3D Cell Culture Using Yield Stress Hydrogel Beads

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Solution Overview

Problem

Conventional 2D cell culture techniques fail to replicate the natural 3D environment experienced by cells in vivo, limiting the accuracy of cell growth and drug testing, as they are often expensive, time-consuming, and restricted in the structures or geometries of tissues that can be grown and tested.

Innovation Solution

An integrated assay system using a 3D cell growth medium made from yield stress materials that can be printed and manipulated to support cells in a 3D geometry, allowing for the creation of specific microenvironments and the use of 3D printing to deposit and retrieve cells without disrupting their geometry, combined with measurement apparatus and bioreactor plates for screening and analysis.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If conventional 2D cell culture techniques are used, then cell growth can be maintained, but the microenvironment does not accurately replicate in vivo 3D conditions

Engineering Contradiction:
Improveaccuracy of cell growth representationVSAvoidability to replicate in vivo environment
Core Design Contradiction:
ReliabilityVSAdaptability or versatility

Solution Approach 1:

The patent transitions from conventional 2D cell culture to 3D cell culture by embedding cells within a hydrogel matrix. This dimensional change allows cells to experience a three-dimensional microenvironment that more closely mimics in vivo conditions, improving the reliability and adaptability of cell growth representation while maintaining ease of operation through standardized plate formats.

Inventive Principle:
Principle #17Another dimension (Dimensionality change)

2Reliability

If 3D cell culture techniques such as hanging drop plates or magnetic levitation are used, then more accurate 3D microenvironments can be created, but the processes become expensive and time consuming

Engineering Contradiction:
Improveaccuracy of 3D microenvironmentVSAvoidtime required for cell culture processing
Core Design Contradiction:
ReliabilityVSLoss of time

Solution Approach 1:

The patent employs pre-formed hydrogel beads that are prepared in advance and can be stored. These pre-prepared beads eliminate the need for time-consuming in-situ gel formation during cell culture experiments. The beads are ready-to-use, allowing researchers to quickly set up 3D cell culture experiments without lengthy preparation steps, thus reducing time loss while maintaining accurate 3D microenvironments.

Inventive Principle:
Principle #10Preliminary action

Solution Approach 2:

The patent uses disposable hydrogel beads that can be easily replaced rather than reusing complex equipment or lengthy protocols. This approach reduces both time and cost by eliminating the need for expensive, time-consuming setup and cleanup procedures associated with traditional 3D culture methods like hanging drop plates or magnetic levitation systems.

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

3Reliability

If complex 3D structures are grown using traditional methods, then in vivo-like environments can be achieved, but the structures and geometries are limited

Engineering Contradiction:
Improvein vivo environment replicationVSAvoidrange of structures and geometries
Core Design Contradiction:
ReliabilityVSAdaptability or versatility

Solution Approach 1:

The patent utilizes hydrogel beads with tunable parameters including size, porosity, and mechanical properties. By adjusting these parameters, researchers can create a wide variety of 3D structures and geometries while maintaining the beneficial 3D microenvironment. This versatility allows for different cell types, tissue models, and experimental configurations without being constrained by the limited geometries of traditional 3D culture methods.

Inventive Principle:
Principle #35Parameter changes

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

Enables rapid and high-throughput testing of cells in structures that mimic in vivo environments, reducing the need for animal testing and providing reliable drug efficacy assessments by allowing cells to be grown in dynamic tissue-like structures with controlled conditions.

Implementation Method 1

providing a three-dimensional (3D) cell growth medium comprising a plurality of hydrogel particles and a liquid cell culture medium, wherein the hydrogel particles are swelled with the liquid cell culture medium to form a granular gel

Methodology Applied
Scientific EffectAbsorption: Absorption (physical)

Implementation Method 2

this involves a solid to liquid phase change at a desired location in a region of yield stress material such that the yield stress material will flow and be displaced when cells are injected

Methodology Applied
Scientific EffectPhase change: Phase Change

Data Source

PatentUS11377634B23D micro fabrication and screening
Publication Date: 2022.07.05 UNIV OF FLORIDA RESEARCH FOUNDATION INC
  • US11377634B2 patent drawing
  • US11377634B2 patent drawing
  • US11377634B2 patent drawing

AI summary

Disclosed herein is an integrated assay system that can be used, for example, to monitor and screen cells in 3D culture. This system involves a 3D cell growth medium made from a yield stress material that allows cells to be deposited, e.g. by 3D printing, samples to be taken, and the extracellular environment manipulated.