**3.1 Introduction**

Biodegradable polymers are non-toxic, possess low immunogenicity and good mechanical properties. Moreover, their degradation rate can be adjusted and therefore recently they have been extensively studied as scaffold matrices for tissue engineering (Shen et al., 2007). This research indicated that due to their hydrophobicity and their low surface energy cells only poorly attach, spread and proliferate on these biodegradable polyesters. Therefore, the surface of these polyesters should usually be modified and already several approaches have been presented to increase their cell affinity (Desmet et al., 2009). Typically the polyesters are chemically modified by introducing specific functional groups on their surface. Two possible wet-chemical routes are surface aminolysis and surface hydrolysis. Surface aminolysis in for example 1,6-hexanediamine leads to the production of free amino groups on the surface of the polyester which improves cell adhesion (Zhu et al., 2002, Zhu et al., 2004). By applying surface hydrolysis with the use of a NaOH solution, the ester group is hydrolyzed by the hydroxide anion leading to a rupture of the polymer chain and the formation of carboxylic acid and hydroxyl groups on the tail ends of the two new chains.

The presence of these groups results in an enhanced hydrophilicity and in improved cellmaterial interactions (Zhu et al., 2002, Zhu et al., 2004). Although these wet-chemical processes have their merit, some disadvantages cannot be neglected. Such surface modifications are quite rough and can thus possibly lead to unwanted side-effects such as a faster degradation rate and a reduction of mechanical performance (Chong et al., 2007, Desmet et al., 2009). In addition, research indicated that these techniques can lead to irregular surface etching and that the degree of modification strongly depends on molecular weight, crystallinity or tacticity and may therefore not be reproducible (Goddard & Hotchkiss, 2007, Desai & Singh, 2004). Moreover, it is clear that these wet-chemical techniques use substantial amounts of water or other liquids and consequentially generate hazardous chemical waste. Other approaches like peroxide oxidation, ozone oxidation, UV- and γ-radiaton can also introduce reactive chemical groups on the polyester surface, however, most of these techniques also lead to degradation of the polyesters (Ho et al., 2007, Koo & Jang, 2008, Loo et al., 2004, Place et al., 2009, Montanari et al., 1998).

Opposite those above-mentioned techniques, plasma-assisted surface modification offers a very suitable strategy to incorporate reactive functional groups on the polyester surface. Without the use of a solvent, these groups are efficiently introduced on the surface without altering the bulk properties of the polymer (Ho et al., 2006, Desmet et al., 2009). In addition, complex shaped scaffolds can be uniformly treated (Shen et al., 2007). Next to the incorporation of functional groups, plasma treatment can also be employed for the deposition of polymer coatings or for the immobilization of proteins or other biomolecules (Yang et al., 2002, Cheng & Teoh, 2004, Barry et al., 2005, Barry et al., 2006, Guerrouani et al., 2007, Zelzer et al., 2009).

Due to these numerous advantages, surface modification of biodegradable polymers by plasma treatment offers several excellent prospects. Therefore, in this section 3, we will give

offers excellent mechanical properties comparable with polyethylene or polypropylene (Li et al., 2005, Vroman & Tighzert, 2009). These characteristics makes PBS an excellent choice for

Biodegradable polymers are non-toxic, possess low immunogenicity and good mechanical properties. Moreover, their degradation rate can be adjusted and therefore recently they have been extensively studied as scaffold matrices for tissue engineering (Shen et al., 2007). This research indicated that due to their hydrophobicity and their low surface energy cells only poorly attach, spread and proliferate on these biodegradable polyesters. Therefore, the surface of these polyesters should usually be modified and already several approaches have been presented to increase their cell affinity (Desmet et al., 2009). Typically the polyesters are chemically modified by introducing specific functional groups on their surface. Two possible wet-chemical routes are surface aminolysis and surface hydrolysis. Surface aminolysis in for example 1,6-hexanediamine leads to the production of free amino groups on the surface of the polyester which improves cell adhesion (Zhu et al., 2002, Zhu et al., 2004). By applying surface hydrolysis with the use of a NaOH solution, the ester group is hydrolyzed by the hydroxide anion leading to a rupture of the polymer chain and the formation of carboxylic acid and

