Fibrillar Collagen Matrix Transparency and Strength Control

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Solution Overview

Problem

Existing methods for preparing collagen matrices face challenges in controlling mechanical and optical properties, particularly in synthesizing transparent matrices with optimal mechanical and optical characteristics, and in shaping collagen matrices to specific forms.

Innovation Solution

A method involving the use of acidic aqueous solutions with a combination of strong and weak acids to control fibrillogenesis, allowing for the modulation of collagen matrix properties, including transparency, by varying collagen concentrations and pH levels, and incorporating a shaping step to create composite matrices with varying optical and mechanical properties.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Strength

If collagen concentration is increased to improve mechanical strength, then the matrix becomes more opaque and loses transparency

Engineering Contradiction:
Improvemechanical strengthVSAvoidtransparency
Core Design Contradiction:
StrengthVSIllumination intensity

Solution Approach 1:

The patent applies parameter changes by systematically varying pH levels (from acidic to basic conditions), ionic strength, and temperature during the fibrillogenesis process. These parameter changes enable control over fibril diameter and spacing, allowing optimization of both mechanical strength and transparency independently of collagen concentration.

Inventive Principle:
Principle #35Parameter changes

Solution Approach 2:

The patent utilizes phase transitions during fibrillogenesis, where collagen molecules transition from soluble monomers to organized fibrillar structures. By controlling the phase transition conditions (pH, ionic strength, temperature), the patent achieves desired fibril morphology that balances mechanical properties and optical transparency.

Inventive Principle:
Principle #36Phase transitions

2Strength

If fibril density is increased to improve mechanical properties, then the matrix becomes less transparent

Engineering Contradiction:
Improvemechanical propertiesVSAvoidtransparency
Core Design Contradiction:
StrengthVSIllumination intensity

Solution Approach 1:

The patent changes physical and chemical parameters during fibrillogenesis, specifically pH and ionic strength, to control fibril packing density and spacing. This enables decoupling of mechanical strength from optical transparency, allowing optimization of both properties independently.

Inventive Principle:
Principle #35Parameter changes

Solution Approach 2:

The patent creates composite-like structures by controlling the hierarchical organization of collagen fibrils within the matrix. Through parameter control, it achieves a composite architecture where fibril distribution and spacing are optimized to provide both mechanical strength and light transmission properties.

Inventive Principle:
Principle #40Composite materials

3Quantity of substance

If collagen solutions are concentrated to form dense matrices, then shaping control becomes more difficult

Engineering Contradiction:
Improvecollagen concentrationVSAvoidshaping control
Core Design Contradiction:
Quantity of substanceVSShape

Solution Approach 1:

The patent applies preliminary action by inducing fibrillogenesis and establishing the desired fibrillar architecture before the final shaping and crosslinking steps. This sequence allows the matrix to be shaped more effectively after the fibrils are already organized, improving formability despite high collagen concentration.

Inventive Principle:
Principle #10Preliminary action

Solution Approach 2:

The patent exploits the dynamic nature of the fibrillogenesis process, where collagen solutions transition from fluid to gel state. By controlling the timing and conditions of this dynamic transition, the patent achieves both high collagen concentration and good shaping control through sequential processing steps.

Inventive Principle:
Principle #15Dynamics

4Ease of manufacture

If traditional single-acid methods are used for fibrillogenesis, then control over fibril architecture is limited

Engineering Contradiction:
Improvefibrillogenesis processVSAvoidfibril architecture control
Core Design Contradiction:
Ease of manufactureVSManufacturing precision

Solution Approach 1:

The patent systematically varies multiple parameters including pH, ionic strength, and temperature during fibrillogenesis to achieve precise control over fibril diameter, length, and spacing. This multi-parameter approach enables fine-tuning of fibril architecture while maintaining process simplicity.

Inventive Principle:
Principle #35Parameter changes

Solution Approach 2:

The patent uses specific acids and salts as intermediaries to control the fibrillogenesis process. These chemical intermediaries mediate the self-assembly of collagen molecules into desired fibrillar structures, providing precise architectural control without complex equipment or procedures.

Inventive Principle:
Principle #24Intermediary (Mediator)

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 transparent and composite fibrillar collagen matrices with controlled mechanical and optical properties, suitable for applications such as corneal substitutes, by modulating fibril growth and spacing, achieving high transparency and tailored mechanical strengths.

Implementation Method 1

The assembly of collagen molecules with one another is conventionally referred to as 'fibrillogenesis'. The interactions between molecules would appear, firstly, to be provided by hydrogen bonds and electrostatic interactions.

Methodology Applied
Scientific EffectFibrillogenesis: Self-Assembly

Implementation Method 2

The interactions between molecules would appear, firstly, to be provided by hydrogen bonds and electrostatic interactions.

Methodology Applied
Scientific EffectHydrogen bonding: Chemical Bonding

Implementation Method 3

The interactions between molecules would appear, firstly, to be provided by hydrogen bonds and electrostatic interactions.

Methodology Applied
Scientific EffectElectrostatic interactions: Electrostatics

Implementation Method 4

The fibrillogenesis of an acid-soluble solution of collagen can therefore be induced by increasing the pH and, in the case of a concentrated solution, a sol-gel transition is then observed.

Methodology Applied
Scientific EffectSol-gel transition: Phase Change

Implementation Method 5

The properties of the resulting collagen matrix can then be improved by means of additional crosslinking or compression steps.

Methodology Applied
Scientific EffectConcentration:

Implementation Method 6

forming the fibrils by treating the collagen solution obtained in step (b) with a basic gas phase or with a neutral or basic liquid phase

Methodology Applied
Scientific EffectpH neutralization: Chemical Bonding

Data Source

PatentUS10596297B2Method for preparing a fibrillar collagen matrix
Publication Date: 2020.03.24 CENT NAT DE LA RECH SCI (C N R S)
  • US10596297B2 patent drawing
  • US10596297B2 patent drawing
  • US10596297B2 patent drawing

AI summary

The present invention relates to a method for preparing a fibrillar collagen matrix, which is advantageously transparent or composite, suitable for being used as a biomaterial, in particular as a corneal substitute.