Skin regeneration with all accessory organs following ablation with irreversible electroporation

Alexander Golberg; Martin Villiger; G Felix Broelsch; Kyle P Quinn; Hassan Albadawi; Saiqa Khan; Michael T Watkins; Irene Georgakoudi; William G Austen Jr; Marianna Bei; Brett E Bouma; Martin C Mihm Jr; Martin L Yarmush

doi:10.1002/term.2374

Skin regeneration with all accessory organs following ablation with irreversible electroporation

J Tissue Eng Regen Med. 2018 Jan;12(1):98-113. doi: 10.1002/term.2374. Epub 2017 May 23.

Authors

Alexander Golberg^{1

2}, Martin Villiger³, G Felix Broelsch⁴, Kyle P Quinn^{5

6}, Hassan Albadawi⁷, Saiqa Khan⁴, Michael T Watkins⁷, Irene Georgakoudi⁵, William G Austen Jr⁴, Marianna Bei¹, Brett E Bouma^{3

8}, Martin C Mihm Jr⁹, Martin L Yarmush^{1

10}

Affiliations

¹ Center for Engineering in Medicine, Department of Surgery, Massachusetts General Hospital, Harvard Medical School, and the Shriners Burns Hospital, Boston, MA, 02114, USA.
² Porter School of Environmental Studies, Tel Aviv University, Tel Aviv, Israel.
³ Wellman Center for Photomedicine and Department of Dermatology, Massachusetts General Hospital and Harvard Medical School, 50 Blossom Street, Boston, Massachusetts, 02114, USA.
⁴ Department of Surgery, Division of Plastic and Reconstructive Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, MA, 02114, USA.
⁵ Department of Biomedical Engineering, Tufts University, Medford, MA, 02155, USA.
⁶ Department of Biomedical Engineering, University of Arkansas, Fayetteville, AR, 72701, USA.
⁷ Division of Vascular and Endovascular Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, MA, 02114, USA.
⁸ Harvard-Massachusetts Institute of Technology Division of Health Sciences and Technology, Cambridge, Massachusetts, 02142, USA.
⁹ Department of Dermatology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, 02115, USA.
¹⁰ Department of Biomedical Engineering, Rutgers University, Piscataway, NJ, 08854, USA.

Abstract

Skin scar formation is a complex process that results in the formation of dense extracellular matrix (ECM) without normal skin appendages such as hair and glands. The absence of a scarless healing model in adult mammals prevents the development of successful therapies. We show that irreversible electroporation of skin drives its regeneration with all accessory organs in normal adult rats. Pulsed electric fields at 500 V, with 70 μs pulse duration and 1000 pulses delivered at 3 Hz, applied through two electrodes separated by 2 mm lead to massive cell death. However, the ECM architecture of the skin was preserved. Six months after the ablation, the epidermis, sebaceous glands, panniculus carnosus, hair follicles, microvasculature and arrector pili muscle were altogether re-formed in the entire ablated area. These results suggest a key role of the ECM architecture in the differentiation, migration and signalling of cells during scarless wound healing. Copyright © 2016 John Wiley & Sons, Ltd.

Keywords: electroporation; extracellular matrix; pulsed electric field; regeneration; scar; scarless; skin.

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

Animals
Electrodes
Electroporation / methods*
Extracellular Matrix / metabolism
Female
Rats, Sprague-Dawley
Regeneration*
Skin / pathology*
Wound Healing

Abstract

Publication types

MeSH terms

Grants and funding