Hypoxia-Treated Extracellular Matrix for Stem Cell Adhesion

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Solution Overview

Problem

Current methods for tissue repair using stem cells and extracellular matrices face challenges with cell adhesion and survival, leading to inefficient tissue repair, particularly due to the high cost and difficulty of implementing adhesion peptides, and the need for improved proliferation and differentiation of mesenchymal stem cells.

Innovation Solution

A method involving the use of a hypoxia-treated extracellular matrix, derived from biological tissue, combined with stem cells, to enhance adhesion, proliferation, and differentiation, utilizing a hydrophilic and porous biocompatible synthetic matrix, which promotes cell adhesion and tissue repair by regulating HIF-1α and HIF-2α heterodimers and stimulating angiogenic factors.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If adhesion peptides are added to the matrix to improve cell adhesion, then cell adhesion is enhanced, but the cost increases significantly and the implementation becomes difficult

Engineering Contradiction:
Improvecell adhesionVSAvoidimplementation difficulty
Core Design Contradiction:
ReliabilityVSEase of manufacture

Solution Approach 1:

The patent changes the chemical parameters of the matrix by treating it with glutaraldehyde, which introduces aldehyde groups that can form covalent bonds with amino groups on cell surface proteins. This chemical modification enables cell adhesion without requiring expensive adhesion peptides, thus resolving the contradiction between improving cell adhesion and reducing implementation difficulty/cost

Inventive Principle:
Principle #35Parameter changes

Solution Approach 2:

The patent uses a simple, inexpensive chemical treatment (glutaraldehyde) instead of expensive, complex adhesion peptides. The glutaraldehyde treatment creates a durable cell-adhesive surface on the matrix that is both cost-effective and easy to implement, directly addressing the contradiction between effectiveness and ease of manufacture

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

2Reliability

If adhesion peptides are added to the matrix to improve cell adhesion, then cell adhesion is enhanced, but the dosage control becomes difficult and may cause too strong adhesion

Engineering Contradiction:
Improvecell adhesionVSAvoiddosage control
Core Design Contradiction:
ReliabilityVSManufacturing precision

Solution Approach 1:

The patent transforms the adhesion mechanism from peptide-based (requiring precise dosage control) to chemistry-based (glutaraldehyde crosslinking). The glutaraldehyde treatment creates a controlled, uniform adhesive surface through chemical reactions with matrix proteins, eliminating the need for precise peptide dosage control while preventing excessive adhesion through controlled reaction conditions

Inventive Principle:
Principle #35Parameter changes

Solution Approach 2:

The glutaraldehyde treatment enables the matrix to self-adhere to cells through spontaneous chemical reactions between aldehyde groups and amino groups on cell surfaces. This self-adhesive property eliminates the need for external adhesion peptides and their associated dosage control problems, allowing the matrix to regulate its own adhesion properties

Inventive Principle:
Principle #25Self-service

3Ease of operation

If stem cells are injected without proper adhesion support, then the procedure is simple, but cell survival is poor and tissue repair is ineffective

Engineering Contradiction:
Improveinjection simplicityVSAvoidcell survival
Core Design Contradiction:
Ease of operationVSReliability

Solution Approach 1:

The patent applies glutaraldehyde treatment to the matrix in advance before cell injection. This preliminary chemical modification creates a cell-adhesive surface that will support cell survival during and after injection. The adhesion-promoting treatment is performed beforehand, allowing simple injection procedures while ensuring high cell survival rates through the pre-prepared adhesive matrix

Inventive Principle:
Principle #10Preliminary action

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 method effectively promotes the adhesion, proliferation, and differentiation of stem cells at tissue repair sites, enhancing tissue repair efficiency while being simple, rapid, and cost-effective, with improved cell survival and angiogenesis.

Implementation Method 1

said matrix is subjected to a hypoxia treatment before said mixing

Methodology Applied
Scientific EffectHypoxia treatment:

Implementation Method 2

utilizing a hydrophilic and porous biocompatible synthetic matrix, which promotes cell adhesion and tissue repair by regulating HIF-1α and HIF-2α heterodimers

Methodology Applied
Scientific EffectHIF-1α and HIF-2α heterodimers regulation:

Implementation Method 3

stimulating angiogenic factors

Methodology Applied
Scientific EffectAngiogenesis stimulation:

Implementation Method 4

utilizing a hydrophilic and porous biocompatible synthetic matrix

Methodology Applied
Scientific EffectPorosity: Porosity

Implementation Method 5

utilizing a hydrophilic and porous biocompatible synthetic matrix

Methodology Applied
Scientific EffectHydrophilicity: Hydrophile

Data Source

PatentEP3512573B1Method for producing a composition for tissue repair
Publication Date: 2021.06.02 SYMBIOKEN
  • EP3512573B1 patent drawingFigure 1
  • EP3512573B1 patent drawingFigure 2~3
  • EP3512573B1 patent drawingFigure 4~5

AI summary

The invention relates to a method for producing a composition to be injected into a biological tissue for tissue repair, by mixing stem cells and a matrix selected from an extracellular matrix obtained from a portion of isolated biological tissue and a porous, positively charged hydrophilic biocompatible synthetic matrix, in which said matrix is subjected to hypoxic treatment before said mixing.