Introduction Oxygen partial pressure measurement What does tumour hypoxia mean? Small molecules and hypoxia What does physioxia mean? Cellular and molecular consequences of physioxia versus normoxia and hypoxia Conclusion Oxygen supply and diffusion into tissues are necessary for survival. The oxygen partial pressure (pO₂), which is a key component of the physiological state of an organ, results from the balance between oxygen delivery and its consumption. In mammals, oxygen is transported by red blood cells circulating in a well‐organized vasculature. Oxygen delivery is dependent on the metabolic requirements and functional status of each organ. Consequently, in a physiological condition, organ and tissue are characterized by their own unique ‘tissue normoxia’ or ‘physioxia’ status. Tissue oxygenation is severely disturbed during pathological conditions such as cancer, diabetes, coronary heart disease, stroke, etc., which are associated with decrease in pO₂, i.e. ‘hypoxia’. In this review, we present an array of methods currently used for assessing tissue oxygenation. We show that hypoxia is marked during tumour development and has strong consequences for oxygenation and its influence upon chemotherapy efficiency. Then we compare this to physiological pO₂ values of human organs. Finally we evaluate consequences of physioxia on cell activity and its molecular modulations. More importantly we emphasize the discrepancy between in vivo and in vitro tissue and cells oxygen status which can have detrimental effects on experimental outcome. It appears that the values corresponding to the physioxia are ranging between 11% and 1% O₂ whereas current in vitro experimentations are usually performed in 19.95% O₂, an artificial context as far as oxygen balance is concerned. It is important to realize that most of the experiments performed in so‐called normoxia might be dangerously misleading.

The maintenance of skin integrity is crucial to ensure the physiological barrier against exogenous compounds, microorganisms and dehydration but also to fulfill social and aesthetic purposes. Besides the development of new actives intended to enter a formulation, innovative technologies based on physical principles have been proposed in the last years. Among them, Cold Atmospheric Plasma (CAP) technology, which already showed interesting results in dermatology, is currently being studied for its potential in skin treatments and cares. CAP bio-medical studies gather several different expertise ranging from physics to biology through chemistry and biochemistry, making this topic hard to pin. In this review we provide a broad survey of the interactions between CAP and skin. In the first section, we tried to give some fundamentals on skin structure and physiology, related to its essential functions, together with the main bases on cold plasma and its physicochemical properties. In the following parts we dissected and analyzed each CAP parameter to highlight the already known and the possible effects they can play on skin. This overview aims to get an idea of the potential of cold atmospheric plasma technology in skin biology for the future developments of dermo-cosmetic treatments, for example in aging prevention.

Tumour microenvironment determines the fate of treatments. Reconstitution of tumour conditions is mandatory for alternative in vitro methods devoted to cancer development and the selection of therapeutic strategies. This work describes a 3D model of melanoma growth in its environment. Introducing means to mimic tumour angiogenesis, which turns on tumour progression, the model shows that melanoma tumour spheroids allow reconstitution of solid tumours with stromal cells. Angiogenesis evidenced the differential recruitment of endothelial cells (EC) from early progenitors (EEPCs) to mature ECs. Hypoxia was the key parameter that selected and stabilized melanoma cancer stem like cells (CSCs) phenotype based on aldehyde dehydrogenase expression as the best criterion. The 3D-tumour-model demonstrated the distinct reactivity of ECs toward tumour cells in terms of cellular cross-talk and humoral response. Intra-spheroid cell-to-cell membrane dye exchanges, mediated by intercellular interactions, uncovered the melanoma-to-EEPC cooperation. The resulting changes in tumour milieu were evidenced by the chemokinic composition and hypoxia-related variations in microRNA expression assessed in each cellular component of the spheroids. This method brings new tools to decipher the molecular mechanism of tumour-mediated cell recruitment and for in vitro assessment of therapeutic approaches.

Several attempts have been made to deliver reactive oxygen and nitrogen species (RONS) produced by non-thermal plasma onto large surfaces in a controllable way compatible with skin treatments. In this paper, the effect of pulse frequency, in the range 0.5–20 kHz, on the discharge behavior was studied on skin tissue models to evaluate potential treatment changes. This has been done through electrical characterization, visualization of the helium flow (by Schlieren technique), produced plasma jet modifications (ICCD imaging) and RONS measurements. The results show that, in addition to its well known important role in the production of the chemical species, the applied discharge frequency plays a very significant role in the size of the treated surface. An enhancement of NO ^* , OH ^* and O ^* production in the gas phase at the higher frequency is reported and assigned to the stronger mixing of the helium flow with ambient air. The efficacy of plasma jet on transporting RONS on/into agarose gel and pig skin has been evaluated. The distribution of the reactive species on the target, or passing through, is strongly dependent on the discharge frequency and consequently induces pH variations. The present study supports a new way for enlarging the treated surface by using a simple jet at high frequency in the 20 kHz range, leading, with appropriate gas flow and distance to target, to conditions of RONS production that are compatible with potential uses for biomedical or cosmetic applications.