## 4 Passive Anti-Biofouling Nanoc Coatings
### Fouling Resistance Strategies. Hydrophilic and Zwitterionic Polymers  
\"Fouling resistance\" aims to prevent the attachment of biofoulants onto the substrate by suppressing the non-specific non-covalent intermolecular forces, developing when an incoming bacterial cell approaches the substrate surface. The main \"fouling resistance\" materials are polyethylene glycol (PEG), zwitterionic polymers, glycomimetic polymers [101], and peptidomimetic polymers [102]. There are two main mechanisms underlying the \"fouling resistance\" strategy: (1) the steric repulsion effect and (2) the formation of a hydration layer [99]. The steric repulsion effect relies on the unfavourable entropy lost originating in the restriction of the free motility of the polymer chains, which are compressed by the foulants during the initial attachment stage [103]. On the other hand, the second mechanism responsible for the antifouling effect of biofouling-resistant coatings involves the formation of a hydration shell through hydrogen bonding in hydrophilic polymers such as PEG or through ion-dipole interactions in the case of zwitterionic polymers. The adsorption of biofoulants requires disruption of the strong associations between the polymer chains and water molecules, which is energetically disfavoured, thereby accounting for the observed antifouling effect [104]. For instance, [PERSON] et al. designed a peptide-peptoid polymer conjugate composed of an antifouling peptoid chain and a biomimetic anchoring peptide. The antifouling peptoid portion consists of a glycine polymer \(N\)-substituted with a methoxyethyl side chain resembling the polar repeating units of the hydrophilic PEG polymer, as shown in Figure 2[102]. The C-terminal surface anchoring peptide was inspired by the mussel adhesive proteins (MAPs), enabling marine mussels to attach to underwater surfaces strongly. Thus, this surface anchor is composed of the following amino acid sequence: L-3,4-dihydroxyphenylalanine (DOPA)-lysine (Lys)-DOPA-Lys-DOPA. The designed bioinspired peptidomimetic polymer exhibited strong antifouling properties resisting mammalian cell attachment for more than five months [102]. [PERSON] et al. [105] ingeniously used the same peptide anchor to graft glycoptids on TiO\({}_{2}\) support chosen as a representative biomaterial that commonly covers the surface of the titanium alloys largely used in many indwelling medical devices. The authors built up the peptide anchor and the antifouling PEG-mimetic peptoid segments through the well-known solid phase peptide synthesis method. Next, the peptoid segment was modified so as to enable coupling to a hydrophilic saccharide moiety via the extremely versatile click chemistry technique, as shown in Scheme 1. The resulted glycocalix-mimetic polymer drastically increased resistance to non-specific fibrinogen adsorption, fiboblasts adhesion, and bacterial colonisation. The authors concluded that the increased fouling resistance of grafted glycoptids compared to bare peptoids is the consequence of a combined effect resulting from the higher number of hydrogen bonds established between water molecules and the interfacial saccharide moieties, which impede interactions with biomolecules and from the steric hindrance of the polymer backbone [105]. The most common hydrophilic polymer widely used in the antifouling surface modification is PEG. The PEG chains are highly hydrated, resulting in a steric hindrance towards bacterial cell attachment derived from the compression of the hydrated layer occurring when bacteria approach the surface, which in turn decreases the conformational entropy of the polymer chains and develops a repulsive elastic force [106; 107]. [PERSON] et al. [108] experimentally demonstrated the direct correlation  
Figure 2: Antifouling peptidomimetic polymer [102]. Reprinted with permission from The New Peptiddomimetic Polymers for Antifouling Surfaces. Copyright (2005) American Chemical Society.