Silk Fibroin Spray Mixing for In Situ Fiber and Aerosol Formation

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Solution Overview

Problem

Current methods for fabricating silk fibroin fibers and aerosols are challenging due to the need for electric fields or compressed gas sources, and there is a lack of simple and effective techniques for in situ formation under ambient conditions, which limits their practical utility in applications such as wound healing and drug delivery.

Innovation Solution

A method involving rapid mixing of a silk fibroin solution and a beta sheet initiation solution under shear force, followed by rapid expansion, to form silk fibroin aerosols or fibers without the need for electric fields or compressed gas, using a spray device with a rapid shear mixing and expansion chamber.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Ease of manufacture

If electric fields or compressed gas sources are used to fabricate silk fibroin fibers and aerosols, then fiber formation is achieved, but device complexity and operational requirements increase

Engineering Contradiction:
Improvefiber fabrication simplicityVSAvoidequipment requirements
Core Design Contradiction:
Ease of manufactureVSDevice complexity

Solution Approach 1:

The patent extracts and removes the complex equipment requirements (electric fields, compressed gas sources) from the fiber fabrication process. By identifying that these external energy sources are not essential for silk fibroin fiber formation, the invention simplifies the manufacturing process to use only ambient conditions and basic mixing equipment, thereby resolving the contradiction between ease of manufacture and device complexity.

Inventive Principle:
Principle #2Taking out (Extraction)

Solution Approach 2:

The invention enables silk fibroin to self-assemble into fibers and aerosols through its inherent properties when mixed with the aqueous solution under ambient conditions. The system uses the natural self-organizing behavior of silk fibroin proteins, eliminating the need for external energy input devices, thus achieving simple manufacture without complex equipment.

Inventive Principle:
Principle #25Self-service

2Reliability

If conventional spray systems are used for drug delivery, then delivery mechanism is established, but retention and bioavailability are reduced

Engineering Contradiction:
Improvedrug retentionVSAvoiddelivery effectiveness
Core Design Contradiction:
ReliabilityVSEase of operation

Solution Approach 1:

The patent utilizes phase transition of silk fibroin from soluble state to self-assembled fiber/aerosol state during the spraying process. This phase transition occurs when the silk fibroin solution is mixed with the aqueous solution and subjected to shear forces during ejection, creating a stable carrier structure that enhances drug retention and controlled release, thereby improving both reliability and effectiveness of drug delivery.

Inventive Principle:
Principle #36Phase transitions

Solution Approach 2:

The invention creates a composite system where silk fibroin proteins form the structural matrix and the aqueous solution provides the delivery medium. This composite structure combines the advantages of fiber morphology (high surface area, controlled release) with the benefits of spray delivery (rapid administration), resolving the contradiction between retention and delivery effectiveness.

Inventive Principle:
Principle #40Composite materials

3Manufacturing precision

If silk fibroin solution is exposed to shear force, pH change, heat, organic solvent, or salts, then beta sheet formation is accelerated, but uncontrolled self-assembly into gels occurs

Engineering Contradiction:
Improvebeta sheet formation controlVSAvoidsolution stability
Core Design Contradiction:
Manufacturing precisionVSStability of the object's composition

Solution Approach 1:

The patent applies dynamic control by subjecting the silk fibroin solution to transient shear forces only during the ejection/spraying moment, rather than continuous exposure. The shear force is applied dynamically during the mixing and ejection process, allowing controlled beta sheet formation at the moment of fiber/aerosol generation without causing premature gelation. This dynamic application resolves the contradiction between manufacturing precision and solution stability.

Inventive Principle:
Principle #15Dynamics

Solution Approach 2:

The invention prepares the silk fibroin solution in advance with controlled molecular weight and concentration parameters that pre-condition the solution for controlled self-assembly. By pre-adjusting the solution properties before the spraying process, the system ensures that beta sheet formation occurs controllably during ejection rather than leading to uncontrolled gelation, thereby maintaining both manufacturing precision and solution stability.

Inventive Principle:
Principle #10Preliminary action

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

Enables the production of silk fibroin aerosols and fibers with hierarchical structure under physiological conditions, facilitating controlled drug delivery and wound healing applications.

Implementation Method 1

this physical phase transition arises from a combination of inter- and intramolecular interactions, including hydrophobic interactions, hydrogen bonding, and electrostatic interactions

Methodology Applied
Scientific EffectHydrophobic interactions:

Implementation Method 2

this physical phase transition arises from a combination of inter- and intramolecular interactions, including hydrophobic interactions, hydrogen bonding, and electrostatic interactions

Methodology Applied
Scientific EffectHydrogen bonding:

Implementation Method 3

this physical phase transition arises from a combination of inter- and intramolecular interactions, including hydrophobic interactions, hydrogen bonding, and electrostatic interactions

Methodology Applied
Scientific EffectElectrostatic interactions:

Implementation Method 4

rapid sol-gel transitions of silk have been developed using sonication, surfactants, and polyethylene glycol (PEG), where this physical phase transition arises from a combination of inter- and intramolecular interactions

Methodology Applied
Scientific EffectSol-gel transition:

Implementation Method 5

rapidly mixing a silk fibroin solution and a beta sheet initiation solution under shear force

Methodology Applied
Scientific EffectShear force: Shear Stress

Implementation Method 6

rapidly expanding the mixed solution, thereby providing elongation force to the mixed solution

Methodology Applied
Scientific EffectElongational force:

Data Source

PatentUS12565521B2Systems, kits, and methods for forming in situ silk fibroin fibers and/or aerosols
Publication Date: 2026.03.03 TRUSTEES OF TUFTS COLLEGE
  • US12565521B2 patent drawing
  • US12565521B2 patent drawing
  • US12565521B2 patent drawing

AI summary

Methods, spray devices, and kits for the in situ formation of silk fibroin fibers and/or aerosols are disclosed. Rapidly mixing a silk fibroin solution and a beta sheet initiation solution forms a mixed solution, which is rapidly expanded to form the silk fibroin fibers and/or aerosols. The beta sheet initiation solution includes a hygroscopic polymer having a molecular weight of between 7.5 kDa and 15.0 kDa. The rapid mixing and rapid expanding occur within one second of one another. Silk fibroin aerosols are formed when a molecular weight distribution of fragments in the silk fibroin solution is below an aerosol-fiber threshold. Silk fibroin fibers are formed when the molecular weight distribution is below the aerosol-fiber threshold.