Triggered Release of Bacteriophage K from Agarose/Hyaluronan Hydrogel Matrixes by Staphylococcus aureus Virulence Factors

The use of hydrogels as safe, biocompatible materials for wound healing has been widely utilized in recent years. Here, we investigated the use of a composite hydrogel to impart a “trigger” mechanism into an antimicrobial hydrogel system. The system was comprised of a bilayer hydrogel architecture: a lower agarose layer containing the antimicrobial virus Bacteriophage K (ΦK) and an upper layer formed of photo-cross-linkable hyaluronic acid methacrylate (HAMA) which creates the hydrogel trigger. This trigger is sensitive to the enzyme hyaluronidase, an enzyme known to be secreted by the majority of Staphylococcus aureus strains. In the presence of hyaluronidase, HAMA is degraded, releasing ΦK into the surrounding environment which consequently go on to kill surrounding bacteria. Our results show that on incubation with hyaluronidase (purified or from S. aureus), large pores form in HAMA as degradation goes on, which facilitates ΦK release.