A novel antimicrobial drug-delivery coating for percutaneous implant devices

• Grant number: 18/20719-3
• Support Opportunities: Research Grants - Young Investigators Grants
• Start date: August 01, 2021
• End date: July 31, 2026
• Field of knowledge: Health Sciences - Dentistry
• Principal Investigator: Érica Dorigatti de Avila
• Grantee: Érica Dorigatti de Avila
• Host Institution: Faculdade de Odontologia (FOA). Universidade Estadual Paulista (UNESP). Campus de Araçatuba. Araçatuba , SP, Brazil
• Associated researchers: Jeroen JJP van den Beucken ; Marlise Inêz Klein Furlan ; Rafael Scaf de Molon ; Rodrigo Fernando Costa Marques ; Valentim Adelino Ricardo Barão
• Associated scholarship(s): 25/07203-1 - Advanced biological seal for soft tissue integration, BP.DD; 24/14873-0 - Advanced biological seal for soft tissue integration, BP.IC; 24/14872-4 - Smart/Stimuli-Responsive Antimicrobial System for Soft Tissue Integration. Antibacterial coating validation in animal model, BP.IC; + associated scholarships 24/14871-8 - Smart/Stimuli-Responsive Antimicrobial System for Soft Tissue Integration. Antibacterial coating validation in animal model, BP.MS; 23/11031-6 - Advanced biological seal on drug delivery system through MAA-based film construction. A complex strategy to fight disease and optimizing soft tissue integration, BP.MS; 21/12175-6 - A novel antimicrobial drug-delivery coating for percutaneous implant devices, BP.IC; 21/10762-1 - Vascular regenerative MAA-based material film on antimicrobial [PAA/PLL]10/TC/anionic B-CD coating for percutaneous implants devices, BP.DD; 21/09434-0 - A novel antimicrobial drug-delivery coating for percutaneous implant devices, BP.JP - associated scholarships

Abstract

Antimicrobial coatings on percutaneous devices (PDs), such as dental implants and exposed pins, are considered an effective strategy to avoid infection progression that might result in PD loss. Our conducted preliminary research validated the tetracycline incorporation method into the layer-by-layer system, assembled by alternating polyelectrolyte layers of poly(acrylic acid) (PAA) and poly(l-lysine) (PLL), through the synthesis of tetracycline with anionic beta cyclodextrin (²-CD). The succeeded [PAA/PLL]10/TC/anionic ²-CD biomaterial coating showed to be readily tunable to different physiological scenarios, with a controlled release of the drug up to 30 days. Antibacterial effect of [PAA/PLL]10/TC/anionic ²-CD was confirmed against Staphylococcus aureus ATCC 25923. The exciting outcomes encouraged us to proceed with the studies and translate the power of antimicrobial multilayer systems in meaningful biomedical applications. Herein, taking into consideration the importance of tissue quality surrounding PDs and the need to protect the drug into the multilayers, in this project, we will focus on the development of acidic pH sensible film with methacrylic acid (MAA)-based vascular regenerative to cover [PAA/PLL]10/TC/anionic ²-CD and to promote vascularization and subsequent wound healing. A detailed multilayer coating characterization will be performed by different microscopy and spectroscopy approaches to probe physical and chemical properties. Coating stability of MAA-film on [PAA/PLL]10/TC/anionic ²-CD system will be confirmed under neutral and acidic pH, mimicking healthy and diseased/inflammatory environments, respectively. Moreover, the molecular and cellular mechanisms of interaction in the presence of MAA-film will be investigated to improve the therapeutic effect of layer-by-layer coating system. Further, in vitro microbiology experiments will be performed to uncover the broad-spectrum of TC/anionic ²-CD against different bacteria involved in implant infection. Additionally, we will further demonstrate the effect of the antimicrobial multilayer system on inflammatory signaling pathways and epithelial downgrowth to facilitate the advancement of regenerative biomaterials for diverse applications, using in vivo model. (AU)

Scientific publications

(12)

(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)

DINI, CAROLINE; PEREIRA, MARTA MARIA ALVES; SOUZA, JOAO GABRIEL SILVA; DE AVILA, ERICA DORIGATTI; BARAO, VALENTIM ADELINO R.. Mapping the trends and impact of research collaboration between countries in oral implantology publications: A bibliometric analysis from 1999 to 2019. JOURNAL OF PROSTHETIC DENTISTRY, v. 132, n. 4, p. 11-pg., 2024-09-27. (20/05231-4, 18/20719-3, 21/09434-0, 20/05234-3, 21/10762-1)

DINI, CAROLINE; COSTA, RAPHAEL CAVALCANTE; BERTOLINI, MARTINNA; SHIBLI, JAMIL AWAD; FERES, MAGDA; KLEIN, MARLISE INEZ; DE AVILA, ERICA DORIGATTI; SOUZA, JOAO GABRIEL SILVA; BARAO, VALENTIM ADELINO RICARDO. In-vitro polymicrobial oral biofilm model represents clinical microbial profile and disease progression during implant-related infections. Journal of Applied Microbiology, v. 134, n. 11, p. 14-pg., 2023-11-29. (20/05231-4, 21/09434-0, 18/20719-3, 20/05234-3)

