Despite considerable progress, cutaneous wounds remain a major health concern. Skin response to injury follows a well-orchestrated integration of complex biological and molecular events to quickly achieve repair. Hence, acute skin wounds heal with scaring but no regeneration. Recent research aims to elucidate homeostatic cues that may drive intrinsic regenerative pathways. However the recent findings in factors involved and in the understanding of the cellular and molecular responses to injury have not led yet to elucidate the process avoiding scar formation. In addition, there are no substantial advances in patient care with a lack of reliable therapies to treat pathological and chronic wounds. Within the past few years, harnessing of cold atmospheric plasmas (CAPs) to medicine has turned into an innovative field of research with diverse applications such as decontamination and sterilization based on the bactericidal activity of plasmas or for the treatment of tumors to inhibit metastasis and induce cancer cell death. More recently CAP treatment was tested for infected wound treatment resulting in a reduction of the bacterial load and suggesting possible positive effect on wound healing. However, to date only few observations are reported from human clinical trial with no supporting pre-clinical data and no understanding of the underlying mechanism of action of CAPs.
In physic, CAPs refer to non-thermal plasmas, partially ionized gases obtained from specific electric shocks. Collisional mechanisms within the gaseous medium lead to the formation of many energetic components with a high reactivity: electrons, ions, neutral particles, numerous excited states, Reactive Oxygen Species (ROS) and Nitrogen Species (RNS), including photons from the UV to IR domain. According to current knowledge physical and chemical mechanisms (caused by reactive species, free radicals, charges, UV photons) and biological mechanisms (such as DNA and membrane damage) are both demonstrated to cause bacteria inactivation and death. However, the reactive species created from defined plasmas are not fully identified in all conditions, and the understanding of their molecular action mechanism in mammal and human living cells is not provided. Therefore, to develop innovative strategies suitable for clinical applications, basic knowledge of the cellular effects of plasmas is mandatory and would be considered as a prerequisite to any extension of plasmas to medical therapies in order to control and optimize efficiency and to avoid any adverse effects.
The PLASMAREGEN project aims (i) to improve CAPs characterization and comparison in order to qualify defined CAPs appropriate for wound healing applications, (ii) to use novel electrochemical sensors and methodological approaches to detect and measure reactive species produced in liquid medium, in cells, in tissue after CAPs exposure, (iii) to investigate the biological effect (toxicity) and therapeutic effect (benefit) of plasma treatment at the level of the cell, the tissue and in animal model of skin wound healing. Our project combines multidisciplinary approaches at the interface of physics, chemistry and biology in order to generate significant advance in the comprehension of plasma action at the molecular, cellular and integrated level in tissue in vivo, opening onto new therapeutic perspectives for the treatment of normal and pathological wounds.
Madame Valérie PLANAT-BENARD (UMR 5373 CNRS, Université P.Sabatier (UPS), EFS, Inserm U1031)
The author of this summary is the project coordinator, who is responsible for the content of this summary. The ANR declines any responsibility as for its contents.
ISM UMR 5255 Institut des Sciences Moléculaires
STROMALab UMR 5373 CNRS, Université P.Sabatier (UPS), EFS, Inserm U1031
IPREM Institut des Sciences analytiques et de physico-chimie pour l'Environnement et les Matériaux
Help of the ANR 596,180 euros
Beginning and duration of the scientific project: September 2014 - 42 Months