Fibrin Sheet Production on Gelatin Hydrogel for Cell Survival
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Solution Overview
Problem
Existing methods for producing fibrin sheets with cells or drugs in a fibrin gel face challenges in achieving uniform shape, ease of production, and minimizing cell damage, particularly when low fibrin concentrations are required for cell survival.
Innovation Solution
A method involving applying a fibrinogen solution containing cells or drugs dropwise onto a gelatin hydrogel substrate, adding thrombin to form a fibrin precursor liquid, placing a support film, and separating the fibrin sheet by melting the gelatin hydrogel at a specific temperature to maintain cell viability and shape flexibility.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Ease of operation
If the fibrin concentration is increased to make handling easier, then the ease of operation is improved, but the cell survival rate deteriorates
Solution Approach 1:
The patent introduces a gelatin hydrogel substrate as an intermediary medium between the fibrinogen solution and the final fibrin sheet. This substrate provides a stable base that allows the use of lower fibrinogen concentrations (improving cell survival) while still enabling easy handling through the substrate's structural support. The gelatin substrate acts as a mediator that decouples the handling ease function from the fibrin concentration.
2Reliability
If the fibrin concentration is decreased to allow cell survival, then the cell survival rate is improved, but the ease of operation deteriorates
Solution Approach 1:
The patent segments the system into two functional parts: the gelatin hydrogel substrate that provides structural support and handling ease, and the fibrinogen solution containing cells that provides the desired low concentration for cell survival. This segmentation allows each component to fulfill its specific function without compromise.
3Manufacturing precision
If a special mold is fabricated to produce fibrin sheets, then the manufacturing precision is improved, but the device complexity increases
Solution Approach 1:
The patent replaces complex, expensive special molds with simple, disposable gelatin hydrogel substrates. These substrates can be easily prepared and discarded after use, eliminating the need for intricate mold fabrication while still achieving uniform fibrin sheet production through the substrates' inherent properties.
4Productivity
If mechanical spreading is used to spread the fibrin precursor liquid, then the productivity is improved, but the cell damage increases
Solution Approach 1:
The patent employs surface tension forces to enable the fibrin precursor liquid to spread automatically across the gelatin substrate without mechanical intervention. The liquid self-spreads due to capillary action and surface tension, achieving both high productivity and zero mechanical cell damage.
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 fibrin sheets uniformly and conveniently, reducing cell damage, and allowing for easy construction of three-dimensional biomaterials for cell replacement therapy and disease treatment.
Implementation Method 1
a step 5 of melting the substrate at a temperature not lower than a melting temperature of the gelatin hydrogel to separate, from the substrate, the fibrin sheet supported by the support film
Implementation Method 2
a step 2 of adding thrombin to the fibrinogen solution on the surface of the substrate: a step 4 of forming a fibrin sheet containing the at least one selected from the group consisting of cells and drugs in a fibrin gel by a reaction between the fibrinogen and the thrombin
Implementation Method 3
the fibrin precursor liquid can be spread between uniform surfaces of the substrate and the support film by surface tension without using any operation which may mechanically damage the cells
Data Source
AI summary
A method for producing a fibrin sheet containing at least one selected from the group consisting of cells and drugs in a fibrin gel, the method comprising:a step 1 of applying a fibrinogen solution containing at least one selected from the group consisting of cells and drugs and fibrinogen dropwise onto a surface of a substrate made of a gelatin hydrogel;a step 2 of adding thrombin to the fibrinogen solution on the surface of the substrate;a step 3 of placing a support film on and in contact with a top surface of the fibrinogen solution to which the thrombin has been added;a step 4 of forming a fibrin sheet containing the at least one selected from the group consisting of cells and drugs in a fibrin gel between the substrate and the support film by a reaction between the fibrinogen and the thrombin; anda step 5 of melting the substrate at a temperature not lower than a melting temperature of the gelatin hydrogel to separate, from the substrate, the fibrin sheet supported by the support film.