Nanotube Array Substrate for Primary Tissue Culture

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Solution Overview

Problem

Current tissue culture substrates are inadequate for long-term in vitro cultivation of adult mammalian organ tissue due to mechanical instability, limited versatility, and inability to maintain physiological conditions, leading to short culture periods and tissue damage.

Innovation Solution

A nanotube array substrate with a surface roughness of 1 nm to 100 nm, preferably made of metal oxides like titanium dioxide, is used within a tissue culture vessel, allowing for horizontal arrangement and capillary feeding of cell culture medium to minimize tissue contact with bulk liquid, ensuring stable nutrient supply and mechanical stability.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Duration of action of stationary object

If conventional cell culture plastic dishes are used for adult organ tissue culture, then the tissue can be cultured, but the culture period is limited to a few days due to non-physiological conditions and tissue damage

Engineering Contradiction:
Improveculture periodVSAvoidtissue viability
Core Design Contradiction:
Duration of action of stationary objectVSReliability

Solution Approach 1:

The patent employs a porous substrate with specific pore sizes (0.2-10 μm) that allows nutrient diffusion while providing mechanical support. The porous structure mimics the extracellular matrix environment, enabling long-term culture of adult organ tissue by maintaining physiological conditions and preventing tissue damage that occurs with conventional non-porous plastic dishes.

Inventive Principle:
Principle #31Porous materials

Solution Approach 2:

The invention uses composite substrate materials combining organic polymers (such as polyacrylonitrile, polyvinylidene fluoride, or cellulose) with inorganic components. This composite structure provides both the mechanical stability needed for robust substrate handling and the biochemical properties necessary for long-term tissue viability, resolving the contradiction between culture duration and tissue reliability.

Inventive Principle:
Principle #40Composite materials

2Strength

If robust substrates such as glass or stainless steel grids are used for adult tissue culture, then mechanical stability is improved, but the tissue dies rapidly due to non-physiological conditions

Engineering Contradiction:
Improvesubstrate stabilityVSAvoidtissue survival
Core Design Contradiction:
StrengthVSReliability

Solution Approach 1:

The patent modifies the physical and chemical parameters of the substrate by controlling pore size (0.2-10 μm), porosity (30-80%), and surface chemistry. These parameter changes transform rigid, non-physiological substrates like glass into soft, physiology-mimicking porous structures that provide mechanical stability while enabling long-term tissue survival through improved nutrient transport and cell interaction.

Inventive Principle:
Principle #35Parameter changes

Solution Approach 2:

The invention creates local variations in substrate properties by incorporating pores of different sizes in specific regions or using gradient porosity. This allows different areas of the substrate to provide different functions: regions with smaller pores for mechanical support and regions with larger pores for enhanced nutrient diffusion, thereby simultaneously achieving substrate stability and tissue survival.

Inventive Principle:
Principle #3Local quality

3Adaptability or versatility

If soft and highly susceptible substrates are used for organ culture, then tissue culture can be performed, but the substrates are not applicable for applications requiring mechanically stable substrates

Engineering Contradiction:
Improvesubstrate applicabilityVSAvoidsubstrate robustness
Core Design Contradiction:
Adaptability or versatilityVSStrength

Solution Approach 1:

The patent employs composite materials combining organic polymers with inorganic reinforcement components. This composite structure provides both the softness and biochemical compatibility needed for versatile tissue culture applications and the mechanical robustness required for stable substrate handling, resolving the contradiction between adaptability and strength.

Inventive Principle:
Principle #40Composite materials

Solution Approach 2:

The invention segments the substrate structure into a rigid support framework and a softer porous culture layer. The rigid framework (which could be glass or stainless steel) provides mechanical stability, while the porous polymer layer provides the soft, physiology-mimicking environment needed for various tissue types, thereby achieving both robustness and versatility.

Inventive Principle:
Principle #1Segmentation

Applied Scientific Principles

This section explains which scientific principles are used to turn an abstract innovation direction into a practical engineering solution.

Function Achieved in This Case

The nanotube array substrate enables successful cultivation of explanted adult tissue for up to 14 days with minimal tissue disruption, allowing for the maintenance of tissue architecture and viability, and can be adjusted for different tissues by varying nanotube properties, such as diameter and surface roughness, for improved adhesion and handling.

Implementation Method 1

capillary feeding of cell culture medium

Methodology Applied
Scientific EffectCapillary action: Capillary Action

Data Source

PatentEP2546332B1Nanotube carrier substrate for primary tissue culture
Publication Date: 2016.06.29 UNIV LEIPZIG
  • EP2546332B1 patent drawingFigure 1A~1B
  • EP2546332B1 patent drawingFigure 2A~2B
  • EP2546332B1 patent drawingFigure 3~5

AI summary

The present invention relates to a carrier substrate for primary tissue culture comprising a nanotube array. In one aspect the invention relates to a tissue culture vessel comprised of an outer vessel and a nanotube carrier substrate, comprising a nanotube array, located within the outer vessel, wherein the surface roughness of the nanotube array is 1 nm to 100 nm. The invention also relates to the use of a nanotube array for in vitro culturing of primary tissue, the use of a tissue culture vessel according to the invention for in vitro culturing of primary tissue and a method for in vitro culturing primary tissue, wherein a nanotube array is arranged essentially horizontal inside an outer cell culture vessel, so that openings of the nanotubes point at least in upward direction, the nanotube array is contacted with cell culture medium and an isolated primary tissue sample is placed on top-side on said nanotube array.