Biocompatible three-dimensional network and use thereof as cell support

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Solution Overview

Problem

Current three-dimensional (3D) networks for cell culture, particularly those made of electrospun fibers, face issues such as low cell infiltration, non-uniform cell distribution, cytotoxicity, and the inability to modulate mechanical properties independently of chemical properties, which limits their effectiveness in studying cellular behaviors like migration and proliferation.

Innovation Solution

A 3D network of crosslinked polymer fibers with diameters between 0.1 and 1.5 μm and interstice sizes between 0.1 and 50 μm, made by electrospinning a polymer solution followed by heat treatment, offering biocompatibility, non-toxicity, and adjustable mechanical properties, allowing for the study of cellular behaviors like survival, proliferation, and migration with enhanced visualization and analysis capabilities.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If electrospun fibers are used to create 3D networks, then the network structure is formed, but cell infiltration is poor and cell distribution is non-uniform

Engineering Contradiction:
Improvecell infiltrationVSAvoidnetwork structure
Core Design Contradiction:
ReliabilityVSDevice complexity

Solution Approach 1:

The patent employs highly porous electrospun fiber networks with controlled pore sizes and interconnected structures that facilitate cell infiltration. The porous architecture allows cells to penetrate deeply into the 3D network while maintaining structural integrity, resolving the contradiction between network formation and cell infiltration capability.

Inventive Principle:
Principle #31Porous materials

Solution Approach 2:

The patent utilizes electrospinning parameters and post-processing treatments to create dynamic, adaptable network structures that can respond to cell infiltration. The fiber arrangement and pore distribution are optimized to guide cell migration and achieve uniform cell distribution throughout the 3D network.

Inventive Principle:
Principle #15Dynamics

2Reliability

If certain materials are used for 3D networks, then the network structure is achieved, but cytotoxicity occurs

Engineering Contradiction:
Improvenetwork structureVSAvoidcytotoxicity
Core Design Contradiction:
ReliabilityVSObject-affected harmful factors

Solution Approach 1:

The patent carefully selects and optimizes material parameters including polymer composition, molecular weight, and processing conditions to eliminate cytotoxicity. The electrospinning parameters, solvent selection, and post-treatment conditions are adjusted to produce biocompatible fiber networks that maintain structural requirements while being non-toxic to cells.

Inventive Principle:
Principle #35Parameter changes

Solution Approach 2:

The patent employs composite material systems combining biocompatible polymers with functional additives or surface modifications. These composite structures achieve the required mechanical and structural properties while incorporating bioactive components that enhance cell compatibility and reduce cytotoxicity effects.

Inventive Principle:
Principle #40Composite materials

3Strength

If mechanical properties are modified in 3D networks, then structural requirements are met, but chemical properties and crosslinking are affected

Engineering Contradiction:
Improvemechanical propertiesVSAvoidcrosslinking chemistry
Core Design Contradiction:
StrengthVSDevice complexity

Solution Approach 1:

The patent separates the optimization of mechanical properties from chemical crosslinking by using physical structuring methods during electrospinning. Fiber diameter, orientation, and network density are controlled independently through electrospinning parameters to achieve desired mechanical properties without relying solely on chemical crosslinking, thereby reducing complexity in the chemical modification process.

Inventive Principle:
Principle #1Segmentation

Solution Approach 2:

The patent introduces intermediate structural features such as fiber crystallinity, orientation patterns, and network porosity that act as mediators between processing conditions and final mechanical properties. These intermediate structures allow mechanical property tuning through physical parameters rather than direct chemical modification, simplifying the overall material design process.

Inventive Principle:
Principle #24Intermediary (Mediator)

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 network provides a biocompatible, non-cytotoxic environment that allows for even cell distribution and infiltration, enabling the study of cellular behaviors with high reproducibility and analytical capabilities, including proteomic and functional analysis, while being easy to produce and integrate into devices like multiwell plates.

Implementation Method 1

A 3D network of crosslinked polymer fibers with diameters between 0.1 and 1.5 μm and interstice sizes between 0.1 and 50 μm, made by electrospinning a polymer solution

Methodology Applied
Scientific EffectElectrospinning: Electrohydrodynamics

Implementation Method 2

followed by heat treatment, offering biocompatibility, non-toxicity, and adjustable mechanical properties

Methodology Applied
Scientific EffectHeat treatment: Heat Treatment

Data Source

PatentEP3752594B1Biocompatible three-dimensional network and use thereof as cell support
Publication Date: 2022.04.06 UNIVERSITY OF MONTPELLIER
  • EP3752594B1 patent drawingFigure 1A~1C
  • EP3752594B1 patent drawingFigure 2A~2F
  • EP3752594B1 patent drawingFigure 3A~3D

AI summary

A subject of the invention is an infusible three-dimensional network of crosslinked-polymer fibres, suitable as a cell support, and in particular characterized in that the diameter of said fibres is between 0.1 and 1.5 μm, the size of the interstices between said fibres is between 0.1 and 50 μm2, and the rigidity of said network is characterized by an elastic modulus of between 0.01 and 10 000 kPa, preferably between 0.1 and 10 000 kPa, preferably between 0.1 and 1000 kPa, more preferentially between 0.1 and 300 kPa. A subject of the invention is also a method for preparing a three-dimensional network of crosslinked-polymer fibres, comprising a step of synthesis of said network by electrospinning of a solution of acrylic-type polymer, more particularly PAN, to which a stiffening agent is optionally added, followed by a step of heat treatment under an oxidizing atmosphere and at a temperature of between 40°C and 400°C, preferably between 200°C and 300°C. Finally, a subject of the invention is an infusible three-dimensional network of crosslinked-polymer fibres as a cell support, that can be used in particular for studying cell survival and migration.