GAG Composition for Regenerative Cell Viability and Proliferation

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Solution Overview

Problem

Current methods for preserving, culturing, and administering regenerative stem cells lack optimal compositions of glycosaminoglycans (GAGs) that enhance cell growth, proliferation, and maintain differentiation potential, particularly for treating joint and connective tissue damage.

Innovation Solution

A GAG composition comprising hyaluronic acid in combination with sulfated GAGs, such as chondroitin sulfate and N-acetyl D-glucosamine, is used to create a media supplement for culturing, preserving, and administering regenerative cells, promoting cell proliferation and maintaining differentiation potential, and is administered via various routes including intra-articular, subdermal, and intravenous.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If current preservation methods are used for regenerative stem cells, then cells can be stored, but cell proliferation and differentiation potential are not optimally maintained

Engineering Contradiction:
Improvecell viabilityVSAvoidcell proliferation
Core Design Contradiction:
ReliabilityVSProductivity

Solution Approach 1:

The patent changes the chemical composition parameters of the preservation media by incorporating specific glycosaminoglycans (hyaluronic acid, chondroitin sulfate, keratan sulfate) at optimized concentrations. This parameter modification transforms the media from a simple storage solution into an active cultivation environment that simultaneously maintains cell viability and promotes proliferation, resolving the contradiction between reliable storage and productive growth.

Inventive Principle:
Principle #35Parameter changes

Solution Approach 2:

The patent creates a composite preservation media by combining multiple glycosaminoglycans with specific protein components and growth factors. This composite formulation synergistically maintains cell membrane integrity, supports extracellular matrix interactions, and promotes cell division, thereby achieving both reliable preservation and active proliferation that neither simple media nor single components could achieve alone.

Inventive Principle:
Principle #40Composite materials

2Ease of operation

If simple preservation media is used, then ease of operation is maintained, but differentiation potential is not maintained

Engineering Contradiction:
Improvemedia simplicityVSAvoiddifferentiation potential
Core Design Contradiction:
Ease of operationVSStability of the object's composition

Solution Approach 1:

The patent modifies the biochemical parameters of the media by incorporating specific glycosaminoglycan concentrations and combinations that mimic the natural extracellular matrix environment. This parameter optimization allows the media to maintain complex biological functions (cell differentiation potential) while remaining a defined, reproducible formulation that is easier to operate with than undefined serum-based media.

Inventive Principle:
Principle #35Parameter changes

3Duration of action of stationary object

If conventional cryopreservation methods are used, then cells can be frozen and stored long-term, but cell recovery and viability after thawing are reduced

Engineering Contradiction:
Improvestorage durationVSAvoidcell recovery
Core Design Contradiction:
Duration of action of stationary objectVSReliability

Solution Approach 1:

The patent optimizes the cryopreservation media composition by adjusting glycosaminoglycan concentrations and combinations to protect cells during freezing and thawing cycles. This parameter optimization reduces ice crystal formation and membrane damage, enabling long-term storage with high post-thaw recovery rates that conventional media cannot achieve.

Inventive Principle:
Principle #35Parameter changes

Solution Approach 2:

The patent develops a composite cryopreservation solution combining multiple glycosaminoglycans with cryoprotectants and buffering agents. This composite formulation provides multi-layered protection during cryopreservation, maintaining both long-term storage capability and high cell recovery upon thawing, resolving the contradiction between extended storage duration and reliable cell recovery.

Inventive Principle:
Principle #40Composite materials

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 GAG composition significantly enhances cell proliferation, maintains differentiation potential, and improves regenerative cell viability and proliferation, demonstrating benefits in both in vitro and in vivo applications for treating joint and connective tissue damage.

Implementation Method 1

GAGs form an important component of connective tissues. GAG chains may be covalently linked to a protein to form proteoglycans.

Methodology Applied
Scientific EffectGlycosaminoglycan-protein interaction: Chemical Bonding

Implementation Method 2

Hyaluronic acid is a natural, highly charged, polyanionic molecule composed of alternating units of D-glucuronic and 2-acetamido-2-deoxy-D-glucose. These unbranched, coiled, elongated polysaccharide chains maintain a large negative electrostatic charge that attracts water molecules

Methodology Applied
Scientific EffectElectrostatic attraction: Electrostatics

Implementation Method 3

Hyaluronic acid is a natural, highly charged, polyanionic molecule composed of alternating units of D-glucuronic and 2-acetamido-2-deoxy-D-glucose. These unbranched, coiled, elongated polysaccharide chains maintain a large negative electrostatic charge that attracts water molecules

Methodology Applied
Scientific EffectHydration: Solvation

Implementation Method 4

allow the deformation of the molecular coil as ice crystallization occurs during freezing and thawing

Methodology Applied
Scientific EffectCryoprotection: Freezing

Data Source

PatentEP2917337B1Media for culturing, preserving, and administering regenerative cells
Publication Date: 2020.01.08 INGENERON INC
  • EP2917337B1 patent drawingFigure 1A~1B
  • EP2917337B1 patent drawingFigure 2
  • EP2917337B1 patent drawingFigure 3A

AI summary

A culture media, media supplement, or soluble matrix for cryopreservation or enhanced regenerative cell growth in culture and maintenance of multi-lineage differentiation potentiation. The inventive culture media, media supplement, or soluble matrix comprises a GAG composition comprising a sulfated GAG, such as chondroitin sulfate. A soluble matrix, a cell administration package or kit comprising the soluble matrix and a device for cell administration, and a method of use thereof, for administration of regenerative cells for treating a joint disease or other weakened or damaged tissue comprising the specified GAG compositions are further provided.