## 6 Combining Active and Passive Antibiofilm Strategies
Obviously, that cannot be achieved unless the two forms of the surface can be reversibly transformed into each other. Three different approaches have been employed so far to gain the reversibility of the switching process. One approach makes use of a reversible cyclization/ring-opening reaction. [PERSON] et al. [137; 138; 139] developed reversibly switchable surfaces based on a series of zwitterionic poly(hydroxy carboxybetaines) (pCB-OH) that can undergo reversible ring closure to the corresponding cationic six-membered ring lactone forms (pCB-Ring). The 2-((2-hydroxy-3-(methacryloyloxy)propyl)dimethylammonio)acetate monomer CB-OH 1 was grown via SIATRP from a gold-coated surface modified with the previously synthesized ATRP initiator mercaptoundecyl bromoisobutyrate to yield the polymer brush pCB-OH 1. The acid-catalyzed lactonization equilibrium \(CB-OH\) 1 \(\rightleftarrows CB-Ring\) 1 was almost completely driven towards the lactone side by using a strong acid catalyst like trifluoroacetic acid (TFA). The cationic bactericidal pCB-Ring 1 surface was obtained by dipping pCB-OH surface in TFA for 20 min., followed by repeated washing with acetonitrile. Under dry conditions, the pCB-Ring 1 polymer brush surface killed more than 99.9% of the _E. coli_ K12 bacteria cells sprayed on it in less than one hour [137]. Wetting with neutral or basic aqueous solutions produced hydrolysis of the lactone rings, converting the pCB-Ring 1 surface to the zwitterionic cell-repellent pCB-OH 1 surface. The latter released 90% of the attached dead cells and also prevented further bacterial colonization [137]. The pCB-Ring 1 surface could be regenerated from the pCB-OH 1 surface in an acidic non-aqueous environment. To conclude, the smart polymer material developed by these authors might be used to coat implantable medical devices. The pCB-Ring 1 surface coating kills the pathogenic bacteria attached to the medical device under dry conditions, while after implantation, upon contact with body fluids, the coating switches to the non-fouling zwitterionic pCB-OH 1 form, thereby resisting biofouling. Another potential application of this material is hospital environmental sanitation; bacteria can be killed by the cationic pCB-Ring 1 form of the polymer brush, the dead bacteria released by the pCB-OH 1 form, and, since the surface can be regenerated to its initial bactericidal form, the kill-release cycle can be repeated for several times without significant loss of the initial bactericidal activity. Similar results were obtained by [PERSON] et al. [140] who additionally introduced a hydrogen bond-forming hydroxyl group in the CB-OH 2 monomer in order to enhance the mechanical strength of the coatings. A completely different switching mechanism was developed by [PERSON] and co-workers [141; 142]. In their approach, the switching between the bacteria attach and kill status and the bacteria release status does not involve any chemical modification of the surface as in the preceding example, but is rather based on reversible and repeated changes in the hydration state of a thermoresponsive polymer brush. Using a combination of interferometric lithography (IL) [143] and surface-initiated activator regenerated by electron transfer atom transfer radical polymerization (ARGET-ATRP) [144], the group of [PERSON] built up a smart surface comprising a nanopatterned thermoresponsive polymer brush/biocidal quaternary ammonium salt composite. First, a self-assembled monolayer (SAM) of the ATRP initiator (3-trimethoxysil)propyl 2-bromo-2-methylpropionate was deposited on the freshly cleaned silicon wafer substrate. Next, the SAM of the ATRP initiator was spatially patterned at the nanoscopic scale by means of UV-IL. Using a two-beam interference system (the so-called Lloyd setup), the authors created a sinusoidally shaped concentration gradient of the ATRP initiator at the silicon wafer surface.