Biological Tissue Drying with Pressure Compensation for Transparency

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Solution Overview

Problem

Existing methods for producing biodegradable biological tissue face challenges such as non-transparency, stiffness due to pressure peaks, and insufficient water exchange, leading to non-biodegradability and hindered substance access.

Innovation Solution

A method involving stabilization with glycerol and polyethylene glycol followed by controlled drying between permeable fabric layers and pressure compensation layers to maintain tissue flexibility and transparency, allowing for biodegradability and mechanical stability.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If decellularized tissue is used as a scaffold, then biocompatibility and structural integrity are improved, but residual cellular material and DNA cause immunogenicity and inflammation

Engineering Contradiction:
ImprovebiocompatibilityVSAvoidimmunogenicity
Core Design Contradiction:
ReliabilityVSObject-affected harmful factors

Solution Approach 1:

The patent employs strong oxidizing agents including sodium hydroxide (NaOH) at concentrations of 0.1-10% for 1-72 hours, hydrogen peroxide (H2O2) at 0.1-10% for 1-48 hours, and ozone treatment at 1-100 mg/L for 1-48 hours. These oxidants effectively remove residual cellular material and DNA from the decellularized tissue scaffold, reducing immunogenicity while preserving the extracellular matrix structure and biocompatibility

Inventive Principle:
Principle #38Strong oxidants (Accelerated oxidation)

Solution Approach 2:

The patent uses combination treatments involving multiple decellularization and sterilization methods. For example, combining mechanical disruption with chemical oxidation (NaOH/H2O2), or combining ozone treatment with UV irradiation. These composite approaches ensure complete removal of immunogenic materials while maintaining scaffold integrity and biological functionality

Inventive Principle:
Principle #40Composite materials

2Loss of substance

If conventional decellularization methods are used, then cellular material is removed, but the process is time-consuming and lacks standardization

Engineering Contradiction:
Improvecellular material removalVSAvoidprocessing time
Core Design Contradiction:
Loss of substanceVSLoss of time

Solution Approach 1:

The patent establishes predetermined standardized protocols for decellularization with specific parameters: NaOH concentration (0.1-10%) and time (1-72 hours), H2O2 concentration (0.1-10%) and time (1-48 hours), ozone concentration (1-100 mg/L) and time (1-48 hours). These pre-established protocols eliminate trial-and-error processes and provide reproducible, time-efficient decellularization procedures

Inventive Principle:
Principle #10Preliminary action

Solution Approach 2:

The patent systematically optimizes and standardizes critical parameters including chemical concentration, treatment duration, temperature, and pH levels. By establishing specific parameter ranges (e.g., NaOH 0.1-10% for 1-72 hours, ozone 1-100 mg/L for 1-48 hours), the method achieves consistent cellular material removal within controlled timeframes, reducing processing variability and overall time

Inventive Principle:
Principle #35Parameter changes

3Object-affected harmful factors

If extensive decellularization treatment is applied, then immunogenicity is reduced, but structural integrity and mechanical properties deteriorate

Engineering Contradiction:
ImproveimmunogenicityVSAvoidstructural integrity
Core Design Contradiction:
Object-affected harmful factorsVSStrength

Solution Approach 1:

The patent applies controlled oxidation treatments with specific concentration and time parameters to achieve sufficient cellular material removal without excessive damage to the extracellular matrix. For example, using NaOH at 0.1-10% for 1-72 hours or H2O2 at 0.1-10% for 1-48 hours provides adequate decellularization while preserving scaffold strength, avoiding the need for prolonged or high-concentration treatments that would compromise structural integrity

Inventive Principle:
Principle #16Partial or excessive action

Solution Approach 2:

The patent employs gentle initial decellularization steps followed by milder finishing treatments. The sequence of treatments (e.g., mechanical disruption first, then controlled chemical oxidation) progressively removes cellular material while preserving the underlying matrix structure. This staged approach cushions the scaffold against excessive mechanical or chemical stress that would compromise structural integrity

Inventive Principle:
Principle #11Beforehand cushioning (Prior cushioning)

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

Results in a biodegradable, transparent, and mechanically stable tissue suitable for medical implants, enabling cellular ingrowth and optical clarity during operations.

Implementation Method 1

ozone at a concentration of 1 to 100 mg/L for a period of 1 to 48 hours

Methodology Applied
Scientific EffectOxidation: Oxidation

Implementation Method 2

hydrogen peroxide for a period of 1 to 48 hours

Methodology Applied
Scientific EffectHomolytic fission:

Implementation Method 3

hydrogen peroxide for a period of 1 to 48 hours

Methodology Applied
Scientific EffectOxidation: Oxidation

Implementation Method 4

sodium hydroxide for a period of 1 to 72 hours

Methodology Applied
Scientific EffectHydrolysis: Hydrolysis

Data Source

PatentEP4514413B1Method for the production of biological tissue
Publication Date: 2026.05.06 BIOTRONIK AG
  • EP4514413B1 patent drawingFigure 1~2
  • EP4514413B1 patent drawingFigure 3
  • EP4514413B1 patent drawingFigure 4A~4F

AI summary

A first aspect of invention relates a method for preparing a biodegradable biological tissue, preferably a collagen containing tissue. The (decellularized) biological tissue is first stabilized by a tissue water replacing material and then dried while applying an elevated pressure to the biological tissue. A second aspect of the invention relates to a method for producing a non-biodegradable biological tissue tube (i.e. hollow cylinder), preferably a collagen containing tissue tube.