**1. Introduction**

#### **1.1. Tissue engineering**

A shortage of organs and tissues for transplantation has been present throughout most of the history of transplantation. Over the past few decades, the increasing incidence of vital organ failure and the severe shortage of donors have created a wide gap between organ supply and organ demand, which resulted in very long waiting times to receive an organ as well as an increasing number of deaths while waiting. Moreover, all manners of projections indicate that this gap will continue to widen making this a main challenge to modern medicine [1, 2].

Over the years and in order to overcome many challenges in the area of healthcare, techno‐ logical advancements rapidly evolved and became a crucial part of modern medicine by helping ensure a better lifestyle and an increased life expectancy. Hence, the field of tissue engineering (TE) emerged in response to that growing need for tissues and organs for transplantation and has rapidly become one of the most exciting advances in regenerative medicine. TE is a multidisciplinary field combining principles of biology, medicine and engineering that aim at generating completely biocompatible fully functional organs or tissues that could be used to replace damaged or missing tissues in reconstructive surgery [3, 4]. The numerous and complex problems arising when replacing tissues set very high and diverse requirements on the used materials: biodegradability, enabling cell attachment and prolifer‐ ation and mechanical strength are some of the possible demands.

It is very difficult to find an adequate material that meets all requirements to function properly in a bio-environment. A way is to select a material having the required bulk properties such as mechanical strength and sometimes biodegradability and modify its surface properties via a surface treatment.

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The success of an implant is determined by the response of its surrounding biological envi‐ ronment. This is governed to a large extent by the surface properties of the biomaterial where the interaction happens. Correspondingly, considerable efforts have been focused on surface engineering of biomaterials in order to give them the ability to promote cell adhesion, proliferation and to maintain cell functions. Therefore, a clear characterization of the physical and chemical properties of the biomaterial surface has a major scientific importance on cellbiomaterial interactions allowing the evaluation of the bioactivity of the surface engineered biomaterial.

Up to present, a large number of surface engineering techniques for improving biocompati‐ bility have been well established. The work generally contains three main steps: after the surface modification of the biomaterial is done, chemical and physical characterizations are conducted followed by a biocompatibility assessment through in vitro cell culture [5, 6].

In the past decades, surface treatment of biomaterials with plasma has been extensively studied [7-9]. Plasma modification of biomaterials gives the opportunity to change the surface characteristics to achieve better biocompatibility without altering the bulk properties. At the same time, plasma surface modification is a very versatile technology: the results of plasma modification can be easily controlled by choosing suitable gases or monomers and the appropriate conditions in the plasma [10].

#### **1.2. Plasma**

In order to introduce plasma it is often stated that plasma is the fourth state of matter in the sequence: solid, liquid, gas, and plasma. The state of matter changes from solid to liquid to gas to plasma by increasing the temperature of the material under consideration (see figure 1).

When gas atoms are subjected to energy (thermal, electrical or light) they become ions by releasing some of their electrons. Collisions between electrons and molecules and bond breaks in molecules create radicals. Energy will also create excited species that will generate photons. This is how plasma is created with a unique mixture of electrons, ions, radicals, photons and neutral atoms and molecules [11, 12].

**Figure 1.** States of matter [90]

Based on the relative temperatures of electrons, ions and neutrals, plasmas are classified as thermal "equilibrium" and non-thermal "non-equilibrium". Due to the light mass of the electrons present in the plasma, these electrons are instantly accelerated by the electric field to higher velocities than the heavier ions in the time available between collisions. When the collision occurs only a small fraction of the electron energy is lost. This is why the electron temperature in the plasma is initially higher than that of heavy particles. The resulting plasma is a non-thermal or cold plasma in which the electron temperature (≈ 10000 °C) is much higher than the gas temperature (< 200 °C). However, if the pressure is so high that the charged particles do not move very far before the next collision or the electrical field is very low, the energy of the electrons may tend towards that of the heavy particles. In this case, the resulting plasma is a thermal or hot plasma.

Plasmas used in "plasma technology" are usually cold plasmas in the sense that only a small fraction of the gas molecules are ionized which can provide electrons and ions at the right energy without excessive heat enabling the use of plasma on heat-sensitive materials such as polymers [13]. The most commonly used method for generating and sustaining a lowtemperature plasma for technological and technical applications is applying an electric field to a pure or mixed gas.

Different plasma sources are available and their dimensions are determined largely by the particular application for which the plasma is intended. There are distinct differences not only in the physical shape of various plasma sources, but also in the temporal behavior of the plasmas that are generated in different sources.
