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Fundamental and applied research on plasma-treated liquids for biomedical applications was boosted in the last few years, dictated by their advantages with respect to direct treatments. However, often, the lack of consistent analysis at a molecular level of these liquids, and of the processes used to produce them, have raised doubts of their usefulness in the clinic. The aim of this article is to critically discuss some basic aspects related to the use of plasma-treated liquids in medicine, with a focus on their chemical composition. We analyze the main liquids used in the field, how they are affected by non-thermal plasmas, and the possibility to replicate them without plasma treatment., Peer Reviewed, Objectius de Desenvolupament Sostenible::3 - Salut i Benestar, Postprint (published version)

Recentment, el plasma no tèrmic ha demostrat ser molt prometedor per diferents aplicacions biomèdiques. Això és degut a que el plasma genera espècies reactives d’oxigen i nitrogen que poden tenir efectes tant regeneratius com citotòxics segons la dosi. Els hidrogels s’han estudiat com potencials medis d’emmagatzematge i d’administració de RONS generats per plasma (tractament indirecte) degut a la seva capacitat de romandre en el lloc d’interès i alliberar RONS de manera controlada. També s’han estudiat com a models per avaluar l’efecte del tractament directe amb plasma en teixits vius. L'objectiu és estudiar la distribució de RONS en la superfície dels hidrogels de gelatina i agarosa i la profunditat de penetració a través d’ells. A més a més, s’estudia la quantificació del transport de RONS a través de fines capes d’hidrogel en una solució aquosa. En el mateix estudi es compara l’efecte del tractament amb plasma sobre la gelatina i l’agarosa. Es van tractar hidrogels mitjançant un raig de plasma a pressió atmosfèrica utilitzant heli. Es van realitzar dos experiments diferents. En un d’ells, els hidrogels contenien reactius colorimètrics per avaluar la distribució i penetració. Els resultats es van avaluar qualitativament, mitjançant un anàlisi visual, y semiquantitativament, amb el software ImageJ. Van mostrar que la distribució de RONS augmentava amb el temps de tractament i tenia una distribució radial en la superfície del hidrogel. Les concentracions de RONS van ser majors en els hidrogels d’agarosa que en els de gelatina. En quant a les profunditats de penetració, es van obtenir resultats similars. Per al segon experiment, es va avaluar la concentració de RONS en una solució aquosa, posant una capa d’hidrogel entre la solució i el plasma. La quantificació es va realitzar utilitzant reactius químics i va mostrar una dependència lineal de la concentració de RONS amb el temps de tractament, y una dependència inversa amb el gruix del hidrogel., El plasma no térmico ha demostrado ser muy prometedor para diferentes aplicaciones biomédicas debido a que el plasma genera especies reactivas de oxígeno y nitrógeno que pueden tener efectos tanto regenerativos como citotóxicos según la dosis. Los hidrogeles se han estudiado como potenciales medios de almacenaje y administración de RONS (tratamiento indirecto) debido a su capacidad para permanecer en el lugar de interés y liberar RONS de forma controlada. Además, se han estudiado como modelos para evaluar el efecto del tratamiento directo con plasma en tejidos vivos. El objetivo es estudiar la distribución de RONS en la superficie de hidrogeles de gelatina y agarosa y la profundidad de penetración. Además, se estudia la cuantificación del transporte de RONS a través de finas capas de hidrogel en una solución acuosa. En el mismo estudio se compara el efecto del tratamiento con plasma sobre la gelatina y la agarosa. Se trataron hidrogeles mediante un chorro de plasma a presión atmosférica utilizando helio. Se realizaron dos experimentos diferentes. En uno de ellos, los hidrogeles contenían reactivos colorimétricos para evaluar la distribución y penetración. Los resultados se evaluaron cualitativamente, mediante un análisis visual, y semicuantitativamente, con el software ImageJ. Mostraron que la distribución de RONS aumentaba con el tiempo de tratamiento y tenía una distribución radial en la superficie del hidrogel. Las concentraciones de RONS fueron mayores en los hidrogeles de agarosa que en los de gelatina. En cuanto a las profundidades de penetración, se obtuvieron resultados similares. Para el segundo tipo de experimento, evaluamos la concentración de RONS en una solución acuosa poniendo una capa de hidrogel entre la solución y el plasma. La cuantificación se realizó utilizando reactivos químicos y mostró una dependencia lineal de la concentración de RONS. Además, también se observa una mayor concentración de RONS en la agarosa que en la gelatina., Non-thermal plasma has been shown to be very promising for different biomedical applications. This is due to the fact that plasma generates reactive oxygen and nitrogen species that can have both regenerative and cytotoxic effects according to their doses. Hydrogels have been studied as potential media for the storage and delivery of plasma-generated RONS due to their capacity to remain in the site of interest and release RONS in a controlled way. Furthermore, hydrogels have been studied as model systems to evaluate the effect of direct plasma treatment in living tissues. The aim of this work is to study the distribution of RONS on the surface of gelatin and agarose hydrogels and the penetration depth through them. Moreover, a quantification of the transport of RONS through thin hydrogel layers in a water solution is studied. We are comparing the effect of plasma treatment on gelatin and agarose within the same study. Gelatin and agarose hydrogels were treated by an atmospheric pressure plasma jet using helium. Two different kinds of experiments were performed. In one of them, the hydrogels contained colorimetric probes to evaluate the distribution and penetration depths. The change of colour on the surface and inside the hydrogels was evaluated qualitatively, by a visual analysis, and semi-quantitatively, with the software ImageJ. The results showed that RONS distribution increased with the treatment time and it had a radial distribution on the hydrogel surface. RONS concentrations were higher in agarose than in gelatin hydrogels. For the penetration depths, similar results have been obtained. For the second experiment, we evaluated the RONS concentration in a water solution putting a hydrogel layer between them. The quantification was done using chemical probes and showed a linear dependence of tRONS concentration with the treatment time, and an inverse dependence with the hydrogel thickness. Moreover, it is also observed a higher RONS concentration in agarose.

Cold atmospheric plasma (CAP) is a source of cell-damaging oxidant molecules that may be used as low-cost cancer treatment with minimal side effects. Liquids treated with cold plasma and enriched with oxidants are a modality for non-invasive treatment of internal tumors with cold plasma via injection. However, liquids are easily diluted with body fluids which impedes high and localized delivery of oxidants to the target. As an alternative, plasma-treated hydrogels (PTH) emerge as vehicles for the precise delivery of oxidants. This study reports an optimal protocol for the preparation of injectable alginate PTH that ensures the preservation of plasma-generated oxidants. The generation, storage, and release of oxidants from the PTH are assessed. The efficacy of the alginate PTH in cancer treatment is demonstrated in the context of cancer cell cytotoxicity and immunogenicity–release of danger signals and phagocytosis by immature dendritic cells, up to now unexplored for PTH. These are shown in osteosarcoma, a hard-to-treat cancer. The study aims to consolidate PTH as a novel cold plasma treatment modality for non-invasive or postoperative tumor treatment. The results offer a rationale for further exploration of alginate-based PTHs as a versatile platform in biomedical engineering., Peer Reviewed, Objectius de Desenvolupament Sostenible::3 - Salut i Benestar, Postprint (published version)

Objective: This study evaluates the application of a plasma discharge for the decontamination and removal of bacterial biofilms in small-diameter polytetrafluoroethylene (PTFE) tubes. The latter simulates the environments of an endoscope working channel., info:eu-repo/semantics/nonPublished

Cold atmospheric plasmas are a known source of reactive species enabling various treatments, from the healing of chronic wounds to the treatment of surface cancers. Therapeutic endoscopic procedures require developing specific flexible tools that can be used through or alongside endoscopes. Plasma devices for endoscopy have aroused significant research interest over the past few decades, but their electrical behaviour is not yet fully understood and predictable. There is thus a clear need for a robust model that provides a way to understand and optimize future devices. In this work, for the first time, an electrical equivalent model of a long plasma source (comprising plasma generation, transport and target interaction) was designed, implemented, and validated. System parameters were estimated based on the system geometry and independent measurements. The model reliably reproduces the double ignition (in the quartz chamber and at the treatment site) observed experimentally. Simulations globally agree with measurements taken for various gas gap distances and input voltages. Internal parameters that are difficult to measure, such as the electrical charge at the gas gaps, were inferred. The model can predict leakage current in the body and current at the target site. This work provides a new understanding of endoscopic plasma systems that could be used in the future to ensure patient and operator safety., SCOPUS: ar.j, info:eu-repo/semantics/published

Previous studies suggest the potential efficacy of neuroprotective effects of gaseous atmospheric-pressure plasma (APP) treatment on neuronal cells. However, it remains unclear if the neuroprotective properties of the gas plasmas benefit the ischemic stroke treatment, and how to use the plasmas in the in vivo ischemic stroke models. Rats were subjected to 90 min middle cerebral artery occlusion (MCAO) to establish the ischemic stroke model and then intermittently inhaled the plasma for 2 min at 60 min MCAO. The regional cerebral blood flow (CBF) was monitored. Animal behavior scoring, magnetic resonance imaging (MRI), 2,3,5-triphenyltetrazolium chloride (TTC) staining, and hematoxylin and eosin (HE) staining were performed to evaluate the therapeutic efficacy of the gas plasma inhalation on MCAO rats. Intermittent gas plasma inhalation by rats with experimental ischemic stroke could improve neurological function, increase regional CBF, and decrease brain infarction. Further MRI tests showed that the gas plasma inhalation could limit the ischemic lesion progression, which was beneficial to improve the outcomes of the MCAO rats. Post-stroke treatment with intermittent gas plasma inhalation could reduce the ischemic lesion progression and decrease cerebral infarction volume, which might provide a new promising strategy for ischemic stroke treatment.

