Flavonoid-laden fibrous scaffolds for modulating the inflammatory response and dentinogenesis in vital pulp therapy: physicochemical and biological analyses

• Grant number: 23/04465-0
• Support Opportunities: Scholarships abroad - Research Internship - Doctorate
• Start date: October 01, 2023
• End date: September 27, 2024
• Field of knowledge: Health Sciences - Dentistry - Dental Materials
• Principal Investigator: Josimeri Hebling Costa
• Grantee: Igor Paulino Mendes Soares
• Supervisor: Marco Cicero Bottino
• Host Institution: Faculdade de Odontologia (FOAr). Universidade Estadual Paulista (UNESP). Campus de Araraquara. Araraquara , SP, Brazil
• Institution abroad: University of Michigan, United States
• Associated to the scholarship: 21/13096-2 - Bioactivity of flavonoids on LPS-challenged human pulp cells and association with fibrous scaffolds for modulating dentinogenesis in a degenerative inflammatory environment, BP.DR

Abstract

Reverting the pro-inflammatory into a pro-regenerative environment remains a challenge in Vital Pulp Therapy (VPT). Although the pulp tissue presents intrinsic protective responses, chronic inflammation from bacterial infection imposes great risks to its vitality and regenerative potential. Biomaterials that mimic the native extracellular matrix have been widely explored for endodontic regeneration, and their functionalization with bioactive molecules could modulate dentinogenesis in degenerative inflammatory environments. Recently, we explored the effects of the flavonoids quercetin, hesperetin, and taxifolin on human dental pulp cells (hDPCs) chronically exposed to lipopolysaccharides. Specific concentrations of each molecule modulated regenerative responses under a bacterial-mediated degenerative inflammatory environment in vitro. Therefore, this research project aims at the functionalization of fibrous scaffolds with flavonoids for modulating the inflammatory response and dentinogenesis in VPT. The controlled release of flavonoids, especially in the first days of direct pulp capping procedures should mitigate the inflammatory response and boost biomineralization processes. Thus, functionalization strategies of fibrous scaffolds with flavonoids will be addressed to deliver bioactive concentrations and the biomaterials will be evaluated for physicochemical properties. Then, the bioactivity of formulations will be evaluated on hDPCs and macrophages in vitro. At last, the fibrous scaffolds will be evaluated for bioactive potential using experimental models simulating bacterial-mediated inflamed dental pulp. The number of replicates (n) will vary according to each experimental protocol based on sample size calculations. Data distribution and variability will guide the selection of the statistical methods considering a level of significance of 5%. (AU)