Renal proximal tubule-on-a-chip in PDMS: fabrication, functionalization, and RPTEC:HUVEC co-culture evaluation

Author(s)

Guimaraes, Ana Paula Pereira ; Calori, Italo Rodrigo ; Stilhano, Roberta Sessa ; Tedesco, Antonio Claudio

• Document type: Journal article
• Source: BIOFABRICATION; v. 16, n. 2, p. 16-pg., 2024-04-01.

Abstract

'On-a-chip' technology advances the development of physiologically relevant organ-mimicking architecture by integrating human cells into three-dimensional microfluidic devices. This method also establishes discrete functional units, faciliting focused research on specific organ components. In this study, we detail the development and assessment of a convoluted renal proximal tubule-on-a-chip (PT-on-a-chip). This platform involves co-culturing Renal Proximal Tubule Epithelial Cells (RPTEC) and Human Umbilical Vein Endothelial Cells (HUVEC) within a polydimethylsiloxane microfluidic device, crafted through a combination of 3D printing and molding techniques. Our PT-on-a-chip significantly reduced high glucose level, exhibited albumin uptake, and simulated tubulopathy induced by amphotericin B. Remarkably, the RPTEC:HUVEC co-culture exhibited efficient cell adhesion within 30 min on microchannels functionalized with plasma, 3-aminopropyltriethoxysilane, and type-I collagen. This approach significantly reduced the required incubation time for medium perfusion. In comparison, alternative methods such as plasma and plasma plus polyvinyl alcohol were only effective in promoting cell attachment to flat surfaces. The PT-on-a-chip holds great promise as a valuable tool for assessing the nephrotoxic potential of new drug candidates, enhancing our understanding of drug interactions with co-cultured renal cells, and reducing the need for animal experimentation, promoting the safe and ethical development of new pharmaceuticals. (AU)

• FAPESP's process: 20/04507-6 - HYDROGENLS CONFINED IN 3D PRINTED MATRIX TO CONTROLLED AND SITE-SPECIFIC DELIVERY OF INGENOL-3-DODECANOATE AND FLUOROCHROME FOR PHOTODIAGNOSTIC AND THERAPY OF CEREBRAL TUMORS
• Grantee: Italo Rodrigo Calori
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• FAPESP's process: 13/50181-1 - Use of drugs containing nanocarriers with photosensitizers and/or other active compounds applied to cell therapy and treatment of central nervous system disorders
• Grantee: Antonio Claudio Tedesco
• Support Opportunities: Research Projects - Thematic Grants
• FAPESP's process: 21/08111-2 - Development of rare earth based light converters: luminescent markers, optical sensors, and amplifiers
• Grantee: Hermi Felinto de Brito
• Support Opportunities: Research Projects - Thematic Grants
• FAPESP's process: 04/08868-0 - Consolidação do Centro de Microscopia Funcional do Campus da USP/ Ribeirão Preto
• Grantee: Roy Edward Larson
• Support Opportunities: Multi-user Equipment Program