Low-Density Fibrin Particles via Microfluidic Shearing
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Solution Overview
Problem
Existing fibrin-based wound healing materials are polymerized at high densities using elevated temperatures, leading to denaturation of proteins and inhibiting wound repair, and lack ease of administration and storability.
Innovation Solution
Low density fibrin particles are produced through a shearing process using a microfluidic device, avoiding elevated temperatures and external crosslinkers, allowing for the inclusion of therapeutic agents and easy application to wounds.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Strength
If fibrin sealants are polymerized at high density to achieve suitable polymerization kinetics and mechanics, then the mechanical strength is improved, but cell migration into the wound is inhibited
Solution Approach 1:
The patent divides the bulk fibrin hydrogel into microscale particles (1-1000 micrometers in diameter). This segmentation creates a porous network structure that maintains mechanical integrity while allowing cell migration through the interconnected pores, thereby resolving the contradiction between strength and cell migration inhibition.
Solution Approach 2:
The patent employs porous fibrin particles with controlled pore sizes that facilitate cell infiltration and migration. The porous structure is achieved through controlled polymerization within microemulsion droplets, creating a network that provides mechanical support while enabling biological functionality.
2Productivity
If elevated temperatures are used during the crosslinking process to achieve polymerization, then the polymerization kinetics are improved, but fibrin proteins are denatured reducing healing efficacy
Solution Approach 1:
The patent changes the polymerization parameters by conducting the reaction at physiological temperatures (37°C or lower) using activated fibrinogen and thrombin. This parameter change maintains rapid polymerization kinetics while preserving protein structure and function, thereby resolving the contradiction between productivity and reliability.
Solution Approach 2:
The patent replaces thermal energy input with enzymatic catalysis (thrombin-mediated conversion of fibrinogen to fibrin). This substitution eliminates the need for elevated temperatures while achieving rapid polymerization, thus preserving protein integrity and healing efficacy.
3Stability of the object's composition
If fibrin particles are prepared using intensive crosslinking and elevated temperatures to achieve polymerization, then the polymerization completeness is improved, but protein denaturation occurs reducing overall healing efficacy
Solution Approach 1:
The patent employs self-assembling properties of fibrinogen-thrombin systems that naturally polymerize to form stable fibrin networks under physiological conditions. This self-service mechanism achieves complete polymerization without external intensive crosslinking or elevated temperatures, thereby maintaining protein functionality and healing efficacy.
4Area of stationary object
If bulk fibrin hydrogels are formed in situ during clinical administration to achieve wound coverage, then the wound coverage is improved, but the dense networks inhibit wound repair
Solution Approach 1:
The patent applies segmented fibrin particles instead of bulk hydrogel. The particles distribute throughout the wound bed providing coverage while their microscale size and porous structure prevent the dense network formation that inhibits repair, thus resolving the contradiction between coverage and repair inhibition.
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 low density fibrin particles enhance wound healing by promoting cell recruitment and providing a carrier for therapeutic agents, improving clinical utility and ease of use.
Implementation Method 1
The particles are prepared by applying a shear stress to an aqueous composition including polymerized fibrin
Implementation Method 2
Platelets generate active thrombin on their cell surfaces. Thrombin catalyzes the conversion of soluble fibrinogen into fibrin
Implementation Method 3
fibrin, which is polymerized primarily through noncovalent interactions
Implementation Method 4
Finally, factor XIII covalently crosslinks the polymerized fibrin to produce a clot
Data Source
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Figure 5~6
AI summary
Disclosed herein are low density particles comprising polymerized fibrin that are micrometer or nanometer sized in diameter. The particles can further include at least one therapeutic agent. The particles may be used to treat wounds, by administration directly or systemically to the site of the wound. Exemplary wounds that may be treated with the fibrin particles include a trauma wound, a surgical wound, a burn wound, or an ulcer wound. Also disclosed herein are methods for preparing the particles using a shearing process.