Dynamic Hydrogel with Segmented Crosslinks for Stress Relaxation
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Solution Overview
Problem
Viscoelastic gels suffer from poor stability due to rapid gel erosion caused by dynamic and reversible crosslinks, while elastic gels lack stress relaxation properties, necessitating a material that balances stability and stress relaxation.
Innovation Solution
A two-component hydrogel matrix system comprising chemically modified hyaluronic acid and elastin-like protein, which form both dynamic and static bonds, allowing for tunable matrix stiffness, stress relaxation rate, and cell-adhesive ligand concentration, enhancing stability and injectability.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Adaptability or versatility
If dynamic and reversible crosslinks are used to achieve viscoelasticity and stress relaxation, then stress relaxation properties are improved, but gel stability deteriorates due to rapid gel erosion
Solution Approach 1:
The crosslinking system is segmented into two distinct types: reversible crosslinks (hydrazone bonds) that provide stress relaxation, and irreversible crosslinks (spot welds) that provide stability. This segmentation allows each crosslink type to fulfill its specific function without compromising the other, resolving the contradiction between stress relaxation and gel stability.
Solution Approach 2:
The patent creates a composite crosslinking system combining two different bond mechanisms: reversible hydrazone bonds and irreversible spot welds. This composite approach integrates the beneficial properties of both dynamic reversibility and static stability into a single hydrogel network, simultaneously achieving stress relaxation and erosion resistance.
2Stability of the object's composition
If static covalent crosslinks are used to achieve high stability, then gel stability is improved, but stress relaxation properties are lost
Solution Approach 1:
The crosslinking system is segmented into two distinct types: reversible crosslinks (hydrazone bonds) that provide stress relaxation, and irreversible crosslinks (spot welds) that provide stability. This segmentation allows each crosslink type to fulfill its specific function without compromising the other, resolving the contradiction between stress relaxation and gel stability.
Solution Approach 2:
The patent creates a composite crosslinking system combining two different bond mechanisms: reversible hydrazone bonds and irreversible spot welds. This composite approach integrates the beneficial properties of both dynamic reversibility and static stability into a single hydrogel network, simultaneously achieving stress relaxation and erosion resistance.
3Ease of operation
If dynamic bonds are used to enable injectability and cell migration, then ease of operation is improved, but gel stability deteriorates due to rapid erosion
Solution Approach 1:
The crosslinking system is segmented into two distinct types: reversible crosslinks (hydrazone bonds) that provide stress relaxation, and irreversible crosslinks (spot welds) that provide stability. This segmentation allows each crosslink type to fulfill its specific function without compromising the other, resolving the contradiction between stress relaxation and gel stability.
Solution Approach 2:
The patent creates a composite crosslinking system combining two different bond mechanisms: reversible hydrazone bonds and irreversible spot welds. This composite approach integrates the beneficial properties of both dynamic reversibility and static stability into a single hydrogel network, simultaneously achieving stress relaxation and erosion resistance.
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 hydrogel system achieves prolonged stability, retaining at least 60% of the elastin-like protein within the gel for several days, maintains structural integrity after extrusion, and exhibits stress relaxation properties, making it suitable for 3D bioprinting and regenerative medicine.
Implementation Method 1
Mixing the modified biopolymers together induces the formation of dynamic bonds between the aldehyde or benzaldehyde containing side group and the hydrazine containing side group (also known as hydrazone bonds)
Implementation Method 2
formation of static bonds between the bicyclononyne containing side group and the azide containing side group (referred to herein as spot welds, and an example from the class of reactions known as strain-promoted azide-alkyne cycloadditions)
Implementation Method 3
Compositions comprising a greater percentage of hyaluronic acid modified with an aldehyde containing functional group increase the average kinetic exchange rate of the gel, leading to a faster stress-relaxation rate
Data Source
AI summary
A two-component hydrogel matrix system is described, which has a variety of benefits for cell and tissue culture; including without limitation hydrogels that allow for cells to more easily migrate into/through, proliferate, spread, and deposit matrix within the gel; stable hydrogels that allow for higher retention that can be held together for prolonged periods of time, etc. The components comprise: (1) chemically modified hyaluronic acid (HA) comprising an aldehyde or benzaldehyde containing side group, and a bicyclononyne containing side group, and (2) chemically modified elastin-like protein (ELP) comprising a hydrazine containing side group and an azide containing side group.