The presence of these groups results in an enhanced hydrophilicity and in improved cellmaterial interactions (Zhu et al., 2002, Zhu et al., 2004). Although these wet-chemical processes have their merit, some disadvantages cannot be neglected. Such surface modifications are quite rough and can thus possibly lead to unwanted side-effects such as a faster degradation rate and a reduction of mechanical performance (Chong et al., 2007, Desmet et al., 2009). In addition, research indicated that these techniques can lead to irregular surface etching and that the degree of modification strongly depends on molecular weight, crystallinity or tacticity and may therefore not be reproducible (Goddard & Hotchkiss, 2007, Desai & Singh, 2004). Moreover, it is clear that these wet-chemical techniques use substantial amounts of water or other liquids and consequentially generate hazardous chemical waste. Other approaches like peroxide oxidation, ozone oxidation, UV- and γ-radiaton can also introduce reactive chemical groups on the polyester surface, however, most of these techniques also lead to degradation of the polyesters (Ho et al., 2007, Koo & Jang, 2008, Loo et al., 2004, Place et al., 2009, Montanari et

Opposite those above-mentioned techniques, plasma-assisted surface modification offers a very suitable strategy to incorporate reactive functional groups on the polyester surface. Without the use of a solvent, these groups are efficiently introduced on the surface without altering the bulk properties of the polymer (Ho et al., 2006, Desmet et al., 2009). In addition, complex shaped scaffolds can be uniformly treated (Shen et al., 2007). Next to the incorporation of functional groups, plasma treatment can also be employed for the deposition of polymer coatings or for the immobilization of proteins or other biomolecules (Yang et al., 2002, Cheng & Teoh, 2004, Barry et al., 2005, Barry et al., 2006, Guerrouani et al.,

Due to these numerous advantages, surface modification of biodegradable polymers by plasma treatment offers several excellent prospects. Therefore, in this section 3, we will give

**3. Plasma-assisted surface modification of biodegradable polyesters** 

use as scaffolds in tissue regeneration.

hydroxyl groups on the tail ends of the two new chains.

**3.1 Introduction** 

al., 1998).

2007, Zelzer et al., 2009).

a more general introduction on plasma-surface interactions, while in section 4 we will focus on some successful examples of plasma modification of biodegradable aliphatic polyesters.

### **3.2 Plasma-surface interactions and surface modification strategies**

Plasma is sometimes referred to as the fourth state of matter as introduced by Langmuir (Langmuir, 1928). Plasma is a partly ionized, but quasi-neutral gas in the form of gaseous or fluid-like mixtures of free electrons, ions and radicals, generally also containing neutral particles (atoms, molecules) (Denes & Manolache, 2004). Some of these particles may be excited and can return to their ground state by emission of a photon. The latter process is at least partially responsible for the luminosity of a typical plasma. In plasma several electrons are not bound to molecules or atoms, but free. Therefore, positive and negative charges can move somewhat independently from each other.

Plasmas are frequently subdivided into equilibrium (or non-thermal/lowtemperature/cold) and non-equilibrium (or thermal/high-temperature/hot) plasmas (Denes & Manolache, 2004, Bogaerts et al., 2002, Fridman et al., 2008). Thermal equilibrium implies that the temperature of all particles (electrons, ions, neutrals and excited species) is the same. This is, for example true for stars, as well as for fusion plasmas. High temperatures are required to form these type of plasmas (Bogaerts et al., 2002, Lieberman & Lichtenberg, 2005). In contrast, plasmas with strong deflection from kinetic equilibrium have electron temperatures that are a lot more elevated than the temperature of the ions and neutrals. Such plasmas are classified as non-equilibrium or non-thermal plasmas. It is clear that the high temperatures used in thermal plasmas are destructive for heat-sensitive polymers and most applications for surface modification of polymers will make use of nonthermal or cold plasmas. Since a non-thermal plasma contains a mixture of reactive species, different interactions between the plasma and a surface are possible, including plasma treatment, plasma polymerization and plasma etching (Denes & Manolache, 2004, Rausher et al., 2010, Gomathi et al., 2008). These different interactions between a plasma and the surface can be divided into 4 different approaches to modify the biodegradable polymer. These 4 approaches will briefly be introduced in the following paragraphs, while section 4 will give some practical examples.

