Development of a skin Cancer-on-a-chip model for testing antitumor compounds incorporated into two types of biomaterials for topical application

• Grant number: 25/03631-9
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• Start date: July 01, 2025
• End date: June 30, 2027
• Field of knowledge: Engineering - Biomedical Engineering - Bioengineering
• Principal Investigator: Rondinelli Donizetti Herculano
• Grantee: Mariza Aires Fernandes
• Host Institution: Faculdade de Ciências Farmacêuticas (FCFAR). Universidade Estadual Paulista (UNESP). Campus de Araraquara. Araraquara , SP, Brazil

Abstract

Skin cancer is one of the most prevalent neoplasms worldwide, necessitating the development of innovative therapeutic approaches. Conventional biological models, such as monolayer cell cultures and animal testing, have significant limitations in replicating the complexity of the tumor microenvironment. In this context, "organ-on-a-chip" technology emerges as a promising alternative, enabling greater experimental control, reproducibility, and the ability to mimic human physiological interactions while reducing reliance on animal experimentation. This project aims to develop a skin-cancer-on-a-chip model focused on testing antitumor compounds incorporated into two types of biomaterials for topical application. For this purpose, three-dimensional microchips will be designed and fabricated using laser-cutting technology and polymethyl methacrylate (PMMA), ensuring precise device construction. Skin-derived cell lines will be incorporated into these microdevices using 3D bioprinting with GelMA, fostering a biomimetic environment suitable for tumor progression and the evaluation of experimental therapies. Model validation will include functional assays to analyze cell viability and metabolic activity, utilizing Prestoblue® and Live/Dead assays. Structural characterization will be performed through fluorescence imaging with F-actin, DAPI, and E-cadherin labeling, ensuring cellular integrity within the reconstituted microenvironment. Additionally, the bioproducts to be tested-latex membranes and functional hydrogels, both containing antitumor compounds-will undergo detailed physicochemical analyses to ensure reproducibility and safety. The efficacy of the compounds will be evaluated through the expression of biomarkers associated with tumor progression and therapeutic response, including MMP-2 and MMP-9 expression, caspase-3/7 activity, and quantification of the pro-inflammatory cytokine IL-6. These analyses will provide a comprehensive understanding of the effects of the tested biomaterials, enabling the identification of promising formulations for topical skin cancer therapies. The expected results will validate the applicability of the skin-cancer-on-a-chip model as an innovative platform for antitumor compound screening, effectively replicating dynamic cellular interactions and physiologically relevant conditions. (AU)