Decellularized Tissue Hydrogels Cross-linked with Polyphenols
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Solution Overview
Problem
Current decellularized tissue hydrogels lack sufficient mechanical strength, flexibility, and resistance to degradation, while also facing issues with toxicity and calcification when cross-linked with existing agents like glutaraldehyde and genipin.
Innovation Solution
Cross-linking decellularized tissue hydrogels with polyphenols, such as proanthocyanidins, to enhance mechanical strength, flexibility, and biocompatibility, while inhibiting calcification and allowing for tailored degradation rates.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Strength
If glutaraldehyde is used to cross-link ECM hydrogels, then mechanical strength and durability are improved, but toxicity and calcification issues arise
Solution Approach 1:
The patent uses genipin as an intermediary cross-linking agent between the ECM hydrogel and the desired mechanical properties. Genipin serves as a mediator that provides cross-linking functionality without the toxic side effects of glutaraldehyde, including calcification and cellular toxicity. This intermediary approach allows achievement of mechanical strength improvement while avoiding harmful effects.
Solution Approach 2:
The patent changes the chemical parameters of the cross-linking agent from glutaraldehyde to genipin, altering the molecular structure and reactivity characteristics. This parameter change transforms the cross-linking process to achieve similar mechanical reinforcement while modifying the biological compatibility profile to eliminate toxicity and calcification issues.
2Strength
If glutaraldehyde is used to cross-link ECM hydrogels, then mechanical strength is improved, but mechanical flexibility is reduced
Solution Approach 1:
The patent modifies the cross-linking chemistry parameters by using genipin instead of glutaraldehyde. This parameter change results in different cross-link bond characteristics that provide mechanical strength while preserving the hydrogel's flexibility and compressibility, enabling the material to maintain adaptability for minimally invasive delivery.
3Object-affected harmful factors
If plant derived cross-linking agents like genipin are used, then biocompatibility is improved, but mechanical strength increase is significantly reduced
Solution Approach 1:
The patent optimizes the concentration and reaction conditions of genipin cross-linking, adjusting parameters such as cross-linking time, temperature, and genipin-to-ECM ratio. These parameter changes maximize the mechanical strength enhancement from genipin cross-linking while maintaining its biocompatibility advantages over glutaraldehyde.
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 use of polyphenols significantly increases the mechanical properties of decellularized tissue hydrogels, making them more compressible, rollable, and biocompatible, while maintaining ECM structure and function, and providing enhanced regenerative capabilities.
Implementation Method 1
ECM hydrogels may be cross-linked to confer structural strength, rigidity or to delay degradation
Implementation Method 2
Hydrogels include three-dimensional polymeric fibre networks which are hydrophilic and swellable when exposed to water
Implementation Method 3
Powdered ECM biomaterials can be solubilised with pepsin
Data Source
AI summary
The invention provides a decellularized tissue hydrogel cross-linked with a polyphenol, and a method of preparing a cross-linked decellularized tissue hydrogel, the method comprising the steps of: a) providing at least one decellularized tissue hydrogel; and b) cross-linking the at least one decellularized tissue hydrogel with a polyphenol.