## 6 Combining Active and Passive Antibiofilm Strategies
The authors ascribed this behavior to the pH-induced physical cross-linking occurring at lower pH values as a consequence of the aggregation of the methacrylic acid portions. Protonation of the carboxylate moieties in the short polymethacrylate segments reinforced the hydrophobic interactions of the \(\alpha\)-methyl groups. On the contrary, increasing the pH values, more and more carboxylic moieties became deprotonated, and the system appeared less compact due to electrostatic repulsions between the negatively charged carboxylate groups [124; 125]. An antimicrobial efficacy test was performed using a hydrogel batch with the following characteristics: a final pH value equal to 5.0, a polymer concentration of 10% (\(w/v\)) and an initial vancomycin concentration equal to 50-fold the MIC that is 50 \(\mathrm{\SIUnitSymbolMicro g}\)/mL or 1% \(w/v\). The test showed that the amount of vancomycin released by this hydrogel was sufficient to inhibit \(S\). _aureus_ growth for 24 h. This is an important result since it suggests that the hydrogel formulation could effectively control the pathogen's growth making external administration of vancomycin no longer necessary [124]. Furthermore, to evaluate comparatively the efficacy of the above hydrogel against \(S\). _aureus_ biofilm formation, the authors used hydroxyapatite doped titanium discs coated with various antibacterial coatings: HA, vancomycin-loaded HA, HA-TBA-EDA-BMP-MANa hydrogel, vancomycin-loaded HA-TBA-EDA-BMP-MANa hydrogel with a final pH of 5.0, as well as uncoated control discs. After \(S\). _aureus_ inoculation, adhesion and formation of bacterial colonies were assessed using SEM imaging. Uniformly distributed clusters of \(S\). _aureus_ were observed on the surface of uncoated titanium discs. The degree of colonization was decreased significantly for HA-coated discs and even more for the vancomycin-loaded HA coatings. No bacterial adhesion could be detected for the substrates coated with the hydrogels based on the HA-TBA-EDA-BMP-MANa copolymer, no matter whether the hydrogel was unloaded or loaded with vancomycin. The authors concluded that due to the synergistic combination of the anti-biofouling properties and drug release modulating capabilities, their newly developed hydrogels based on a graft copolymer derivative of HA bearing pH-responsive functionalities could represent a biomatrix suitable for the coating of implantable orthopedic prostheses. [PERSON] et al. [127] modified the surface of polyvinylidene dil fluoride (PVDF) membranes fabricated through the non-solvent induced phase separation method with an amphiphilic block-like copolymer nanocoating consisting of three polymeric segments with distinct properties, specifically, low surface energy poly(hexafluorobutyl methacrylate) (PHFBM), hydrophilic poly(poly(ethylene glycol) methyl ether methacrylate) (PEGMA), and antibacterial poly[2-(methacryloyoxy)ethyl trimethylammonium chloride] (PMTAC) (Figure 8). The amphiphilic membrane surface modifier was obtained via AIBN initiated free radical polymerization. In the course of PVDF membrane fabrication, during the phase inversion process, the hydrophilic PEGMA and PMTAC segments spontaneously segregate at the water/membrane interface, while the hydrophobic PHFBM segment undergoes forced surface segregation being dragged by the spontaneously segregated hydrophilic segments to which is covalently linked. Thereby, the PVDF membrane is endowed with both passive antifouling and active contact killing properties. Integration of the active and passive antifouling mechanism resulted in reaching nearly 100% efficiency against \(E\). _coli_ and \(S\). _aureus_ surface colonization. Applying Active and Passive Strategies One at a Time and Reversibly Switching between the Two Approaches  
Another successful antibiofilm strategy based on combining into a single platform, both non-fouling and bactericidal properties, consists of developing a surface that is able to execute both functions sequentially, rather than simultaneously as presented in the previous paragraph.