Phage-Derived Depolymerase-Functionalized Coatings Prevent Staphylococcal Biofilm Formation

Biofilm-associated infections caused by Staphylococci remain a major challenge in the context of biomedical implants due to their tolerance to antibiotics and resistance to host defenses. Here, we report the identification of a novel phage-derived depolymerase (DPO2) targeting staphylococcal biofilms and its integration into hyaluronic acid-based layer-by-layer (LbL) coatings. DPO2 was produced recombinantly and proved more effective preventing biofilm formation than destroying preformed Staphylococcus epidermidis biofilms. DPO2 antibiofilm activity was retained and even enhanced upon immobilization within DPO2/Hyaluronic Acid multilayered coatings. The resulting functionalized surfaces exhibited potent inhibition of biofilm formation by multiple S. epidermidis and Staphylococcus aureus strains from orthopedic infections, reaching nearly complete suppression under the tested conditions. This work demonstrates the potential of combining phage-derived enzymes with biomaterial surface engineering to develop efficient, non-antibiotic antibiofilm strategies. Such coatings represent a promising approach for preventing implant-associated infections.