ECM®

The Basic Science of ECM® Regeneration

The extracellular matrix, or ECM®, is the part of a tissue outside the cell and is the natural information and signaling context for cells. Rather than a passive structural matrix on which cells reside the ECM® provides for bi-directional information exchange necessary for cell survival and function. This “Dynamic Reciprocity”1, as coined by Mina Bissell, provides the communication link whereby the ECM® directs cell phenotype, differentiation, migration, and function. Now, abundantly clear in the literature, the structural and functional proteins within the ECM® are necessary for normal homeostasis.

Utilizing proliferative matrices a number of medical devices have been designed to regenerate specific tissues. Newer generations of matrices have been developed which can direct host cells and stem cells toward the formation of functional tissue constructs. It is the goal of CorMatrix to harness this regenerative potential for the cardiovascular applications including heart failure (HF), valvular disease, and other applications.

Features

  • The ECM®, via cell transmembrane receptors, directs cellular gene expression and protein. production.
  • The ECM® provides a very specific micro-environment. Cells recognize collagen fiber orientation, types of structural proteins, pore size, sequestered paracrine factors, and many other components of the matrix that are specific for each tissue.
  • The matrix is also dynamic and may be altered due to disease, remodeling mechanical forces, or during the regeneration of tissues.
  • Mechanical forces as well as various cytokines are transmitted to the cell from the ECM® with the cells then responding by producing the factors necessary, including more ECM® components, for that tissue to function properly.

Mechanism of Action

An intact decellularized or acellular ECM® is one in which the structural and functional proteins are still intact but where the cells have been removed leaving a microenvironment capable of attracting cells and forming new tissue. Producing the ideal medical ECM® is a continuous and evolving technological goal but one that will direct host cells toward tissue regeneration rather than scar formation. To achieve that the following principles must be observed: *H&E X40 improved acellular matrix with no nuclear remnants or lipid cell wall fragments.

CorMatrix Mechanism of Action

Proliferative ECM®

The ECM® of some tissues support cell proliferation and some do not, the latter being very static in nature with little cell turnover. To regenerate tissue the ECM® must support cell migration and proliferation essentially recapitulating the original formation of that tissue.

Immunomodulatory ECM®

The default mechanism of healing in mammals is an inflammatory response followed by scar tissue formation. To alter this toward a regenerative response the cellular milieu responding to the injury must be altered. This can be achieved in some ECM®s.

Angiogenesis

This is the formation of new blood vessels. Blood vessel and capillary formation is the hallmark of healing tissue and is required for regeneration.


  1. Mina J. Bissell, H. Glenn Hall and Gordon Parry: How does the Extracellular Matrix Direct Gene Expression? J Theoretical Biology. 99, 31-68, (1982)