Plasma, the fourth and most pervasive state of matter in the visible universe, is a fascinating medium that is connected to the beginning of our universe itself. Man-made plasmas are at the core of many technological advances that include the fabrication of semiconductor devices, which enabled the modern computer and communication revolutions. The introduction of low temperature, atmospheric pressure plasmas to the biomedical field has ushered a new revolution in the healthcare arena that promises to introduce plasma-based therapies to combat some thorny and long-standing medical challenges. This article presents an overview of where research is at today and discusses innovative concepts and approaches to overcome present challenges and take the field to the next level. It is written by a team of experts who took an in-depth look at the various applications of plasma in hygiene, decontamination, and medicine, made critical analysis, and proposed ideas and concepts that should help the research community focus their efforts on clear and practical steps necessary to keep the field advancing for decades to come.

Endoscopic Mucosal Ablation (EMA) is a minimally invasive procedure which eradicates adiseased mucosa to enable regeneration to a healthy state. The procedure is used in clinical practiceto treat a precancerous condition of the esophagus called Barrett’s Esophagus (BE). Anotherpromising indication being studied is the treatment of the mucosa in the first part of the intestine(the duodenum) to improve conditions linked to insulin resistance, including Type 2 Diabetes Mellitus(T2DM) and Non-Alcoholic SteatoHepatitis (NASH). This work aims to propose an alternativetechnique for EMA, in order to improve the treatment of BE and propose a new treatment modalityfor T2DM and NASH. To this end, Cold Atmospheric Plasma (CAP) is considered. CAP is anionized gas containing reactive species which produces a biochemical effect on tissues at ambienttemperature. Over the past two decades plasma treatment has proliferated mainly for the propertiesof its Reactive Oxygen and Nitrogen Species (RONS) on cells. RONS induce an oxidative stressand trigger signaling cascades, resulting in a large range of effects from stimulation (proliferation,regeneration) to cell death, notably by apoptosis, a natural programmed cell death which can reduceinflammation and post-op burden. CAP being a reactive gaseous medium, its diffusion would offera homogeneous, fast, safe, versatile and convenient way of treating large portions of mucosa withminimal complications. In order to assess the potential of CAP EMA, this thesis presents thedesign and optimization of a cold plasma generation, transport and application system followedby an assessment of safety, feasibility and efficacy of the procedure. After establishing the clinical,functional, and safety requirements, a plasma generation and transport system is presented. Itincludes a helium carrier gas ignited by a nanosecond pulsed high voltage generator in a DielectricBarrier Discharge chamber. The latter contains a copper wire to maintain the plasma activ, Doctorat en Sciences de l'ingénieur et technologie, info:eu-repo/semantics/nonPublished

This experimental study characterized the effect of carrier gas flow on an endoscopic plasma jet. This system generates and transports helium plasma in a tube over several meters, along with a separate channel transporting oxygen to enhance plasma reactivity on site. The resulting plasma plume exiting the tube allows treatment of tissue surfaces in an endoscopic setting with a view to perform therapeutic operations in the gastrointestinal tract. In a closed cavity simulating the tract, the carrier gas flow was studied by a combined approach investigating plasma plume chemistry, fluid dynamics, and plasma effects on the surface of a hydrogel tissue model reporting oxidation. These three aspects are shown to be closely inter-related. Plasma plume length, intensity, and shape strongly depend on helium content, velocity, turbulence, and environment. Optical emission spectroscopy was used to show that the helium gas flow rate increases the amount of helium and reactive oxygen species (ROS) in the plume. Schlieren imaging was used to visualize the transition of the fluid from buoyant to laminar and finally turbulent depending on flow rate, with a backflow in a closed cavity. Finally, the frontal and radial treatment of the cavity was assessed by measuring ROS delivery to a KI-starch agarose gel model. Helium flow rate had a noticeable effect on the treatment distribution profile and treatment intensity, with different maxima for frontal and radial treatments. This combined approach, in an accurate simulation of the target configuration (i.e. a closed, cylindrical cavity), is necessary to optimize treatment, as its outcome depends on a balance between ROS production, transport, and distribution., SCOPUS: ar.j, info:eu-repo/semantics/published

The emerging field of plasma medicine opens new therapeutic opportunities with the use of coldatmospheric plasma as a versatile tool for the treatment of tissues in various medical indications.Yet, the complexity of this very reactive medium combined with a high dependence on itsenvironment and generation parameters make it difficult to predict and optimize such treatment.To this end, a simple yet robust and accurate tissue phantom allowing to study the penetrationand distribution of plasma action in simulated in vivo conditions has been developed by severalgroups. It combines a hydrogel-based matrix closely resembling tissues and chemical reportersincorporated in the gel to measure the delivery of reactive oxygen and nitrogen species (RONS)by the plasma. This paper reports the use of these models in the literature to give an overview ofthe state of the art, their capabilities and the further research required to improve it. First thehydrogels composition (i.e. gelatin and agarose) is discussed, as well as the parameters allowingto fine tune the model. In particular, we show that modifying mass fraction has been reported tomimic several types of tissues and that different model configurations allow to test differenttreatments conditions, including the barrier effect of skin or the direct treatment of a tissue bulk.The role of other critical parameters is highlighted, including manufacturing, diffusion,electrical characteristics but also liquid composition, thickness, aging and temperatureinfluence. Secondly, RONS reporters used in the plasma medicine literature(colorimetric/fluorometric dyes) are summarized. The analysis techniques are discussed and thedyes characteristics (i.e. wavelength, specificity, and concentrations) are reported. Finally, theinfluence of medium and time on these measurements are covered. Main achievements, as wellas limitations of these models are presented and linked to potential improvements and further research., SCOPUS: ar.j, info:eu-repo/semantics/published

En els darrers anys, s'ha mostrat que l'aplicació del plasma atmosfèric fred és molt prometedora per al creixement de les aplicacions en l'àrea de la biomedicina. Això es deu al fet que un plasma està compost per una gran varietat d'elements actius, com camps electromagnètics, radiació UV-Vis-IR i espècies químiques reactives que actuen sinèrgicament sobre una mostra tractada. Una de les aplicacions més prometedores del plasma en el sector biomèdic és el seu ús en tractaments dermatològics. Aquest projecte estudia els efectes fisicoquímics induïts per l'aplicació de plasma a solucions de gelatina com a model de la pell per a tractaments dermatològics. El projecte també investiga la possible aplicació del plasma per a l'eliminació de tatuatges, ja que se sap que el plasma degrada els colorants orgànics en solució. L'ús de la gelatina com a model de pell es deu al fet que és el principal component proteic de la pell, en forma de col·lagen. Per aconseguir aquests objectius, es van tractar mostres de gelatina mitjançant un raig de plasma a pressió atmosfèrica utilitzant dues maneres d'aplicació diferents, el tractament puntual i el tractament superficial. Els efectes dels tractaments sobre l'hidrogel es van analitzar mitjançant tècniques de reologia i espectroscòpia Raman. També es van estudiar en detall els efectes de la temperatura i l'evaporació induïda pel tractament amb plasma en les mostres. A més, per determinar els efectes del plasma sobre les tintes de tatuatge en solucions líquides i sòlides, es van realitzar mesuraments òptiques abans i després del tractament. Les tècniques utilitzades per dur a terme aquests experiments van ser l'espectroscòpia d'absorbència UV-Vis i la colorimetria. Els resultats es van avaluar acuradament i es van comparar amb altres mètodes existents per a l'eliminació de tintes de tatuatges., Recientemente, se ha mostrado que la aplicación del plasma atmosférico frío es muy prometedora para el crecimiento de las aplicaciones en el área de la biomedicina. Esto se debe al hecho de que un plasma está compuesto por una gran variedad de elementos activos, como campos electromagnéticos, radiación UV-Vis-IR y especies químicas reactivas que actúan sinérgicamente sobre una muestra tratada. Una de las aplicaciones más prometedoras del plasma en el sector biomédico es su uso en tratamientos dermatológicos. Este proyecto estudia los efectos físico-químicos inducidos por la aplicación de plasma a soluciones de gelatina como modelo de la piel para tratamientos dermatológicos. El proyecto también investiga la posible aplicación del plasma para la eliminación de tatuajes, ya que se sabe que el plasma degrada los colorantes orgánicos en solución. El uso de la gelatina como modelo de piel se debe a que es el principal componente proteico de la piel, en forma de colágeno. Para lograr estos objetivos, se trataron muestras de gelatina mediante un haz de plasma a presión atmosférica utilizando dos modos de aplicación diferentes, el tratamiento puntual y el tratamiento superficial. Los efectos de los tratamientos sobre el hidrogel se analizaron mediante técnicas de reología y espectroscopia Raman. También se estudiaron en detalle los efectos de la temperatura y la evaporación inducida por el tratamiento con plasma en las muestras. Además, para determinar los efectos del plasma sobre las tintas de tatuaje en soluciones líquidas y sólidas, se realizaron mediciones ópticas antes y después del tratamiento. Las técnicas utilizadas para llevar a cabo estos experimentos fueron la espectroscopia de absorbencia UV-Vis y la colorimetría. Los resultados se evaluaron cuidadosamente y se compararon con otros métodos existentes para la eliminación de tintas de tatuajes., Recently, the application of cold atmospheric plasma has been shown to be very promising for the growth of applications in the area of biomedicine. This is due to the fact that a plasma is composed of a great variety of active elements, such as electromagnetic fields, UV-vis-IR radiation and reactive chemical species that act synergistically on a treated sample. One of the most promising application of plasma in the biomedical sector is their use in dermatological treatments. This project studies the physico-chemical effects induced by the application of plasma to gelatine solutions as a model of the skin for dermatological treatments. The project also investigates the possible application of plasma for tattoo removal since plasma is known to degrade organic dyes in solution. The use of gelatine as a skin model is due to the fact it is the main proteic component of skin, in the form of collagen. To achieve these objectives, gelatin samples were treated by an atmospheric pressure plasma jet using two different modes of application, point treatment and surface treatment. The effects of the treatments on the hydrogel were analysed by means of rheology techniques and Raman spectroscopy. We studied also in details the temperature effects and the evaporation induced by the plasma treatment on the samples. In addition, to determine the effects of plasma on tattoo inks in liquid and solid solutions, optical measurements were performed before and after the treatment. The techniques used to carry out these experiments were UV-Vis absorbance spectroscopy and colorimetry. The results were carefully evaluated and compared with other existing methods for tattoo inks removal., Incoming

