Microfluidic Organ-on-Chip with Segmented Lamina Propria Layers
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Solution Overview
Problem
Current in vitro tissue model systems, such as cell lines and three-dimensional primary cell organoid cultures, face limitations in reproducibility and short-term nature, particularly in modeling inflammatory diseases and drug testing for epithelial regions.
Innovation Solution
An in vitro microfluidic 'organ-on-chip' system is developed, featuring a multicellular, layered culture that mimics epithelial tissue structures and functions, allowing interactions between lamina propria-derived cells and epithelial/endothelial cells for modeling inflammatory tissues and comparing different tissue types and disease states, with applications in drug testing and inflammation reduction.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If traditional cell line or organoid culture systems are used, then the models are simple to establish, but they lack reproducibility and have short-term stability
Solution Approach 1:
The tissue model is segmented into multiple distinct cell layers (epithelial layer, lamina propria layer, muscularis layer) separated by porous membranes within the microfluidic device. This segmentation allows each cell type to be cultured and maintained in its appropriate microenvironment while ensuring reproducibility through controlled layer-by-layer construction
Solution Approach 2:
The microfluidic device structure serves multiple functions simultaneously: it provides physical separation of cell layers, enables controlled fluid flow for nutrient delivery, allows application of mechanical stretch, and facilitates long-term culture. This multi-functionality achieves high reliability without proportionally increasing complexity
2Duration of action of stationary object
If traditional organoid culture systems are used, then the models can be established relatively quickly, but they are limited to short-term studies
Solution Approach 1:
The microfluidic system enables continuous perfusion of culture media through the tissue model, ensuring constant supply of nutrients and removal of waste products. This continuous action supports long-term culture duration, allowing studies to extend beyond the limitations of traditional static organoid systems
Solution Approach 2:
The device incorporates dynamic mechanical stretch applied to the tissue layers, mimicking physiological conditions. This dynamic element, combined with continuous fluid flow, creates a living, evolving system that maintains viability and relevance for extended culture periods
3Adaptability or versatility
If simple cell line cultures are used, then the systems are easy to operate, but they cannot model complex tissue interactions or inflammatory diseases
Solution Approach 1:
The microfluidic device segments different tissue compartments (epithelium, lamina propria, muscle layers) into distinct regions separated by porous membranes. This segmentation enables modeling of complex tissue interactions while maintaining operational simplicity through standardized layer construction protocols
Solution Approach 2:
The porous membranes act as intermediaries between different cell layers, allowing controlled paracrine signaling and molecular exchange while maintaining physical separation. This intermediary structure enables complex biological interactions to be modeled without requiring direct cell-to-cell contact, simplifying the operational aspects of studying tissue communication
Data Source
AI summary
An in vitro microfluidic “organ-on-chip” is described herein that mimics the structure and at least one function of specific areas of the epithelial system in vivo. In particular, a multicellular, layered, microfluidic culture is described, allowing for interactions between lamina propria-derived cells and the associated tissue specific epithelial cells and endothelial cells. This in vitro microfluidic system can be used for modeling inflammatory tissue, e.g., autoimmune disorders involving epithelia and diseases involving epithelial layers. These multicellular, layered microfluidic “organ-on-chip”, e.g. “epithelia-on-chip” further allow for comparisons between types of epithelia tissues, e.g., lung (Lung-On-Chip), bronchial (Airway-On-Chip), skin (Skin-On-Chip), cervix (Cervix-On-Chip), blood brain barrier (BBB-On-Chip), etc., in additional to neurovascular tissue, (Brain-On-Chip), and between different disease states of tissue, i.e. healthy, pre-disease and diseased areas. Additionally, these microfluidic “organ-on-chips” allow identification of cells and cellular derived factors driving disease states in addition to drug testing for reducing inflammation effecting epithelial regions.