Preventing Scars after Injury with Partial Irreversible Electroporation

Abstract

Preventing the formation of hypertrophic scars, especially those that are a result of major trauma or burns, would have enormous impact in the fields of regenerative and trauma medicine. In this report, we introduce a non-invasive method to prevent scarring based on non-thermal partial irreversible electroporation. Contact burn injuries in rats were treated with varying treatment parameters to optimize the treatment protocol. Scar surface area and structural properties of the scar were assessed with histology and non-invasive, longitudinal imaging with polarization-sensitive optical coherence tomography. We found that partial irreversible electroporation using 200 pulses of 250 V and 70 μs duration, delivered at 3 Hz every 20 days during a total of five therapy sessions after the initial burn injury resulted in a 57.9% reduction of the scar area in comparison with untreated scars and structural features approaching those of normal skin. Noteworthy, unlike humans, rats do not develop hypertrophic scars. Therefore, the use of a rat animal model is the limiting factor of this work.

Skin regeneration with all accessory organs following ablation with irreversible electroporation

“…Furthermore, we have recently shown that completely ablated normal rat liver regenerates without fibrosis (Golberg et al, 2016a), confirming the earlier hypothesis . In addition, we have also shown that partial IRE reduces scars after burn injury in rats (Golberg et al, 2016b). The importance of the ECM for functional tissue regeneration has long been recognized, and multiple attempts of tissue engineering aspire to re-engineer the matrix architecture (Place et al, 2009).…”

Prediction of Scar Size in Rats Six Months after Burns Based on Early Post-injury Polarization-Sensitive Optical Frequency Domain Imaging

“…For statistical prediction of the resulting scar size, a dataset with a range of different scar sizes is needed. We used the data from our previous work where we showed the ability of partially irreversible electroporation (pIRE) to reduce the size of scars in rats, 6 months after injury (Golberg et al, 2016 ). Third degree burns were treated at various time points after injury with different pulsed electric field parameters, resulting in a range of scar sizes 6 months after the initial injury, as reported in Golberg et al ( 2016 ).…”

“…In brief, animals were anesthetized with isoflurane and their fur was clipped along the dorsal surfaces. Burns were incurred by pressing the end of a pre-heated (≥95°C) brass block against the rat's dorsum for 10 s, resulting in a non-lethal, full-thickness, third-degree burn, measuring ~1 cm 2 , which is 0.25% of the total body surface area (TBSA; Golberg et al, 2016 ). Four burn injuries were performed on each animal at sites separated by 2 cm along the head to tail axis, accounting for 1% TBSA of total burn area.…”

“…Compared to normal skin with heterogeneous birefringence and low DOP, HTS was characterized by an initially low birefringence, which increased as collagen fibers remodeled, and a persistently high DOP (Lo et al, 2016 ). In additional work, we showed that PS-OFDI signature could differentiate between third-degree burn scars treated with different therapy plans of partially irreversible electroporation (Golberg et al, 2016 ).…”

Rejuvenation of aged rat skin with pulsed electric fields

“…Although PEFs can kill (Davalos, Mir, & Rubinsky, ) and injure cells (Golberg et al, ), they preserve the ECM architecture. What is more, the permanent nanoscale defects permit molecules, such as growth factors, to come out from the targeted cells, and the locally released multiple growth factors induce new cell and tissue growth (Golberg, Broelsch, et al, ; Golberg, Bruinsma, Jaramillo, Yarmush, & Uygun, ; Golberg et al, ; Golberg, Khan, et al, ; Phillips, Narayan, Padath, & Rubinsky, ; Rubinsky, Onik, & Mikus, ).…”