Advances in digital technologies have opened new opportunities for creating more reliable, time- and cost-effective, safer and mobile methods of diagnosing, managing and treating diseases. A few examples of advanced nano- and digital technologies are already FDA-approved for diagnosing and treating diseases. Plasma treatment is still emerging as a new healthcare technology, but it is showing a strong potential for treatment of many diseases including cancers and antimicrobial-resistant infections, with little or no adverse side effects. Here, we argue that with the ever-increasing complex healthcare challenges facing communities, including the ongoing COVID-19 pandemic, it is critical to consider combining unique properties of emerging healthcare technologies into a single multimodal treatment modality that could lead to unprecedented healthcare benefits. In this article, we focus on the healthcare opportunities created by establishing a nexus between plasma, nano- and digital technologies. We argue that the combination of plasma, nano- and digital technologies into a single multimodal healthcare package may significantly improve patient outcomes and comfort, and reduce the economic burden on community healthcare, as well as alleviate many problems related to overcrowded healthcare systems.

Although the externally controllable extracellular supply of the short-lived reactive oxygen and nitrogen species, such as O2•−, •NO, and ONOO−, could potentially manipulate cellular functions, their simple administration to cells is likely to be ineffective due to their rapid deactivation. In this study, we found a method of a continuous supply of O2•−/ONOO− over a few minutes, which is triggered by irradiation of a nonequilibrium atmospheric pressure plasma to commonly used organic buffers (e.g., 4-(2-hydroxyethyl)-1-piperazineethanesulfonic acid, HEPES). In addition, a continuous low-dose O2•−/ONOO− supply was shown to induce a physiologically relevant Ca2+ response and subsequently the uptake of a large cation mediated by transient receptor potential channel family member(s). Our results provide a novel approach to the continuous O2•−/ONOO− supply, requiring controllable and mass-volume treatments.

En los últimos años ha cobrado importancia el uso de los plasmas atmosféricos fríos en aplicaciones biomédicas, ya que que ofrecen la posibilidad de tratar tejidos vivos debido a su baja temperatura de tratamiento, y las especies reactivas que producen al tratar líquidos permiten una acción terapéutica similar en tejidos vivos. Investigaciones recientes han demostrado que el tratamiento con plasma tiene diversas aplicaciones de interés (ayuda a la cicatrización de heridas, esterilización de dispositivos médicos, etc..) El grupo de Medicina Plasma del BBT (UPC) utiliza esta tecnología para estudiar un posible tratamiento para el osteosarcoma, en combinación con hidrogeles de biopolímeros dentro del proyecto APACHE (Atmospheric Pressure plasma meets biomaterials for bone Cancer Healing) financiado por el Consejo Europeo de Investigación (ERC). Los biopolímeros están emergiendo como materiales adecuados para muchas aplicaciones en medicina, debido a su versatilidad y biocompatibilidad. El tratamiento con plasma de hidrogeles es muy novedoso, y se ha visto que puede producir una gran cantidad de especies reactivas de oxígeno y nitrógeno que pueden almacenarse de manera efectiva y liberarse al entorno biológico. Se ha demostrado que estas especies matan selectivamente las células cancerosas si se dosifican adecuadamente, pero se desconoce aun cómo se modifica el polímero por efecto del tratamiento de plasma y que repercusiones puede tener esto. El objetivo de este Proyecto Final de Grado es doble: por una parte explorar la literatura con el fin de encontrar posibles estrategias para abordar el efecto del tratamiento con plasmas fríos en soluciones de alginato, a nivel molecular, que dependen del uso de moléculas trazadoras; para descubrir cómo otros grupos usaron moléculas trazadoras para estudiar los efectos de los plasmas fríos en un sistema más complejo e identificar las características de una buena molécula trazadora. Por otra parte, en la segunda parte del proyecto, In the last years the importance of cold atmospheric plasma has grown in many fields and especially in medicine because of its versatility in terms of production of reactive species, low power delivered to the target, possibility of direct or indirect treatment and low cost. Recent studies highlighted the many advantages of cold plasmas in different applications, namely sterilization, wound healing, or cancer treatment. The Plasma Medicine group of BBT at UPC uses this technology to study a possible treatment to osteosarcoma, in combination with hydrogel biopolymers within the project APACHE (Atmospheric Pressure plasma meets biomaterials for bone Cancer Healing) funded by European Research Council (ERC). Biopolymers are emerging as materials suitable for many applications in medicine, due to their versatility, biocompatibility and low density. Plasma treatment of hydrogels produces high amount of reactive oxygen and nitrogen species that can be effectively stored and delivered to the target. These species have been proven to selectively kill cancer cells if properly dosed. Plasma treatment of alginate has been studied recently and the polymer has proven to be a good substrate for high generation of reactive species and their storage in time. The chemical mechanisms responsible to these effects are still under study, but it is not an easy task due to the high complexity of the system and the impossibility to apply the most common analytical techniques to polymer solutions. A possible strategy to overcome this issue is to find a molecular model that is chemically similar to alginate and to study the effects of cold plasma on it. The aim of this final degree project is to scout the literature in order to find possible strategies to tackle the aforementioned issue (study the effect of cold plasma treatment on alginate solutions on a molecular level) that rely on the use of tracer molecules; to find how other groups used tracer molecules to study the effects of cold pla, En els últims anys ha cobrat importància l'ús dels plasmes atmosfèrics freds en aplicacions biomèdiques, ja que que ofereixen la possibilitat de tractar teixits vius per la seva baixa temperatura de tractament, i les espècies reactives que produeixen a l'tractar líquids permeten una acció terapèutica similar en teixits vius. Investigacions recents han demostrat que el tractament amb plasma té diverses aplicacions d'interès (esterilització de dispositius mèdics, curació de ferides, tractament de cancer) El grup de Medicina Plasma del BBT (UPC) utilitza aquesta tecnologia per estudiar un possible tractament per l'osteosarcoma, en combinació amb hidrogels de biopolímers dins el projecte APACHE (Atmospheric Pressure plasma meets biomaterials for bone Cancer Healing) finançat pel Consell Europeu de Recerca (ERC). Els biopolímers estan emergint com materials adequats per a moltes aplicacions en medicina, per la seva versatilitat i biocompatibilitat. El tractament amb plasma d'hidrogels és molt novedos, i s'ha vist que pot produir una gran quantitat d'espècies reactives d'oxigen i nitrogen que poden emmagatzemar-se de manera efectiva i alliberar-se a l'entorn biològic. S'ha demostrat que aquestes espècies maten selectivament les cèl·lules canceroses si es dosifiquen adequadament, però es desconeix encara com es modifica el polímer per efecte de l'tractament de plasma i quines repercussions pot tenir això. L'objectiu d'aquest projecte de grau final és doble: d'una banda explorar la literatura per tal de trobar possibles estratègies per abordar l'efecte de l'tractament amb plasma fred a les solucions d'alginat a nivell molecular que depenen de l'ús de molècules traçadores; descobrir com altres grups han emprat molècules traçadores per estudiar els efectes dels plasmes freds en un sistema més complex i identificar les característiques d'una bona molècula traçadora. D'altra banda, en la segona part del projecte, apliquem aquest coneixement per a dissenyar i validar un possible

This paper discusses the mechanisms by which a low-temperature plasma produced at atmospheric pressure and low power level interacts with the cell membrane of living matter, within the context of the so-called plasma medicine. The different mechanisms of interaction with the cell membrane and cell wall in bacteria are reviewed, with considerations on the possibility of giving rise to resistance to the plasma action. The interaction with animal cells is also considered, from the perspective of exploiting the ability of the plasma to allow the insertion of large molecules, in particular genetic material, into the cells, in the so-called transfection process.

