Developing a Kidney-on-a-Chip Platform to Understand the Physiopathology in Nephron Architecture and Design a New Generation Dialysis for Enhanced Absorption and Reabsorption.
Implementing Organization
Indian Institute Of Technology Madras
Principal Investigator
Prof. Sarit Kumar Das
Indian Institute Of Technology Madras
skdas@iitm.ac.in
Project Overview
Chronic kidney disease (CKD) is a significant global health concern, leading to high morbidity and mortality rates. Current in-vitro models and animal studies fail to accurately mimic how the nephron's intricate curvature, permeability variations, and pressure dynamics influence each other, which is essential for understanding absorption and reabsorption efficiency. The inability of existing kidney-on-a-chip models to replicate these biophysical factors collective influence limits their effectiveness in drug testing and treatment optimization. This project aims to develop an advanced kidney-on-a-chip platform that integrates 3D microchannels mimicking nephron-like architecture, i.e., curvature, varying wall permeability, and pressure conditions along the axial direction. The model will incorporate both tubular and vascular networks to closely replicate the physiological microenvironment of the kidney. By simulating mechanical factors such as shear stress, pressure variations, and extracellular matrix (ECM) stiffness, this study will analyze their collective impact on kidney epithelial and endothelial cell morphology and function. A key objective of this study is to design and validate optimized dialysis units based on insights gained from the kidney-on-a-chip model. The dialysis units will be engineered to incorporate nephron-like architecture with varying analyte diffusion along the length of the dialyzer to enhance absorption and reabsorption efficiency, addressing a major limitation of current dialysis technologies. The project will further extend to developing a chronic kidney disease-on-a-chip model, simulating pathological conditions like increased/decreased ECM stiffness, blood pressure, and volume to study CKD progression and potential therapeutics. This research is expected to lead to significant advancements in kidney-on-a-chip technology, enhancing its utility for studying kidney function, drug toxicity screening, and personalized medicine. Additionally, the findings will contribute to the development of next-generation dialysis units with improved efficiency, reducing the burden of CKD and improving patient outcomes. The integration of nephron architecture into dialysis design holds great promise for transforming CKD treatment and dialysis technology, making it more effective and patient-specific.