SANTANA, AMANDA PAINO; MULINARI-SANTOS, GABRIEL; PEREIRA, MARTA MARIA ALVES; CUNHA, DANIELA MOREIRA; GUERREIRO, MARIANA MARTINS; WAINWRIGHT, MARK; THEODORO, LETICIA HELENA; DE AVILA, ERICA DORIGATTI; ASSUNCAO, WIRLEY GONCALVES. Photosensitizers as potential culprits for compensatory benefits of aPDT in the treatment of peri-implantitis: Unraveling the fundamental knowledge and bounded clinical applications of the aPDT. Photochemistry and Photobiology, v. N/A, p. 23-pg., 2025-06-02. (24/14871-8, 21/09434-0, 21/10762-1, 23/11031-6, 18/20719-3)

MIRANDA, LUIS FERNANDO B.; LIMA, CAROLINA V.; PAGIN, RAFAELA; COSTA, RAPHAEL C.; PEREIRA, MARTA MARIA A.; DE AVILA, ERICA D.; BERTOLINI, MARTINNA; RETAMAL-VALDES, BELEN; SHIBLI, JAMIL A.; FERES, MAGDA; et al. Effect of Processing Methods of Human Saliva on the Proteomic Profile and Protein-Mediated Biological Processes. JOURNAL OF PROTEOME RESEARCH, v. 22, n. 3, p. 14-pg., 2023-03-03. (21/09434-0, 18/20719-3, 20/10436-4, 21/10762-1)

VAN OIRSCHOT, BART A. J. A.; ZHANG, YANG; ALGHAMDI, HAMDAN S.; CORDEIRO, JAIRO M.; NAGAY, BRUNA E.; BARAO, VALENTIM A. R.; DE AVILA, ERICA DORIGATTI; VAN DEN BEUCKEN, JEROEN J. J. P.. Surface Engineering for Dental Implantology: Favoring Tissue Responses Along the Implant. TISSUE ENGINEERING PART A, v. 28, n. 11-12, p. 18-pg., 2022-06-01. (20/05231-4, 18/20719-3, 21/09434-0, 19/17238-6, 17/01320-0, 15/03567-7)

DE AVILA, ERICA D.; NAGAY, BRUNA E.; PEREIRA, MARTA M. A. .; BARAO, VALENTIM A. . R. .; PAVARINA, ANA CLAUDIA; VAN DEN BEUCKEN, JEROEN J. J. P.. Race for Applicable Antimicrobial Dental Implant Surfaces to Fight Biofilm-Related Disease: Advancing in Laboratorial Studies vs Stagnation in Clinical Application. ACS BIOMATERIALS SCIENCE & ENGINEERING, v. 8, n. 8, p. 12-pg., 2022-07-11. (21/09434-0, 18/20719-3, 20/05231-4)

DE MOLON, RAFAEL SCAF; ALVES PEREIRA, MARTA MARIA; DE AVILA, ERICA DORIGATTI. p Implant surface features as key role on cell behavior. BIOCELL, v. 46, n. 5, p. 1151-1156, 2022. (18/20719-3)

COSTA, RAPHAEL C.; NAGAY, BRUNA E.; VILLA, JAVIER E. L.; SOTOMAYOR, MARIA D. P. T.; NERES, LARIEL CHAGAS DA SILVA; BENSO, BRUNA; AGUAYO, SEBASTIAN; SACRAMENTO, CATARINA M.; RUIZ, KARINA G. S.; SPADA, FERNANDA P.; et al. Pathogenesis-Guided Engineering: pH-Responsive Imprinted Polymer Co-Delivering Folate for Inflammation-Resolving as Immunotherapy in Implant-Related Infections. ADVANCED FUNCTIONAL MATERIALS, v. 34, n. 42, p. 16-pg., 2024-07-23. (20/05231-4, 18/20719-3, 20/10436-4, 22/16267-5, 21/09434-0)

PEREIRA, MARTA M. A.; DINI, CAROLINE; SOUZA, JOAO G. S.; BARAO, VALENTIM A. R.; AVILA, ERICA D. DE. Industry support for dental implant research: A metatrend study of industry partnership in the development of new technologies. JOURNAL OF PROSTHETIC DENTISTRY, v. 132, n. 1, p. 9-pg., 2024-07-02. (20/05231-4, 18/20719-3, 21/09434-0, 20/05234-3, 21/10762-1)

PEREIRA, MARTAMARIA ALVES; PIAZZA, RODOLFO; SANTANA, AMANDA PAINO; BARAO, VALENTIM ADELINO RICARDO; MALHEIROS, SAMUEL SANTANA; VAN DEN BEUCKEN, JEROEN J. J. P.; DE MOLON, RAFAEL SCAF; DE AVILA, ERICA DORIGATTI. Unraveling the Applicability of LbL Coatings for Drug Delivery in Dental Implant-Related Infection Treatment. ACS BIOMATERIALS SCIENCE & ENGINEERING, v. N/A, p. 20-pg., 2024-11-30. (18/20719-3, 21/10762-1, 22/16267-5, 23/15750-7, 21/09434-0)

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)