Background: To optimize wound healing, the use of low-temperature atmospheric pressure plasma (ionized gas) has been proposed as an innovative therapeutic method for treating extensive and chronic wound. The aim of this study was to evaluate the specific effects of an indirect helium plasma treatment in a sheep surgical wound model based on clinical, histopathological and molecular analyses. This study was part of a larger study aimed at assessing five different wound healing improvement methods. Methods: Six sheep were used in this study. Six square wounds were performed on the back of each sheep. Five of the lesions were used to analyze the effect of five different treatments, one of which was the plasma treatment. The sixth lesions was used as control. A 2-min plasma treatment was daily performed, using a radiofrequency helium plasma source for indirect treatments, until complete wound healing was obtained. Biopsies were performed at two and six weeks. The plasma effects were tested through clinical evaluation, histopathological and immunohistological evaluation, real time PCR analysis, bacteriological evaluation and intracellular ROS evaluation. Results: Wound closure time for the plasma-treated wounds was quicker than that of the control group. Plasma treatment drastically reduced the bacterial load in the wounds. A strong increase in intracellular ROS was observed. After six weeks, the inflammatory process was significantly reduced in the plasma-treated case with respect to the control. The plasma treatment was found to lead to an anticipated induction of blood vessel formation, as detected through mRNA expression of VEGF. The high Ki67-positivity at two weeks indicated a strong stimulation of cell proliferation induced by the plasma treatment. The expression of the hair keratine (hKER) at six weeks indicated that the plasma was promoting hair regrowth. The plasma treatment induced an increased rate of reformation of cutaneous adnexa at six weeks. Conclusions

El uso de plasma atmosférico frío en tratamientos contra el cáncer ha demostrado ser eficaz y selectivo, distinguiendo su acción entre células sanas y células cancerígenas fruto del aporte de especies reactivas de oxígeno y nitrógeno (RONS) a las células. Complementándose con un principio activo antitumoral utilizado comúnmente en los tratamientos actuales, como lo es la doxorubicina, podría conseguirse una mayor efectividad así como reducir la propia cantidad de agente antitumoral usado en terapia. En el presente proyecto, se pretende fabricar y caracterizar un material compuesto por un hidrogel tratado con plasma atmosférico y microesferas de hidroxiapatita deficiente en calcio cargadas con doxorrubicina, para su posterior uso como plataforma de liberación dual de agentes activos para terapia de cáncer de hueso. Para ello, se han preparado microesferas a partir de una emulsión de un cemento de fosfato de calcio y posteriormente se han cargado dichas microesferas con doxorrubicina. Las microesferas se han añadido a un hidrogel compuesto de gelatina y alginato previamente tratado con plasma frío a presión atmosférica. Se ha estudiado la liberación de RONS así como la liberación de doxorrubicina en un medio acuoso a partir del material diseñado. En paralelo, se ha evaluado la posibilidad de realizar un recubrimiento a las microesferas con policaprolactona (PCL) mediante polimerización por plasma y se ha estudiado cómo influye sobre la cinética de liberación de la doxorubicina a partir del material compuesto. Los resultados indican que el material compuesto libera RONS y doxorubicina al medio de liberación., The use of cold atmospheric plasma in cancer treatments has been shown to be effective in creating a selectivity between healthy cells and cancer cells as a result of the contribution of reactive oxygen and nitrogen species (RONS) to the cells. Complementing it with an anti-cancer drug commonly used in current treatments, such as doxorubicin, greater effectiveness could be achieved as well as a reduction of the amount of antitumoral drug used in such therapy. In the present project, it is intended to synthesize and characterize a material composed of a hydrogel treated with cold atmospheric plasma and calcium-deficient hydroxyapatite microspheres loaded with doxorubicin, for its posterior use as dual release platform for bone cancer therapy. For this, microspheres have been successfully synthesized by emulsion of a calcium phosphate cement and microspheres have been loaded with doxorubicin. The microspheres have been added to a hydrogel composed of gelatin and alginate previously treated with cold atmospheric pressure plasma. The release of RONS and doxorubicin has been studied from the designed material to an aqueous medium. In parallel, it has been evaluated the relevance of proceeding to the coating of microspheres with polycaprolactone (PCL) by plasma polymerization and it has been studied how it influences the release kinetics of doxorubicin from the composite material. The results indicate that the composite material releases RONS and doxorubicin to the release medium.

We propose a mathematical model for uptake and diffusion of air plasma-generated reactive nitrogen species (RNS) in a model keratinized membrane, such as a thin slice of bovine hoof or human nail material. An experimental system consisting of a surface microdischarge (SMD) in air was designed for the purpose of developing and validating a reaction-diffusion model to describe this system. Key variables such as membrane effective diffusivity, surface reaction rate coefficients, and other parameters are determined through comparison between the model predictions and experimental measurements. The model results yield spatial and temporal concentration profiles of RNS inside the keratinized membrane, leading to an improved understanding of transport and reaction of plasma generated RNS through the membrane. This work offers insights into possible mechanisms underlying plasma treatment of toenail fungus.

Treatment of biological tissue by non-thermal atmospheric pressure plasmas in air can often cause beneficial biological outcomes, commonly by generation and delivery of reactive oxygen and nitrogen species (RONS). Biological plasma treatment is often mediated through plasma-liquid interactions, wherein plasma-generated RONS are dissolved into the liquid phase and subsequently initiate liquid-phase chemistry. In this paper we report observations on plasma-liquid interactions using a biologically inert perfluorocarbon solvent - perfluorodecalin (PFD) - that is known to be useful in other biomedical applications. The present paper concerns thin films of liquid PFD applied to porous and non-porous surfaces and subsequent plasma exposure of these films. With PFD application as a thin film prior to plasma exposure, we observe evidence of delayed, but ultimately enhanced RONS delivery to non-porous surfaces and through porous underlying surfaces. We demonstrate that PFD dissolves and retains relatively high concentrations of plasma-produced RONS, especially NO2. When the thin liquid film of PFD evaporates during plasma exposure, there appears to be a relatively rapid release of dissolved RONS, potentially aiding certain applications.

We report on the electrical and optical characterization of the Plasma Coagulation Controller (PCC) device, a low temperature atmospheric plasma source for biomedical applications. This device, designed for the study of plasma-induced blood coagulation, has been developed to operate flexibly in several operational conditions, since it is possible to vary the applied voltage Vp and the pulse repetition rate f in a quite wide range ( Vp range: 2–12 kV, f range: 1–40 kHz). Emission spectroscopy measurements were conducted by varying the line of sight along the axis of helium and neon plasma plumes. The increase of the Reactive Oxygen and Nitrogen Species (RONS) has been observed, as one moves from inside the gas pipe to the outside, as a consequence of the gas mixture with the surrounding air. Furthermore, high-speed photographs of the plasma jet were taken, showing that the plasma is not uniformly distributed in a continuous volumetric region, the plasma being concentrated in localized structures called Pulsed Atmospheric-pressure Plasma Streams (PAPS). The propagation velocities of these objects have been examined, noting that they are not related to the propagation of ion sound waves. Rather, we provide indications that the streamer propagation speed is proportional to the electron drift velocity.

Plasma Medicine tools exploit the therapeutic effects of the exposure of living matter to plasma produced at atmospheric pressure. Since these plasmas are usually characterized by a non-thermal equilibrium (highly energetic electrons, low temperature ions), thermal effects on the substrate are usually considered negligible. Conversely, reactive oxygen and nitrogen species (RONS), UV radiation and metastables are thought to play a major role. In this contribution, we compare the presence of thermal effects in different operational regimes (corresponding to different power levels) of the Plasma Coagulation Controller (PCC), a plasma source specifically designed for accelerating blood coagulation. In particular, we analyze the application of PCC on human blood samples (in vitro) and male Wistar rats tissues (in vivo). Histological analysis points out, for the highest applied power regime, the onset of detrimental thermal effects such as red cell lysis in blood samples and tissues damages in in-vivo experiments. Calorimetric bench tests performed on metallic targets show that the current coupled by the plasma on the substrate induces most of measured thermal loads through a resistive coupling. Furthermore, the distance between the PCC nozzle and the target is found to strongly affect the total power.

