Fibrin Hydrogel Salt Reduction for Wound Healing
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Solution Overview
Problem
Current methods for delivering fibrin for wound healing, such as in situ generation and fibrin glue, often result in high salt concentrations that can cause tissue irritation and damage during the healing process, limiting their effectiveness.
Innovation Solution
A method for forming a fibrin hydrogel composition involving an aqueous solution with fibrinogen, a fibrin-forming enzyme, and a fibrin hydrogel forming salt, where the salt concentration is initially above a threshold to create a fibrin hydrogel, then reduced below the threshold to minimize tissue irritation, and the hydrogel is dehydrated to increase fibrin concentration and promote healing.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If in situ generation of fibrin glue is used to deliver fibrin for wound healing, then fibrin can be formed at the wound site, but high salt concentrations cause tissue irritation and damage
Solution Approach 1:
The patent extracts and removes excess salt from the fibrin hydrogel through dialysis against low ionic strength buffer or water, or through freeze-drying processes. This separation of fibrin from harmful salt concentrations allows the beneficial wound healing properties to remain while eliminating the harmful effects of high salt on surrounding tissues.
Solution Approach 2:
The patent changes the salt concentration parameter from high (harmful) to low (beneficial) through controlled dialysis or dehydration processes. By adjusting the ionic strength of the buffer during dialysis or controlling the dehydration程度, the salt concentration is reduced to levels that promote wound healing without causing tissue damage.
2Stability of the object's composition
If salt concentration is increased to form fibrin hydrogel, then fibrin gel structure is formed, but tissue damage occurs due to high salt levels
Solution Approach 1:
The patent performs preliminary dialysis or freeze-drying treatment on the fibrin hydrogel before application to the wound site. This preliminary removal of excess salt ensures that when the fibrin is applied to promote hydrogel formation and wound healing, the salt concentration is already reduced to safe levels, preventing subsequent tissue damage.
3Productivity
If fibrin concentration is increased to promote wound healing, then healing rate improves, but salt concentration also increases causing tissue irritation
Solution Approach 1:
The patent selectively extracts salt from the fibrin preparation through dialysis or freeze-drying processes, separating the harmful salt component from the beneficial fibrin. This allows high concentration fibrin to be delivered without the accompanying high salt concentration that would cause tissue irritation.
Solution Approach 2:
The patent independently controls and changes the fibrin concentration parameter upward (for improved healing) while simultaneously changing the salt concentration parameter downward (for reduced irritation) through controlled dialysis or dehydration processes, decoupling these two parameters that are normally linked.
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 enhances wound healing by reducing salt concentration to prevent tissue damage, increasing fibrin concentration, and promoting faster re-epithelialization and wound closure, as demonstrated by increased biomarker production and improved tissue repair in in-vivo studies.
Implementation Method 1
Fibrinogen is cleaved and polymerized into fibrin using thrombin in a well-characterized process. Thrombin cleaves fibrinogen, forming fibrin monomers.
Implementation Method 2
Once fibrinogen is cleaved, fibrin monomers come together and form a covalently crosslinked fibrin network in the presence of factors, such as Factor XIII, normally present in blood.
Implementation Method 3
The salt concentration is reduced below the threshold concentration to form a fibrin hydrogel
Data Source
AI summary
A method of forming a fibrin hydrogel composition is described. The method comprises forming an aqueous solution comprising fibrinogen, fibrin-forming enzyme, and a fibrin hydrogel forming salt. The fibrin hydrogel forming salt concentration is greater than or equal to the threshold concentration to form a fibrin hydrogel. The method further comprises reducing the salt concentration below the threshold concentration to form a fibrin hydrogel. In some embodiments, the aqueous solution further comprises a plasticizer. A fibrin composition is also described comprising a fibrin hydrogel having a fibrin concentration ranging from 0.1 to 10 wt-%; and a fibrin hydrogel forming salt. The fibrin hydrogel forming salt has a concentration less than a threshold concentration to form the fibrin hydrogel. The fibrin hydrogel or dehydrated fibrin hydrogel can be in various physical forms such a sheet, foam, or plurality of pieces. Also described are methods of forming a fibrin article, wound dressings and a method of treatment of a wound.