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

VSEngineering 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

Engineering Contradiction:
Improvedefined tissue compartments with specific cell types in specific positionsVSAvoidbioprinting technique complexity
Core Design Contradiction:
Manufacturing precisionVSDevice complexity

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.

Inventive Principle:
Principle #1Segmentation

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.

Inventive Principle:
Principle #3Local quality

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

Engineering Contradiction:
Improvetissue construct viability periodVSAvoidtissue construct functionality consistency
Core Design Contradiction:
Duration of action of stationary objectVSReliability

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.

Inventive Principle:
Principle #10Preliminary action

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.

Inventive Principle:
Principle #25Self-service

3Productivity

If current methods for generating liver tissue constructs are used, then tissue constructs can be produced, but the process is inefficient and laborious

Engineering Contradiction:
Improvetissue construct production efficiencyVSAvoidtissue construct fabrication time
Core Design Contradiction:
ProductivityVSLoss of time

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.

Inventive Principle:
Principle #28Mechanics substitution (Replace mechanical system)

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.

Inventive Principle:
Principle #35Parameter changes

Data Source

PatentEP2970896B1Engineered liver tissues, arrays thereof, and methods of making the same
Publication Date: 2024.04.24 ORGANOVO INC
  • EP2970896B1 patent drawingFigure 1
  • EP2970896B1 patent drawingFigure 2A~2X
  • EP2970896B1 patent drawingFigure 3A~3D

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.