Salt-Induced Fibrinogen Self-Assembly for Scaffold Production

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Solution Overview

Problem

Current methods for producing fibrous fibrinogen scaffolds face challenges such as low yield, low surface coverage, and the need for expensive and complex equipment, with previous approaches requiring high concentrations of fibrinogen, enzyme use, and non-physiological conditions, which hinder the development of effective three-dimensional scaffolds for tissue engineering and wound healing.

Innovation Solution

A method involving salt-induced self-assembly of fibrinogen fibers in a physiological buffer system at neutral pH, allowing for controlled detachment or immobilization of fibrous fibrinogen biomaterials, using low fibrinogen concentrations and standard lab equipment, to create nano- and microfibrous scaffolds that mimic in vivo fibrinogen fibers.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Ease of manufacture

If electrospinning is used to produce fibrinogen fibers, then fiber formation is achieved, but high concentrations of fibrinogen, high electric fields, and organic solvents are required

Engineering Contradiction:
Improveease of manufactureVSAvoidconcentration of fibrinogen
Core Design Contradiction:
Ease of manufactureVSQuantity of substance

Solution Approach 1:

The invention changes the physical-chemical parameters of the system by using salt-induced self-assembly instead of electrospinning. This allows fiber formation at physiological salt concentrations (150-500 mM NaCl) and neutral pH, replacing the need for high electric fields (20 kV) and organic solvents like 1,1,1,3,3,3-hexafluoro-2-propanol. The salt concentration parameter is optimized to induce controlled fibrillogenesis without requiring extreme conditions.

Inventive Principle:
Principle #35Parameter changes

Solution Approach 2:

The invention replaces the mechanical-electrical system of electrospinning with a chemical-self-assembly system. Instead of using high voltage electric fields to force fiber formation, the patent employs salt-induced conformational changes in fibrinogen molecules that spontaneously self-assemble into fibers. This substitution eliminates the need for complex electrospinning equipment and reduces fibrinogen concentration requirements.

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

2Productivity

If thrombin is used to convert fibrinogen to fibrin, then clot formation is achieved, but enzyme use and non-physiological conditions are required

Engineering Contradiction:
Improvefiber formation efficiencyVSAvoidcomplexity of equipment and reagents
Core Design Contradiction:
ProductivityVSDevice complexity

Solution Approach 1:

The invention enables fibrinogen to self-assemble into fibers through salt-induced conformational changes without requiring external enzymatic catalysis. The fibrinogen molecules themselves undergo structural transitions and self-organize into fibrous networks when exposed to physiological salt concentrations, eliminating the need for thrombin enzyme and associated activation protocols.

Inventive Principle:
Principle #25Self-service

Solution Approach 2:

The invention changes the environmental parameters from enzymatic activation conditions to salt-concentration-driven self-assembly conditions. By optimizing NaCl concentration (150-500 mM) and pH (neutral), the system achieves fiber formation through physical-chemical parameter control rather than biochemical enzymatic conversion, simplifying the overall process.

Inventive Principle:
Principle #35Parameter changes

3Shape

If high electric fields are applied for electrospinning, then fiber formation is achieved, but expensive and complex equipment is required

Engineering Contradiction:
Improvefiber structureVSAvoidcomplexity of equipment
Core Design Contradiction:
ShapeVSDevice complexity

Solution Approach 1:

The invention replaces the complex electrospinning apparatus (high voltage power supply, needle assembly, collector system) with simple salt solution addition and incubation equipment. The fiber formation occurs through spontaneous self-assembly in solution, requiring only standard laboratory glassware and salt buffers, thereby dramatically reducing equipment complexity and cost.

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

4Ease of manufacture

If organic solvents are used for electrospinning, then fiber formation is achieved, but non-physiological conditions are created

Engineering Contradiction:
Improveease of manufactureVSAvoidbiological functionality of fibrinogen
Core Design Contradiction:
Ease of manufactureVSObject-affected harmful factors

Solution Approach 1:

The invention changes the solvent system from organic solvents (1,1,1,3,3,3-hexafluoro-2-propanol) to aqueous physiological buffers containing salt (150-500 mM NaCl). This parameter change maintains fibrinogen's native conformation and biological functionality while enabling fiber formation through salt-induced self-assembly, eliminating the harmful effects of organic solvents on protein structure and activity.

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 method enables the production of dense, high-yield fibrous fibrinogen scaffolds with controlled dimensions and morphology, suitable for various biomedical applications, including tissue engineering and wound healing, without the need for expensive equipment or enzymes, and maintains the biological functionality of fibrinogen.

Implementation Method 1

A method involving salt-induced self-assembly of fibrinogen fibers in a physiological buffer system at neutral pH

Methodology Applied
Scientific EffectSelf-assembly: Self-Assembly

Implementation Method 2

The methods of this invention enable the controlled detachment of fibrous fibrinogen scaffolds in vitro. The fibrous fibrinogen biomaterials generated by the methods of this invention can be detached in a solution.

Methodology Applied
Scientific EffectDetachment:

Data Source

PatentEP3801657B1Methods of production of fibrous fibrinogen scaffolds and products thereof
Publication Date: 2024.09.04 UNIV OF BREMEN
  • EP3801657B1 patent drawingFigure 1
  • EP3801657B1 patent drawingFigure 2~2a
  • EP3801657B1 patent drawingFigure 2b

AI summary

The present invention relates to methods for producing fibrous fibrinogen biomaterials that can be used as three-dimensional scaffolds. The methods of this invention enable the controlled detachment of fibrous fibrinogen scaffolds in vitro. The fibrous fibrinogen biomaterials generated by the methods of this invention can be detached in a solution. Alternatively, the fibrous fibrinogen scaffolds of this invention can be immobilized on a surface. The fibrous fibrinogen biomaterial can be used in medicine, such as in wound healing, regenerative medicine, dermal reconstruction, skin repair, bone vessel repair, blood vessel regeneration, tissue engineering, and implant coatings. The biomaterials can be generated "on-demand" and can be transferred to a site of injury, such as to a wound.