Hybrid Hydrogel Crosslinking for Stability and Adaptability

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Solution Overview

Problem

Current viscoelastic hydrogels used in therapeutic settings suffer from substantial degradation and mass loss, limiting their long-term utility due to their unstable mechanical properties, which are not adequately matched to the native extracellular matrix.

Innovation Solution

The development of hybrid network hydrogels composed of a first polymer backbone functionalized with hyaluronic acid and an 8-arm poly(ethylene glycol) backbone, incorporating strained cyclooctyne or bicyclononyne, which form stable crosslinks without external stimulation, enhancing stability and adaptability.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Adaptability or versatility

If viscoelastic hydrogels are used to match mechanical properties of native extracellular matrix, then adaptability and biocompatibility are improved, but stability and durability deteriorate due to substantial degradation and mass loss

Engineering Contradiction:

Improvemechanical property matchingVSAvoidstability

Core Design Contradiction:

Adaptability or versatilityVSReliability

Solution Approach 1:

The patent employs a composite hydrogel system consisting of hyaluronic acid backbone functionalized with both aldehyde and hydrazide groups, crosslinked with 8-arm PEG functionalized with strained cyclooctyne. This composite structure combines the biocompatibility and cell recognition properties of hyaluronic acid with the mechanical stability and controlled degradation of PEG, resolving the contradiction between adaptability and stability.

Inventive Principle:

Principle #40Composite materials

Solution Approach 2:

The hydrogel exhibits local quality differentiation through distinct crosslinking regions: hydrazone bonds provide reversible, adaptive crosslinking for viscoelasticity and cell interaction, while triazole bonds from strained cyclooctyne provide stable, irreversible crosslinking for structural integrity. This spatial and functional differentiation allows simultaneous achievement of adaptability and stability.

Inventive Principle:

Principle #3Local quality

2Reliability

If hydrogels are designed for long-term stability, then durability is improved, but adaptability and mechanical property matching deteriorate

Engineering Contradiction:

ImprovestabilityVSAvoidmechanical property matching

Core Design Contradiction:

ReliabilityVSAdaptability or versatility

Solution Approach 1:

The hydrogel incorporates dynamic hydrazone bonds that can reversibly break and reform, allowing the network to adapt its mechanical properties in response to environmental conditions and cellular activities. This dynamic character enables the hydrogel to maintain stability over time while simultaneously adapting to match the mechanical properties of native extracellular matrix.

Inventive Principle:

Principle #15Dynamics

3Strength

If crosslinking density is increased to improve mechanical stability, then strength is improved, but injectability and processability deteriorate

Engineering Contradiction:

Improvemechanical stabilityVSAvoidinjectability

Core Design Contradiction:

StrengthVSEase of operation

Solution Approach 1:

The hydrogel precursors are designed to undergo self-crosslinking upon mixing, forming the stable PEG-triazole network in advance. This preliminary action allows the hydrogel to achieve high mechanical stability before injection, while the injectable formulation maintains lower crosslinking density during administration, resolving the contradiction between strength and injectability.

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

These hydrogels exhibit improved stress relaxation properties and prolonged stability, allowing for sustained therapeutic delivery and enhanced cellular interactions, such as increased stem cell migration and cytokine secretion, while maintaining injectability and viscoelasticity.

Implementation Method 1

incorporating strained cyclooctyne or bicyclononyne, which form stable crosslinks without external stimulation

Methodology Applied

Scientific EffectStrain-promoted azide-alkyne cycloaddition: Chemical Bonding

Implementation Method 2

a first polymer backbone having at least one hyaluronic acid backbone functionalized with an aliphatic aldehyde and at least one hyaluronic acid backbone functionalized with a hydrazide

Methodology Applied

Scientific EffectCondensation reaction: Chemical Bonding

Data Source

PatentUS20240050586A1Compositions and methods for making and using double network hydrogels

Publication Date: 2024.02.15 THE REGENTS OF THE UNIVERSITY OF COLORADO

AI summary

Embodiments of the instant disclosure relate to novel compositions, combination compositions, methods, and systems for generating and using hydrogels. In certain embodiments, the present disclosure provides for compositions including a polymer backbone having at least one hyaluronic acid backbone functionalized with an aliphatic aldehyde and at least one hyaluronic acid backbone functionalized with a hydrazide and a second polymer backbone including at least one 8-arm poly(ethylene glycol) (PEG). In certain embodiments, the present disclosure provides methods of treating a condition in a subject including administering hydrogels to the subject in the absence or presence of one or more therapeutic agent or cell.