Flow-Oriented Collagen Gel via Hydrodynamic Shear

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Solution Overview

Problem

Existing collagen gels for drug delivery and tissue engineering face challenges due to high pore size, which complicates controlled release and mechanical strength, and current methods for creating oriented gels are impractical for commercial production, such as requiring strong magnetic fields or leading to adverse cytotoxicity.

Innovation Solution

The production of flow-oriented collagen gels using hydrodynamics to influence collagen fiber assembly by subjecting highly concentrated monomeric collagen solutions to shear and extensional flow during deposition under a high pH buffer, eliminating the need for magnetic fields and enhancing the mechanical properties of the gels.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Strength

If collagen gels are used for drug delivery and tissue engineering, then they provide visco-elastic properties and flow capability under stress, but they exhibit high pore size which makes controlled release difficult

Engineering Contradiction:
Improvemechanical strengthVSAvoidhigh pore size
Core Design Contradiction:
StrengthVSObject-generated harmful factors

Solution Approach 1:

The patent changes the physical-chemical parameters of collagen by subjecting it to high shear rates (100-1000 s^-1) and extensional flow during deposition. This parameter change induces fiber alignment and reduces pore size while maintaining the gel's visco-elastic properties, thereby improving mechanical strength and enabling controlled release without adverse effects on drug delivery functionality.

Inventive Principle:
Principle #35Parameter changes

2Ease of manufacture

If unoriented collagen gels are produced by warming neutralized solution, then they can be produced simply, but they are too weak to bear tensile loads or for surgical manipulation

Engineering Contradiction:
Improveproduction simplicityVSAvoidtensile strength
Core Design Contradiction:
Ease of manufactureVSStrength

Solution Approach 1:

The patent applies preliminary action by inducing fiber orientation during the deposition process itself through high shear rates and extensional flow. This preliminary orientation of collagen fibers before gelation occurs allows the gel to develop enhanced tensile strength while maintaining production simplicity, as the orientation is achieved during manufacturing rather than requiring post-processing.

Inventive Principle:
Principle #10Preliminary action

3Shape

If magnetic field is used to induce collagen fiber orientation, then oriented collagen gels can be produced, but it requires strong magnetic field (0.5-5 Tesla) making it impractical for commercial production

Engineering Contradiction:
Improvefiber orientationVSAvoidmagnetic field requirement
Core Design Contradiction:
ShapeVSDevice complexity

Solution Approach 1:

The patent replaces the magnetic field system with a hydrodynamic system. Instead of using strong magnetic fields (0.5-5 Tesla) to induce orientation, the invention uses high shear rates (100-1000 s^-1) and extensional flow during deposition to achieve fiber alignment. This mechanical substitution eliminates the need for complex magnetic field generation equipment while achieving the same orientation effect, making the process practical for commercial production.

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

4Strength

If collagen gels are cross-linked or combined with composites to increase strength, then mechanical properties can be altered, but some methods lead to degradation of collagen or adverse cytotoxicity on cell growth

Engineering Contradiction:
Improvemechanical strengthVSAvoidcytotoxicity
Core Design Contradiction:
StrengthVSObject-affected harmful factors

Solution Approach 1:

The patent applies preliminary action by achieving fiber orientation during deposition through high shear rates and extensional flow, before any cross-linking or composite formation occurs. This preliminary structural organization provides enhanced mechanical strength through alignment alone, avoiding or reducing the need for aggressive cross-linking methods that cause collagen degradation or cytotoxicity. The orientation itself contributes to strength, allowing milder subsequent processing.

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

This method produces highly oriented 3D scaffolds that induce contact guidance for mammalian cell growth, mimicking in vivo collagen fibers and improving the industrial applications of collagen gels in drug delivery and tissue engineering without adverse cytotoxicity.

Implementation Method 1

Highly concentrated monomeric solutions of collagen are subjected to shear and extensional flow as they are drawn onto a substrate to induce fibrillogenesis

Methodology Applied
Scientific EffectShear flow: Shear Stress

Implementation Method 2

Highly concentrated monomeric solutions of collagen are subjected to shear and extensional flow as they are drawn onto a substrate

Methodology Applied
Scientific EffectExtensional flow: Deformation

Implementation Method 3

The present invention provides techniques for the production of flow-oriented collagen gels using hydrodynamics to influence the assembly of collagen fibers

Methodology Applied
Scientific EffectHydrodynamics:

Data Source

PatentUS8329246B2Oriented collagen gel
Publication Date: 2012.12.11 THE BOARD OF TRUSTEES OF THE LELAND STANFORD JUNIOR UNIV
  • US8329246B2 patent drawing
  • US8329246B2 patent drawing
  • US8329246B2 patent drawing

AI summary

Techniques for the production of flow-oriented collagen gels using hydrodynamics to influence the assembly of collagen fibers. Highly concentrated monomeric solutions of collagen are subjected to shear and extensional flow as they are drawn onto a substrate to induce fibrillogenesis under a high Ph buffer. The produced gel captures the flow induced ordering of molecular collagen upon fibril formation. The depositing or the induction of fibrillogenosis occurs without the application of a magnetic field to the concentration of collagen. These highly oriented 3D scaffolds are capable inducing contact guidance and guiding mammalian cell growth. The collagen fibers mimic the construction of in vivo fibers with the characteristic D-periodicity and the integrin receptors on the fibroblasts respond to this organization. The industrial applications of three-dimensional collagen gels as a biomaterial are widespread from drug delivery to burn repair or tissue engineering system.