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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 type:Scholarships in Brazil - Doctorate
Effective date (Start): August 01, 2021
Effective date (End): February 29, 2024
Field of knowledge:Health Sciences - Dentistry - Dental Clinics
Principal researcher:Valentim Adelino Ricardo Barão
Grantee:Raphael Cavalcante Costa
Home 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)

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