Triple Cross-Linked Collagen for Medical Implants
Find Innovative SolutionsGenerate Solutions
Solution Overview
Problem
Current methods for manufacturing cross-linked collagen for medical implants face challenges such as low melting point, high enzyme degradation, and toxicity from residual cross-linking agents, limiting their application to temporary implants and specific treatments.
Innovation Solution
A method involving sequential cross-linking with different agents (aldehyde, imine, and epoxide) to achieve a triple cross-linked collagen with high degree of cross-linking, high melting point, and low enzyme degradation, using agents like glutaraldehyde, EDC/NHS, and BDDE, and subsequent washing with glycine solution to enhance stability.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Stability of the object's composition
If chemical cross-linking reaction is used to manufacture cross-linked collagen, then the structure stability is improved, but the melting point is low and enzyme degradation ratio is high
Solution Approach 1:
The patent divides the cross-linking process into three sequential stages using different cross-linking agents (aldehyde, imine, and epoxide agents), creating a triple cross-linked collagen structure. This segmentation allows each cross-linking type to contribute differently to the overall structure, with the combination achieving both high stability and high melting point without excessive enzyme degradation.
Solution Approach 2:
The patent creates a composite cross-linking system by combining three different cross-linking agents (aldehyde, imine, and epoxide agents) to form a triple cross-linked collagen structure. This composite approach leverages the complementary strengths of each cross-linking type to achieve superior overall performance, including high melting point and stability with controlled enzyme degradation.
2Stability of the object's composition
If chemical cross-linking reaction is used to manufacture cross-linked collagen, then the structure stability is improved, but the enzyme degradation ratio is high
Solution Approach 1:
The patent segments the cross-linking process into three distinct stages using different agents, creating a multi-layered cross-linked structure. This segmentation allows the collagen to have different degrees of cross-linking at different levels, with the combined effect providing high stability while maintaining controlled enzyme degradation through the specific sequence and types of cross-links formed.
Solution Approach 2:
The patent changes the cross-linking parameters by using three different cross-linking agents with different chemical mechanisms and bonding characteristics. This parameter variation creates a diverse cross-linked network that provides high stability through multiple bonding types while maintaining appropriate enzyme degradation characteristics through the specific chemical properties of each cross-linking agent.
3Ease of manufacture
If physical cross-linking reaction is used to manufacture cross-linked collagen, then the manufacturing simplicity is improved, but the collagen is apt to be destroyed, denatured, or degraded
Solution Approach 1:
The patent uses chemical cross-linking agents as intermediaries to create stable covalent bonds between collagen molecules. These intermediary substances facilitate the formation of strong, stable cross-links that prevent collagen destruction and denaturation, overcoming the limitations of physical cross-linking methods while maintaining manufacturing feasibility through a systematic three-step process.
4Manufacturing precision
If conventional chemical cross-linking reaction is used, then the cross-linking degree is insufficient, but the manufacturing complexity is low
Solution Approach 1:
The patent segments the cross-linking process into three sequential steps, each using a specific cross-linking agent targeted at different functional groups or bonding types. This segmentation enables progressive cross-linking that achieves high cross-linking degree (70-90%) by accumulating cross-links from each step, while the systematic approach keeps the manufacturing process organized and controllable despite the increased complexity.
Solution Approach 2:
The patent implements continuous cross-linking action through three sequential steps where each step builds upon the previous one. The useful action of cross-linking is applied continuously rather than in a single step, allowing the cross-linking degree to accumulate to high levels (70-90%) while maintaining process control through the systematic progression from one cross-linking agent to the next.
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 collagen with 70-90% cross-linking, a melting point of 80-95°C, and enzyme degradation ratio of 10% or less, improving stability and suitability for long-term medical implants.
Implementation Method 1
The first cross-linking agent is one selected from the group consisting of an aldehyde cross-linking agent, an imine cross-linking agent, and an epoxide cross-linking agent
Implementation Method 2
The second cross-linking agent is one selected from the group consisting of an aldehyde cross-linking agent, an imine cross-linking agent, and an epoxide cross-linking agent
Implementation Method 3
The third cross-linking agent is one selected from the group of consisting an aldehyde cross-linking agent, an imine cross-linking agent, and an epoxide cross-linking agent
Data Source
AI summary
The present invention relates to a method for manufacturing a triple cross-linked collagen, which comprises the following steps: providing a soluble collagen sample; mixing the collagen sample with a first cross-linking agent to form a one cross-linked collagen; mixing the first cross-linked collagen with a second cross-linking agent to form a second cross-linked collagen; and mixing the second cross-linked collagen with a third cross-linking agent to form a triple cross-linked collagen, wherein each of the first cross-linking agent, the second cross-linking agent, and the third cross-linking agent is selected from the group consisting of an aldehyde cross-linking agent, an imine cross-linking agent, and an epoxide cross-linking agent. In addition, the first cross-linking agent is different form the second cross-linking agent, and the third cross-linking agent is different form the first cross-linking agent and the second cross-linking agent.