Articular Cartilage Cryopreservation via Sequential CPA Permeation

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Solution Overview

Problem

Current cryopreservation techniques are ineffective for articular cartilage due to inadequate permeation and toxicity of cryoprotectant agents (CPAs), limiting the preservation and transplantation of this tissue type.

Innovation Solution

A method involving a sequence of multiple CPAs, such as dimethyl sulfoxide, ethylene glycol, propylene glycol, glycerol, formamide, and ethanol, is used to permeate articular cartilage, forming combined CPAs with a concentration distribution that vitrifies and cryopreserves the sample, minimizing toxicity and optimizing permeation.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Ease of manufacture

If a single cryoprotectant agent (CPA) is used to permeate articular cartilage, then the permeation process is simple, but the CPA toxicity is high and permeation is inadequate

Engineering Contradiction:

Improvesimplicity of permeation processVSAvoidCPA toxicity

Core Design Contradiction:

Ease of manufactureVSObject-affected harmful factors

Solution Approach 1:

The patent divides the CPA permeation process into multiple sequential steps, each using a different CPA at progressively lower temperatures. This segmentation allows each CPA to contribute to the overall cryoprotection while reducing individual CPA concentrations and toxicity, resolving the contradiction between process simplicity and reduced toxicity.

Inventive Principle:

Principle #1Segmentation

Solution Approach 2:

The patent changes temperature parameters during the permeation process, progressively lowering the temperature with each CPA step. This parameter change optimizes CPA permeation at each stage while minimizing toxicity, addressing both the permeation adequacy and toxicity reduction requirements.

Inventive Principle:

Principle #35Parameter changes

2Reliability

If high concentration of CPA is used to achieve adequate permeation, then permeation is sufficient, but CPA toxicity increases

Engineering Contradiction:

Improveadequacy of permeationVSAvoidCPA toxicity

Core Design Contradiction:

ReliabilityVSObject-affected harmful factors

Solution Approach 1:

The patent segments the total CPA protection function across multiple different CPAs, each applied at lower concentrations. This segmentation achieves adequate overall permeation and cryoprotection while maintaining lower individual CPA concentrations, thereby reducing toxicity.

Inventive Principle:

Principle #1Segmentation

Solution Approach 2:

The patent uses a composite approach by combining multiple different CPAs (dimethyl sulfoxide, ethylene glycol, propylene glycol, glycerol, formamide, and ethanol) in a sequential manner. This composite CPA strategy achieves sufficient permeation and cryoprotection while reducing the toxicity associated with any single high-concentration CPA.

Inventive Principle:

Principle #40Composite materials

3Object-affected harmful factors

If multiple CPAs are used in sequence to reduce toxicity, then CPA toxicity is reduced, but the process complexity increases

Engineering Contradiction:

ImproveCPA toxicityVSAvoidcomplexity of permeation process

Core Design Contradiction:

Object-affected harmful factorsVSDevice complexity

Solution Approach 1:

The patent segments the permeation process into distinct sequential steps, each with a specific CPA and temperature range. While this increases process complexity, it enables toxicological management through progressive CPA exchange and concentration reduction, making the complex process controllable and effective.

Inventive Principle:

Principle #1Segmentation

Solution Approach 2:

The patent performs preliminary actions by pre-cooling the cartilage and preparing the CPA solutions at appropriate temperatures before each permeation step. This preliminary preparation simplifies the execution of the multi-CPA process by establishing optimal conditions in advance for each sequential step.

Inventive Principle:

Principle #10Preliminary action

4Speed

If room temperature CPA permeation is used, then the permeation process is fast, but CPA toxicity is high

Engineering Contradiction:

Improverate of permeationVSAvoidCPA toxicity

Core Design Contradiction:

SpeedVSObject-affected harmful factors

Solution Approach 1:

The patent changes the temperature parameter from room temperature to progressively lower temperatures for each CPA step. This parameter change slows the permeation rate slightly but dramatically reduces CPA toxicity by enabling the use of multiple CPAs at lower concentrations, achieving an optimal balance between speed and safety.

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

This method effectively cryopreserves articular cartilage by reducing toxicity and improving permeation, allowing for successful preservation and potential transplantation with high cell viability.

Implementation Method 1

permeating a sample of articular cartilage with a sequence of at least two different CPAs

Methodology Applied

Scientific EffectDiffusion: Diffusion

Implementation Method 2

the concentration distribution of the combined CPAs being selected so that upon cooling of the sample, the combined CPAs vitrify and cryopreserve the sample

Methodology Applied

Scientific EffectVitrification: Vitrification

Data Source

PatentUS8758988B2Cryopreservation of articular cartilage

Publication Date: 2014.06.24 THE GOVERNORS OF THE UNIV OF ALBERTA

AI summary

The invention relates generally to methods and compositions for the cryopreservation and/or vitrification of tissue including articular cartilage and the preparation of said tissue for clinical or research use, including but not limited to joint replacement and the treatment and prevention of osteoarthritis.