Hyaluronidase‐Responsive MSN – HA Coatings for Infection‐Triggered Antibiotic Delivery on Titanium Surfaces

Implant-associated infections remain a major challenge due to biofilm formation and uncontrolled antibiotic release from conventional coatings. This study presents an enzyme-responsive nanoparticle-based coating designed to enable localized and on-demand antibiotic delivery on titanium implant surfaces. Hyaluronidase-sensitive ciprofloxacin-loaded mesoporous silica nanoparticles (MSNs) coated with hyaluronic acid (MSN-CIP-HA) were synthesized and deposited onto titanium substrates via electrophoretic deposition (EPD). The nanoparticles and coated surfaces were characterized in terms of morphology, surface properties, and wettability. Drug release behavior was evaluated under physiological (pH 7.4) and infection-mimicking acidic (pH 5) conditions in the presence and absence of hyaluronidase. After 72 h, ciprofloxacin release from coated titanium reached 0.51 μg at pH 7.4 without enzyme and increased to 2.63 μg in the presence of hyaluronidase. Similarly, release at pH 5 increased from 0.93 to 3.31 μg following enzyme addition, indicating effective enzyme-triggered degradation of the HA coating layer. Antibacterial performance against Escherichia coli and Staphylococcus aureus demonstrated reduced bacterial adhesion on coated surfaces and enhanced antibacterial efficacy under enzyme-responsive conditions. The developed coating therefore combines anti-adhesive surface properties with controlled, infection-triggered antibiotic release, limiting unnecessary drug exposure while improving localized antibacterial activity. These findings highlight the potential of HA-coated MSN coatings as smart implant surface modifications for reducing implant-associated infections and biofilm formation.