Rotary Casting of Autologous Fibrin Tissue Constructs
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Solution Overview
Problem
Current methods for producing bioartificial tissue constructs using decellularized allogeneic extracellular matrices face challenges with immunological compatibility and stability, while autologous fibrin-based methods are limited by rapid fibrinogen preparation workability and production time.
Innovation Solution
A rotary casting method is employed to mold a fibrinogen preparation with cells into a hollow mold, using a two-component fibrinogen preparation that is crosslinked within minutes to form a stable fibrin matrix, allowing for rapid production of tubular or other geometric tissue constructs with autologous cells and matrix, ensuring immunological compatibility and structural similarity to natural tissues.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Strength
If decellularized allogeneic extracellular matrix is used, then structural support is provided, but immunological compatibility deteriorates
Solution Approach 1:
The patent extracts and removes the problematic immunological components (cells and debris) from the allogeneic extracellular matrix through decellularization processes, retaining only the structural framework. This allows the structural support function to be preserved while eliminating the harmful immunological factors that would cause rejection responses.
Solution Approach 2:
The patent introduces an intermediary processing step (decellularization) between the allogeneic matrix and the final tissue construct. This intermediary process transforms the immunologically incompatible allogeneic material into a biocompatible scaffold that can be further populated with patient-specific or allogeneic cells in a controlled manner.
2Object-affected harmful factors
If autologous fibrinogen preparation is used, then immunological compatibility is improved, but production time increases
Solution Approach 1:
The patent performs preliminary preparation of the autologous fibrinogen matrix before cell seeding, including crosslinking and structural formation. By preparing the matrix framework in advance, the actual tissue construction phase is accelerated, as the scaffold is already in place and ready for rapid cell population.
Solution Approach 2:
The patent replaces traditional mechanical cell seeding methods with a more efficient cell incorporation approach where cells are mixed into the fibrinogen preparation before crosslinking. This substitution of the cell incorporation mechanism significantly reduces production time while maintaining immunological compatibility through the use of autologous materials.
3Loss of time
If rapid crosslinking of fibrinogen is performed, then production time is reduced, but structural stability deteriorates
Solution Approach 1:
The patent optimizes the crosslinking parameters including crosslinking agent concentration, temperature, pH, and humidity to achieve rapid crosslinking while maintaining structural stability. By carefully controlling these parameters, the fibrinogen matrix crosslinks quickly to form a stable structure that supports the incorporated cells without requiring extended processing times.
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 method enables the rapid production of stable, autologous bioartificial tissue constructs with viable cells in a fibrin matrix, suitable for vascular prostheses and tissue patches, offering improved stability and reduced production time, while ensuring immunological acceptance and structural similarity to natural tissues.
Implementation Method 1
The fibrinogen preparation can consist of a plurality of separated components which are first combined during the application into the hollow mold, or immediately before. The cells are used as a cell suspension directly from a cell culture or from a cell sorting fraction. They can be obtained from blood tissue or fat tissue or other sources
Implementation Method 2
a matrix material and cells are molded by means of a rotary casting method in a hollow mold to give an, in particular, tubular hollow body
Data Source
AI summary
The tissue construct with viable cells in an extracellular matrix made of fibrin is produced with a special method, in which a matrix material and cells are shaped into a hollow body, in particular a tubular hollow body, by means of a rotational casting method in a hollow mould (1), the method comprising the following steps: (a) introduction of cells of at least one cell type and/or a fibrinogen preparation into the rotating hollow mould (1) with the aid of an applicator (4), said applicator (4) being displaced along the rotational axis during the introduction and step (a) being performed one or more times; (b) continuation of the rotation process until the fibrinogen solidifies into a dimensionally stable matrix, obtaining a primarily solidified tissue construct; (c) removal of the tissue construct from the mould. The construct can also he obtained in a relatively short time from autologous materials.