Development of a Synthetic 3D Platform for Compartmentalized Kidney In Vitro Disease Modeling.

Abstract

3D in vitro tissue and disease models have emerged as an important tool for diagnostic and therapeutic screenings, as they offer a closer approximation toward native environments than traditional 2D cell culture. Kidney disease modeling in particular has progressed to using induced pluripotent stem cells (iPSCs) and microfluidic platforms to replicate the complex microenvironment of the kidney. However, current models lack mature tissue development, scalability, tunability, and spatial organization. In this study, a fully synthetic, 3D kidney disease platform that addresses these challenges is presented. This model comprises a compartmentalized poly (ethylene glycol) (PEG)-based hydrogel matrix with anisotropic PEG-based microgels. This multiphasic hydrogel system provides control over spatially organizing a triple-co-culture of key renal cell types: tubule-epithelial cells (CD10⁺), endothelial cells (CD31⁺), and fibroblasts (PDGFRβ⁺). Structural control and compartmentalization are enabled through enzymatically degradable rod microgels produced using microfluidics, allowing for a modular system. This study characterizes the synthetic models and analyzes the functionality of the system by examining cell-material interactions. The use of this system as a promising disease model is demonstrated through the addition of TGFβ, inducing fibrosis. This work highlights a novel approach to building a fully synthetic, scalable, modular kidney model with a tunable microenvironment.