The role of biomaterial-derived microenvironmental challenges on the disruption of peri-implant host-microbiome homeostasis

• Grant number: 23/00382-2
• Support Opportunities: Scholarships abroad - Research
• Start date: November 01, 2023
• End date: October 31, 2024
• Field of knowledge: Health Sciences - Dentistry - Dental Clinics
• Principal Investigator: Ewerton Garcia de Oliveira Mima
• Grantee: Ewerton Garcia de Oliveira Mima
• Host Investigator: Georgios Kotsakis
• Host Institution: Faculdade de Odontologia (FOAr). Universidade Estadual Paulista (UNESP). Campus de Araraquara. Araraquara , SP, Brazil
• Institution abroad: Rutgers The State University of New Jersey, Newark, United States

Abstract

Peri-implantitis (PI) is an immune-mediated, inflammatory disease of the oral mucosa around dental implants, which serves as an excellent model to study the host- microbiome dynamic interactions. Interestingly, peri-implant microbiomes are under the constant pressure of biomaterial-derived microenvironmental challenges that arise from the in situ breakdown of the implant biomaterial in the form of titanium particles. These Implant-derived Titanium Particles (i-TiPs) act as abiotic environmental factors that affect the healthy tissue-microbiome equilibrium. However, human multiomic investigations have not been deployed yet to unravel the specific compositional or functional shifts of the microbiome that participate in destructive inflammation in PI. Therefore, in this study we will evaluate two specific aims: 1) what is the effect that i- TiPs have on the peri-implant microbiome; and, 2) how do i-TiPs affect the host functional responses to the peri-implant microbiome. In aim 1, peri-implant plaque samples will be obtained from individuals with peri-implantitis and the samples will be categorized into titanium positive or negative based on ICP-MS. All samples will be sequenced using 16S rRNA gene amplification for community characterization to determine species directly associated with the presence of titanium. Alpha and beta diversity of microbiome will be analyzed to assess community shifts in the presence of i- TiPs. In aim 2, the samples with the presence/absence of i-TiPs will be injected in a mouse model of titanium-mediated inflammation and compared against an intermediate group of titanium-negative plaques spiked with exogenous titanium particles to assess how host responsiveness to the microbiome is altered by i-TiPs. The capacity of thehost to effectively resolve the microbial challenge will be assessed clinically using an abscess model of infection, followed by tissue proteomic analyses to determine the functional changes that are triggered by i-TiPs, which can provide candidate pharmacological targets to manage peri-implant inflammatory disease in the future. (AU)