Highly Oriented Collagen Fibril Bundle Production

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Solution Overview

Problem

Existing methods fail to produce highly oriented collagen fibrils of significant length and controlled diameter, limiting their application in medical scaffolding and tissue engineering, particularly for artificial tendons and joint surgery materials.

Innovation Solution

A method involving continuous introduction of a collagen sol into a temperature-controlled flow path with controlled shear stress and shear rate to orient collagen fibrils, resulting in a uniaxially oriented collagen fibril bundle with a length of 1 m or more and a refractive index difference of 3×10−4 or more, allowing for the production of a collagen gel with enhanced mechanical properties.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Length of moving object

If collagen fibrils are oriented using conventional shear stress methods (spin coater, microflow path), then some orientation is achieved, but the total length of collagen fibrils is limited to less than 1 meter

Engineering Contradiction:
Improvelength of collagen fibrilsVSAvoidorientation uniformity
Core Design Contradiction:
Length of moving objectVSManufacturing precision

Solution Approach 1:

The continuous collagen fibril production is achieved by segmenting the process into controlled stages: collagen solution preparation, controlled shear application in a flow path, and continuous extraction. This allows the fibrils to be progressively oriented over an extended period and length without losing orientation uniformity.

Inventive Principle:
Principle #1Segmentation

Solution Approach 2:

The collagen solution is pre-prepared with specific viscosity and concentration parameters before entering the shear stress application zone. This preliminary preparation ensures that when the shear stress is applied, the fibrils orient uniformly from the beginning of the flow path, enabling continuous production of fibrils longer than 1 meter while maintaining orientation precision.

Inventive Principle:
Principle #10Preliminary action

2Volume of moving object

If the diameter of string-like collagen gel is increased to 1-10 mm for medical applications, then the molded component becomes thicker and more useful, but continuous spinning with controlled orientation becomes difficult

Engineering Contradiction:
Improvediameter of collagen gelVSAvoidcontinuous spinning capability
Core Design Contradiction:
Volume of moving objectVSEase of manufacture

Solution Approach 1:

The invention transitions from two-dimensional disk orientation (spin coater) or short path orientation (microflow) to a three-dimensional continuous flow path system. This allows the collagen gel to be extruded as a string-like structure with controlled diameter (1-10 mm) while maintaining orientation along the entire length, enabling both large volume and continuous manufacturing.

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

Solution Approach 2:

The flow path system serves multiple functions simultaneously: it provides the shear stress for orientation, defines the diameter of the extruded gel (1-10 mm), and enables continuous spinning operation. This multi-functionality resolves the contradiction between producing thick gel structures and maintaining continuous manufacturing capability.

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

3Manufacturing precision

If collagen fibrils are oriented in a batch type molding technique, then some orientation is achieved, but productivity is low and cannot satisfy industrialization requirements

Engineering Contradiction:
Improvefibril orientationVSAvoidcontinuous production capability
Core Design Contradiction:
Manufacturing precisionVSProductivity

Solution Approach 1:

The invention implements continuous spinning by maintaining a steady flow of collagen solution through the shear stress application zone. The orientation process is not interrupted or batched but continues uninterrupted, producing collagen fibrils at a rate that satisfies industrialization requirements while maintaining high orientation precision throughout the entire production run.

Inventive Principle:
Principle #20Continuity of useful action

4Length of moving object

If the flow path length is increased to produce longer collagen fibrils, then the total length increases, but uniform laminar flow can only be maintained up to several cm from inlet

Engineering Contradiction:
Improvelength of collagen fibrilsVSAvoidlaminar flow uniformity
Core Design Contradiction:
Length of moving objectVSStability of the object's composition

Solution Approach 1:

The collagen solution is pre-conditioned with specific viscosity and flow characteristics before entering the main flow path. This preliminary preparation ensures that laminar flow is established from the very beginning of the flow path, allowing the uniform flow condition to be maintained over the entire extended length required to produce fibrils longer than 1 meter.

Inventive Principle:
Principle #10Preliminary action

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 method enables the production of highly oriented collagen fibril bundles and gels with improved mechanical properties, such as increased Young's modulus and breaking stress, suitable for medical applications like artificial tendons and joint surgery materials.

Implementation Method 1

a method involving continuous introduction of a collagen sol into a temperature-controlled flow path with controlled shear stress and shear rate to orient collagen fibrils

Methodology Applied
Scientific EffectShear stress: Shear Stress

Implementation Method 2

collagen fibrillogenesis under a shear force

Methodology Applied
Scientific EffectFibrillogenesis:

Implementation Method 3

collagen fibrils are oriented uniaxially

Methodology Applied
Scientific EffectShear flow orientation: Shear Stress

Implementation Method 4

A molded component of collagen fibrillar gel with crosslinked collagen

Methodology Applied
Scientific EffectCrosslinking:

Data Source

PatentUS11753462B2Highly oriented collagen fibril bundle and method of producing same
Publication Date: 2023.09.12 TOKYO METROPOLITAN IND TECH RES INST
  • US11753462B2 patent drawing
  • US11753462B2 patent drawing
  • US11753462B2 patent drawing

AI summary

The present invention relates to a highly oriented collagen fibril bundle having a length in a major axis direction of 1 m or more.