Decellularized Tissue Scaffold Oscillation

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Solution Overview

Problem

Current methods for producing extracellular matrix (ECM) scaffolds are inefficient, as they require prolonged exposure to decellularization reagents, often damage the tissue surface, and are not effective for small-scale tissues, leading to incomplete decellularization and loss of ECM integrity.

Innovation Solution

A method involving high-frequency oscillation of tissue samples during treatment with osmotic reagents and detergents, which enhances reagent distribution and cell lysis, allowing for rapid and complete decellularization while preserving the 3D architecture and bioactivity of the ECM.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If prolonged exposure to decellularization reagents is used, then complete decellularization is achieved, but ECM integrity and bioactivity are damaged

Engineering Contradiction:
Improvedecellularization completenessVSAvoidECM integrity
Core Design Contradiction:
ReliabilityVSStability of the object's composition

Solution Approach 1:

The patent applies high-frequency oscillation (3-100 Hz) with displacement of 1 mm or more during decellularization treatment. This mechanical vibration enhances reagent distribution throughout the tissue, improves penetration into dense ECM structures, and accelerates cell lysis without requiring prolonged exposure times, thereby preserving ECM integrity while achieving complete decellularization

Inventive Principle:
Principle #18Mechanical vibration

Solution Approach 2:

The patent changes the physical parameters of the treatment process by introducing oscillation frequency (3-100 Hz) and displacement (1 mm or more) as key control variables. This parameter modification transforms a static, prolonged treatment into a dynamic, accelerated process that maintains ECM stability while improving decellularization efficiency

Inventive Principle:
Principle #35Parameter changes

2Reliability

If prolonged exposure to decellularization reagents is used, then complete decellularization is achieved, but processing time is extended

Engineering Contradiction:
Improvedecellularization completenessVSAvoidprocessing time
Core Design Contradiction:
ReliabilityVSLoss of time

Solution Approach 1:

High-frequency oscillation (3-100 Hz) is applied during treatment to accelerate reagent penetration and cell lysis kinetics. This mechanical energy input speeds up the decellularization reaction, reducing processing time from weeks to hours while maintaining complete decellularization effectiveness

Inventive Principle:
Principle #18Mechanical vibration

Solution Approach 2:

The patent employs rapid oscillatory treatment that rushes through the decellularization process by enhancing mass transfer and reaction kinetics. The high-frequency mechanical action allows the process to complete decellularization much faster than conventional static methods, skipping the prolonged exposure period

Inventive Principle:
Principle #21Skipping (Rushing through)

3Ease of manufacture

If conventional decellularization methods are used, then treatment is simplified, but reagent distribution within tissue is poor

Engineering Contradiction:
Improveprocess simplicityVSAvoidreagent distribution
Core Design Contradiction:
Ease of manufactureVSManufacturing precision

Solution Approach 1:

The oscillation mechanism physically agitates the tissue sample, creating enhanced convection currents and preventing reagent pooling or stagnation. This mechanical action ensures uniform reagent distribution throughout the tissue matrix, addressing the poor penetration issue while adding only a single oscillation parameter to the otherwise simple treatment protocol

Inventive Principle:
Principle #18Mechanical vibration

4Ease of manufacture

If conventional decellularization methods are used, then treatment is simplified, but cell lysis efficiency is reduced

Engineering Contradiction:
Improveprocess simplicityVSAvoidcell lysis efficiency
Core Design Contradiction:
Ease of manufactureVSProductivity

Solution Approach 1:

The high-frequency oscillation mechanically disrupts cell membranes and enhances detergent penetration into cellular structures, significantly accelerating cell lysis. This mechanical assistance works synergistically with chemical reagents to achieve rapid and complete cell removal while keeping the overall process relatively simple

Inventive Principle:
Principle #18Mechanical vibration

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 enables the production of decellularized tissue scaffolds that retain the native ECM composition and bioactivity, reducing processing time to less than 6 hours and ensuring efficient removal of cellular components without damaging the ECM, thus maintaining the tissue's structural and functional properties.

Implementation Method 1

the tissue sample is subjected to oscillation with a displacement of 1 mm or more and a frequency of 3 to 100 Hz during steps (i) and (ii)

Methodology Applied
Scientific EffectOscillation: Vibration

Implementation Method 2

treating a sample of tissue with an osmotic reagent

Methodology Applied
Scientific EffectOsmotic pressure: Osmotic Pressure

Implementation Method 3

treating the sample with a detergent

Methodology Applied
Scientific EffectDetergent action: Surfactant

Data Source

PatentEP3328992B1Methods for the production of decellularised tissue scaffolds
Publication Date: 2020.11.04 UCL BUSINESS LTD
  • EP3328992B1 patent drawingFigure 1
  • EP3328992B1 patent drawingFigure 2
  • EP3328992B1 patent drawingFigure 3

AI summary

This invention relates to a method of producing a decellularised tissue scaffold which comprising treating a sample of tissue with an osmotic reagent and a detergent whilst subjecting the tissue sample to oscillation with a displacement of 1 mm or more and a frequency of 3 Hz or more during these treatment steps. This method may be useful in producing acellular scaffolds that maintain the 3-D architecture and extracellular matrix composition and morphology of the native tissue.