### **3.2.1 Plasma treatment**

Plasma treatment is mostly used to enhance the surface energy of a polymer. Figure 1 shows the decrease in contact angle of a PLA surface after treatment in different discharge atmospheres. Oxygen or nitrogen containing groups are introduced on the surface of a (biodegradable) polymer when the material is exposed to a cold plasma generated in O2, N2, air or NH3 (Morent et al., 2008a, Morent et al., 2008b). These functionalities are polar hydrophilic groups which are formed during the interaction of the plasma active species with the polymer molecules. Next to oxygen- and nitrogen-containing discharges, plasmas generated in pure helium or argon will lead to the creation of free radicals that can be used for cross-linking or grafting of oxygen-containing groups when the surface is exposed to oxygen or air after the treatment (Desmet et al., 2009, De Geyter et al., 2007, Ding et al., 2004). Finally, it should be mentioned that the induced surface characteristics are not permanent. The treated surfaces will tend to partially recover to their untreated state during storage in e.g. air (so-called hydrophobic recovery) and they will also undergo post-plasma oxidation reactions (De Geyter et al., 2008, Morent et al., 2010, Siow et al., 2006).

Fig. 1. Water contact angles as a function of energy density for air, nitrogen, argon and helium plasma-treated PLA samples. (Reprinted from (De Geyter et al., 2010) with permission of Elsevier).

### **3.2.2 Plasma post-irradiation grafting**

Plasma post-irradiation grafting is a two-step process of which the first step is a plasma treatment as described in the previous paragraph. The induced functionalities can then be applied to initiate polymerization reactions (Desmet et al., 2009). In contrast to plasma treatment, this technique results in a permanent effect. In the second step, the activated polymer surface is brought into direct contact with a monomer. The monomer can be in the gas phase or the substrate can be immersed into a monomer solution (Vasilets et al., 1997, Zhu et al., 2007). It is important to notice that in both cases the monomer is not subject to the reactive plasma environment. Therefore, the grafted polymers will have similar characteristics as polymers synthesized by conventional polymerization processes (Desmet et al., 2009).

### **3.2.3 Plasma syn-irradiation**

Firstly, a monomer is adsorbed to a material, after which the substrate is exposed to a plasma (Ding et al., 2004). This plasma will generate radicals in the adsorbed monomer layer and the surface of the substrate. This approach will lead to a cross-linked polymer top-layer (Desmet et al., 2009). Opposite to the plasma post-irradiation grafting described in the previous paragraph, the monomer is in plasma syn-irradiation directly subjected to the plasma.

### **3.2.4 Plasma polymerization**

Thin films with unique chemical and physical properties can be developed by plasma polymerization and are called plasma polymers (Gomathi et al., 2008). During plasma

Fig. 1. Water contact angles as a function of energy density for air, nitrogen, argon and helium plasma-treated PLA samples. (Reprinted from (De Geyter et al., 2010) with

Plasma post-irradiation grafting is a two-step process of which the first step is a plasma treatment as described in the previous paragraph. The induced functionalities can then be applied to initiate polymerization reactions (Desmet et al., 2009). In contrast to plasma treatment, this technique results in a permanent effect. In the second step, the activated polymer surface is brought into direct contact with a monomer. The monomer can be in the gas phase or the substrate can be immersed into a monomer solution (Vasilets et al., 1997, Zhu et al., 2007). It is important to notice that in both cases the monomer is not subject to the reactive plasma environment. Therefore, the grafted polymers will have similar characteristics as polymers synthesized by conventional polymerization processes (Desmet

Firstly, a monomer is adsorbed to a material, after which the substrate is exposed to a plasma (Ding et al., 2004). This plasma will generate radicals in the adsorbed monomer layer and the surface of the substrate. This approach will lead to a cross-linked polymer top-layer (Desmet et al., 2009). Opposite to the plasma post-irradiation grafting described in the previous paragraph, the monomer is in plasma syn-irradiation directly subjected to the

Thin films with unique chemical and physical properties can be developed by plasma polymerization and are called plasma polymers (Gomathi et al., 2008). During plasma

permission of Elsevier).

et al., 2009).

plasma.

**3.2.3 Plasma syn-irradiation** 

**3.2.4 Plasma polymerization** 

**3.2.2 Plasma post-irradiation grafting** 

polymerization, gaseous or liquid monomers are typically via a carrier gas inserted into the discharge zone in which they are converted into reactive fragments (Morent et al., 2009). These reactive fragments recombine to polymers and a polymer film is deposited on the substrate exposed to the plasma. The formed plasma polymers will not necessarily have the same chemical structure and composition as polymers obtained via conventional polymerization processes (Desmet et al., 2009). In general, plasma polymers are pinhole-free and highly cross-linked and are therefore insoluble, thermally stable, chemically inert and mechanically tough. Furthermore, such films are often highly coherent and adherent to a variety of substrates including conventional polymer, glass and metal surfaces (Morent et al., 2011, Morent et al., 2009).
