The Role of Cold Atmospheric Plasma in Wound Healing Processes in Critically Ill Patients

Abstract

Critically ill patients are at risk of skin wounds, which reduce their quality of life, complicate their pharmacological regimens, and prolong their hospital stays in intensive care units (ICUs), while also increasing overall mortality and morbidity rates. Cold atmospheric plasma (CAP) has been proposed as a viable option for many biological and medical applications, given its capacity to reduce wound bacterial contamination and promote wound healing. The aim of this narrative review is to describe how CAP works and its operating mechanisms, as well as reporting its possible applications in critical care settings. The success of CAP in the treatment of wounds, in particular, bedsores or pressure sores, presents an innovative path in the prevention of nosocomial infections and an opportunity of reducing the negative implications of these diseases for the NHS. This narrative review of the literature was conducted following the 'Scale for the Assessment of Narrative Review Articles' (SANRA) methodology. Previous literature highlights three biological effects of plasma: inactivation of a wide range of microorganisms, including those that are multi-drug-resistant; increased cell proliferation and angiogenesis with a shorter period of plasma treatment; and apoptosis stimulation with a longer and more intensive treatment. CAP is effective in many areas of the medical field, with no significant adverse effects on healthy cells. However, its use can produce potentially serious side effects and should, therefore, be used under expert supervision and in appropriate doses.

Keywords: cold atmospheric plasma; critical care; infection; wound.

Figure 1

With the application of CAP on the wound, there is an increase in growth factors such as Tumor Growth Factor-β 1 and 2; Insulin Growth Factor 1 and 2; Vascular-Endothelial Growth Factor-α; Granulocyte-Macrophage Colony-Stimulating Factor, which facilitate angiogenesis with the anti-inflammatory effect of interleukin-8. Finally, the wound heals with re-epithelialization and synthesis of a new matrix, thanks to the fibroblasts and cytokines, Membrane Cofactor Protein-1 and Interleukin-6.

Figure 2

Reactive oxygen and reactive nitrogen species (ROS and RNS) related to CAP are divided into short- and long-lived molecules, which play different roles in the treating skin diseases. CAP promotes wound healing through antiseptic and pro-angiogenic effects, stimulating the proliferation and migration of skin cells by activating/inhibiting integrin receptors.

Figure 3

The treatment of CAP on a wound. When the skin was injured, the first step was to form a blood scab to protect the wound. CAP could accomplish wound healing through short-lived and long-lived ROS and RNS. CAP could promote the formation of new blood vessels, strengthen the release of Connective Tissue Growth Factor (CTGF) and Vascular Endothelial Growth Factor (VEGF), activate the Yes-Associated Protein (YAP) pathway, and upregulate the expression of Connexin 43 (Cx43) and Cysteine-rich angiogenic inducer 61 (Cyr61).

Figure 4

Schematic representation of bacterial reduction induced by CAP.