Cartilage ECM Stromal Material for 3D Cell Encapsulation

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Solution Overview

Problem

Existing cell culture methods, such as 2D and 3D culture, face inefficiencies and challenges in maintaining cell phenotype and providing an optimal microenvironment for cell growth and expansion, particularly in the context of cell therapy applications.

Innovation Solution

A preparation method for a stromal material using mammalian cartilage extracellular matrix to create microparticles with specific size and composition, involving decellularization and enzymatic treatments to produce a material rich in type II collagen and glycosaminoglycans, which can encapsulate and protect cells during culture, preservation, and transportation, and facilitate cluster formation.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Ease of operation

If 2D culture in vitro is used for cell expansion, then cell culture is simple to operate, but cell expansion efficiency is low and cell phenotype maintenance is poor

Engineering Contradiction:
Improveease of cell culture operationVSAvoidcell expansion efficiency
Core Design Contradiction:
Ease of operationVSProductivity

Solution Approach 1:

The patent transitions from 2D cell culture to 3D cell culture by using porous microcarrier beads as a three-dimensional scaffold. Cells are cultured on the surface and within the pores of the spherical beads, creating a three-dimensional microenvironment that better mimics in vivo conditions and significantly improves cell expansion efficiency while maintaining phenotype.

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

Solution Approach 2:

The patent introduces porous microcarrier beads as an intermediary carrier between the culture medium and cells. These beads provide a large surface area and porous structure that serve as a scaffold for cell attachment, proliferation, and differentiation, thereby enhancing cell expansion efficiency while maintaining operational simplicity.

Inventive Principle:
Principle #24Intermediary (Mediator)

2Reliability

If synthetic polymer materials are used for porous microcarriers, then biocompatibility is good and structure is stable, but immunogenicity and cytotoxicity may occur

Engineering Contradiction:
Improvebiocompatibility and structural stabilityVSAvoidimmunogenicity and cytotoxicity
Core Design Contradiction:
ReliabilityVSObject-affected harmful factors

Solution Approach 1:

The patent changes the material composition parameter of microcarriers from synthetic polymers to natural extracellular matrix components (collagen, gelatin, chitosan, alginate). This parameter change maintains structural stability and biocompatibility while significantly reducing immunogenicity and cytotoxicity, as these natural materials are biologically compatible and closely resemble the native cell environment.

Inventive Principle:
Principle #35Parameter changes

Solution Approach 2:

The patent uses composite natural materials for microcarrier preparation, combining multiple biocompatible components such as collagen, gelatin, chitosan, and alginate. These composite natural materials provide both structural stability and excellent biocompatibility while minimizing immunogenic responses.

Inventive Principle:
Principle #40Composite materials

3Object-affected harmful factors

If natural materials are used for porous microcarriers, then immunogenicity is reduced, but manufacturing complexity increases due to purification requirements

Engineering Contradiction:
ImproveimmunogenicityVSAvoidmanufacturing process complexity
Core Design Contradiction:
Object-affected harmful factorsVSDevice complexity

Solution Approach 1:

The patent extracts and purifies specific extracellular matrix components (collagen, gelatin, chitosan, alginate) from natural sources to create microcarriers. This extraction process removes immunogenic and cytotoxic components while retaining the beneficial biocompatible and structurally supportive properties of natural materials.

Inventive Principle:
Principle #2Taking out (Extraction)

Solution Approach 2:

The patent performs preliminary purification and preparation of natural materials before microcarrier fabrication. This includes pre-extraction of extracellular matrix components, pre-purification to remove contaminants, and pre-characterization of material properties, which simplifies the overall manufacturing process by addressing complexity issues before the actual microcarrier formation.

Inventive Principle:
Principle #10Preliminary action

4Stability of the object's composition

If cell clusters are formed during culture, then cell phenotype is better maintained, but cell deaggregation and uniform distribution are difficult to control

Engineering Contradiction:
Improvecell phenotype maintenanceVSAvoidcell deaggregation control
Core Design Contradiction:
Stability of the object's compositionVSEase of operation

Solution Approach 1:

The patent creates local quality variations in the microcarrier system by providing different microenvironments within the porous structure. The porous architecture allows cells to form clusters in specific regions while maintaining access to nutrients and oxygen through the pore network, enabling phenotype maintenance without requiring uniform deaggregation throughout the entire culture.

Inventive Principle:
Principle #3Local quality

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 stromal material provides a natural, biocompatible microenvironment for cell culture, promoting cluster formation and protecting cells from adverse conditions, while maintaining high viability and reducing immunogenicity and cytotoxicity.

Implementation Method 1

Extracellular matrix has a complex spatial network structure, provides a microenvironment for cell growth and activity. The interaction between cells and extracellular matrix has a regulatory effect on cell functions and behaviors

Methodology Applied
Scientific EffectExtracellular matrix interaction:

Implementation Method 2

can be used as cell encapsulation stroma (CES) for encapsulation and protection of cells during cell preservation and transportation process

Methodology Applied
Scientific EffectEncapsulation:

Data Source

PatentEP4435092B1Stromal material for encapsulating cells, preparation method therefor, and application thereof
Publication Date: 2026.02.25 BEIJING RUIJIAN GAOKE BIOTECH
  • EP4435092B1 patent drawingFigure 1~2
  • EP4435092B1 patent drawingFigure 3~4
  • EP4435092B1 patent drawingFigure 5~6

AI summary

A stromal material for encapsulating cells, a preparation method therefor, and an application thereof. The material is prepared from the cartilage of mammals such as pigs, cows, sheep, horses, and deer by means of cutting, low-temperature micronization grinding, enzymolysis treatment, cell component removal, virus inactivation, freeze-drying, and irradiation sterilization treatment. The method is used for a non-diagnostic purpose; the stromal material can be used for 3D biological printing independently or together with encapsulated cells; the main components of the material are type II collagen, chondroitin sulfate, and hyaluronic acid; the material is free of cross-linking agent toxicity, has the advantages of being low in immunogenicity, good in biocompatibility, and capable of being implanted into a human body, has a good surface topological structure in structure, provides an in vivo-like tissue microenvironment for in-vitro cell culture, and not only can be used as a microcarrier for cell culture, but also can promote the formation of cell clusters; and in the cell preservation and transportation process, the cells are encapsulated in a gel-state stroma, such that the cells can be protected from the influence of a bad environment, improving the cell viability.