Marta Maria Alves Pereira, Rodolfo Debone Piazza, Paula Aboud Barbugli, Oya Tagit, Jeroen J.J.P. van den Beucken, Abhijna Das, Cleyton Alexandre Biffe, Valentim Adelino Ricardo Barão, Stéfany Barbosa Alves da Cruz, Edilson Ervolino, Leonardo Perez Faverani, Vinícius Franzão Ganzaroli, Daniela Leal Zandim-Barcelos, Magda Feres, Belén Retamal‐Valdes, Denise Madalena Palomari Spolidorio, Ana Cláudia Pavarina, Amanda Paino Santana, Beatriz Severino Verza, Rodrigo Fernando Costa Marques, Rafael Scaf de Molon, Érica Dorigatti de Ávila
High Resolution Image Download MS PowerPoint Slide A stimuli-responsive drug delivery coating is proposed for titanium (Ti) implants to locally treat infectious and peri-implant inflammatory diseases. The system integrates a pH-responsive film based on poly(methacrylic acid) (PMAA) film over a layer-by-layer (LbL) drug delivery platform containing tetracycline (TC) complexed with anionic beta cyclodextrin (βCD). This smart coating was designed to control drug release, maintain antimicrobial activity against biofilm-forming pathogens, and enhance soft tissue sealing at the implant interface. The coating effectively regulated drug release, exhibited favorable hydrophilicity, and reduced surface roughness compared with untreated Ti surfaces. Cytocompatibility was confirmed in both monolayer cell cultures and collagen matrix environments, with no cytotoxic effects observed up to 6 days. Atomic force microscopy (AFM) revealed enhanced interactions between the PMAA film and cellular components, as evidenced by filopodial projections at the cell margins. The coating’s antibacterial properties were validated using human saliva-derived biofilms, demonstrating broad-spectrum antimicrobial activity against pathogens typically involved in dental implant infections. In vivo, a rat subcutaneous tissue model was used to evaluate the immune response. The LbL/TCβCD/PMAA coating significantly reduced inflammation, increased collagen deposition, and elevated CD206 expression, indicating a shift toward an anti-inflammatory and tissue-repair phenotype. This stimuli-responsive coating represents a promising strategy for localized infection control, drug delivery, and soft tissue integration on implant surfaces.