Fast-Relaxing Hydrogels via Ionic Crosslinking for Bone Regeneration

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Solution Overview

Problem

Current hydrogels used in tissue engineering are typically elastic and fail to mimic the viscoelastic properties of natural extracellular matrices, which are essential for regulating cell behavior and tissue regeneration, particularly in bone regeneration where stress relaxation is crucial.

Innovation Solution

Development of fast-relaxing hydrogels composed of alginate polymer chains ionically cross-linked with spacer molecules, such as polyethylene glycol (PEG), that exhibit a stress relaxation rate of 1000 seconds or less, allowing for independent tuning of mechanical properties like initial elastic modulus and cell adhesion ligand density.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Strength

If hydrogels are made elastic to maintain structural stability, then mechanical strength is improved, but stress relaxation capability deteriorates

Engineering Contradiction:

Improvemechanical strengthVSAvoidstress relaxation capability

Core Design Contradiction:

StrengthVSDuration of action of moving object

Solution Approach 1:

The patent changes the crosslinking mechanism from covalent to ionic crosslinks, which fundamentally alters the mechanical behavior of the hydrogel. Ionic crosslinks provide sufficient mechanical strength while enabling stress relaxation through reversible binding, thus resolving the contradiction between strength and relaxation capability

Inventive Principle:

Principle #35Parameter changes

Solution Approach 2:

The patent creates a composite hydrogel system combining alginate polymer chains with ionic crosslinkers (such as calcium ions). This composite structure allows the hydrogel to exhibit both elastic properties for structural stability and viscoelastic properties for stress relaxation, overcoming the limitation of traditional elastic hydrogels

Inventive Principle:

Principle #40Composite materials

2Stability of the object's composition

If hydrogels are designed with fixed elastic modulus to provide mechanical support, then structural stability is improved, but ability to regulate cell behavior deteriorates

Engineering Contradiction:

Improvestructural stabilityVSAvoidability to regulate cell behavior

Core Design Contradiction:

Stability of the object's compositionVSAdaptability or versatility

Solution Approach 1:

The patent introduces dynamic stress relaxation behavior to the hydrogel, allowing it to transition from a static elastic structure to a dynamic viscoelastic system. This enables the hydrogel to adapt its mechanical properties over time, providing structural stability initially while subsequently regulating cell behavior through controlled stress relaxation

Inventive Principle:

Principle #15Dynamics

Solution Approach 2:

By controlling the ionic crosslinking density and hydrogel composition, the patent achieves independent tuning of stress relaxation rate and elastic modulus. This parameter control allows the hydrogel to maintain structural stability while providing regulated mechanical cues for cell behavior modulation

Inventive Principle:

Principle #35Parameter changes

3Ease of manufacture

If hydrogels use traditional crosslinking methods to achieve gelation, then manufacturing simplicity is improved, but stress relaxation control deteriorates

Engineering Contradiction:

Improvegelation process simplicityVSAvoidstress relaxation rate control

Core Design Contradiction:

Ease of manufactureVSManufacturing precision

Solution Approach 1:

The patent utilizes ionic crosslinking parameters (crosslinker concentration, ionic strength, pH) to precisely control stress relaxation rate while maintaining simple gelation procedures. By adjusting these parameters, the stress relaxation can be tuned independently without complicating the manufacturing process

Inventive Principle:

Principle #35Parameter changes

Solution Approach 2:

The patent replaces complex mechanical crosslinking systems with simpler ionic crosslinking mechanisms. This substitution maintains ease of manufacture through simple mixing procedures while enabling precise control of stress relaxation properties through ionic strength and crosslinker concentration adjustments

Inventive Principle:

Principle #28Mechanics substitution (Replace mechanical system)

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

These hydrogels enhance cell spreading, proliferation, and differentiation, particularly promoting osteogenic differentiation and bone regeneration by mimicking the stress relaxation behavior of natural tissues, thereby facilitating tissue regeneration and repair.

Implementation Method 1

a plurality of alginate polymer chains are ionically cross-linked to each other

Methodology Applied

Scientific EffectIonic cross-linking: Chemical Bonding

Implementation Method 2

the hydrogel is characterized by a fast stress relaxation rate (τ1/2)

Methodology Applied

Scientific EffectStress relaxation: Stress Relaxation

Implementation Method 3

each of the plurality of spacer molecules comprises a first end and a second end, wherein the first end is attached to an alginate polymer chain

Methodology Applied

Scientific EffectMolecular attachment: Chemical Bonding

Data Source

PatentUS11806441B2Viscoelastic hydrogels with fast stress relaxation

Publication Date: 2023.11.07 PRESIDENT & FELLOWS OF HARVARD COLLEGE

AI summary

Provided are fast relaxing hydrogels that are useful for regulating cell behavior and enhancing tissue regeneration, e.g., bone regeneration.