Plasma is an ionized gas. It is typically formed at high temperature. As a result of both the development of low-temperature plasma sources and a better understanding of complex plasma phenomena over the last decade, "plasma medicine" has become a booming interdisciplinary research topic of growing importance that explores enormous opportunities at the interface of chemistry, plasma physics, and biomedical sciences with engineering. This review presents the latest development in plasma medicine in the area of the central nervous system and aims to introduce cutting-edge plasma medicine to clinical and translational medical researchers and practitioners.

Atmospheric pressure plasma jet (APPJ) has recently been the focus of cytoprotective research due to the physiological roles of ROS and RNS. In the current study, we investigated the effect of APPJ treatment on the hypoxia (1% oxygen) induced cell injuries. SH-SY5Y cells were treated by APPJ for different duration and incubated in normoxic condition (20% oxygen) for 5 h followed by 24 h hypoxia treatment. Cell viability was evaluated by lactate dehydrogenase (LDH) release and further monitored using the electric cell-substrate impedance sensing (ECIS) system after APPJ treatment. Results showed that APPJ could reduce cell injuries after 24 h hypoxia, which was consistent with the ECIS results. Furthermore, extracellular NO and H2O2 production was significantly increased with the APPJ treatment. It was also interesting to find that APPJ treatment reduced SH-SY5Y cells proliferation in the hypoxic microenvironment during the first 20 h of hypoxia. Although more work was still need to clarify whether the cell viability maintenance was related to the cell proliferation during hypoxia, our results provide the first evidence of real-time cell viability changes after APPJ treatment under both normoxic and hypoxic conditions, which could provide evidence for the neuroprotective applications of APPJ.

Integrity of the ocular surface and transparency of the cornea as “window of the eye,” necessary to achieve a good visual acuity, are essential of every persons’ quality of life and for their ability to professionally and socially interact in the community. The homeostasis at the ocular surface is constantly endangered both by microbes and by intrinsic factors, such as metabolic disturbances (e.g., diabetes) reducing the wound healing capability. In addition, the popular use of contact lenses poses a considerable risk for microbial infection due to poor hygiene or overwearing. Infections at the ocular surface clinically present as infections of the conjunctiva (=conjunctivitis) or of the cornea (=keratitis). In advanced stages, corneal defects can result with loss of stromal tissue and potential risk of perforation of the eye. Current treatments involve topical or i.v. use of e.g., antibiotics or of antimycotics and require hospitalization in severe cases. However, some microbes can be therapy-refractive or even -resistent leading to worsening of the clinical situation. Plasma medicine and its desinfective properties open new ways for treatment of microbial infections of the cornea. This can lead to shortening of treatment time, faster recovery for the patient and to an overall reduction of costs for health systems.

In this contribution we present the main features of the plasma coagulation con­troller (PCC) device, a cold atmospheric pressure plasma source based on the dielectric barrier discharge (DBD) scheme, specifically designed for accelerating blood coagulation. The device is controlled by a microcontroller and can be used to explore different operational parameters in terms of discharge repetition rate (1-20 kHz) and applied voltage (2-8 kV). Helium is used as a working gas. Effective current measured on a metallic target is of the order of 1 mA and, thus, is suitable for application on the human body. Emission spectroscopy analysis is performed: the presence in the plasma of reactive oxygen species (ROS) and reactive nitrogen species (RNS) is highlighted in the different operational regimes. We present the results ofmultiple tests using the device in different biological processes, including reactive species production, bacterial removal, and in vitro blood coagulation. Interestingly, tests on blood samples exposed to the helium plasma at different times show a significant reduction ofthe coagulation compared to control samples.

This paper reports the characterization of a low-power, atmospheric pressure plasma source developed for and successfully tested in applications of plasma medicine. The source produces plasma by ionizing a helium flow containing traces of air. The effluent gas is thus enriched in reactive oxygen and nitrogen species as well as helium metastable excited states. Electrical measurements, Schlieren imaging, OES and various chemical analyses and probes enabled us to fully characterize the plasma source and to determine some fundamental parameters for treating living samples such as the power feeding the discharge, the optimal source to target distance, the maximum exposure time, and to identify the major chemical species responsible for the biological action on exposed living matter.

Atmospheric pressure plasma jets (APPJs) have been identified as a promising tool for plasma medicine. This paper aims to demonstrate the importance of using model-based feedback control strategies for safe, reproducible, and therapeutically effective application of APPJs for dose delivery to a target substrate. Key challenges in model-based control of APPJs arise from: (i) the multivariable, nonlinear nature of system dynamics, (ii) the need for constraining the system operation within an operating region that ensures safe plasma treatment, and (iii) the cumulative, nondecreasing nature of dose metrics. To systematically address these challenges, we propose a model predictive control (MPC) strategy for real-time feedback control of a radio-frequency APPJ in argon. To this end, a lumped-parameter, physics-based model is developed for describing the jet dynamics. Cumulative dose metrics are defined for quantifying the thermal and nonthermal energy effects of the plasma on substrate. The closed-loop performance of the MPC strategy is compared to that of a basic proportional-integral control system. Simulation results indicate that the MPC stategy provides a versatile framework for dose delivery in the presence of disturbances, while the safety and practical constraints of the APPJ operation can be systematically handled. Model-based feedback control strategies can lead to unprecedented opportunities for effective dose delivery in plasma medicine.

Bioelectrics is a rapidly growing field at the intersection of the biological and physical sciences. Research has focused on understanding the basic interactions of pulse electric fields on biological systems, development of therapeutic and diagnostic approaches, and environmental applications. This chapter focuses on potential therapeutic and prophylactic applications of bioelectrics in human and veterinary medicine. Pulse electric fields can be ultrashort (picosecond to nanosecond) or longer (microsecond to millisecond), and dependent on the param eters of the applied pulse, the cellular effects on cells can be direct or indirect. Direct effect can include exciting cells or induction of apoptosis and/or necrosis. Indirect effects have been used to deliver molecules such as chemotherapeutics, nucleic acids, or protein into the cell interior. Therapeutic applications of bio electrics have been developed for a large number of indications including many medical conditions including cancer, wound healing, ischemia, cardiovascular, and diabetes. The utilization of bioelectric-based medical techniques has recently surged, and the potential of such techniques has stemmed from a more wholistic understanding of the fundamental biophysical mechanisms driving underlying success.

Biomedical applications of non-equilibrium atmospheric pressure plasmas have attracted intense interest in the past few years. Many plasma sources of diverse design have been proposed for these applications, but the relationship between source characteristics and application performance is not well-understood, and indeed many sources are poorly characterized. This circumstance is an impediment to progress in application development. A reference source with well-understood and highly reproducible characteristics may be an important tool in this context. Researchers around the world should be able to compare the characteristics of their own sources and also their results with this device. In this paper, we describe such a reference source, developed from the simple and robust micro-scaled atmospheric pressure plasma jet (μ-APPJ) concept. This development occurred under the auspices of COST Action MP1101 'Biomedical Applications of Atmospheric Pressure Plasmas'. Gas contamination and power measurement are shown to be major causes of irreproducible results in earlier source designs. These problems are resolved in the reference source by refinement of the mechanical and electrical design and by specifying an operating protocol. These measures are shown to be absolutely necessary for reproducible operation. They include the integration of current and voltage probes into the jet. The usual combination of matching unit and power supply is replaced by an integrated LC power coupling circuit and a 5 W single frequency generator. The design specification and operating protocol for the reference source are being made freely available.

Background: Atmospheric pressure cold plasma (APCP) might be considered a novel tool for tissue disinfection in medicine since the active chemical species produced by low plasma doses, generated by ionizing helium gas in air, induces reactive oxygen species (ROS) that kill microorganisms without substantially affecting human cells. Objectives: In this study, we evaluated morphological and functional changes in human corneas exposed for 2 minutes (min) to APCP and tested if the antioxidant n-acetyl l-cysteine (NAC) was able to inhibit or prevent damage and cell death. Results: Immunohistochemistry and western blotting analyses of corneal tissues collected at 6 hours (h) post-APCP treatment demonstrated no morphological tissue changes, but a transient increased expression of OGG1 glycosylase that returned to control levels in 24 h. Transcriptome sequencing and quantitative real time PCR performed on different corneas revealed in the treated corneas many differentially expressed genes: namely, 256 and 304 genes showing expression changes greater than ± 2 folds in the absence and presence of NAC, respectively. At 6 h post-treatment, the most over-expressed gene categories suggested an active or enhanced cell functioning, with only a minority of genes specifically concerning oxidative DNA damage and repair showing slight over-expression values (<2 folds). Moreover, time-related expression analysis of eight genes up-regulated in the APCP-treated corneas overall demonstrated the return to control expression levels after 24 h. Conclusions: These findings of transient oxidative stress accompanied by wide-range transcriptome adjustments support the further development of APCP as an ocular disinfectant Copyright

Strategies that confine antibacterial and/or antifouling property to the surface of the implant, by modifying the surface chemistry and morphology or by encapsulating the material in an antibiotic-loaded coating, are most promising as they do not alter bulk integrity of the material. Among them, plasma-assisted modification and catechol chemistry stand out for their ability to modify a wide range of substrates. By controlling processing parameters, plasma environment can be used for surface nano structuring, chemical activation, and deposition of biologically active and passive coatings. Catechol chemistry can be used for material-independent, highly-controlled surface immobilisation of active molecules and fabrication of biodegradable drug-loaded hydrogel coatings. In this article, we comprehensively review the role plasma-assisted processing and catechol chemistry can play in combating bacterial colonisation on medically relevant coatings, and how these strategies can be coupled with the use of natural antimicrobial agents to produce synthetic antibiotic-free antibacterial surfaces.

