Enzymes used in decellularization treatments are used to break the bonds and interactions between nucleic acids, interacting cells through neighboring proteins, and other cellular components. Lipases, thermolysin, galactosidase, nucleases, and trypsin have all been used in the removal of cells.  After a cell is lysed with a detergent, acid, physical pressure, etc., endonucleases and exonucleases can begin the degradation of the genetic material.  Endonucleases cleave DNA and RNA in the middle of sequences.  Benzoase, an endonuclease, produces multiple small nuclear fragments that can be further degraded and removed from the ECM scaffold.  Exonucleases act at the end of DNA sequences to cleave the phosphodiester bonds and further degrade the nucleic acid sequences.
Enzymes such as trypsin act as proteases that cleave the interactions between proteins. Although trypsin can have adverse effects of collagen and elastin fibers of the ECM, using it in a time-sensitive manner controls any potential damage it could cause on the extracellular fibers. Dispase is used to prevent undesired aggregation of cells, which is beneficial in promoting their separating from the ECM scaffold.  Experimentation has shown dispase to be most effective on the surface of a thin tissue, such as a lung in pulmonary tissue regeneration.  To successfully remove deep cells of a tissue with dispase, mechanical agitation is often included in the process.
Collagenase is only used when the ECM scaffold product does not require an intact collagen structure. Lipases are commonly used when decellularized skin grafts are needed.  Lipase acids function in decellularizing dermal tissues through delipidation and cleaving the interactions between heavily lipidized cells. The enzyme, α-galactosidase is a relevant treatment when removing the Gal epitope antigen from cell surfaces.