Synthesis of a bilayer coating functionalized with zinc and photoactivated chitosan-antibiotic complex for controlled drug release in dental implants

• Grant number: 22/15677-5
• Support Opportunities: Scholarships in Brazil - Master
• Start date: May 01, 2023
• End date: February 28, 2025
• Field of knowledge: Health Sciences - Dentistry - Dental Clinics
• Principal Investigator: Valentim Adelino Ricardo Barão
• Grantee: Samuel Santana Malheiros
• Host Institution: Faculdade de Odontologia de Piracicaba (FOP). Universidade Estadual de Campinas (UNICAMP). Piracicaba , SP, Brazil

Abstract

Titanium (Ti) coatings deposited by plasma electrolytic oxidation (PEO) exhibit satisfactory biological results. However, the addition of antimicrobial agents such as chemical elements and antibiotics is necessary. Unlike other elements, zinc (Zn) demonstrates good antibacterial capacity and excellent cytocompatibility. The antibiotic demeclocycline (DMC) stands out for presenting, in addition to its bacteriostatic effect, the ability to generate reactive oxygen species when irradiated, being a photosensitizer in antimicrobial photodynamic therapy. Therefore, the aim of this study is to develop a new coating containing calcium, phosphorus and Zn deposited by PEO and coated by a chitosan film for controlled release of DMC, in addition to evaluating its cytocompatibility and antibacterial effect associated or not with light. Initially, the minimum inhibitory concentration (MIC) and the minimum bactericidal concentration (MBC) of the DMC will be determined to establish the initial concentration of the drug to be incorporated into the film. Thus, the following groups will be tested: (I) machined and polished Ti (control); (II) Ti treated with PEO; (III) Ti with PEO and zinc; (IV) Ti with PEO, zinc and chitosan film; (V) Ti with PEO, zinc and chitosan film with DMC and (VI) Ti with PEO, zinc and chitosan film with DMC associated with light. The surface of the discs will be characterized by confocal laser scanning microscopy (CLSM), scanning electron microscopy (SEM), energy dispersive spectroscopy, X-ray photoelectron spectroscopy, X-ray diffraction, profilometry, surface free energy, and photocatalytic activity. The degradation of the chitosan film will be evaluated by SEM. The release of Zn2+ and demeclocycline from the surfaces will be evaluated using inductively coupled plasma analysis and spectrophotometry, respectively. The antimicrobial activity of the surfaces will be evaluated in the absence and presence of light (415 nm; light dose of 10 J/cm2) using a microcosm model. Quantification of colony forming units (CFU/mL), structural analysis of the biofilm by SEM and CLSM, and microbial composition by DNA-DNA checkerboard will be performed. Protein adsorption will be evaluated through bovine serum albumin plasma protein. The cytocompatibility of MC3T3-E1 cells will be evaluated by MTT and fluorescence assay, morphological evaluation by SEM and CLSM, alkaline phosphatase enzyme activity and production of mineralization nodules. Quantitative data will be submitted to descriptive statistics and assumptions check to determine appropriate statistical tests. The significance level will be 0.05.

Scientific publications

(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)

MALHEIROS, SAMUEL S.; NAGAY, BRUNA E.; BERTOLINI, MARTINNA M.; DE AVILA, ERICA D.; SHIBLI, JAMIL A.; SOUZA, JOAO GABRIEL S.; BARAO, VALENTIM A. R.. Biomaterial engineering surface to control polymicrobial dental implant-related infections: focusing on disease modulating factors and coatings development. Expert Review of Medical Devices, v. 20, n. 7, p. 17-pg., 2023-05-31. (21/09434-0, 22/15677-5, 20/05231-4, 18/20719-3, 19/17238-6)

ANDRADE, CATIA SUFIA; BORGES, MARIA HELENA R.; SILVA, JOAO PEDRO; MALHEIROS, SAMUEL; SACRAMENTO, CATHARINA; RUIZ, KARINA G. S.; DA CRUZ, NILSON C.; RANGEL, ELIDIANE C.; FORTULAN, CARLOS; FIGUEIREDO, LUCIENE; et al. Micro-arc driven porous ZrO₂ coating for tailoring surface properties of titanium for dental implants application. COLLOIDS AND SURFACES B-BIOINTERFACES, v. 245, p. 20-pg., 2024-09-17. (22/07353-5, 22/15677-5, 22/16267-5)

DINI, CAROLINE; BORGES, MARIA HELENA ROSSY; MALHEIROS, SAMUEL SANTANA; PIAZZA, RODOLFO DEBONE; VAN DEN BEUCKEN, JEROEN J. J. P.; DE AVILA, ERICA DORIGATTI; SOUZA, JOAO GABRIEL S.; BARAO, VALENTIM A. R.. Progress in Designing Therapeutic Antimicrobial Hydrogels Targeting Implant-associated Infections: Paving the Way for a Sustainable Platform Applied to Biomedical Devices. ADVANCED HEALTHCARE MATERIALS, v. N/A, p. 35-pg., 2024-10-23. (22/15677-5, 18/20719-3, 22/07353-5, 22/16267-5, 20/05234-3, 21/09434-0, 23/02180-8)