Background: Cold atmospheric pressure plasma (CAP) with its many bioactive properties has defined a new medical field: the plasma medicine. However, in the related form of high-frequency therapy, CAP was even used briefly a century ago. The aim of this study was to review historic CAP treatments and to obtain data regarding the antimicrobial efficacy of a historical high-frequency plasma device.Methods: First, historic literature regarding the history of CAP treatment was evaluated, because in the modern literature no data were available. Second, the susceptibility of 5 different bacterial wound isolates, cultured on agar, to a historic plasma source (violet wand [VW]) and two modern devices (atmospheric pressure plasma jet [APPJ] and Dielectric Barrier Discharge [DBD]) was analyzed . The obtained inhibition areas (IA) were compared.Results: First, the most convenient popular historical electromedical treatments produced a so-called effluvia by using glass electrodes, related to today's CAP. Second, all three tested plasma sources showed complete eradication of all tested microbial strains in the treated area. The "historical" cold VW plasma showed antimicrobial effects similar to those of modern APPJ and DBD regarding the diameter of the IA.Conclusion: Some retrograde evidence may be deducted from this, especially for treatment of infectious diseases with historical plasma devices. The underlying technology may serve as model for construction of modern sucessive devices., Hintergrund: Kaltes Atmosphärendruckplasma (CAP) hat durch seine mannigfaltigen bioaktiven Eigenschaften ein neues medizinisches Feld definiert: die Plasmamedizin. Allerdings wurde vor etwa 100 Jahren CAP in verwandter Form in der Hochfrequenztherapie genutzt. Zielsetzung dieser Studie war eine Übersicht über die historischen Plasmabehandlungen zu gewinnen und Daten bezüglich der antimikrobiellen Wirkung eines historischen Hochfrequenzapparats zu gewinnen.Methode: Erstens wurde historische Literatur bezüglich CAP-Behandlungen ausgewertet, da aus dem heutigen Schrifttum keine Angaben gewonnen werden konnten. Zweitens wurde die Empfindlichkeit von fünf verschiedenen bakteriellen Wundisolaten auf Agar gegenüber einer historischen Plasmaquelle (violet wand [VW]) und zwei modernen Geräten (atmospheric pressure plasma jet [APPJ] und Dielectric Barrier Discharge [DBD]) ermittelt. Die erzielten Hemmhöfe wurde verglichen. Ergebnisse: Die seinerzeit populärsten elektromedizinischen Anwendungen erzeugten durch Glaselektroden sogenannte Effluvien, die mit modernem CAP verwandt sind. Alle drei untersuchten Plasmaquellen zeigten eine vollständige Eradikation aller behandelter Isolate im plasmabehandelten Bereich. Die historische Plasmaquelle (VW) war dabei ähnlich wirksam wie die modernen Plasmaquellen. Schlussfolgerung: In begrenztem Umfang kann retrograd ein Wirksamkeitsnachweis der historischen Plasmabehandlungen abgeleitet werden, insbesondere bei der Behandlung infektiöser Erkrankungen. Die zugrunde liegende Technologie könnte für die Entwicklung moderner Nachfolgegeräte genutzt werden.

Non-thermal atmospheric pressure plasmas are being developed for a wide range of health care applications, including wound healing. However in order to exploit the potential of plasma for clinical applications, the understanding of the mechanisms involved in plasma-induced activation of fibroblasts, the cells active in the healing process, is mandatory. In this study, the role of helium generated plasma in the tissue repairing process was investigated in cultured human fibroblast-like primary cells, and specifically in hepatic stellate cells and intestinal subepithelial myofibroblasts. Five minutes after treatment, plasma induced formation of reactive oxygen species (ROS) in cultured cells, as assessed by flow cytometric analysis of fluorescence-activated 2',7'-dichlorofluorescein diacetate probe. Plasma-induced intracellular ROS were characterized by lower concentrations and shorter half-lives with respect to hydrogen peroxide-induced ROS. Moreover ROS generated by plasma treatment increased the expression of peroxisome proliferator activated receptor (PPAR)-gamma, nuclear receptor that modulates the inflammatory responses. Plasma exposure promoted wound healing in an in vitro model and induced fibroblast migration and proliferation, as demonstrated, respectively, by trans-well assay and partitioning between daughter cells of carboxyfluorescein diacetate succinimidyl ester fluorescent dye. Plasma-induced fibroblast migration and proliferation were found to be ROS-dependent as cellular incubation with antioxidant agents (e.g. N-acetyl L-cysteine) cancelled the biological effects. This study provides evidence that helium generated plasma promotes proliferation and migration in liver and intestinal fibroblast-like primary cells mainly by increasing intracellular ROS levels. Since plasma-evoked ROS are time-restricted and elicit the PPAR-gamma anti-inflammatory molecular pathway, this strategy ensures precise regulation of human fibroblast activation and can be conside

A source for the production of low-power plasmas at atmospheric pressure, to be used for the nondamaging sterilization of living tissues, is presented. The source, powered by radiofrequency and working with a helium flow, has a specific configuration, studied to prevent the formation of electric arcs dangerous to living matter. It is capable of killing different types of bacteria with a decimal reduction time of 1-2 min; on the contrary, human cells such as conjunctival fibroblasts were found to be almost unharmed by the plasma. A high concentration of OH radicals, likely to be the origin of the sterilizing effect, is detected through their UV emission lines. The effect of the UV and the OH radicals on the fibroblasts was analysed and no significant effects were detected.

On the basis of our current knowledge about the physical properties and biological effects of low temperature plasmas the possibilities and prospects of plasma medicine are discussed in an interdisciplinary dialogue in order to generate hypotheses for further basic and applied research. The following possibilities are seemed feasible for the medical application of low-temperature plasmas: Prevention and treatment of diseases (chronic wounds, skin and mucosal infectious diseases, localized tumors, keloid formation, promotion of angiogenesis, tissue ablation, hemostasis) Inhibition of biofilm formation by surface treatment and by direct action on biofilms Promotion of incorporation of implants into viable tissue by changing the surface (hydrophobicity, plasma steered application of antimicrobial active layers with drug delivery function) Promotion of improved penetration of topically applied drugs with therapeutic outcome Employment for veterinary indications Improved cleaning performance in the treatment process of medical devices by surface modification., Auf der Grundlage des aktuellen Wissenstands zu den physikalischen Eigenschaften und den biologischen Wirkungen von Tissue Tolerable Plasma (TTP) werden die Möglichkeiten und Perspektiven der Plasmamedizin diskutiert, um im interdisziplinären Dialog Hypothesen für die weitere Grundlagen- und Anwendungsforschung zu generieren. Folgende Möglichkeiten bieten sich zur medizinischen Anwendung von TTP an: Prävention und Therapie von Erkrankungen (chronische Wunden, infektiöse Haut- und Schleimhauterkrankungen, lokalisierte Tumoren, Keloidbildung, Förderung der Angiogenese, Gewebeabtragung, Blutstillung) Hemmung der Biofilmbildung durch Oberflächenbehandlung und durch direkte Einwirkung auf Biofilme Förderung der Einheilung von Implantaten durch veränderte Oberflächen (Hydrophobie, plasmagesteuerte Auftragung antimikrobiell wirksamer Schichten mit der Funktion eines Drug delivery Systems) Förderung der Penetration topisch applizierter Arzneimittel mit verbessertem Therapieergebnis Einsatz für veterinärmedizinische Indikationen Verbesserte Reinigungsleistung im Aufbereitungsprozess von Medizinprodukten durch Oberflächenveränderung.

