Physical plasma therapy accelerates wound re‐epithelialisation and enhances extracellular matrix formation in cutaneous skin grafts

Abstract

Skin grafting is a surgical method of cutaneous reconstruction, which provides volumetric replacement in wounds unable to heal by primary intention. Clinically, full-thickness skin grafts (FTSGs) are placed in aesthetically sensitive and mechanically demanding areas such as the hands, face, and neck. Complete or partial graft failure is the primary complication associated with this surgical procedure. Strategies aimed at improving the rate of skin graft integration will reduce the incidence of graft failure. Cold atmospheric plasma (CAP) is an emerging technology offering innovative clinical applications. The aim of this study was to test the therapeutic potential of CAP to improve wound healing and skin graft integration into the recipient site. In vitro models that mimic wound healing were used to investigate the ability of CAP to enhance cellular migration, a key factor in cutaneous tissue repair. We demonstrated that CAP enhanced the migration of epidermal keratinocytes and dermal fibroblasts. This increased cellular migration was possibly induced by the low dose of reactive oxygen and nitrogen species produced by CAP. Using a mouse model of burn wound reconstructed with a full-thickness skin graft, we showed that wounds treated with CAP healed faster than did control wounds. Immunohistochemical wound analysis showed that CAP treatment enhanced the expression of the dermal-epidermal junction components, which are vital for successful skin graft integration. CAP treatment was characterised by increased levels of Tgfbr1 mRNA and collagen I protein in vivo, suggesting enhanced wound maturity and extracellular matrix deposition. Mechanistically, we show that CAP induced the activation of the canonical SMAD-dependent TGF-β1 pathway in primary human dermal fibroblasts, which may explain the increased collagen I synthesis in vitro. These studies revealed that CAP improved wound repair and skin graft integration via mechanisms involving extracellular matrix formation. CAP offers a novel approach for treating cutaneous wounds and skin grafts.

Non‐invasive physical plasma (NIPP) treatment of a hedgehog with head injury: A novel therapy in veterinary medicine

“…For instance, stimulation of the immune system accompanied by the activation of wound‐associated skin cells leads to effective regeneration of the wound 27–29 . The combination of all NIPP‐induced processes eventually leads to significantly accelerated wound closure in human wound patients 24 , 25 …”

“…These NIPPs do not cause nonspecific thermal effects, but mainly induce ROS-mediated cellular responses, 12 which are primarily responsible for the protherapeutic efficacy. [15][16][17][18]24 The NIPP device used in this case report generates nonthermal physical plasma. It has been shown that temperatures of up to 45 • C can be reached inside the device at the surface of the grid electrode.…”

Plasma Dermatology: Skin Therapy Using Cold Atmospheric Plasma

“…In the recipient site, Frescaline et al. found that CAP could enhance extracellular matrix (ECM) formation through activating the canonical SMAD-dependent TGF-β1 pathway ( 47 ).…”

“…donor site, Heinlin et al conducted a randomized placebocontrolled trial and observed improved wound reepithelialisation and fewer fibrin layers and blood crusts after CAP treatment(49). In the recipient site, Frescaline et al found that CAP could enhance extracellular matrix (ECM) formation through activating the canonical SMAD-dependent TGF-b1 pathway(47).…”

Low‐intensity cold atmospheric plasma reduces wrinkles on photoaged skin through hormetic induction of extracellular matrix protein expression in dermal fibroblasts

“…Therefore, cold atmospheric plasma (CAP) devices can be used effectively for the selective elimination of oxidative stress‐vulnerable cells, such as cancer cells, or pathologic microorganisms 4 . Meanwhile, a growing body of evidence suggests that CAP can induce skin rejuvenation by upregulating the production of extracellular matrix proteins at low densities 5–9 . The authors explained this ironic phenomenon with hormesis , a term indicating the dose–response relationship phenomenon characterized by low‐dose stimulation and high‐dose inhibition 10 .…”