Stiff Collagen Hydrogels via Blocking Polymers

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Solution Overview

Problem

Collagen hydrogels used in tissue engineering are weak and poorly organized due to their high water content, which limits their mechanical properties and affects cell behavior, and artificial cross-linking to improve stiffness is cytotoxic, preventing cell seeding and requiring a lengthy and variable process.

Innovation Solution

Blending polymeric and monomeric collagen with non-collagenous blocking polymers to create stiff collagen hydrogels that reduce liquid flow and damage to cells during compression, while increasing cargo particle entrapment and retention, using a method that involves mixing collagen solutions with cargo particles and non-collagen blocking polymers and allowing the mixture to solidify before compressing to reduce liquid content.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Strength

If artificial cross-linking is used to improve collagen matrix stiffness, then mechanical strength is improved, but cell viability deteriorates due to cytotoxicity

Engineering Contradiction:

Improvecollagen matrix stiffnessVSAvoidcell cytotoxicity

Core Design Contradiction:

StrengthVSObject-affected harmful factors

Solution Approach 1:

The patent introduces a non-collagenous blocking polymer as an intermediary substance that mediates between the collagen fibrils and cells. This polymer blocks the interface between collagen fibrils and cell membranes, preventing direct contact and cytotoxic effects while still allowing the collagen matrix to achieve enhanced stiffness through fibrillogenesis. The blocking polymer acts as a protective barrier that enables mechanical reinforcement without compromising cell viability.

Inventive Principle:

Principle #24Intermediary (Mediator)

2Strength

If collagen hydrogel is compressed to improve mechanical properties, then matrix stiffness is improved, but cell damage increases due to compression stress

Engineering Contradiction:

Improvematrix stiffnessVSAvoidcell damage

Core Design Contradiction:

StrengthVSObject-affected harmful factors

Solution Approach 1:

The non-collagenous blocking polymer is incorporated into the collagen hydrogel beforehand to provide cushioning protection. This polymer creates a protective microenvironment that cushions cells against compression stresses during the mechanical processing and implantation phases. By pre-establishing this protective barrier, the cells are shielded from the harmful effects of compression while the matrix itself can be strengthened through fibrillogenesis.

Inventive Principle:

Principle #11Beforehand cushioning (Prior cushioning)

3Ease of operation

If monomeric collagen is used to form hydrogel, then cell seeding is facilitated, but matrix organization deteriorates resulting in weak gels

Engineering Contradiction:

Improvecell seeding capabilityVSAvoidmatrix organization

Core Design Contradiction:

Ease of operationVSStability of the object's composition

Solution Approach 1:

The patent creates a composite collagen system combining monomeric collagen (for cell compatibility) with non-collagenous blocking polymers (for structural reinforcement). This composite approach allows the monomeric collagen to maintain its cell-seeding advantages while the blocking polymer contributes to improved matrix organization and strength. The combination results in a hybrid material that integrates the beneficial properties of both components.

Inventive Principle:

Principle #40Composite materials

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 produces stiffer collagen biomaterials with improved entrapment and retention of cargo particles and reduced cell damage, allowing for the production of cellular constructs with enhanced mechanical properties and viability of mammalian cells.

Implementation Method 1

the incorporation of non-collagenous blocking polymers into these stiff collagen hydrogel constructs can increase the entrapment and retention of cargo particles during compression

Methodology Applied

Scientific EffectPhysical containment: Physical Containment

Implementation Method 2

the gels rely on the fibrillogenesis (gelling) of collagen monomer around the cells

Methodology Applied

Scientific EffectFibrillogenesis:

Implementation Method 3

reducing the amount of liquid in the collagen hydrogel to produce a compressed collagen biomaterial

Methodology Applied

Scientific EffectCompression: Compression

Data Source

PatentUS10525163B2Collagen biomaterials

Publication Date: 2020.01.07 WONG JOSEPHINE

AI summary

This invention relates to methods of producing collagen biomaterials by admixing (i) a solution of monomeric collagen, (ii) a solution of polymeric collagen, (ii) cargo particles, and (iv) a non-collagen blocking polymer, to produce a collagen solution. The collagen solution is then allowed to solidify to produce a collagen hydrogel. This may be useful in improving the stiffness of collagen hydrogel constructs and increasing the entrapment and retention of cargo particles.