Synthesis, characterization and biological performance of pH-sensitive nanopolymers produced by molecular printing for the treatment of peri-implant infections

• Grant number: 20/10436-4
• Support Opportunities: Scholarships in Brazil - Doctorate
• Effective date (Start): August 01, 2021
• Effective date (End): June 30, 2023
• Field of knowledge: Health Sciences - Dentistry - Dental Clinics
• Principal Investigator: Valentim Adelino Ricardo Barão
• Grantee: Raphael Cavalcante Costa
• Host Institution: Faculdade de Odontologia de Piracicaba (FOP). Universidade Estadual de Campinas (UNICAMP). Piracicaba , SP, Brazil

Abstract

Smart biomaterials aimed at the synergistic control of biofilm and inflammation are promising for peri-implant disease treatment. In this way, the objective is to develop a new dual-functionalized nanopolymer with povidone-iodine (PVP-I) and folic acid (AF) synthesized by molecular printing for pH-controlled release and evaluate their properties in silico, in vitro, in situ, and in vivo. Four studies will be conducted: (1) in silico study, to evaluate the viability of synthesis of the experimental Molecularly Imprinted Polymer (MIP) by computer simulation based on molecular dynamics; (2) in vitro study, to characterize MIP in terms of morphology, polymer dimension, physicochemical properties, and kinetics of agents' release. Mono (Streptococcus mutans) and multispecies (microcosm) biofilms formed on titanium (Ti) discs will be used to evaluate the effect of PVP-I functionalized on MIP on the degradation of the biofilm matrix (polysaccharide dosage, Gtfs enzyme expression, biovolume of matrix/cells, dispersion of MIP in the matrix) and antimicrobial activity (bacterial viability, live/dead cells and biofilm composition). Human gingival fibroblasts will be used to assess biocompatibility, macrophage culture (RAW 264.7) to analyze the expression of folate receptors (RF) and a 3D human soft tissue model used to investigate the expression of pro-inflammatory genes and cytokines ( IL-1, IL-6, TNF-); (3) in situ study, double-blind, crossover, 3-phase study (7 days) will be conducted to prove MIP's effectiveness alone and in antibiotic combination (amoxicillin + metronidazole) on biofilms formed in oral conditions by biofilm morphology, cell viability, and microbiological composition; (4) in vivo study, using contaminated Ti implants in the tibia of rats with bone defects produced to simulate a condition of peri-implantitis and evaluate the effect of treatment with MIPs by histological, immunohistochemical analysis, pro-inflammatory cytokine dosage, bacterial counts, and microbiological composition. Quantitative data will be subjected to appropriate statistical analysis with a 5% significance level. (AU)

Scientific publications

(8)

(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)

COSTA, RAPHAEL C.; BERTOLINI, MARTINNA; COSTA OLIVEIRA, BARBARA E.; NAGAY, BRUNA E.; DINI, CAROLINE; BENSO, BRUNA; KLEIN, MARLISE I.; BARAO, VALENTIM A. R.; SOUZA, JOAO GABRIEL S.. Polymicrobial biofilms related to dental implant diseases: unravelling the critical role of extracellular biofilm matrix. CRITICAL REVIEWS IN MICROBIOLOGY, v. N/A, p. 21-pg., 2022-05-18. (20/10436-4, 20/05231-4)

SAHA, SOUMYA; COSTA, RAPHAEL CAVALCANTE; SILVA, MIRELA CAROLINE; FONSECA-SANTOS, JOAO MATHEUS; CHEN, LIN; PHAKATKAR, ABHIJIT H.; BHATIA, HARSHDEEP; FAVERANI, LEONARDO P.; BARAO, VALENTIM A. R.; SHOKUHFAR, TOLOU; et al. Collagen membrane functionalized with magnesium oxide via room-temperature atomic layer deposition promotes osteopromotive and antimicrobial properties. BIOACTIVE MATERIALS, v. 30, p. 16-pg., 2023-12-01. (22/16267-5, 20/05231-4, 20/10436-4)

VALENTIM A. R. BARÃO; RAPHAEL C. COSTA; JAMIL A. SHIBLI; MARTINNA BERTOLINI; JOÃO GABRIEL S. SOUZA. Emerging titanium surface modifications: The war against polymicrobial infections on dental implants. Brazilian Dental Journal, v. 33, n. 1, p. 1-12, 2022-03-07. (20/05231-4, 20/10436-4)

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)

COSTA, RAPHAEL C.; NAGAY, BRUNA E.; BERTOLINI, MARTINNA; COSTA-OLIVEIRA, BARBARA E.; SAMPAIO, ALINE A.; RETAMAL-VALDES, BELEN; SHIBLI, JAMIL A.; FERES, MAGDA; BARAO, VALENTIM A. R.; SOUZA, JOAO GABRIEL S.. Fitting pieces into the puzzle: The impact of titanium-based dental implant surface modifications on bacterial accumulation and polymicrobial infections. ADVANCES IN COLLOID AND INTERFACE SCIENCE, v. 298, DEC 2021. (20/05231-4, 20/10436-4)

SOUZA, JOAO G. S.; COSTA, RAPHAEL C.; SAMPAIO, ALINE A.; ABDO, VICTORIA L.; NAGAY, BRUNA E.; CASTRO, NIDIA; RETAMAL-VALDES, BELEN; SHIBLI, JAMIL A.; FERES, MAGDA; BARAO, VALENTIM A. R.; et al. Cross-kingdom microbial interactions in dental implant-related infections: is Candida albicans a new villain?. ISCIENCE, v. 25, n. 4, p. 21-pg., 2022-03-16. (20/05231-4, 20/10436-4, 19/17238-6)

SOUZA, JOAO GABRIEL S.; OLIVEIRA, BARBARA E. COSTA; COSTA, RAPHAEL C.; BECHARA, KAREN; CARDOSO-FILHO, OTAVIO; BENSO, BRUNA; SHIBLI, JAMIL AWAD; BERTOLINI, MARTINNA; BARAO, VALENTIM A. R.. Bacterial-derived extracellular polysaccharides reduce antimicrobial susceptibility on biotic and abiotic surfaces. ARCHIVES OF ORAL BIOLOGY, v. 142, p. 9-pg., 2022-08-18. (20/05231-4, 20/10436-4)

ABDO, VICTORIA L.; SUAREZ, LINA J.; DE PAULA, LUCCA GOMES; COSTA, RAPHAEL C.; SHIBLI, JAMIL; FERES, MAGDA; BARA, VALENTIM A. R.; BERTOLINI, MARTINNA; SOUZA, JOAO GABRIEL SILVA. Underestimated microbial infection of resorbable membranes on guided regeneration. COLLOIDS AND SURFACES B-BIOINTERFACES, v. 226, p. 16-pg., 2023-04-17. (20/05231-4, 20/10436-4)

Academic Publications

(References retrieved automatically from State of São Paulo Research Institutions)

COSTA, Raphael Cavalcante. Biomaterials for controlling dental implant infections: biological mechanisms, modulating factors, and new treatment strategies. 2023. Doctoral Thesis - Universidade Estadual de Campinas (UNICAMP). Faculdade de Odontologia de Piracicaba (FOP) Piracicaba, SP.