Nízkoteplotná plazma nachádza veľké využitie v súčasnej medicíne. Predstavuje celú radu aktívnych častí ako sú nabité častice, UV žiarenie, elektrické pole, radikály, excitované atómy a molekuly. Táto komplikovaná chémia vedie k nespočetným interakciám medzi studenou plazmou a biologickými systémami, vrátane buniek a tkanív. Synergia účinkov týchto premenných ponúka široké spektrum priaznivých účinkov na organizmus. Táto práca sa venuje účinku studenej plazmy na hojenie rán. V tejto štúdií boli použité dva rôzne typy systémov mikrovlnnej plazmy. Prvým bol plazmatický výboj generovaný povrchovou vlnou v argóne s použitím kremennej kapiláry, druhým bol fakľový výboj so spätným vírovým prúdením pracovného plynu. Diagnostika plazmovej trysky prostredníctvom optickej emisnej spektroskopie ukázala prítomnosť aktívnych častíc vo výboji, ktoré sú zodpovedné za mnohé z účinkov plazmy. Koncentrácie aktívnych častíc generovaných plazmou závisia na podmienkach generácie plazmy, ako sú výkon generátora a prietok pracovného plynu. Pre vizuálny dôkaz účinkov aktívnych častíc na kožu bola pripravená simulácia kožného tkaniva. Interakcia medzi plazmatickou tryskou a umelým kožným tkanivom ukázala, že UV žiarenie a teplota nie sú zodpovedné za všetky efekty, ktoré sú pozorované po aplikácii plazmy. Časť experimentov bola realizovaná v spolupráci s Lekárskou univerzitou v Sofii v Bulharsku. Teória urýchleného liečenia rán spôsobeného plazmou bola podporená pozorovaním účinkov plazmy na umelo vytvorené rany laboratórnych myší. Bolo dokázané, že proces hojenia rán je významne kratší po použití plazmovej terapie v porovnaní s prirodzeným hojením. Aplikácia plazmy v trvaní 10 sekúnd, opakovaná s odstupom jedného dňa sa javí ako efektívnejšia ako aplikácia plazmy len jeden deň. Táto práca je súčasťou medzinárodného projektu PLASMABORDER, programu Interreg V-A Slovenská republika – Česká republika, s registračným číslom 304011P709, ktorý je spolufinancovaný z Európskeho fondu regionálneho r, Non-thermal plasma has a lot of ways for using in nowadays medicine. It presents many useful actions like charged particles, UV light, electric field, radicals, excited atoms and molecules. That complicated chemistry directs to uncountable synergistic interaction between cold plasma and biological systems, involve cells and tissues. This thesis is about effects of cold plasma to wound healing. Two different microwave plasma systems were used for the presented study. The first one was argon plasma torch generated by surface wave using the quartz capillary, the second one was plasma torch with reverse vortex argon flow. Diagnostics of plasma jet by optical emission spectroscopy shown the presence of active particles, which are responsible for a lot of impact of plasma treatment. Concentrations of active particles generated by plasma are dependent on conditions of plasma generation like power of generator and gas flow. For visual evidence of effects on skin caused by active particles was created simulation of skin tissue. Interaction between plasma jet and artificial skin tissue shown that UV light and temperature are not responsible for all observed effects which are noticed after plasma treatment. Some part of experiments was realized in collaboration with Medical University of Sofia in Bulgaria. The theory of positive effect to wound healing was supported by experiments based on treating artificially created wounds on laboratory mice by cold plasma. It was proved, that process of wound healing is significantly shorter after using plasma treatment in comparison with normal wound healing. Plasma treating of wound for 10 seconds in two consequent days seems like more effectively than application of plasma only one day. This Thesis was carried out as a part of international project PLASMABORDER that was supported by European commission under cohesion funds; programme INTEREG SK-CZ under contract No. 304011P709.

Nízkoteplotná plazma nachádza veľké využitie v súčasnej medicíne. Predstavuje celú radu aktívnych častí ako sú nabité častice, UV žiarenie, elektrické pole, radikály, excitované atómy a molekuly. Táto komplikovaná chémia vedie k nespočetným interakciám medzi studenou plazmou a biologickými systémami, vrátane buniek a tkanív. Synergia účinkov týchto premenných ponúka široké spektrum priaznivých účinkov na organizmus. Táto práca sa venuje účinku studenej plazmy na hojenie rán. V tejto štúdií boli použité dva rôzne typy systémov mikrovlnnej plazmy. Prvým bol plazmatický výboj generovaný povrchovou vlnou v argóne s použitím kremennej kapiláry, druhým bol fakľový výboj so spätným vírovým prúdením pracovného plynu. Diagnostika plazmovej trysky prostredníctvom optickej emisnej spektroskopie ukázala prítomnosť aktívnych častíc vo výboji, ktoré sú zodpovedné za mnohé z účinkov plazmy. Koncentrácie aktívnych častíc generovaných plazmou závisia na podmienkach generácie plazmy, ako sú výkon generátora a prietok pracovného plynu. Pre vizuálny dôkaz účinkov aktívnych častíc na kožu bola pripravená simulácia kožného tkaniva. Interakcia medzi plazmatickou tryskou a umelým kožným tkanivom ukázala, že UV žiarenie a teplota nie sú zodpovedné za všetky efekty, ktoré sú pozorované po aplikácii plazmy. Časť experimentov bola realizovaná v spolupráci s Lekárskou univerzitou v Sofii v Bulharsku. Teória urýchleného liečenia rán spôsobeného plazmou bola podporená pozorovaním účinkov plazmy na umelo vytvorené rany laboratórnych myší. Bolo dokázané, že proces hojenia rán je významne kratší po použití plazmovej terapie v porovnaní s prirodzeným hojením. Aplikácia plazmy v trvaní 10 sekúnd, opakovaná s odstupom jedného dňa sa javí ako efektívnejšia ako aplikácia plazmy len jeden deň. Táto práca je súčasťou medzinárodného projektu PLASMABORDER, programu Interreg V-A Slovenská republika – Česká republika, s registračným číslom 304011P709, ktorý je spolufinancovaný z Európskeho fondu regionálneho r, Non-thermal plasma has a lot of ways for using in nowadays medicine. It presents many useful actions like charged particles, UV light, electric field, radicals, excited atoms and molecules. That complicated chemistry directs to uncountable synergistic interaction between cold plasma and biological systems, involve cells and tissues. This thesis is about effects of cold plasma to wound healing. Two different microwave plasma systems were used for the presented study. The first one was argon plasma torch generated by surface wave using the quartz capillary, the second one was plasma torch with reverse vortex argon flow. Diagnostics of plasma jet by optical emission spectroscopy shown the presence of active particles, which are responsible for a lot of impact of plasma treatment. Concentrations of active particles generated by plasma are dependent on conditions of plasma generation like power of generator and gas flow. For visual evidence of effects on skin caused by active particles was created simulation of skin tissue. Interaction between plasma jet and artificial skin tissue shown that UV light and temperature are not responsible for all observed effects which are noticed after plasma treatment. Some part of experiments was realized in collaboration with Medical University of Sofia in Bulgaria. The theory of positive effect to wound healing was supported by experiments based on treating artificially created wounds on laboratory mice by cold plasma. It was proved, that process of wound healing is significantly shorter after using plasma treatment in comparison with normal wound healing. Plasma treating of wound for 10 seconds in two consequent days seems like more effectively than application of plasma only one day. This Thesis was carried out as a part of international project PLASMABORDER that was supported by European commission under cohesion funds; programme INTEREG SK-CZ under contract No. 304011P709.

Nízkoteplotná plazma nachádza veľké využitie v súčasnej medicíne. Predstavuje celú radu aktívnych častí ako sú nabité častice, UV žiarenie, elektrické pole, radikály, excitované atómy a molekuly. Táto komplikovaná chémia vedie k nespočetným interakciám medzi studenou plazmou a biologickými systémami, vrátane buniek a tkanív. Synergia účinkov týchto premenných ponúka široké spektrum priaznivých účinkov na organizmus. Táto práca sa venuje účinku studenej plazmy na hojenie rán. V tejto štúdií boli použité dva rôzne typy systémov mikrovlnnej plazmy. Prvým bol plazmatický výboj generovaný povrchovou vlnou v argóne s použitím kremennej kapiláry, druhým bol fakľový výboj so spätným vírovým prúdením pracovného plynu. Diagnostika plazmovej trysky prostredníctvom optickej emisnej spektroskopie ukázala prítomnosť aktívnych častíc vo výboji, ktoré sú zodpovedné za mnohé z účinkov plazmy. Koncentrácie aktívnych častíc generovaných plazmou závisia na podmienkach generácie plazmy, ako sú výkon generátora a prietok pracovného plynu. Pre vizuálny dôkaz účinkov aktívnych častíc na kožu bola pripravená simulácia kožného tkaniva. Interakcia medzi plazmatickou tryskou a umelým kožným tkanivom ukázala, že UV žiarenie a teplota nie sú zodpovedné za všetky efekty, ktoré sú pozorované po aplikácii plazmy. Časť experimentov bola realizovaná v spolupráci s Lekárskou univerzitou v Sofii v Bulharsku. Teória urýchleného liečenia rán spôsobeného plazmou bola podporená pozorovaním účinkov plazmy na umelo vytvorené rany laboratórnych myší. Bolo dokázané, že proces hojenia rán je významne kratší po použití plazmovej terapie v porovnaní s prirodzeným hojením. Aplikácia plazmy v trvaní 10 sekúnd, opakovaná s odstupom jedného dňa sa javí ako efektívnejšia ako aplikácia plazmy len jeden deň. Táto práca je súčasťou medzinárodného projektu PLASMABORDER, programu Interreg V-A Slovenská republika – Česká republika, s registračným číslom 304011P709, ktorý je spolufinancovaný z Európskeho fondu regionálneho r, Non-thermal plasma has a lot of ways for using in nowadays medicine. It presents many useful actions like charged particles, UV light, electric field, radicals, excited atoms and molecules. That complicated chemistry directs to uncountable synergistic interaction between cold plasma and biological systems, involve cells and tissues. This thesis is about effects of cold plasma to wound healing. Two different microwave plasma systems were used for the presented study. The first one was argon plasma torch generated by surface wave using the quartz capillary, the second one was plasma torch with reverse vortex argon flow. Diagnostics of plasma jet by optical emission spectroscopy shown the presence of active particles, which are responsible for a lot of impact of plasma treatment. Concentrations of active particles generated by plasma are dependent on conditions of plasma generation like power of generator and gas flow. For visual evidence of effects on skin caused by active particles was created simulation of skin tissue. Interaction between plasma jet and artificial skin tissue shown that UV light and temperature are not responsible for all observed effects which are noticed after plasma treatment. Some part of experiments was realized in collaboration with Medical University of Sofia in Bulgaria. The theory of positive effect to wound healing was supported by experiments based on treating artificially created wounds on laboratory mice by cold plasma. It was proved, that process of wound healing is significantly shorter after using plasma treatment in comparison with normal wound healing. Plasma treating of wound for 10 seconds in two consequent days seems like more effectively than application of plasma only one day. This Thesis was carried out as a part of international project PLASMABORDER that was supported by European commission under cohesion funds; programme INTEREG SK-CZ under contract No. 304011P709.

