## 1 Introduction  
Hyaluronan (HA) is a glycosaminoglycan and a main component of the extracellular matrix (ECM). HA can be found in connective tissues, cartilage, and in the vitreous body of vertebrates. This long-chain, linear polysaccharide is formed by hyaluron synthases; it is then transported through the plasma membrane of the cell and into the ECM by ABC transporters [1; 2; 3; 4; 5; 6]. HA plays an important role in cell attachment, proliferation, and migration and is a target molecule for improving initial cell adhesion to biomaterials used in implantology [7; 8; 9]. Fast cell attachment on the biomaterial surface regulates the cell-material contact and affects the \"race for the surface\" [10]. Positively charged biomaterial surfaces are shown to enhance the initial osteoblast cell adhesion by electrostatically attracting the cells through their pericellular HA coat [11; 12; 13; 14]. After attachment of the cells to the biomaterial, the HA coat is degraded, and the cells build tighter connections by cell-ECM and cell-cell receptor interactions [15]. In cells' lives, HA has a divergent role depending on maturation and differentiation of the cell [16]. HA expression is high in cells with low differentiation or in tissues with high turnover, e.g., in wound healing. During mitosis, the expression of the HA pericellular coat contributes to the detachment of the cell from their surrounding as a precondition for cell division. After division, daughter cells attach to the surface again and degrade the hyaluron by hyaluronages (HAdase) [16]. However, tumor cells retain their HA coat and show high proliferation, but low differentiation rates, and HA is overexpressed in various tumor cells, e.g., in lung, colorectal, prostate, bladder, or breast carcinoma [1; 17; 18]. Tumors are formed from cellular and acellular components and build up a so-called tumor microenvironment. In this complex system, besides malignant, immune, and stroma cells, the ECM components and secreted factors play an important role [19]. In tumors, stroma cells produce high amounts of HA, and accelerated HA synthesis is correlated with the aggressive behavior of tumor cells and tumor spreading [20; 21]. Experimentally enhanced HA production stimulates tumor growth and metastasis in xenograft models, induces drug resistance, and promotes the invasiveness of tumor cells [22; 23; 24]. New tumor therapy strategies involve the inhibition of HA production and the promotion of the degradation of HA [21; 25; 26; 27; 28]. Another new approach in tumor therapy is the application of cold atmospheric plasma (CAP). Plasma medicine is a relatively new research field, which combines projects in physics, chemistry, biology, and medicine [29; 30; 31]. Physical plasmas are ionized gases consisting of ions, electrons, radicals, ultraviolet photons, and uncharged atoms or molecules. Plasma can be formed by supplying gases with high energy under atmospheric pressure. Cold plasma can be formed by supplying gases with high energy under atmospheric or low pressure. Low-pressure plasmas are used for decontamination/sterilization in the food industry and in medicine or for the specific modification of the surface properties of materials. For this purpose, samples are inserted into a chamber, which is evacuated and filled with certain gases; a discharge is then applied [12; 32; 33]. Here, we focused on cold atmospheric plasmas (CAP). For the generation of CAP, different plasma devices are used, for example, plasma jets or a dielectric barrier discharge [34]. Plasma medicine research focusses on the possibilities of medical applications of CAP to promote wound healing, disinfection, and tissue regeneration and in tumor therapy [34; 35; 36]. The influence of CAP on cells depends on the exposure time and the plasma strength, which is determined by parameters, such as distance from the nozzle, discharge voltage, gas composition, flow rate, and humidity [34; 37; 38; 39]. Cold atmospheric plasmas generate short-lived molecules, such as reactive oxygen and nitrogen species (RONS).