Irreversible Electroporation Promotes Scarless Tissue Regeneration

Local blood flow was evaluated with Laser Doppler Imaging, which revealed preservation of blood flow in the rats ablated with PEFs, in contrast to the burned area, which suffered a decrease in blood flow. The results showed that IRE appears to selectively destroy all cells in skin tissue, while preserving the extracellular matrix (ECM) tissue structure including the local blood supply, needed for healthy tissue growth and functional regeneration.

One day after the procedure, massive inflammation was observed along with damage to muscle fibers, degranulation of mast cells, cell fusion and apoptosis in sebaceous glands, and damaged hair follicles. But two months after the ablation, complete regeneration of epidermis, hair follicles, sebaceous glands, and the panniculus carnosusis was observed. There was no evidence of scar tissue formation. The ECM collagen maintained its normal architecture, in contrast to complete loss of collagen architecture in the burned skin, along with lack of regeneration of sebaceous glands and hair follicles. The study was published in the September 24, 2013, (inaugural) issue of the journal Technology.

“Previously, scarless regeneration has only been observed in adult amphibians and early in mammalian fetuses, both of which do not have an adaptive immune response,” said senior author Martin L. Yarmush, MD, PhD, director of the MGH Center for Engineering in Medicine. “Even though our rodents had an intact adaptive immune system, we were able to generate scarless skin regeneration in these adult mammals. Further study of this technique will help us better understand the mechanism of scarring.”

“We compared this technique with thermal burns and found many different aspects post-injury, both in terms of the extent of damage and the dynamics of recovery,” added lead author Alexander Golberg, PhD. “This development not only holds a great promise for unraveling many aspects of the complex wound healing process but also to potentially lead to new therapies. We believe that this model will enable other laboratories to learn and uncover new aspects of adult tissue growth and development.”

The researchers added that the irreversible electroporation (IRE) caused by the PEFs caused large pores to appear in cell membranes, eventually leading to cell death. But IRE also induced temporary vasoconstriction, which conversely reduced the immune response, thus allowing for more rapid tissue regeneration with decreased scarring.

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