Design and validation of a bioactive and antimicrobial coating through advanced deposition strategies for biomedical applications.

peri-Implant infections remain a major challenge to the long-term biointegration of dental implants, requiring coating strategies that simultaneously prevent bacterial infection and promote soft tissue integration. Here, we report a bifunctional polyelectrolyte multilayer Layer-by-Layer (LbL) coating combining poly(L-lysine) (PLL30), hyaluronic acid (HA), and fibronectin (Fn) rationally engineered through architectural control and translated from dip-coating to a clinically applicable spray-assisted deposition. Multilayers were fabricated by dip-coating, with Fn either intercalated throughout the film or confined to the outermost layers. Systematic optimization established that terminal confinement of Fn - Top-Layer Fn architecture (PLL30-HA)6 + (PLL30-Fn)6 - achieves complete inhibition of bacterial adhesion against Staphylococcus aureus and Aggregatibacter actinomycetemcomitans while maintaining cytocompatibility (78% human gingival fibroblast viability), whereas intercalating Fn throughout the film compromises cell compatibility, despite equivalent inhibition of bacterial adhesion. This architecture was successfully translated to a clinically scalable spray-assisted deposition using a dual-syringe spray device (coating time < 1 minute). Spray-coated titanium preserved bifunctionality achieving a significant reduction of S. aureus and a complete inhibition of A. actinomycetemcomitans, and 88% fibroblast viability after serum coating preconditioning. This work establishes a translational pathway of bifunctional coatings to clinical application, offering possibilities for both preventive and curative strategies against peri-implantitis and other implant-associated infections.