ECM Technology Overview

About CorMatrix ECM^® Technology

Found in all humans and animals, extracellular matrix or ECM is the naturally-occurring bioscaffold that surrounds cells in almost all tissues and organ structures. It has both structural and functional roles, and while the composition of the ECM varies by tissue, it is generally composed of four major types of molecules:

• Structural proteins, such as collagen and elastin
• Adhesion glycoproteins, such as fibronectin and laminin
• Glycosaminoglycans (GAGs) and proteoglycans, such as hyaluronan, heparin sulfate, heparin and dermatan sulfate
• Matricellular proteins, such as thrombospondins, osteopontin and tenascins

CorMatrix ECM Technology is a unique extracellular matrix that combines the innate attributes of nature with the precision of science to help the heart heal itself. It is an acellular biomaterial that does not encapsulate when surgically implanted, but is gradually remodeled, leaving behind organized and healthy tissue. The body’s tissue begins remodeling at the surgical site while the ECM maintains the needed tissue support. When implanted, the ECM acts as a scaffold into which the patient’s cells migrate and integrate, stimulating the patient’s natural wound-healing mechanisms. As the patient’s cells become active, they lay down their own collagen, which matures over time to form strong and permanent tissue repair without leaving behind permanent foreign material. Because the ECM contains primarily collagen, the device is gradually replaced as the patient’s tissue gradually turns over in a natural state of self-renewal.

History of CorMatrix ECM Technology

Research on extracellular matrix materials began in the 1980’s at Purdue University. Found in all animals, extracellular matrix is the naturally-occurring critical scaffold that cells hold onto as they divide and grow into tissues. Prior to the 80’s, it was believed that the extracellular matrix in humans served little function.  Referred to as the “ground substance,” it was not well-studied. But as research in regenerative medicine advanced, scientists zeroed in on the extracellular matrix and its role in supporting and promoting new tissue growth.

Robert G. Matheny, MD, Co-Founder and Chief Scientific Officer of CorMatrix, gained his interest and experience with extracellular matrix materials while he was a private practice cardiac surgeon. Realizing the potential of these unique materials for cardiac tissue repair, he further increased his study and preclinical work in matrix materials and tissue repair and later founded CorMatrix with David Camp to develop ECM technology into a commercially-viable product for use in cardiovascular surgery. After licensing the rights from Purdue University to research, develop, manufacture and market naturally occurring extracellular matrix materials for cardiovascular applications, and subsequently entering into a cross-license agreement with Cook Biotech, the Company began its acceleration.

In 2005, CorMatrix received its first FDA clearance and shifted its focus from development stage to an integrated research, development and commercial entity.

The Manufacturing Process

CorMatrix ECM Technology is produced from porcine small intestinal submucosa (SIS), a naturally occurring and harvestable ECM.

The submucosa is located between the mucosal and muscular layers of the small intestine. In addition to being a repository for growth factors, the submucosal layer provides strength to the small intestine through a complex organization of collagen that forms a fibrous matrix. The SIS is extracted from the intestine in a manner that removes all cells, but leaves the complex extracellular matrix intact. Careful processing and manufacturing leaves the naturally fibrous and porous nature of the matrix available for new cell in-growth while making it safe for implantation. Not all extracellular matrix materials are alike. Over-processing of the source material can have negative effects on the underlying components and structure, which will result in a material that does not remodel normally.

To enhance patient safety, the base material undergoes a high-level disinfection and decellularization process. As a final step in the process, all implants are sterilized by validated sterilization cycles.

CorMatrix ECM Technology products are rigorously tested to confirm that they are biocompatible. In vitro test results demonstrate that the human complement cascade is not activated following implantation, indicating that they do not elicit an acute rejection response.

How Does it Work?

CorMatrix ECM Technology supports tissue repair and results in remodeled, functional tissue without leading to encapsulation, premature breakdown of the material, calcification, or tissue erosion that can be caused by synthetic materials.

Following implantation by a cardiac surgeon, CorMatrix ECM ultimately helps remodel, regrow and restore damaged tissue through a four-step process:

• Signaling the Body

Unlike synthetic materials or some other biologic grafts, CorMatrix ECM communicates with the body, signaling surrounding healthy tissue to grow across and incorporate into the extracellular matrix. The result is completely remodeled, strong, fully vascularized tissue where damaged tissue once existed.

• Providing Resistance to Infection

For a biomaterial to be able to repair a complex and contaminated tissue defect, it must be able to signal the influx of host defenses to fend off infection. Because CorMatrix ECM products facilitate angiogenesis and rapidly remodel into vascularized tissue, they allow the body's own defense mechanisms to react and respond to any potential infection.

• Enabling Complete Remodel

Ideally, a biomaterial should produce a permanent repair without leaving behind a permanent material. CorMatrix ECM products facilitate this type of remodeling. Following implantation, the site-specific remodeled tissue displays similar physiologic and morphologic characteristics as the native tissue. During the healing process, CorMatrix ECM products are replaced by the body's native tissue – developing into a permanent repair without the long-term presence of a foreign body.

• Providing Long-Term Strength

CorMatrix ECM products are designed to support the mechanical requirements necessary for site specific repair. Over time, CorMatrix ECM remodels to maintain strength while allowing growth of the patient's own tissue.