rights Reserved. Contents are confidential

List of work Create target (CSR, CSP, VAS?) Good product knowledge Good publications knowledge Preparations of booklets with publications, diffrent for diffrent departments (CAS, SCR, SCP) FU first implantations The mailings Staying in touch in case od new indications Events like wetlab, congresses

Questions

For a nurse meeting Which Dr doing the most operations? Which operations? How many procedures? What materials are using? How big orders of competition? Which of them most frequently? How are ordering? When the tender is planned? Other products questions...

For a junior/assistant dr meeting Which operations are doing? How many procedures? What are using? To which procedures what? What problems are facing?

For a prof/chief meeting Which operations are doing? How many procedures? What kind of materials are using? To which procedures what? What problems are facing?