Curcumin-loaded Hydrogel generating Photo-antimicrobial Surfaces for the treatment of Periprosthetic Joint Infections

Periprosthetic joint infections (PJI) after the surgery are disastrous complications, leading to a severe health and financial burden for patients. PJI events are mainly caused by Staphylococcus aureus and nearly 60% of them are methicillin-resistant S. aureus (MRSA) resulting in a high rate of treatment failure. The current antibiotic therapy mainly relies on vancomycin (Van) use, even if various reports showed the emergence of vancomycin-resistant enterococci (VRE). At the same time, Van may also have some considerable side effects, such as ototoxicity and nephrotoxicity, during the antibacterial treatment. To overcome these drawbacks, antimicrobial photodynamic therapy (aPDT) is a good candidate both to prevent and fight the PJI.1 Within our ongoing research on novel biomaterials based on nanophototherapeutics,2,3 here we adapted the properties of antimicrobial surface by spreading a resorbable hydrogel based on DAC® (hyaluronic acid conjugated to polylactic acid, HA-PLA ) produced by Novagenit1 (Mezzolombardo, Trento) loaded with curcumin (Curc) capable of increasing water solubility, bioavailability and to control the release of Curc within the infection site. With the aim of helping to overcome antimicrobial-resistance and reduce the antibiotic dosage with minimal side effects, an analogue hydrogel was formulated in the presence of both Curc and Van. The interaction between Curc and DAC® in the hydrogel was studied using complementary spectroscopic techniques such as UV/Vis spectroscopy, fluorescence, Dynamic Light Scattering (DLS), and ζ-potential measurements. The stability and erosion kinetics of the hydrogels were evaluated in biologically relevant media to ensure control over time and efficacy. In addition, titanium surfaces mimicking prostethic scaffolds were coated by hydrogels and on them the photo-antimicrobial activity against MRSA, VRE, and Pseudomonas aeruginosa strains was evaluated using time-kill assay.