Bioprinted Liver Tissue Constructs with Defined Compartments
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Solution Overview
Problem
Current methods for generating liver tissue constructs are inefficient, laborious, and fail to produce defined tissue compartments with specific cell types in specific positions, lacking native-like structures and microvasculature, which limits their longevity and functionality.
Innovation Solution
Engineered, living, three-dimensional liver tissue constructs are created using bioprinting techniques, comprising parenchymal and non-parenchymal cells without a pre-formed scaffold, with controlled architecture and geometry, allowing for the formation of planar and laminar geometries that mimic native liver tissue.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Manufacturing precision
If current methods for generating liver tissue constructs are used, then tissue constructs can be produced, but they lack defined tissue compartments with specific cell types in specific positions and lack native-like structures
Solution Approach 1:
The liver tissue construct is segmented into distinct compartments with specific cell types positioned in defined regions. Parenchymal cells are segregated from non-parenchymal cells into separate zones, creating functionally distinct tissue compartments that mimic native liver architecture.
Solution Approach 2:
Different cell types are placed in specific local positions within the construct to create region-specific tissue properties. The bioprinting process enables spatial variation in cell composition, with parenchymal cells in metabolic zones and non-parenchymal cells in supportive regions, achieving local quality differentiation.
2Duration of action of stationary object
If current methods for generating liver tissue constructs are used, then tissue constructs can be produced, but they fail to retain viability and functionality over extended periods
Solution Approach 1:
The bioprinting process preliminarily establishes proper tissue architecture and cell positioning before functional maturation occurs. By pre-organizing cells into native-like structures with appropriate spatial relationships, the construct is primed for long-term viability and consistent functionality.
Solution Approach 2:
The tissue construct self-organizes and matures in vitro after bioprinting, developing native-like structures and microvasculature autonomously. The cells self-assemble into functional tissue architecture without continuous external intervention, enabling extended viability periods.
3Productivity
If current methods for generating liver tissue constructs are used, then tissue constructs can be produced, but the process is inefficient and laborious
Solution Approach 1:
Manual tissue construction methods are replaced with bioprinting technology, substituting mechanical hand assembly with automated computer-controlled deposition systems. This substitution dramatically improves production efficiency and reduces fabrication time while enabling precise spatial control of cell placement.
Solution Approach 2:
The fabrication process parameters are optimized for high-throughput production, including controlled deposition rates, temperature, and humidity conditions. These parameter changes enable efficient tissue construct production while maintaining manufacturing precision.
Data Source
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AI summary
Engineered, living, three-dimensional liver tissue constructs comprising: one or more layers, wherein each layer contains one or more liver cell types, the one or more layers cohered to form a living, three-dimensional liver tissue construct. In some embodiments, the constructs are characterized by having at least one of: at least one layer comprising a plurality of cell types, the cell types spatially arranged relative to each other to create a planar geometry; and a plurality of layers, at least one layer compositionally or architecturally distinct from at least one other layer to create a laminar geometry. Also disclosed are arrays and methods of making the same. Also disclosed are engineered, living, three-dimensional liver tissue constructs for use in the augmentation or restoration of one or more liver functions, by in vivo delivery of tissue or utilization of tissue in an extracorporeal device.