CorMatrix_English by Anna Sucharska

Autotransplantation on the cells level

CorMatrix速 Extracellular Matrix (ECM速)

CorMatrix is an open, scaffold-like structure. It is biological sceleton, found in almost all tissuesâ&#x20AC;Ś it is space or sceleton for local cells ingrowth

CorMatrix

Is remodeled, not simply re-absorbed, forming an organized, recapitulated tissue (in 4-8 weeks) Is NOT a long-term foreign body, unlike many synthetics or cross-linked biol. tissues Is very Safe & remarkably Strong

CorMatrix

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.

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  .....360 different proteins are identified in matrix

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

ECM

Collagen

500X

How Stem Cells React to their Environment

Micro- Architecture: 3-D Physical Stress: Pliability, shear, tension, and compression factors Pericardium

Biochemical Composition

Although it is well known that cells respond differently to distinct matrix molecules, they also respond to differences in the physical stress as well as the distinct architectural characteristics of the ECM.

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

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

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CorMatrix ECM for Cardiac Tissue Repair: 1 st Implant August 2007

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CorMatrix ECM for Carotid Repair: FDA Clearance received July 27, 2011

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45,000+ human cardiovascular implants to-date

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Utilized in over 400 hospitals in the U.S.

• 50% increase in implant rates in 2011 vs. 2010 • Only Company in the world to be granted a claim of regeneration

(CE Mark-European grant)

• Presently has 38 employees

Licensing & Application Areas • World-wide exclusive Intellectual Property license for the cardiovascular field from Purdue University and Cook Biotech. • Multiple product applications:

• Pericardial Reconstruction • Cardiac Tissue Repair • Carotid Repair • Heart Muscle Regeneration/ Congestive Heart Failure • Vascular Grafts/Conduits • Heart Valve Repair & Replacement • Stent Coatings © 2011 CorMatrix, Inc. All Rights Reserved. Contents are confidential

Versatility of ECM’s: Current Clinical Applications Glabellar Lines Dural Substitute Corneoplasty Facial Reconstruction Periodontal Graft Tracheoplasty Staple Line Reinforcement Hemi-nephrectomy Cover Gastrocutaneous Fistulas Inguinal Hernia Pelvic Organ Prolapse Pubovaginal Sling Urethral Repair Vaginal Reconstruction on Rectovaginal Fistula Venous Ulcers

Tympanoplasty Palate Repair Lip Augmentation Carotid Patch Pericardial Patch Lung Perforation Repair Diaphragmatic Hernia Paraesophageal Hernia Gastric Bypass Ventral Hernia Anal Fistula Peyronie’s Repair Diabetic Ulcers Pressure Ulcers

Publications (As of July 1, 2011) SIS Manuscripts: 887 

       

133  Ophthalmology Colorectal 58  Orthopedics 63 Dental 2 Gastroenterology 62  Plastic Surgery Human General Surgery Use Manuscripts 114  Review Papers 261 Immunology 13  Thoracic Surgery Material Properties 36  Urology Neurology 13  Vascular Surgery OB/GYN 22  Veterinary Medicine  Wound Care (Dermal) Biochemistry/Cell Biology

18 72 9 152 68 16 32

Pre-clinical studies Structures Regenerated from ECM’s Animal Studies

Canine Bladder

Porcine RV patch

 Esophagus  Tendon  Bladder  Urethra  Trachea  Artery

Canine Achilles tendon

Porcine heart valve

 Vein  Myocardium  Valve

An E xt rac ell ular Ma trix B iosca ffold for Orthop edic S oft Ti ssu e Repa ir

Pericardial Reconstruction

CorMatrix for Pericardial Closure Clinical Experience

Running suture down left and right sides

Opening for chest tubes

CorMatrix

CorMatrix for Pericardial Closure Clinical Follow-Up: Adult Applications

12 months post-op RV

Follow up CT scans at 10 months in 2 adult patients

Neo-pericardium

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

Pericardial Closure and VAD Insertion

CorMatrix for Pericardial Closure

Potential Impact on Reducing New Onset Post-Op Atrial Fibrillation Published Article reporting a 54% reduction in post-op Atrial Fibrillation following pericardial reconstruction using CorMatrix

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

RV ECM-patch Histology Low Power

TISSUE ENGINEERING: Part A Volume 15, Number 00, 2009

Carotid Repair

CorMatrix for Carotid Repair

Vascular Grafts/Conduits

CorMatrix for Vascular Graft Applications Animal Testing

Gluteraldehyde treated Pericardium

CorMatrix ECM

Native Tissue or Scar?

CorMatrix has Traditional cross-linked pericardium remodeled toGluteraldehyde normal bovine pericardium has thickness of native not changed and will Pulmonary Artery ultimately scar and calcify

ECM remodeling

Gluteraldehyde pericardium

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.

CorMatrix for Vascular Graft Applications Animal Testing

Heart Valve Repair & Replacement

CorMatrix for Heart Valve Repair & Replacement Animal Testing

Early animal testing on one CorMatrix valve design accepted for presentation at The Society for Heart Valve Disease Meeting

ECM Valve Conduit at 3 months

CorMatrix for Heart Valve Repair & Replacement Animal Testing

Open PA and leaflets

SEM of mid-ventricularis

intact and confluent endothelium, NOS producing (green) cells

Slide 3

20X

Figure 1

Use of a Novel Acellular Xenograft as a Patch for Aortic Annular Enlargemen Gerdisch, Marc W.; Akinwande, Akindolapo O.; Matheny, Robert G. Innovations:Technology and Techniques in Cardiothoracic and Vascular Surgery. 5(1):60-62, January/February 2010.

FIGURE 1. Intraoperative photographs. A, Aorta, annulus, and anterior mitral leaflet incised. ECM xenograft (arrows) sewn into place; (B) seen through the seated valve; and (C) extending into the aortic root (D). ÂŠ 2011 CorMatrix, Inc. All Rights Reserved. Contents are confidential

Figure 2

Distal prior to hydrating

ECM Valve Conduit, Hydrated

ECM valve implanted on pulmonary position, construction of conduit on pulmonary artery

Heart Muscle Regeneration - Congestive Heart Failure -

CorMatrix Injectable for Congestive Heart Failure CorMatrix Injectable

GLP Large Animal Study using Injectable CorMatrix to treat Heart Failure

Infarct Area

Chronic CHF Study

Absolute LV Ejection Fraction Change, original EF<45

EMU = CorMatrix Injectable

Significant improvement in heart function following injection of CorMatrix

Stent Coatings

CorMatrix for Stent Coatings Animal Testing

Stent constructs comprising CorMatrix currently undergoing feasibility testing

Non Cardiovascular Application

Second/Third Degree Steam Burns

ECM Applied to Burn Area

Burn healed following 2 treatments after 21 days, including fingerprints.

Movie done by National Geographic â&#x20AC;&#x153;How to build a beating heartâ&#x20AC;?

video.nationalgeographic.com/video/player/national