Cardiac Organoid Chamber Bioreactor for Independent Load Control
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Solution Overview
Problem
Existing in vitro models for drug development, particularly for heart-related compounds, lack physiological relevance and complexity, limiting their ability to accurately predict human responses and recapitulate heart disease phenotypes, and current cardiac organoid chambers (COCs) lack independent control of preload and afterload, complicating heart failure studies.
Innovation Solution
A bioreactor system for fabricating and testing cardiac organoid chambers (COCs) with modular design, allowing independent control of preload and afterload through separate inlets and outlets, and featuring a top section for fluid flow, a middle section for holding the OC, and a bottom section for culture medium, with integrated valves and electrical stimulation, pressure measurement, and electrophysiology monitoring.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Device complexity
If a single inlet/outlet design is used in cardiac organoid chambers, then the device complexity is reduced, but the ability to independently control preload and afterload conditions is lost
Solution Approach 1:
The patent divides the single inlet/outlet system into separate inlet and outlet channels, allowing independent control of preload (inlet) and afterload (outlet) conditions. This segmentation enables researchers to apply different pressure conditions to each end of the cardiac organoid chamber independently, resolving the contradiction between simplicity and functional versatility.
2Ease of manufacture
If simple in vitro models like monolayers or tissue strips are used, then the ease of manufacture is improved, but the physiological relevance and ability to recapitulate heart disease phenotypes deteriorates
Solution Approach 1:
The patent creates a cardiac organoid chamber with a specific 3D hollow spherical structure that locally replicates the physiological environment of heart tissue. This localized 3D architecture provides mechanical cues and spatial organization that monolayers and simple strips cannot provide, thereby improving physiological relevance while maintaining relative ease of manufacture through standardized fabrication protocols.
3Reliability
If complex 3D models with hollow centers are used, then the physiological relevance is improved, but the fabrication and culture complexity increases
Solution Approach 1:
The patent employs preliminary action by pre-forming the 3D hollow spherical structure before seeding cardiac cells. The chamber architecture is fabricated in advance with defined inlet/outlet ports, allowing cells to be seeded into a pre-established 3D framework. This approach simplifies the overall fabrication process compared to attempting to self-organize complex 3D structures from cell aggregates, thereby reducing fabrication and culture complexity while maintaining physiological relevance.
Data Source
AI summary
Provided are multi-layer bioreactors for growing, maintaining, stimulating, monitoring and testing organoids and tissues derived from or representing hollow organs in organoid chambers. Also provided are uses of those bioreactors in modeling a disease process for monitoring disease progress and/or for assessing a biological effect, such as therapeutic efficacy and/or toxicity, e.g., organotoxicity. Also disclosed are bioreactors comprising organoid chambers that are useful as systems for measuring the volume, pressure, contractility, pump function, or electrophysiology of an organoid chamber as well as systems for controlling the pressure experienced by an organoid or tissue in an organoid chamber.