Oriented Collagen Films via Shear Alignment

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Solution Overview

Problem

Existing methods for forming collagen films and matrices fail to maintain and preserve the native liquid crystal structure of collagen, limiting their ability to mimic the semi-crystalline structures found in living biological systems, and lack robustness and repeatability in producing collagen-based materials with long-range orientation.

Innovation Solution

The development of monolayers or multilayers comprising crimped fibrils with a uniaxial orientation, formed through a process involving shearing of a concentrated collagen solution, which aligns the fibrils in a specific pattern with controlled orientation, and optionally incorporating additives like ATP to promote orientation, and further enhanced with cross-links for stability.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Manufacturing precision

If conventional methods are used to form collagen films and matrices, then the collagen can be deposited, but the native liquid crystal structure and long-range orientation are lost

Engineering Contradiction:
Improvelong-range orientationVSAvoidstructure preservation
Core Design Contradiction:
Manufacturing precisionVSReliability

Solution Approach 1:

The patent applies parameter changes by controlling the concentration of collagen solution (using concentrated solutions above the critical concentration for liquid crystal formation), adjusting pH levels, and controlling temperature to maintain the liquid crystal phase during film formation. These parameter optimizations enable the preservation of long-range molecular orientation that conventional methods fail to achieve.

Inventive Principle:
Principle #35Parameter changes

Solution Approach 2:

The patent employs preliminary action by pre-forming the collagen solution in its liquid crystal state before deposition, and by using substrates with pre-established orientation patterns (such as rubbed polyethylene terephthalate or aligned nanofibers). This preliminary preparation ensures that the collagen molecules maintain their oriented structure during the film formation process, rather than forming random networks after deposition.

Inventive Principle:
Principle #10Preliminary action

2Manufacturing precision

If shear force is applied to align fibrils, then uniaxial orientation is achieved, but the process complexity increases

Engineering Contradiction:
Improveuniaxial orientationVSAvoidshear alignment mechanism
Core Design Contradiction:
Manufacturing precisionVSDevice complexity

Solution Approach 1:

The patent applies self-service by utilizing the intrinsic properties of concentrated collagen solutions that naturally form liquid crystal phases with spontaneous molecular alignment. The shear force application is simplified to basic techniques such as bar coating, doctor blade methods, or simple substrate movement, allowing the collagen system to self-organize into uniaxial orientation without requiring complex alignment devices or multiple processing steps.

Inventive Principle:
Principle #25Self-service

Solution Approach 2:

The patent replaces complex mechanical alignment systems with simpler mechanical approaches. Instead of using sophisticated optical, magnetic, or electric field-based alignment mechanisms, the invention uses straightforward shear forces applied during coating processes, leveraging the rheological properties of concentrated collagen solutions to achieve molecular alignment through simple relative motion between coating tools and substrates.

Inventive Principle:
Principle #28Mechanics substitution (Replace mechanical system)

3Strength

If cross-links are added to enhance stability, then material strength increases, but the manufacturing process becomes more complex

Engineering Contradiction:
Improvematerial stabilityVSAvoidprocess simplicity
Core Design Contradiction:
StrengthVSEase of manufacture

Solution Approach 1:

The patent applies self-service by utilizing natural cross-linking mechanisms that occur spontaneously in collagen systems. Collagen molecules contain natural cross-linking sites that form intermolecular bonds without requiring external agents or complex processing. The oriented structure formed during liquid crystal phase deposition promotes spontaneous cross-linking, achieving material stability through the material's inherent properties rather than added chemicals or complex treatment steps.

Inventive Principle:
Principle #25Self-service

Solution Approach 2:

The patent optimizes cross-linking by controlling parameters such as pH, temperature, and ionic strength to promote natural cross-linking reactions. By adjusting these parameters within specific ranges, the invention enhances the formation of stable cross-linked networks in the oriented collagen structure without requiring additional cross-linking agents or complex multi-step processing, thereby maintaining ease of manufacture while achieving improved material stability.

Inventive Principle:
Principle #35Parameter changes

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 allows for the creation of collagen layers with high uniformity and parallel orientation, maintaining the native liquid crystal structure, enabling the production of collagen-based materials that closely resemble native collagen matrices, thus supporting cell attachment and differentiation.

Implementation Method 1

Collagen matrix in many biological systems has a liquid crystal structure. It is the natural state of the collagen, which provides a long-range orientation.

Methodology Applied
Scientific EffectLiquid crystal: Liquid Crystals

Implementation Method 2

The development of monolayers or multilayers comprising crimped fibrils with a uniaxial orientation, formed through a process involving shearing of a concentrated collagen solution, which aligns the fibrils in a specific pattern with controlled orientation

Methodology Applied
Scientific EffectShear stress: Shear Stress

Implementation Method 3

optionally incorporating additives like ATP to promote orientation

Methodology Applied
Scientific EffectAdenosine triphosphate (ATP):

Implementation Method 4

further enhanced with cross-links for stability

Methodology Applied
Scientific EffectCross-linking: Chemical Bonding

Data Source

PatentEP2148887B1Oriented collagen-based materials, films and methods of making same
Publication Date: 2014.04.30 FIBRALIGN CORP
  • EP2148887B1 patent drawingFigure 1A~3
  • EP2148887B1 patent drawingFigure 4(a)~6
  • EP2148887B1 patent drawingFigure 7A~7B

AI summary

In general, the present invention is related to collagen compositions and thin films, and to methods of making and using the same. In some embodiments, the present invention is directed to "uniaxial pattern" or "linear pattern" collagen materials, compositions and thin films, and methods of making.