Micro-organ composite for in vitro skin model

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Solution Overview

Problem

Current methods for creating skin equivalents for wound healing and pharmaceutical research are costly, labor-intensive, and require complex techniques, with existing skin substitutes often relying on animal-derived scaffolds and having limited applicability for deep skin damage and widespread epidermal damage.

Innovation Solution

A micro-organ composite comprising a core group of mesenchymal cells fully encapsulated by an outer layer of epithelial cells, formed through a hanging drop culture method, which interacts to form a basement membrane without added biomaterials, allowing for the creation of a versatile in vitro skin model for wound healing and disease studies.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If commercial skin equivalents are used, then skin substitutes are available for wound healing, but they are expensive and require complicated techniques with considerable manpower and long periods of time

Engineering Contradiction:
Improveavailability of skin substitutesVSAvoidcomplexity of culturing techniques
Core Design Contradiction:
ReliabilityVSDevice complexity

Solution Approach 1:

The patent uses a disposable gelatin microsphere scaffold that can be easily fabricated and discarded after use, eliminating the need for complex reusable equipment and extensive cleaning protocols. The microspheres are prepared once and used immediately for cell seeding, then discarded after the skin equivalent is harvested.

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

Solution Approach 2:

The patent changes the physical state of gelatin from solid to gel by controlling temperature (melting at 37°C, setting at lower temperatures), allowing the scaffold to be easily handled in different states during preparation and then provide structural support when needed for cell culture.

Inventive Principle:
Principle #35Parameter changes

2Ease of manufacture

If animal-derived scaffolds are used, then skin equivalents can be constructed, but the scaffolds require optimization for implantation and may have limited applicability

Engineering Contradiction:
Improveease of constructing skin equivalentsVSAvoidapplicability for deep skin damage
Core Design Contradiction:
Ease of manufactureVSAdaptability or versatility

Solution Approach 1:

The patent extracts only the essential functional properties needed for skin equivalent formation (porosity, degradation, cell support) and implements them through a simplified gelatin microsphere system, removing the complexity of animal-derived scaffold preparation and optimization requirements.

Inventive Principle:
Principle #2Taking out (Extraction)

Solution Approach 2:

The gelatin microsphere scaffold serves multiple functions: providing structural support during cell culture, degrading to release space for tissue formation, and being easily fabricated without specialized equipment. The same basic scaffold design can be used for various skin damage types by adjusting cell seeding density and culture conditions.

Inventive Principle:
Principle #6Universality (Multi-functionality)

3Productivity

If cultured epidermis is used, then grafting can be performed, but the thin and fragile nature limits usage when deep skin damage is involved

Engineering Contradiction:
Improvegrafting capabilityVSAvoidstrength of cultured epidermis
Core Design Contradiction:
ProductivityVSStrength

Solution Approach 1:

The patent creates a nested structure where epidermal cells are seeded on the outer surface of gelatin microspheres that contain dermal cells within. This forms a multi-layered construct with dermal cells nested inside and epidermal cells on the outside, creating a stronger, more complete skin equivalent that can handle deep skin damage.

Inventive Principle:
Principle #7Nested doll (Nesting)

Solution Approach 2:

The patent combines gelatin (biodegradable polymer), dermal cells (fibroblasts), and epidermal cells (keratinocytes) to create a composite tissue construct that mimics the structure and function of native skin, providing both strength and grafting capability.

Inventive Principle:
Principle #40Composite materials

Data Source

PatentEP2737055B1Micro organ comprising mesenchymal and epithelial cells
Publication Date: 2020.11.11 UNIVERSITY OF DURHAM
  • EP2737055B1 patent drawingFigure 1
  • EP2737055B1 patent drawingFigure 2~3
  • EP2737055B1 patent drawingFigure 4~5

AI summary

The invention provides a micro-organ composite which comprises a core group of cells and an outer layer of cells, wherein the cells of the core group are mesenchymal cells and the cells of the outer layer are epithelial cells or wherein the cells of the core group are epithelial cells and the cells of the outer layer are mesenchymal cells, and wherein the core group of cells is at least partially encapsulated by the outer layer of cells.