Bioprosthetic Tissue Sterilization via Supercritical CO2 and Glycerol Drying

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Solution Overview

Problem

Current sterilization methods for biological tissue medical devices, such as ethylene oxide, pose health risks and regulatory challenges, while existing supercritical carbon dioxide (sCO2) methods are ineffective due to tissue dehydration issues when used with wet or glutaraldehyde-treated tissues.

Innovation Solution

A method involving a series of treatments including chemical fixation, bioburden reduction, anti-calcification, tissue purification, and drying with glycerol, followed by supercritical carbon dioxide sterilization in a gas permeable pouch, which maintains tissue integrity and allows multiple sterilization cycles without dehydration.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If ethylene oxide is used for sterilization of biological tissue medical devices, then sterilization is achieved, but harmful carcinogenic effects and regulatory compliance issues arise

Engineering Contradiction:
Improvesterilization effectivenessVSAvoidcarcinogenic effects
Core Design Contradiction:
ReliabilityVSObject-affected harmful factors

Solution Approach 1:

The patent changes the sterilization parameter from ethylene oxide chemical gas to supercritical carbon dioxide physical state, fundamentally altering the sterilization mechanism while eliminating carcinogenic effects. The supercritical fluid state of CO2 provides effective sterilization through physical properties rather than chemical toxicity.

Inventive Principle:
Principle #35Parameter changes

Solution Approach 2:

The patent employs a disposable gas permeable pouch that is discarded after a single use, eliminating the need for expensive continuous emissions monitoring systems and complex regulatory compliance infrastructure required for EO sterilization facilities.

Inventive Principle:
Principle #27Cheap short-living objects (Disposable)

2Reliability

If supercritical carbon dioxide is used to sterilize wet or glutaraldehyde-treated biological tissue, then sterilization is attempted, but tissue freezes and becomes brittle and unusable

Engineering Contradiction:
Improvesterilization effectivenessVSAvoidtissue integrity
Core Design Contradiction:
ReliabilityVSStability of the object's composition

Solution Approach 1:

The patent applies preliminary action by treating the biological tissue with glutaraldehyde solution before packaging in the gas permeable pouch. This pre-treatment creates a protective effect that prevents tissue freezing during subsequent sCO2 sterilization, allowing the tissue to maintain its structural integrity while still achieving effective sterilization.

Inventive Principle:
Principle #10Preliminary action

Solution Approach 2:

The gas permeable pouch acts as an intermediary between the tissue and the supercritical CO2 environment. It allows controlled interaction while protecting the tissue from direct exposure to freezing conditions, enabling sterilization without compromising tissue stability.

Inventive Principle:
Principle #24Intermediary (Mediator)

3Ease of manufacture

If biological tissue is packaged and delivered in dry form, then storage and delivery are improved, but sterilization becomes more challenging

Engineering Contradiction:
Improvepackaging and deliveryVSAvoidsterilization process
Core Design Contradiction:
Ease of manufactureVSDevice complexity

Solution Approach 1:

The gas permeable pouch serves multiple functions simultaneously: it maintains tissue moisture during storage and delivery, enables sCO2 sterilization penetration, and acts as a single-use barrier system. This multi-functionality simplifies the overall process by combining packaging and sterilization capabilities in one component.

Inventive Principle:
Principle #6Universality (Multi-functionality)

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 effectively sterilizes biological tissue without compromising its integrity, achieving significant microbial log reduction and allowing for dry packaging and delivery of bioprosthetic devices, thus addressing the limitations of existing methods.

Implementation Method 1

contacting the piece of soft mammalian tissue with supercritical carbon dioxide

Methodology Applied
Scientific EffectSupercritical fluid: Supercritical Fluid

Implementation Method 2

contacting the piece of soft mammalian tissue with a tissue drying mixture comprising an aqueous mixture comprising less than 95% by weight glycerol, less than 70% by weight ethanol, and less than 5% water

Methodology Applied
Scientific EffectSolvation: Solvation

Data Source

PatentEP4378309A1Sterilizing biological tissue with supercritical carbon dioxide
Publication Date: 2024.06.05 INNOVMEDICS LLC
  • EP4378309A1 patent drawingFigure 1~2
  • EP4378309A1 patent drawingFigure 3~4
  • EP4378309A1 patent drawingFigure 5~6

AI summary

A method of sterilizing biological tissue such as soft mammalian tissue that can be used to make bioprosthetic devices is disclosed. The method comprises contacting biological tissue with a bioburden reduction mixture, contacting biological tissue with a tissue drying mixture, and thereafter sterilizing the dry tissue with supercritical carbon dioxide. Bioprosthetic devices made using the methods disclosed herein include bioprosthetic heart valves and surgical tissue patches.