Kidney-on-a-chip with horizontal multi-compartment structure for renal fibrosis screening
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Solution Overview
Problem
Current models for renal fibrosis, including animal models and existing kidney organ-on-chips, fail to accurately mimic human renal fibrosis due to structural limitations and the inability to co-culture renal tubular epithelial cells and renal fibroblasts effectively.
Innovation Solution
Development of a kidney-on-a-chip with a horizontal multi-compartment structure, where renal tubular epithelial cells are cultured in a renal tubule culture part and renal fibroblasts and vascular endothelial cells are cultured in an interstitium culture part, allowing for co-culture and mimicking of renal fibrosis.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Adaptability or versatility
If a separate culture solution feeding channel is added to enable drug administration and substance exchange, then the functionality for screening renal fibrosis therapeutic agents is improved, but the device complexity and manufacturing cost increase
Solution Approach 1:
The culture chamber serves multiple functions: it acts as both the culture environment for renal tubular epithelial cells and renal fibroblasts, and as the direct administration channel for drugs and culture solutions. The interstitium chamber similarly serves as both culture space and substance exchange pathway, eliminating the need for separate feeding channels while maintaining full functionality for therapeutic agent screening
Solution Approach 2:
The patent merges the culture chamber and feeding channel into a single integrated structure. The culture chamber directly receives and processes culture solutions and drugs without requiring separate transport pathways, thereby simplifying the overall device structure while preserving all necessary functions for co-culture and therapeutic agent administration
2Reliability
If animal models are used to represent human renal fibrosis, then the physiological relevance is improved, but the cost and ethical issues increase
Solution Approach 1:
The patent creates a simplified copy of the human renal interstitium using renal fibroblasts and extracellular matrix components in a controlled in vitro environment. This cell-based model replicates the essential physiological features of human renal fibrosis without requiring animal subjects, thereby maintaining physiological relevance while eliminating the ethical and cost burdens associated with animal experimentation
3Reliability
If renal tubular epithelial cells and renal fibroblasts are co-cultured to accurately represent renal fibrosis, then the pathological accuracy is improved, but the culture system complexity increases
Solution Approach 1:
The patent divides the culture system into two distinct but interconnected chambers: the culture chamber for renal tubular epithelial cells and the interstitium chamber for renal fibroblasts. This segmentation allows each cell type to be cultured in its optimal environment while maintaining physiological interactions through controlled substance exchange, thereby achieving pathological accuracy without excessive system complexity
Solution Approach 2:
The culture medium acts as an intermediary between the two cell types, carrying signaling molecules, growth factors, and other substances that mediate the interaction between renal tubular epithelial cells and renal fibroblasts. This intermediary mechanism enables accurate representation of renal fibrosis pathology through cell-cell communication without requiring direct physical contact or complex co-culture structures
Data Source
AI summary
The present invention relates to: an organ-on-a-chip for mimicking kidney tissue in which renal tubular epithelial cells and renal fibroblasts are co-cultured; a method for manufacturing the organ-on-a-chip; a device for co-culturing three types of cells; and a method for screening for renal fibrosis therapeutic agents by using the organ-on-a-chip. A kidney-on-a-chip according to one embodiment of the present invention has the excellent effects of enabling the time and errors required in screening for renal fibrosis therapeutic agents to be minimized and renal fibrosis therapeutic agents to be more conveniently and simply screened for through an objective evaluation index.