Controlled Protein Cross-Linking for Biocompatible Scaffolds
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Solution Overview
Problem
Existing methods for forming protein structures for biomedical applications often rely on synthetic materials that are not biocompatible with human tissue, limiting their effectiveness and safety for implantation or application in the body.
Innovation Solution
A method involving the preparation of a protein solution in a benign solvent, such as a water-alcohol-salt mixture, followed by electrospinning to form intermediate protein structures, which are then cross-linked using specific ratios of chemical cross-linking agents like N-hydroxysuccinimide (NHS) and 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide hydrochloride (EDC), to create stable, biocompatible final protein structures that mimic the extracellular matrix.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Ease of manufacture
If synthetic materials are used to construct products or devices for biomedical applications, then manufacturing ease and structural control are improved, but biocompatibility with human tissue deteriorates
Solution Approach 1:
The patent changes the chemical composition parameters by using naturally occurring proteins (collagen, gelatin, elastin, fibroin) instead of synthetic polymers. This parameter change maintains biocompatibility while achieving desired mechanical and structural properties through controlled processing conditions and cross-linking ratios
Solution Approach 2:
The patent creates composite protein structures by combining multiple naturally occurring proteins in specific ratios and applying controlled cross-linking. This approach integrates the advantages of different biocompatible materials to achieve both biocompatibility and structural integrity
2Reliability
If protein structures are cross-linked to improve stability and biocompatibility, then reliability and structural integrity are improved, but processing complexity increases
Solution Approach 1:
The patent applies preliminary action by incorporating cross-linking agents (EDC and NHS) into the protein solution before electrospinning. This allows cross-linking to occur during or immediately after fiber formation, eliminating the need for separate post-processing cross-linking steps and reducing overall processing complexity
Solution Approach 2:
The patent merges the cross-linking process with the electrospinning process by adding cross-linking agents to the solution beforehand. This combines two previously separate operations (fiber formation and cross-linking) into a single integrated process, reducing processing steps and complexity
3Reliability
If specific ratios of cross-linking agents are used to achieve optimal cross-linking, then cross-linking efficiency and structural stability are improved, but manufacturing precision requirements increase
Solution Approach 1:
The patent optimizes the cross-linking agent ratio parameter to 2:1 (NHS:EDC), which provides optimal cross-linking efficiency. This specific parameter value balances reaction effectiveness with ease of preparation, reducing the need for extreme precision while achieving reliable cross-linking results
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 method produces biocompatible protein structures that are stable, non-water-soluble, and capable of mimicking the extracellular matrix, facilitating tissue engineering and wound care by promoting cell growth and tissue regeneration while being safe for use in the human body.
Implementation Method 1
The solution is electrospun to form an intermediate protein structure
Implementation Method 2
The intermediate protein structure is cross-linked by providing for a specific ratio of chemical cross-linking agents to form the final protein structure
Data Source
AI summary
A method of forming a cross-linked protein structures includes preparing a solution of protein dissolved in a benign solvent and forming an intermediate protein structure from the solution. The intermediate protein structure can be cross-linked by providing for a specific ratio of chemical cross-linking agents to form the cross-linked protein structure. The solution can be prepared by adding a cross-linker of N-hydroxysuccinimide (NHS) and 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (EDC) at a ratio of two-to-one of NHS to EDC to alcohol. PBS buffer (20×) can be added to the solution until the volume ratio of PBS buffer (20×) to alcohol is about one-to-one. About 16 percent by weight of protein can be dissolved in the solution. The solution can be electrospun to form an intermediate protein structure. After a period of time, the protein structure can be cross-linked to form the cross-linked protein structure.