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Bacterial adhesion on medical implants and the subsequent development of biofilms are major causes of revision surgeries, with costs reaching up to 150, 000 per operation. Once encapsulated within a protective biofilm, successful eradication of the bacteria requires significantly higher doses of antibiotics, which can promote the proliferation of bacterial persisters, ultimately leading to prolonged infections and implant failure. Although polymer brushes have been reported to provide antifouling properties and can serve as drug-releasing platforms, the total amount of antibiotic they can store is relatively low and released rapidly. In the present work, we report a novel polymer brush prodrug platform in which an antibiotic is chemically linked to the side group of the polymer chain and released via hydrolysis. Using a surface-initiated reversible addition-fragmentation chain-transfer (SI-RAFT) polymerization technique, the antibiotic-containing monomer forms a polymer brush layer on titanium-coated glass substrates, enabling efficient drug loading. The thickness-dependent release of the antibiotic is investigated, and chemical as well as morphological changes in the polymer brush film are analyzed, confirming a hydrolysis-based drug-release mechanism. A prolonged and enhanced release of the model drug is observed, delivering concentrations which are capable of eradicating three tested strains of Staphylococcus aureus. • New concept of polymer brush prodrug platform with covalently attached antibiotic • Hydrolysis-based drug release mechanism confirmed • Eradication of planktonic S. aureus demonstrated for three strains • Release platform minimizes the risk of biofilm formation
Schumacher et al. (Mon,) studied this question.