## 6 Combining Active and Passive Antibiofilm Strategies
Yet, the amphipathic antimicrobial peptide molecules attached to these chains are no longer exposed but rather tend to hide slightly deeper in the more hydrophobic environment provided by the collapsing brush. The paper of [PERSON] et al. is the first one reporting on a surface that switches from cell-killing to cell-repellent upon increasing temperature and a promise for further development of medical device coatings exhibiting antibacterial properties at room temperature, which after their implantation, turn into non-fouling coatings at the body temperature. The \"resist and kill\" strategy was used by [PERSON] et al. [136] to impede bacterial adhesion to medical devices during the first 24 h after implantation, a period that is viewed as being decisive for biofilm formation. Their approach is based on the build-up of a multilayer film by a LbL self-assembly process. The multilayer film was deposited on silicon wafers or glass slides substrates previously cleaned by the Piranha solution and covered with a precursor layer of the branched cationic polyelectrolyte PEI. In fact, the film was composed of two distinct coatings stacked one upon another. The first deposited coating consisted of ten heparin (HEP)/CHI bilayers in which the two polysaccharides self-assembled by electrostatic attraction between the negatively charged HEP and the positively charged CHI. This coating has a CHI-ending layer conferring bacterial contact killing properties. The second coating comprised 10 polyvinylpyrrolidone (PVP)/poly(acrylic acid) (PAA) bilayers. Unlike the construction of the first coating, the build-up of the second coating was based on a hydrogen bond-driven self-assembly process. Hydrogen-bonding LbL coatings are pH-sensitive and prone to disassembly at neutral or basic pH as the carboxylic acid moieties undergo deprotonation resulting in breakage of the hydrogen bonds. Hence, the upper (PVP/PAA)\({}_{10}\) multilayer coating constructed at pH 4.0 was readily disassembled in a few minutes in PBS buffer at pH 7.4 at 37 \({}^{\circ}\)C. Therefore, to resist bacterial adhesion for 24 h, the disassembly rate of the upper coating had to be slowed down, which was achieved by thermal treatment at 110 \({}^{\circ}\)C for 16 h when covalent cross-linking of PAA segments through anhydride groups occurred. Since the anhydride moieties are readily hydrolyzable, the disassembly rate of the upper coating could be controlled by the cross-linking density. It is this continuous removal of the outermost surface that impedes bacteria adhesion. After complete top-down destruction of the upper (PVP/PAA)\({}_{10}\) coating, the bottom bactericidal (HEP/CHI)\({}_{10}\) coating was eventually exposed. The authors demonstrated the enhanced antibiofilm properties of these coatings against _S. aureus_ used as a model bacterium. Only a few viable bacterial cells could be observed by SEM and fluorescence microscopy imaging on the surface of (HEP/CHI)\({}_{10}\)-(PVP/PAA)\({}_{10}\) multilayer film coating samples that were cross-linked as previously described [136]. **Scheme 16. ** Synthesis of a bactericidal quaternized chitosan (CHI) non-woven substrate surface and its conversion to the non-fouling zwitterionic form [130]. Adapted with permission from Facile fabrication of bactericidal and antifouling switchable chitosan wound dressing through a 'click'-type interfacial reaction. Copyright (2015) Elsevier. Surfaces that irreversibly change their status from initial bactericidal to non-fouling can be categorized as \"one-time-switch\" surfaces since they cannot be restored to their initial form. The already mentioned basic hydrolysis of cationic polycarboxylatebetaine esters to zwitterionic polycarboxybetaines (Scheme 16) is a convenient way to irreversibly modify surface status. However, to resist bacterial adhesion and biofilm formation for a prolonged period of time, the development of smart materials capable of repeatedly switching between the active contact killing and the passive non-fouling status is highly desirable.