Nízkoteplotná plazma nachádza veľké využitie v súčasnej medicíne. Predstavuje celú radu aktívnych častí ako sú nabité častice, UV žiarenie, elektrické pole, radikály, excitované atómy a molekuly. Táto komplikovaná chémia vedie k nespočetným interakciám medzi studenou plazmou a biologickými systémami, vrátane buniek a tkanív. Synergia účinkov týchto premenných ponúka široké spektrum priaznivých účinkov na organizmus. Táto práca sa venuje účinku studenej plazmy na hojenie rán. V tejto štúdií boli použité dva rôzne typy systémov mikrovlnnej plazmy. Prvým bol plazmatický výboj generovaný povrchovou vlnou v argóne s použitím kremennej kapiláry, druhým bol fakľový výboj so spätným vírovým prúdením pracovného plynu. Diagnostika plazmovej trysky prostredníctvom optickej emisnej spektroskopie ukázala prítomnosť aktívnych častíc vo výboji, ktoré sú zodpovedné za mnohé z účinkov plazmy. Koncentrácie aktívnych častíc generovaných plazmou závisia na podmienkach generácie plazmy, ako sú výkon generátora a prietok pracovného plynu. Pre vizuálny dôkaz účinkov aktívnych častíc na kožu bola pripravená simulácia kožného tkaniva. Interakcia medzi plazmatickou tryskou a umelým kožným tkanivom ukázala, že UV žiarenie a teplota nie sú zodpovedné za všetky efekty, ktoré sú pozorované po aplikácii plazmy. Časť experimentov bola realizovaná v spolupráci s Lekárskou univerzitou v Sofii v Bulharsku. Teória urýchleného liečenia rán spôsobeného plazmou bola podporená pozorovaním účinkov plazmy na umelo vytvorené rany laboratórnych myší. Bolo dokázané, že proces hojenia rán je významne kratší po použití plazmovej terapie v porovnaní s prirodzeným hojením. Aplikácia plazmy v trvaní 10 sekúnd, opakovaná s odstupom jedného dňa sa javí ako efektívnejšia ako aplikácia plazmy len jeden deň. Táto práca je súčasťou medzinárodného projektu PLASMABORDER, programu Interreg V-A Slovenská republika – Česká republika, s registračným číslom 304011P709, ktorý je spolufinancovaný z Európskeho fondu regionálneho r, Non-thermal plasma has a lot of ways for using in nowadays medicine. It presents many useful actions like charged particles, UV light, electric field, radicals, excited atoms and molecules. That complicated chemistry directs to uncountable synergistic interaction between cold plasma and biological systems, involve cells and tissues. This thesis is about effects of cold plasma to wound healing. Two different microwave plasma systems were used for the presented study. The first one was argon plasma torch generated by surface wave using the quartz capillary, the second one was plasma torch with reverse vortex argon flow. Diagnostics of plasma jet by optical emission spectroscopy shown the presence of active particles, which are responsible for a lot of impact of plasma treatment. Concentrations of active particles generated by plasma are dependent on conditions of plasma generation like power of generator and gas flow. For visual evidence of effects on skin caused by active particles was created simulation of skin tissue. Interaction between plasma jet and artificial skin tissue shown that UV light and temperature are not responsible for all observed effects which are noticed after plasma treatment. Some part of experiments was realized in collaboration with Medical University of Sofia in Bulgaria. The theory of positive effect to wound healing was supported by experiments based on treating artificially created wounds on laboratory mice by cold plasma. It was proved, that process of wound healing is significantly shorter after using plasma treatment in comparison with normal wound healing. Plasma treating of wound for 10 seconds in two consequent days seems like more effectively than application of plasma only one day. This Thesis was carried out as a part of international project PLASMABORDER that was supported by European commission under cohesion funds; programme INTEREG SK-CZ under contract No. 304011P709.

Nízkoteplotná plazma nachádza veľké využitie v súčasnej medicíne. Predstavuje celú radu aktívnych častí ako sú nabité častice, UV žiarenie, elektrické pole, radikály, excitované atómy a molekuly. Táto komplikovaná chémia vedie k nespočetným interakciám medzi studenou plazmou a biologickými systémami, vrátane buniek a tkanív. Synergia účinkov týchto premenných ponúka široké spektrum priaznivých účinkov na organizmus. Táto práca sa venuje účinku studenej plazmy na hojenie rán. V tejto štúdií boli použité dva rôzne typy systémov mikrovlnnej plazmy. Prvým bol plazmatický výboj generovaný povrchovou vlnou v argóne s použitím kremennej kapiláry, druhým bol fakľový výboj so spätným vírovým prúdením pracovného plynu. Diagnostika plazmovej trysky prostredníctvom optickej emisnej spektroskopie ukázala prítomnosť aktívnych častíc vo výboji, ktoré sú zodpovedné za mnohé z účinkov plazmy. Koncentrácie aktívnych častíc generovaných plazmou závisia na podmienkach generácie plazmy, ako sú výkon generátora a prietok pracovného plynu. Pre vizuálny dôkaz účinkov aktívnych častíc na kožu bola pripravená simulácia kožného tkaniva. Interakcia medzi plazmatickou tryskou a umelým kožným tkanivom ukázala, že UV žiarenie a teplota nie sú zodpovedné za všetky efekty, ktoré sú pozorované po aplikácii plazmy. Časť experimentov bola realizovaná v spolupráci s Lekárskou univerzitou v Sofii v Bulharsku. Teória urýchleného liečenia rán spôsobeného plazmou bola podporená pozorovaním účinkov plazmy na umelo vytvorené rany laboratórnych myší. Bolo dokázané, že proces hojenia rán je významne kratší po použití plazmovej terapie v porovnaní s prirodzeným hojením. Aplikácia plazmy v trvaní 10 sekúnd, opakovaná s odstupom jedného dňa sa javí ako efektívnejšia ako aplikácia plazmy len jeden deň. Táto práca je súčasťou medzinárodného projektu PLASMABORDER, programu Interreg V-A Slovenská republika – Česká republika, s registračným číslom 304011P709, ktorý je spolufinancovaný z Európskeho fondu regionálneho r, Non-thermal plasma has a lot of ways for using in nowadays medicine. It presents many useful actions like charged particles, UV light, electric field, radicals, excited atoms and molecules. That complicated chemistry directs to uncountable synergistic interaction between cold plasma and biological systems, involve cells and tissues. This thesis is about effects of cold plasma to wound healing. Two different microwave plasma systems were used for the presented study. The first one was argon plasma torch generated by surface wave using the quartz capillary, the second one was plasma torch with reverse vortex argon flow. Diagnostics of plasma jet by optical emission spectroscopy shown the presence of active particles, which are responsible for a lot of impact of plasma treatment. Concentrations of active particles generated by plasma are dependent on conditions of plasma generation like power of generator and gas flow. For visual evidence of effects on skin caused by active particles was created simulation of skin tissue. Interaction between plasma jet and artificial skin tissue shown that UV light and temperature are not responsible for all observed effects which are noticed after plasma treatment. Some part of experiments was realized in collaboration with Medical University of Sofia in Bulgaria. The theory of positive effect to wound healing was supported by experiments based on treating artificially created wounds on laboratory mice by cold plasma. It was proved, that process of wound healing is significantly shorter after using plasma treatment in comparison with normal wound healing. Plasma treating of wound for 10 seconds in two consequent days seems like more effectively than application of plasma only one day. This Thesis was carried out as a part of international project PLASMABORDER that was supported by European commission under cohesion funds; programme INTEREG SK-CZ under contract No. 304011P709.