Decellularization

Stephen F. Badylak pioneered the process of decellularization at the McGowan Institute for Regenerative Medicine at the University of Pittsburgh.

[2] This process creates a natural biomaterial to act as a scaffold for cell growth, differentiation and tissue development.

In contrast to cell surface antibodies, the biochemical components of the ECM are conserved between hosts, so the risk of a hostile immune response is minimized.

[5] As far as introducing the different liquidized chemicals and enzymes to an organ or tissue, perfusion and immersion decellularization techniques have been used.

[citation needed] The most common physical methods used to lyse, kill, and remove cells from the matrix of a tissue through the use of temperature, force and pressure, and electrical disruption.

By quickly freezing a tissue, microscopic ice crystals form around the plasma membrane and the cell is lysed.

Temperature methods conserve the physical structure of the ECM scaffold, but are best handled by thick, strong tissues.

The cells eventually turn to death after their homeostatic electrical balance is ruined through the applied stimulus.

[2] The proper combination of chemicals is selected for decellularization depending on the thickness, extracellular matrix composition, and intended use of the tissue or organ.

[citation needed] The ionic detergent, sodium dodecyl sulfate (SDS), is commonly used because of its high efficacy for lysing cells without significant damage to the ECM.

EDTA is often used with trypsin, an enzyme that acts as a protease to cleave the already existing bonds between integral proteins of neighboring cells within a tissue.

After a cell is lysed with a detergent, acid, physical pressure, etc., endonucleases and exonucleases can begin the degradation of the genetic material.

Benzoase, an endonuclease, produces multiple small nuclear fragments that can be further degraded and removed from the ECM scaffold.

To successfully remove deep cells of a tissue with dispase, mechanical agitation is often included in the process.

Lipase acids function in decellularizing dermal tissues through delipidation and cleaving the interactions between heavily lipidized cells.

[5] A natural ECM scaffold provides the necessary physical and biochemical environment to facilitate the growth and specialization of potent progenitor and stem cells.

The limits to myocardial tissue engineering come from the ability to immediately perfuse and seed and implemented heart into a patient.

The in vitro-produced lung was successfully implemented into a rat, which attests to the possibilities of translating an in vitro produced organ into a patient.

Other success for decellularization has been found in small intestinal submucosa (SIS), renal, hepatic,[17] and pancreatic engineering.

[6] The future applications of decellularized tissue matrix is still being discovered and is considered one of the most hopeful areas in regenerative research.