Scaffold-Free 3D Cell Structure Fabrication via Temporary Thread Support

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Solution Overview

Problem

Existing methods for fabricating three-dimensional cellular structures using cell aggregates face challenges such as scaffold materials blocking oxygen and nutrient delivery, limitations in size and shape due to scaffold shape retention, and potential adverse effects from scaffold materials when transplanted, as well as high manufacturing costs and complexity in needle array processes.

Innovation Solution

A method involving the use of thread or needle-shaped members to form a net-shaped space for cell aggregates, allowing for layering and subsequent removal of these members to create a scaffold-free three-dimensional cellular structure, utilizing automated dispensing equipment and supports with multiple frames and thread or needle-shaped members to hold cell aggregates, and forming masks or bonding wires to create the necessary structures.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Stability of the object's composition

If scaffold materials are used to support cell aggregates, then cell adhesion and structural stability are improved, but oxygen and nutrient delivery are blocked

Engineering Contradiction:
Improvestructural stabilityVSAvoidoxygen and nutrient delivery blockage
Core Design Contradiction:
Stability of the object's compositionVSObject-affected harmful factors

Solution Approach 1:

The invention removes the scaffold material entirely from the final tissue structure. Thread or needle-shaped members are used only temporarily during fabrication to position cell aggregates, then they are removed before transplantation. This extraction principle eliminates the harmful blockage of oxygen and nutrient delivery while maintaining structural stability during the critical fabrication phase.

Inventive Principle:
Principle #2Taking out (Extraction)

Solution Approach 2:

The thread or needle-shaped members perform their supportive function in advance during the fabrication process, holding cell aggregates in the desired three-dimensional configuration. Once the tissue structure is formed and stabilized through cell adhesion, the temporary support members are removed. This preliminary action allows scaffold-free final products with improved permeability.

Inventive Principle:
Principle #10Preliminary action

2Manufacturing precision

If needle array process is used to position cell aggregates, then positioning precision is improved, but manufacturing cost and process complexity increase

Engineering Contradiction:
Improvepositioning precisionVSAvoidprocess complexity
Core Design Contradiction:
Manufacturing precisionVSDevice complexity

Solution Approach 1:

The invention replaces complex, expensive, and reusable needle array systems with simple, disposable thread or needle-shaped members. These temporary support elements are inexpensive to manufacture and can be easily discarded after use, eliminating the need for sophisticated positioning equipment while maintaining adequate positioning precision for tissue fabrication.

Inventive Principle:
Principle #27Cheap short-living objects (Disposable)

Solution Approach 2:

The thread or needle-shaped members serve as simple intermediary tools that facilitate cell aggregate positioning without requiring complex control systems. These mediators are manually or automatically positioned to hold cell aggregates, then removed after serving their temporary purpose, greatly simplifying the overall manufacturing process.

Inventive Principle:
Principle #24Intermediary (Mediator)

3Strength

If scaffold materials are used to maintain shape, then structural integrity is improved, but size and shape flexibility are limited

Engineering Contradiction:
Improvestructural integrityVSAvoidshape flexibility
Core Design Contradiction:
StrengthVSAdaptability or versatility

Solution Approach 1:

The invention transitions from static scaffold structures that constrain tissue geometry to dynamic cell-driven self-organization. Cell aggregates naturally adhere and reorganize into stable three-dimensional structures without rigid external form constraints, enabling flexible adaptation to various tissue types and geometries while maintaining structural integrity through cellular interactions rather than material constraints.

Inventive Principle:
Principle #15Dynamics

Data Source

PatentEP3514227B1Method for producing three-dimensional cell structure and support used for same
Publication Date: 2020.06.10 ONO JIRO
  • EP3514227B1 patent drawingFigure 1~2
  • EP3514227B1 patent drawingFigure 3~4(C)
  • EP3514227B1 patent drawingFigure 5(A)~5(B)

AI summary

[Problem] To provide: a method that is capable of more easily producing a three-dimensional cell structure than conventional methods; and a support used for the same. [Solution] This support 1 includes frame bodies 10A, 10B, 10C, 10D on four sides; and X- and Y-direction string members 20 extending between the frame bodies 10. The string members 20 form, in the support 1, a plurality of meshed rectangular spaces. In the meshed spaces of the support 1, cell aggregates are dispensed from a dispenser, and a plurality of such supports 1 are stacked. Finally, the support 1 and the string members 20 are removed from the three-dimensional cell structure formed by the adhesion and fusion of the cell aggregates.