Principles of tissue engineering with nonthermal irreversible electroporation

Nonthermal irreversible electroporation (NTIRE) is an emerging tissue ablation modality that may be ideally suited in developing a decellularized tissue graft. NTIRE utilizes short electric pulses that produce nanoscale defects in the cell membrane lipid bilayer. The electric parameters can be chosen in such a way that Joule heating to the tissue is minimized and cell death occurs solely due to loss in cell homeostasis. By coupling NTIRE with the body's response, the cells can be selectively ablated and removed, leaving behind a tissue scaffold. Here, we introduce two different methods for developing a decellularized arterial scaffold. The first uses an electrode clamp that is applied to the outside of a rodent carotid artery and the second applies an endovascular minimally invasive approach to apply electric fields from the inner surface of the blood vessels. Both methods are first modeled using a transient finite element analysis of electric and thermal fields to ensure that the electric parameters used in this study will result in minimal thermal damage. Experimental work demonstrates that both techniques result in not only a decellularized arterial construct but an endothelial regrowth is evident along the lumen 7 days after treatment, indicating that the extracellular matrix was not damaged by electric and thermal fields and is still able to support cell growth.