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

"On-a-chip" technology advances the development of physiologically relevant organ-mimicking devices by integrating human cells into a three-dimensional microfluidic architecture that simulates the fluid dynamics of the target tissue. This approach also creates minimal functional units, enabling compartmentalized research on the effects of drugs on individual organ components. In this study, we describe the construction and evaluation of a convoluted renal proximal tubule-on-a-chip (PT-on-a-chip), which consists of a co-culture of Renal Proximal Tubule Epithelial Cells (RPTEC) and Human Umbilical Vein Endothelial Cells (HUVEC) in a polydimethylsiloxane (PDMS) microfluidic device fabricated using 3D printing and molding. Remarkably, the RPTEC:HUVEC co-culture displayed rapid cell adhesion within 30 min on microchannels functionalized with plasma, APTES, and type-I collagen, thus significantly reducing the necessary incubation time before initiating medium perfusion. In contrast, other functionalization methods such as plasma alone and plasma plus polyvinyl alcohol were effective only in promoting cell attachment to plannar 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.