Targeted Infection Control and Tissue Integration via pH-Sensitive Smart Coatings on Implant Surfaces

Sep 30, 2026

A stimuli-responsive drug delivery coating is proposed for titanium (Ti) implants to locally treat infectious and periimplant inflammatory diseases. The system integrates a pH-responsive poly(methacrylic acid) (PMAA) film over a layer-by-layer drug delivery platform containing tetracycline (TC) complexed with anionic beta cyclodextrin (βCD). The coating controlled drug release, preserved antimicrobial activity against biofilm-forming pathogens, and improved soft tissue sealing. It showed favorable hydrophilicity, reduced surface roughness, and no cytotoxicity up to 6 days. AFM indicated enhanced PMAA-cell interactions and antibacterial validation using human saliva-derived biofilms, while in vivo rat tissue models showed reduced inflammation, increased collagen deposition, and elevated CD206 consistent with anti-inflammatory tissue repair.

LanguageEnglish

CategoryHealthcare

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Pages20

Reading Time50 min

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Introduction

This article is licensed under CC-BY 4.0 [www.acsami.org](www.acsami.org) Research Article Targeted Infection Control and Tissue Integration via pH-Sensitive Smart Coatings on Implant Surfaces 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 Bar̃ao, Stéfany Barbosa Alves da Cruz, Edilson Ervolino, Leonardo Perez Faverani, Vinicius Franzao Ganzaroli, Daniela Leal Zandim-Barcelos, Magda Feres, Belén Retamal-Valdes, Denise Madalena Palomari Spolidorio, Ana Claudia Pavarina, Amanda Paino Santana, Beatriz Severino Verza, Rodrigo Fernando Costa Marques, Rafael Scaf de Molon, and Erica Dorigatti de Avila * Cite This: [https://doi.org/10.1021/acsami.5c19344](https://doi.org/10.1021/acsami.5c19344) Read Online | | | | | | | | --- | --- | --- | --- | --- | --- | | ACCESS | Metrics & More | | Article Recommendations | | *sı Supporting Information | ABSTRACT: A stimuli-responsive drug delivery coating is proposed for titanium (Ti) implants to locally treat infectious and periimplant 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 stimuliresponsive coating represents a promising strategy for localized infection control, drug delivery, and soft tissue integration on implant surfaces. KEYWORDS: drug delivery system, stimuli-responsive biomaterial, antimicrobial coating, smart coating, implant 1. INTRODUCTION According to the World Health Organization (WHO), severe periodontal diseases are estimated to affect more than 1 billion cases worldwide ([https://www.who.int/news-room/fact](https://www.who.int/news-room/fact)sheets/detail/oral-health). Importantly, a patient’s history of periodontitis represents a significant risk factor for periimplantitis. The use of dental implants is growing fast, especially in high-income countries, which raises concerns | Received: | September 26, 2025 | | | --- | --- | --- | | Revised: | November 30, 2025 | | | Accepted: | December 4, 2025 | | © XXXX The Authors. Published by American Chemical Society A [https://doi.org/10.1021/acsami.5c19344](https://doi.org/10.1021/acsami.5c19344)[ ](https://doi.org/10.1021/acsami.5c19344)ACS Appl. Mater. Interfaces XXXX, XXX, XXX−XXX about peri-implant diseases, such as peri-implant mucositis and peri-implantitis. Peri-implantitis clearly poses a growing public health problem due to its high prevalence and the dreaded associated consequences that might transcend implant and implant-supported prosthesis loss. As a chronic inflammatory condition, during disease progression the environmenta

FAQs

What implant coating strategy is proposed in this study?

The study proposes a pH-responsive smart coating for titanium implants that integrates a PMAA film with a layer-by-layer drug delivery platform containing tetracycline complexed with anionic beta cyclodextrin.

How does the coating address infection and inflammation at the implant interface?

It aims to locally treat infectious and periimplant inflammatory diseases by controlling drug release, maintaining antimicrobial activity against biofilm-forming pathogens, and enhancing soft tissue sealing at the implant interface.

What evidence supports the coating’s performance in vitro and in vivo?

In vitro results include regulated drug release, improved hydrophilicity, reduced surface roughness, and cytocompatibility without cytotoxic effects up to 6 days, supported by AFM observations. In vivo testing in a rat subcutaneous tissue model showed reduced inflammation, increased collagen deposition, and elevated CD206 expression.

Sep 30, 2026

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