Bone Matrix Dissolution Using HFP TFE TFA Solvents
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Solution Overview
Problem
Dissolving bone matrix while maintaining its native structure and biological activities is challenging due to the disruption of collagen triple helices by solvents, and existing methods fail to effectively dissolve the complex mixture of collagen, minerals, and proteins in bone tissue.
Innovation Solution
Using an anhydrous solvent combination of hexafluoroisopropanol (HFP) or 2,2,2-trifluoroethanol (TFE) with at least 5 wt% trifluoroacetic acid (TFA) to dissolve bone, which allows for the formation of a bone matrix solution that can be evaporated to create a colloidal gel and hardened into a predetermined shape, preserving the native structure of collagen type I.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Quantity of substance
If conventional solvents are used to dissolve bone matrix, then dissolution occurs, but the native structure of collagen triple helices is disrupted
Solution Approach 1:
The patent applies parameter changes by using a specific solvent composition (trifluoroacetic acid at least 5 wt% in combination with HFP or TFE) and controlling dissolution temperature (0-22°C) to achieve bone matrix dissolution while preserving collagen structure. This resolves the contradiction by modifying solvent parameters and process conditions to prevent collagen denaturation during dissolution.
Solution Approach 2:
The patent uses a composite solvent system combining trifluoroacetic acid with either HFP or TFE, creating a synergistic effect that enables effective bone matrix dissolution while maintaining collagen triple helix stability. The composite solvent approach allows dissolution of the complex bone mixture without disrupting the native collagen structure.
2Quantity of substance
If existing methods are used to dissolve bone tissue, then some dissolution occurs, but the complex mixture of collagen, minerals, and proteins cannot be effectively dissolved
Solution Approach 1:
The patent modifies dissolution parameters by using a specific solvent composition (trifluoroacetic acid at least 5 wt% with HFP or TFE) and temperature control (0-22°C) to achieve complete dissolution of the complex bone mixture including collagen, minerals, and proteins, overcoming the limitations of existing methods.
Solution Approach 2:
The patent employs a composite solvent system that combines trifluoroacetic acid with HFP or TFE, creating a powerful dissolution medium capable of effectively dissolving all components of bone tissue (collagen, minerals, proteins) that existing single solvents cannot dissolve.
3Ease of manufacture
If bone matrix is dissolved to create implants, then the bone matrix solution can be formed, but maintaining the native structure during processing is challenging
Solution Approach 1:
The patent controls processing parameters including dissolution temperature (0-22°C), solvent composition (trifluoroacetic acid at least 5 wt% with HFP or TFE), and pH to maintain collagen triple helix structure throughout the bone matrix solution formation process, enabling easy manufacturing while preserving native structure.
Solution Approach 2:
The patent uses the specific solvent system (trifluoroacetic acid with HFP or TFE) as an intermediary medium that allows bone matrix dissolution and solution formation while protecting and maintaining the native collagen structure throughout the processing steps.
4Shape
If the bone matrix solution is evaporated to form colloidal gel, then the implant shape can be formed, but solvent removal must be controlled
Solution Approach 1:
The patent utilizes controlled phase transition from liquid bone matrix solution to colloidal gel through solvent evaporation, allowing the formation of predetermined implant shapes while maintaining the stability and structure of the colloidal gel network.
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 effectively dissolves bone without disrupting its native structure, enabling the production of bone matrix implants and scaffolds that promote osteogenesis, chondrogenesis, and ligament/tendon differentiation, with high cell attachment and recruitment, and demonstrates enhanced osteoinductive and chondroinductive properties.
Implementation Method 1
dissolving bone in an amount of an anhydrous solvent comprising (i) hexafluoroisopropanol (HFP) or 2, 2, 2-trifluoroethanol (TFE) and (ii) at least about 5 wt % trifluoroacetic acid (TFA) sufficient to form the bone matrix solution
Implementation Method 2
exposing the bone solution to conditions sufficient to evaporate an amount of the solvent to form a colloidal gel
Data Source
AI summary
The invention relates to methods of preparing a bone matrix solution, a bone matrix implant, and variants thereof. The invention also relates to methods of cell culture using the same. The invention further relates to bone matrix scaffolds comprising one or more bone matrix nanofibers, methods of preparing, and methods of use thereof. The invention also relates to methods of culturing cells and promoting differentiation of stem cells using the same.