Nano-Pulse Stimulation Therapy Initiates Regulated Cell Death in Skin, Unlike Bovie Radiofrequency Ablation and Cryoablation.

Abstract

This study describes a unique new bioelectric approach for clearing skin lesions and illustrates the clinical and histological differences between this new method and the standards of cryoablation and Bovie® radiofrequency ablation (RFA). To determine the advantage of stimulating regulated cell death with nanosecond pulsed electric fields over the necrosis response elicited by thermal ablation modalities. Human abdominal skin was treated with cryoablation, Bovie® RFA, and nano-pulse stimulation (NPS) therapy four times before an abdominoplasty procedure was performed to collect skin for histology. The clinical appearance and corresponding histology of each treatment were documented over time and compared. NPS therapy triggered regulated cell death as indicated by the appearance of activated Caspase-3 at 2 h post treatment and the absence of nuclear staining 1 day post treatment. Epidermal regeneration follows without impacting the noncellular dermis in contrast to cryoablation and Bovie® RFA which trigger necrosis and often cause scarring, inflammation, or permanent pigmentary changes. The main differences between NPS therapy and other ablation modalities are the level of fibrosis, amount of scarring, elastic fiber concentration, and inflammation. An analysis of the skin thickness 30 days after the treatment indicates that NPS-treated skin is the most similar to untreated skin but cryoablated and RF-ablated skin were 2- and 3.5-fold thicker, respectively, suggesting that they initiate necrosis rather than regulated cell death. We conclude that NPS therapy is a unique nonthermal modality that may be applied for clearing benign skin lesions by initiating the skin's own programmed cell death pathway instead of necrosis as used by cryoablation and Bovie® RFA.