Fibrin Particle Formation via Microfluidic Polymerization
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Solution Overview
Problem
Conventional methods for forming fibrin compositions face challenges such as rapid polymerization, low solubility of fibrinogen, heat sensitivity, and poor mechanical properties of fibrin particles, which limit their use in tissue engineering and other applications.
Innovation Solution
A method involving a microfluidic device where fibrinogen and thrombin solutions are introduced with a buffer containing amino acids, mixed with a fluorocarbon oil and surfactant, and subjected to controlled flow and heating to form consistently sized fibrin particles with supraphysiological mechanical properties, avoiding the need for cold temperatures and harsh solvents.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Speed
If conventional methods maintain solutions at temperatures near freezing to slow polymerization, then polymerization rate is controlled, but manufacturing cost increases and scalability is reduced
Solution Approach 1:
The invention changes the temperature parameter from near-freezing conditions to physiological temperature (37°C) by introducing a calcium ion-containing buffer solution that controls polymerization kinetics at elevated temperatures, eliminating the need for costly refrigeration infrastructure while maintaining controllable polymerization rates
Solution Approach 2:
A calcium ion-containing buffer solution is introduced as an intermediary substance that mediates the polymerization process, allowing controlled fibrin formation at physiological temperatures without requiring extreme cold conditions, thus enabling scalable manufacturing
2Speed
If heavy mineral oils are used to slow down polymerization, then polymerization rate is controlled, but harsh solvent wash steps are required that kill cells and proteins
Solution Approach 1:
The invention extracts and eliminates the harmful mineral oil component from the system by using a water-based calcium ion-containing buffer solution instead, achieving controlled polymerization without requiring subsequent harsh solvent wash steps that damage biological materials
Solution Approach 2:
The calcium ion-containing buffer solution serves as a disposable, biocompatible alternative to mineral oils, allowing controlled polymerization and subsequent removal without leaving harmful residues that would require damaging wash steps
3Reliability
If rapid polymerization is used to maintain hemostasis, then hemostatic function is achieved, but mechanical properties and consistency of fibrin particles are poor
Solution Approach 1:
The invention introduces dynamic control of polymerization through a calcium ion-containing buffer system that allows adjustment of polymerization kinetics, enabling transition from rapid uncontrollable polymerization to controlled polymerization that produces consistent particle sizes while maintaining hemostatic functionality
Solution Approach 2:
The calcium ion-containing buffer is prepared in advance to pre-establish controlled polymerization conditions, allowing fibrin particles to form with consistent mechanical properties and size uniformity before application, rather than relying on uncontrolled rapid polymerization
4Strength
If fibrinogen concentration is increased to improve scaffold strength, then mechanical properties improve, but solubility decreases making handling difficult
Solution Approach 1:
The invention changes the chemical environment parameters by introducing a calcium ion-containing buffer solution that maintains fibrinogen solubility at higher concentrations, enabling preparation of strong scaffolds with improved mechanical properties without precipitation or handling difficulties
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
This approach enables the production of fibrin particles with robust mechanical properties and high solubility, allowing for tunable mechanical properties and overcoming the limitations of conventional methods, including minimizing device clogging and enabling applications in tissue engineering.
Implementation Method 1
Fibrin forms by thrombin-catalyzed polymerization of fibrinogen, and the polymerized fibrin scaffold then clots at the wound site
Implementation Method 2
contacting the mixture with a fluorocarbon oil and a surfactant to form fibrinogen-containing particles
Implementation Method 3
applying positive pressure to the microfluidic device to cause the fibrinogen-containing particles to flow towards a second end of the microfluidic device
Implementation Method 4
heating the dispersion under conditions effective to form fibrin particles
Data Source
AI summary
The present disclosure generally relates to compositions comprising fibrin and to methods of forming such compositions. In an embodiment, a method of forming fibrin particles is provided. The method includes introducing a buffer, a fibrinogen solution, and a thrombin solution to a first end of a microfluidic device to form a mixture, the buffer comprising one or more amino acids. The method further includes contacting the mixture with a fluorocarbon oil and a surfactant to form fibrinogen-containing particles, and applying positive pressure to the microfluidic device to cause the fibrinogen-containing particles to flow towards a second end of the microfluidic device. The method further includes collecting the fibrinogen-containing particles at the second end of the microfluidic device; and polymerizing the fibrinogen-containing particles to form fibrin particles.