## 4 Microbial Adhesion
### Control of Bacterial Adhesion
#### 4.5.1 Antibacterial Agent Release Coatings  
Use of antibacterial agents is a successive and simple option to biofilms. Microbes in a biofilm are more protected due to the adaptability of the EPS layer protecting the bacteria from antibiotics [64]. Biofilms-based pathogenic bacteria resist antibiotics and this fact is ascribed to long-standing bacterial infections. Essentially, a release-based coating exerts antibacterial activity by accounting antibacterial compounds over time. The antibacterial compounds make sure that both adherent and adjacent planktonic bacteria are killed during the process. The purvey of antibacterial agents is attained by diffusion into the aqueous medium [44]. The advantage of antibacterial agents is that the elution from the material surface locally increases the concentration of the antibacterial agent, without transcending the toxicity limits, when compared to traditional delivery methods for antibiotics. It accouters antibacterial substances only where there is need of, thus eliminating resistance activity and obviating the potentially deleterious systemic incidences. Several design strategies that are used with antibacterial agent release coatings are described in a review that was conducted by Cloutier et al. [65]. These strategies  
Figure 4: Biofilm detection and measuring techniques [55; 56; 57; 58].  
can be separated into three groups: passive approaches, active approaches, and bacteria triggered approaches [65].  
The passive approach focuses on the different variables that have shown to be an influence on release kinetics and that do not have an active trigger when to release antibacterial agents. This can be based on either the properties of the antibacterial agent, the carrier matrix, or the overall micro/nanostructure of the antibacterial coating [66; 67]. On the other hand, the active approach uses stimuli-responsive materials. These types of coatings require a trigger before releasing the antibacterial agents. Physical exogenous stimuli are the most commonly used triggers. According to Cloutier et al., these approaches offer great signal control and they are not restricted by diffusion, which gives them the potential for the use of bioactive coatings [65]. These bioactive coatings can produce antibacterial agents on demand. This also leads to improved useful longevity of the coating [68].  
Lastly, bacteria-triggered approaches activate the release profiles of antibacterial agents when the bacteria are in the vicinity or are getting in touch with the coating. There are two ways of triggering the release of antibacterial agents: (1) pH-responsive coatings and (2) enzyme responsive coatings. In the process of bacterial growth, metabolism occurs where acidic acids, like lactic acid or acetic acids, are produced. Zhuk et al. used poly-electrolyte multilayers (PEM) films as a release mechanism [69]. The antibiotics release activity is influenced from the pH conditions. Lu et al. used self-defensive layer-by-layer coatings in the form of hydrogels stimulating the antibiotic release [70]. It is also cited that another mechanism makes use of the cleavage of imine bonds [71].  
The enzyme responsive coatings have an advantage in comparison to the pH-responsive coatings. Enzyme-responsive coatings target specific bacteria, because they can differentiate between the different bacteria strains. However, this approach is new and is not well known. Up to now, two distinct ways of release have been reported, which are coating degradation and the cleavage of chemical bonds [72; 73; 74]. Coatings with multiple functions are necessary to achieve better performance in their environments and for specific applications due to the complexity and the hierarchical structure of the biological systems, and they are divided into three groups: multi-release, multi-approach, or multi-property [65].