Enzyme-Free Hydrogel Production Without Proteolytic Contamination
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Solution Overview
Problem
Existing hydrogel production processes involve enzymatic digestion, which can leave proteolytic enzymes in the final products, making them unsuitable for human application due to potential tissue degradation.
Innovation Solution
An enzyme-free process is developed to produce tissue-specific extracellular matrix solutions and hydrogels by decellularizing tissues and hydrolyzing the matrix in an acidic environment without proteolytic enzymes, followed by pH neutralization and cross-linking to create stronger and faster-crosslinking hydrogels.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Ease of manufacture
If enzymatic digestion is used to produce hydrogels, then the hydrogel production process is simplified, but proteolytic enzymes remain in the final product causing tissue degradation
Solution Approach 1:
The patent removes the harmful proteolytic enzymes from the hydrogel production process by using a chemical hydrolysis method instead of enzymatic digestion. This extraction eliminates the source of contamination while maintaining the ability to break down extracellular matrix proteins for hydrogel formation.
Solution Approach 2:
The patent replaces the biological enzymatic system with a chemical hydrolysis system. Instead of using proteolytic enzymes to break down extracellular matrix proteins, the process uses chemical hydrolysis in an acidic environment, substituting a mechanical/chemical process for a biological one to eliminate enzyme contamination.
2Productivity
If proteolytic enzymes are used for extracellular matrix digestion, then protein breakdown is efficient, but the final hydrogel becomes unsuitable for human application
Solution Approach 1:
The patent changes the fundamental parameter of the digestion method from enzymatic to chemical hydrolysis. By using acidic hydrolysis conditions instead of enzymatic processes, the patent achieves protein breakdown efficiency while eliminating the reliability issue of enzyme contamination in human applications.
3Reliability
If enzyme-free hydrolysis is used, then the hydrogel is suitable for human application, but the cross-linking speed and strength are reduced
Solution Approach 1:
The patent performs preliminary hydrolysis of the extracellular matrix proteins in an acidic environment before the cross-linking step. This preliminary action prepares the protein structure to enable faster and stronger cross-linking in the subsequent step, compensating for the enzyme-free approach and achieving both human applicability and cross-linking performance.
4Ease of manufacture
If enzymatic digestion is used, then the extracellular matrix is broken down effectively, but the process leaves residual enzymes that cause unwanted proteolysis
Solution Approach 1:
The patent substitutes the enzymatic digestion system with a chemical hydrolysis system that does not leave residual active enzymes. The chemical hydrolysis process breaks down the extracellular matrix effectively while not introducing proteolytic activity that could cause unwanted proteolysis in the final hydrogel product.
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 enzyme-free process results in hydrogels suitable for human application, with enhanced strength and speed of cross-linking, reducing the risk of tissue rejection and enabling therapeutic uses for tissue regeneration.
Implementation Method 1
hydrolyze the isolated extracellular matrix in an acidic environment, in the absence of proteolytic enzymes
Implementation Method 2
cross-linking to create stronger and faster-crosslinking hydrogels
Data Source
AI summary
The present invention is in the field of tissue and organ bioengineering and refers to an enzyme-free process to produce a tissue-specific extracellular matrix solution, based on a decellularized extracellular matrix, comprising: (a) decellularizing a tissue or organ to obtain the isolated extracellular matrix; and (b) hydrolyzing the isolated extracellular matrix in an acidic environment, in the absence of proteolytic enzymes, optionally followed by purification of the solution. Still, the present invention refers to an enzyme-free process to produce a tissue-specific hydrogel. Thus, the present invention also relates to hydrogels produced according to the current processes, and to ancillary inventions, having the tissue-specific extracellular matrix solution, the hydrogel, and/or the products derived from the tissue-specific extracellular matrix solution as the core that connects the inventive aspects disclosed in this document.