Decellularized Heart Valve Composite for Endothelialization

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Solution Overview

Problem

Pure decellularized heart valves (DHVs) lack effective endothelial cell coverage, leading to increased thrombosis and embolism risks due to plasma protein adsorption and platelet activation, which affects valve function and remodeling post-implantation.

Innovation Solution

A DHV composite is prepared by reacting decellularized heart valves with a copper chloride-dopamine hydrochloride mixed solution followed by a GDF11 solution, enhancing copper ion modification and endothelialization, resulting in improved blood compatibility and accelerated endothelialization.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Ease of manufacture

If pure decellularized heart valves are used, then the valve structure is simple and easy to manufacture, but the blood compatibility is poor due to lack of endothelial cell coverage leading to platelet activation and thrombosis risk

Engineering Contradiction:
Improveease of manufactureVSAvoidblood compatibility
Core Design Contradiction:
Ease of manufactureVSReliability

Solution Approach 1:

The patent creates a composite structure by combining decellularized heart valve matrix with copper ions and GDF11 growth factor. The copper ions are embedded in the valve matrix through soaking in copper chloride-dopamine hydrochloride solution, forming a composite material that provides both structural integrity and enhanced biological functionality including improved blood compatibility and endothelialization promotion.

Inventive Principle:
Principle #40Composite materials

Solution Approach 2:

The patent applies preliminary action by pre-modifying the decellularized heart valve with copper ions and GDF11 before implantation. The copper chloride-dopamine hydrochloride mixed solution treatment is performed in advance to embed copper ions in the valve matrix, and GDF11 is pre-loaded to facilitate subsequent endothelial cell colonization and reduce thrombosis risk upon implantation.

Inventive Principle:
Principle #10Preliminary action

2Ease of manufacture

If pure decellularized heart valves are used, then the manufacturing process is simple, but the valve function is compromised due to increased thrombosis and embolism risks

Engineering Contradiction:
Improvemanufacturing process simplicityVSAvoidthrombosis and embolism risk
Core Design Contradiction:
Ease of manufactureVSObject-generated harmful factors

Solution Approach 1:

The patent converts the harmful thrombogenic surface of the decellularized valve into a beneficial endothelialization-promoting surface. By embedding copper ions and GDF11 in the valve matrix, the originally harmful surface that activated platelets is transformed into a surface that attracts and supports endothelial cell growth, thereby converting the thrombosis risk into a protective endothelial layer.

Inventive Principle:
Principle #22Blessing in disguise (Convert harm into benefit)

3Reliability

If decellularized heart valves are modified with copper ions and GDF11, then the endothelialization is accelerated and blood compatibility is improved, but the manufacturing process becomes more complex

Engineering Contradiction:
Improveblood compatibilityVSAvoidmanufacturing process complexity
Core Design Contradiction:
ReliabilityVSDevice complexity

Solution Approach 1:

The patent merges multiple functions into a single integrated modification process. The copper chloride-dopamine hydrochloride mixed solution simultaneously serves as both the copper ion source and the dopamine-containing compound for embedding copper ions in the valve matrix. This combined approach consolidates what could be separate complex steps into one unified treatment process.

Inventive Principle:
Principle #5Merging (Combining)

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 DHV composite demonstrates reduced platelet activation, enhanced endothelialization, and improved mechanical properties, promoting in vivo remodeling and regeneration, thus addressing the limitations of existing valve substitutes.

Implementation Method 1

copper ions embedded in the valve matrix... catalyze the decomposition of S-nitrosothiols to generate nitric oxide

Methodology Applied
Scientific EffectCatalysis: Catalysis

Implementation Method 2

copper chloride-dopamine hydrochloride mixed solution... dopamine-containing compounds for embedding copper ions in the valve matrix

Methodology Applied
Scientific EffectCoordination complex formation: Chemical Bonding

Implementation Method 3

GDF11 solution... GDF11, a growth factor

Methodology Applied
Scientific EffectGrowth factor signaling:

Data Source

PatentUS20240226379A9Decellularized heart valve (DHV) composite, and preparation method and use thereof
Publication Date: 2024.07.11 XIEHE HOSPITAL ATTACHED TO TONGJI MEDICAL COLLEGE HUAZHONG SCI & TECH UNIV
  • US20240226379A9 patent drawing
  • US20240226379A9 patent drawing
  • US20240226379A9 patent drawing

AI summary

Some embodiments of the disclosure provide a decellularized heart valve (DHV) composite, a preparation method of the DHV composite, and a use of the DHV composite. In some examples, the preparation method of the DHV composite includes the following steps: S1, conducting a reaction I on a DHV with a copper chloride-dopamine hydrochloride mixed solution to obtain a copper ion-modified DHV; and S2, conducting a reaction II on the copper ion-modified DHV with a GDF11 solution to obtain the DHV composite. In other examples, the present disclosure provides a use of the DHV composite in preparation of a tissue-engineered heart valve (TEHV). In further examples, the TEHV is a heart valve (HV) with remodeling and regeneration capabilities.