Education

The Science of Tissue Engineering

Tissue engineering is subset of the field of biotechnology. It has been defined by the National Science Foundation as the application of the principles of engineering and the life sciences toward the understanding of normal tissue structure and function and the repair and restoration of damaged or missing tissues and organs. (Skalak and Fox, 1988).

Within the field of tissue engineering, the strategies for the replacement and repair of damaged or missing tissues and organs can generally be placed in three categories:

Scaffold-based approach
Cell/gene-based approach
Bioactive molecule (growth factors) approach

ACell’s focus is strongly centered on the scaffold-based solutions.

Natural, Biological Scaffolds

The replacement or repair of any body tissue or organ will, at some point, require a scaffold or template upon which cells attach, migrate, proliferate, and differentiate. Scaffolds can be:

Synthetic or naturally occurring
Resorbable or non-resorbable
Cellular or acellular

The tissue engineering products discovered, developed, and marketed by ACell are extra cellular matrix (ECM) scaffolds that are:

Entirely naturally occurring. This has significant advantages over synthetic scaffolds because the naturally occurring origin of the scaffold material provides for a unique combination of structural and functional molecules that cannot be reproduced in the laboratory by synthetic methods.
Completely resorbable. The body usually resorbs the ACell scaffold within two to three months following surgical implantation. This eliminates the possibility of a chronic host inflammatory response against a permanently implanted foreign material.
Totally acellular. The acellular nature of our scaffold removes the antigenic stimulus (i.e., cell markers) that would otherwise cause an adverse immune response. The acellular matrix appears to provide signals to the host immune system that stimulate an adaptive or accommodative response that is ideal for both wound healing and three-dimensional growth of various cell types.

Urinary Bladder is Ideal Scaffold Material

The extracellular matrix of the ACell scaffold technology is derived from the urinary bladder of pigs and is referred to as UBM (Urinary Bladder Matrix). Following mechanical and chemical processing that eliminates the superficial cellular layer, and substantially all of the deeper muscular layers of the urinary bladder, the remaining acellular matrix represents ideal scaffold material.

UBM scaffold technology is distinguished from other ECM scaffold technology by its unique bimodal surface characteristics. One surface consists of basement membrane ECM and the opposite surface consists of non-basement membrane ECM. The ECM consists of a collection of both structural and functional proteins that are arranged in a three-dimensional ultra structure that is virtually impossible to replicate in the laboratory. The technical approach of other companies in the field of tissue engineering usually involves the use of one or more of the components of the ECM scaffold. For example, purified Type I collagen has been extensively used as a scaffold for skin repair, plastic surgery, and repair of the lower urinary tract. Likewise, growth factors found in the ECM, such as vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (BFGF), are used therapeutically to stimulate the growth of new blood vessels and the proliferation of connective tissue cells.

We believe that the ACell UBM contains the appropriate ratio of structural and functional molecules for optimal wound healing and accounts for the observed biologic response that is characteristic of the ACell UBM technology.

Fundamentally Altering the Way the Body Responds to Injury

Following the implantation of an ACell UBM scaffold at a site of damaged or missing tissue, a very strong angiogenic (i.e., new blood vessel formation) response is observed. This is followed by an abundant infiltration of numerous cell types including mononuclear cells that appear to have the potential to differentiate into numerous types of tissue. In preclinical animal trials, the UBM scaffold has shown the ability to form new esophageal tissue, urinary bladder, vocal cord and laryngeal tissue, skeletal muscle and body wall, heart valves, and even new myocardium (i.e., heart tissue).

During the process of tissue reconstruction, the implanted UBM scaffold is gradually degraded until, eventually, only the cells and tissues that have been deposited by the host remain in place of the scaffold. Stated differently, the UBM scaffold fundamentally alters the way in which mammals respond to injury. The UBM serves as an inductive scaffold for tissue replacement. Rather than simple scar tissue formation or a lack of any healing response at all, the body is stimulated (i.e., induced) to deposit organized tissues reminiscent of the phenomenon that occurs during fetal development.

Summary

In summary, ACell’s technology is based upon an acellular, naturally occurring, totally resorbable scaffold material derived from the extra cellular matrix of the porcine urinary bladder. The scaffold material serves as an inductive template around which mammalian tissues grow and differentiate in a manner that ACell believes would otherwise not be possible