ECM Conduits for Heart Valve Replacement

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Solution Overview

Problem

Current heart valve replacement options, such as mechanical, allograft tissue, and xenograft tissue valves, face challenges including blood clot formation, durability issues, immune rejection, and complex implantation procedures, necessitating a readily available, durable, and anatomically accurate tissue prosthesis for regenerating atrioventricular valves.

Innovation Solution

Development of extracellular matrix (ECM) material conduits that are sterile and acellular, designed to mimic the anatomy of native heart valves, which are implanted to replace defective AV valves, utilizing methods like rapid depressurization and sterilization with supercritical CO2 to maintain native growth factors and enhance decellularization, allowing for integration and remodeling into functional valve tissue.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Duration of action of stationary object

If mechanical heart valves are used, then long-term durability is improved, but blood clot formation and need for lifelong anticoagulant therapy worsen

Engineering Contradiction:
ImprovedurabilityVSAvoidblood clot formation
Core Design Contradiction:
Duration of action of stationary objectVSObject-affected harmful factors

Solution Approach 1:

The patent changes the material parameter from mechanical components to biological tissue (pericardium), fundamentally altering the interaction with blood. The pericardium valve is processed (lyophilization, sterilization) to maintain durability while preserving blood compatibility, eliminating the need for anticoagulant therapy while achieving long-term durability through tissue processing and structural design

Inventive Principle:
Principle #35Parameter changes

2Object-affected harmful factors

If allograft tissue valves are used, then blood clot formation is reduced, but availability and ease of implantation worsen

Engineering Contradiction:
Improveblood clot formationVSAvoidavailability
Core Design Contradiction:
Object-affected harmful factorsVSEase of manufacture

Solution Approach 1:

The patent uses readily available bovine pericardium tissue that can be processed and stored long-term through lyophilization. The valve is designed as a complete replacement system that is easy to implant, with the pericardium material being abundant and the processing methods (sterilization, lyophilization) enabling long-term storage and on-demand availability without the scarcity issues of human allografts

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

3Object-affected harmful factors

If xenograft tissue valves are used, then blood clot formation is reduced, but durability and resistance to calcification worsen

Engineering Contradiction:
Improveblood clot formationVSAvoiddurability
Core Design Contradiction:
Object-affected harmful factorsVSDuration of action of stationary object

Solution Approach 1:

The patent applies specific processing parameters to bovine pericardium (lyophilization, sterilization methods) to enhance durability and resistance to calcification while maintaining blood compatibility. The controlled processing transforms the raw tissue into a durable, long-lasting valve that resists degeneration and calcification, achieving durability comparable to or exceeding traditional xenograft valves

Inventive Principle:
Principle #35Parameter changes

Solution Approach 2:

The patent creates a composite structure by combining processed pericardium tissue with a supporting framework or sewing ring, enhancing overall durability and structural integrity. The composite construction allows the valve to withstand mechanical stresses and resist calcification while maintaining the blood-compatible properties of the pericardium material

Inventive Principle:
Principle #40Composite materials

4Object-affected harmful factors

If chemical treatments are applied to xenograft valves to reduce antigenicity, then immune rejection is reduced, but post-implantation durability worsens

Engineering Contradiction:
Improveimmune responseVSAvoidpost-implantation durability
Core Design Contradiction:
Object-affected harmful factorsVSDuration of action of stationary object

Solution Approach 1:

The patent extracts and removes cellular components from the pericardium tissue through decellularization processes, eliminating antigens that would trigger immune responses while preserving the extracellular matrix structure. This extraction of cellular material reduces immune rejection while maintaining the structural integrity and durability of the valve tissue

Inventive Principle:
Principle #2Taking out (Extraction)

Solution Approach 2:

The patent applies controlled chemical or physical treatment parameters to modify the tissue properties, reducing antigenicity while preserving structural integrity. The processing parameters (sterilization, lyophilization, decellularization) are optimized to remove immunogenic elements without compromising the mechanical properties and durability of the pericardium valve

Inventive Principle:
Principle #35Parameter changes

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 ECM material conduits provide a durable, anatomically accurate, and functional AV valve replacement with reduced immune rejection and prolonged functionality, as demonstrated by successful implantation and remodeling in animal models, achieving normal valve function and tissue similarity to native valves over time.

Implementation Method 1

utilizing methods like rapid depressurization and sterilization with supercritical CO2 to maintain native growth factors and enhance decellularization

Methodology Applied
Scientific EffectRapid depressurization: Depressurisation

Implementation Method 2

utilizing methods like rapid depressurization and sterilization with supercritical CO2 to maintain native growth factors and enhance decellularization

Methodology Applied
Scientific EffectSupercritical fluid sterilization: Supercritical Fluid

Data Source

PatentEP2714068B1Extracellular matrix material conduits and methods of making and using same
Publication Date: 2019.02.27 CORMATRIX CARDIOVASCULAR INC
  • EP2714068B1 patent drawingFigure 1
  • EP2714068B1 patent drawingFigure 2
  • EP2714068B1 patent drawingFigure 3

AI summary

Extracellular matrix (ECM) material conduits are disclosed. Methods for regenerating atrioventricular valves to replace defective atrioventricular valves within a heart of a subject using the ECM material conduits are also disclosed. Methods of sterilizing and decellularizing an ECM material are also disclosed.