Development of immunocompetent and endothelialized 3D skin models, colonized by microbiota microorganisms, for evaluating the effect of environmental stressors

• Grant number: 25/14417-8
• Support Opportunities: Regular Research Grants
• Start date: November 01, 2025
• End date: October 31, 2028
• Field of knowledge: Health Sciences - Pharmacy - Pharmaceutical Technology
• Principal Investigator: Lorena Rigo Gaspar Cordeiro
• Grantee: Lorena Rigo Gaspar Cordeiro
• Host Institution: Faculdade de Ciências Farmacêuticas de Ribeirão Preto (FCFRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil
• City of the host institution: Ribeirão Preto
• Associated researchers: Charles Benjamin Naman ; Hosana Maria Debonsi ; Susana Cristine de Matos Fernandes

Abstract

Reconstructed human skin models mimic the architecture and functions of the epidermis and dermis, allowing the analysis of morphological changes, cell viability, gene expression, and inflammatory cytokine production, among other markers of cutaneous response, exposed to external factors. 3D skin models, standardized by our group, have shown relevant responses to oxidative stress induced by UVA radiation and pollution. Models containing microbiota microorganisms, endothelial cells, and dendritic cells have also been developed. This project aims to standardize 3D skin models colonized with microorganisms under symbiotic and dysbiotic conditions, also containing endothelial cells and immune system cells, by evaluating their protection against dysbiosis and inflammatory response induction by environmental stressors. Initially, endothelialized and immunocompetent models will be standardized, containing dendritic cells and/or T lymphocytes. The models will also be colonized with Staphylococcus epidermidis, Staphylococcus aureus, and Malassezia furfur (in symbiosis or dysbiosis). Further associations between the developed models will be performed to evaluate the best responses to environmental stressors. Subsequently, the models will also be challenged with new substances of marine and plant origin, analogous to UV-filters, obtained through partnerships in Brazil and abroad. Thus, the developed models will be employed for the evaluation of new compounds that can protect the skin against radiation/pollution induced damage, also protecting the skin microbiota. The environmental stressors effects and the protective potential of analyzed compounds will be evaluated through histomorphological analyses, immunolabeling, gene expression assays to assess antioxidant defense mechanisms and the activation of pathways such as the aryl hydrocarbon receptor, the immune and inflammatory response, as well as production of antimicrobial peptides. (AU)