Dermal Papilla Cell Aggregation via Hyaluronidase Treatment

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Solution Overview

Problem

Current methods for promoting hair growth and forming hair follicles are limited by the inability to maintain the inductive properties of dermal papilla cells in culture, leading to the loss of their ability to induce hair follicle formation upon re-implantation.

Innovation Solution

A method involving the aggregation of dermal papilla cells in suspension culture, treated with hyaluronidase to degrade hyaluronic acid and maintain CD44-mediated pathways, combined with the use of soluble factors like Wnt10b, periostin, and follistatin, to promote hair follicle formation and growth.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If dermal papilla cells are cultured in suspension culture without specific treatment, then cells can be maintained in culture, but the inductive properties are lost and hair follicle formation ability is reduced

Engineering Contradiction:
Improveinductive propertiesVSAvoidculture maintenance
Core Design Contradiction:
ReliabilityVSDuration of action of stationary object

Solution Approach 1:

The patent applies preliminary action by treating dermal papilla cells with hyaluronidase before implantation to pre-degrade hyaluronic acid, and by pre-culturing cells in suspension with soluble factors like Wnt10b, periostin, and follistatin to pre-establish inductive properties. This preliminary preparation ensures cells maintain their hair follicle induction capability upon implantation, resolving the contradiction between culture maintenance and property retention.

Inventive Principle:
Principle #10Preliminary action

Solution Approach 2:

The patent employs parameter changes by modifying the extracellular matrix composition through hyaluronidase treatment to reduce hyaluronic acid levels, and by adjusting culture conditions to include specific soluble factors (Wnt10b, periostin, follistatin) at controlled concentrations. These parameter modifications enable cells to maintain inductive properties during culture while preserving hair follicle formation ability.

Inventive Principle:
Principle #35Parameter changes

2Reliability

If dermal papilla cells are treated with hyaluronidase to degrade hyaluronic acid, then CD44-mediated pathways are maintained, but the process becomes more complex

Engineering Contradiction:
ImproveCD44-mediated pathwaysVSAvoidtreatment process
Core Design Contradiction:
ReliabilityVSDevice complexity

Solution Approach 1:

The patent applies the extraction principle by using hyaluronidase to specifically remove and degrade hyaluronic acid from the extracellular matrix, isolating and eliminating the problematic component that interferes with CD44-mediated pathways. This targeted extraction simplifies the overall system by removing the inhibitory substance rather than attempting to control its presence, thereby maintaining pathway reliability without excessive complexity.

Inventive Principle:
Principle #2Taking out (Extraction)

Solution Approach 2:

The patent uses hyaluronidase as an intermediary substance that mediates the degradation of hyaluronic acid, enabling the maintenance of CD44-mediated pathways indirectly. The enzyme acts as a tool to remove the interfering hyaluronic acid component, allowing the CD44 pathway to function properly without directly manipulating the pathway itself, thus reducing operational complexity.

Inventive Principle:
Principle #24Intermediary (Mediator)

3Productivity

If soluble factors like Wnt10b, periostin, and follistatin are used to promote hair follicle formation, then hair growth is enhanced, but the method becomes more complex

Engineering Contradiction:
Improvehair follicle formationVSAvoidculture conditions
Core Design Contradiction:
ProductivityVSDevice complexity

Solution Approach 1:

The patent applies the merging principle by combining multiple soluble factors (Wnt10b, periostin, and follistatin) into a single suspension culture system, allowing them to work synergistically to promote hair follicle formation. Rather than applying each factor separately through complex procedures, the patent merges them into one integrated culture condition, simplifying the overall method while enhancing productivity.

Inventive Principle:
Principle #5Merging (Combining)

Solution Approach 2:

The patent employs universality by using a suspension culture system that can simultaneously support multiple functions: cell proliferation, maintenance of inductive properties, and promotion of hair follicle formation through the combined action of soluble factors. This multi-functional culture approach eliminates the need for separate treatment protocols, reducing complexity while enhancing overall effectiveness.

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

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 approach effectively maintains the inductive properties of dermal papilla cells, allowing for the successful formation and growth of hair follicles by recreating the natural developmental process, enhancing the ability to induce hair follicles and promote hair growth.

Implementation Method 1

treated with hyaluronidase to degrade hyaluronic acid

Methodology Applied
Scientific EffectEnzyme: Enzyme

Data Source

PatentUS9109204B2Methods for compact aggregation of dermal cells
Publication Date: 2015.08.18 UNIVERSITY OF DURHAM
  • US9109204B2 patent drawing
  • US9109204B2 patent drawing
  • US9109204B2 patent drawing

AI summary

The invention provides for a method for aggregating dermal papilla cells or dermal sheath cells or a combination thereof, the method comprising: growing dermal papilla cells or dermal sheath cells or a combination thereof in suspension culture; and contacting the culture with an effective amount of an enzyme, wherein a substrate of the enzyme is an extracellular matrix molecule in the suspension culture, so as to aggregate dermal papilla cells or dermal sheath cells. The culture may be a hanging drop culture and the enzyme may be a hyaluronidase.