Metal-Organic Framework Coatings for Nitric Oxide Release

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Solution Overview

Problem

Current medical devices face complications due to incompatibility with human blood and tissue, leading to issues like thrombosis, inflammation, cell proliferation, and infection, and existing nitric oxide-releasing materials have inadequate NO loading dosages and structural limitations, making them unsuitable for long-term clinical use.

Innovation Solution

Development of a modular biomaterial using metal-organic frameworks that release nitric oxide, capable of producing therapeutic amounts for extended periods while maintaining structural integrity, by combining metals with organic linkers and incorporating nitric oxide-releasing functional groups, such as S-nitrosothiols or diazeniumdiolates, to create stable and biocompatible coatings for medical devices.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If conventional materials are used for medical devices, then device simplicity and ease of manufacture are maintained, but device failures occur due to thrombosis, inflammation, cell proliferation, and infection

Engineering Contradiction:
Improvedevice failure rateVSAvoidmaterial complexity
Core Design Contradiction:
ReliabilityVSDevice complexity

Solution Approach 1:

The patent uses composite materials consisting of metal-organic frameworks (MOFs) integrated with medical device surfaces. These composites combine the structural integrity of metals with the functional properties of organic linkers that can release nitric oxide, thereby reducing device failures from thrombosis and infection while maintaining manufacturability through coating applications

Inventive Principle:
Principle #40Composite materials

2Reliability

If systemic drug therapies are administered to prevent device complications, then thrombosis and inflammation are reduced, but systemic side effects and increased morbidity occur

Engineering Contradiction:
Improvedevice biocompatibilityVSAvoidsystemic side effects
Core Design Contradiction:
ReliabilityVSObject-affected harmful factors

Solution Approach 1:

The patent employs nitric oxide-releasing metal-organic frameworks as intermediary materials that locally deliver therapeutic nitric oxide at the device-tissue interface. This localized delivery mechanism prevents systemic circulation of drugs, thereby eliminating systemic side effects while maintaining anti-thrombotic and anti-inflammatory effects at the implant site

Inventive Principle:
Principle #24Intermediary (Mediator)

Solution Approach 2:

The invention implements local quality by concentrating nitric oxide release functionality directly at the blood-contacting surface of the device through MOF coatings. This localized therapeutic action provides high drug concentration where needed while avoiding systemic exposure, thus preventing complications without causing systemic morbidity

Inventive Principle:
Principle #3Local quality

3Reliability

If existing nitric oxide-releasing materials are used, then some thromboresistivity is achieved, but inadequate NO loading dosages and short duration of action limit clinical utility

Engineering Contradiction:
ImprovethromboresistivityVSAvoidNO release duration
Core Design Contradiction:
ReliabilityVSDuration of action of moving object

Solution Approach 1:

The patent utilizes parameter changes by systematically varying the metal nodes and organic linker compositions in metal-organic frameworks to optimize nitric oxide loading capacity and release kinetics. This modular approach enables tuning of NO release duration from hours to weeks, providing sustained thromboresistivity and extending clinical utility beyond short-term applications

Inventive Principle:
Principle #35Parameter changes

Solution Approach 2:

The invention employs porous metal-organic framework structures that provide high surface area and internal volume for nitric oxide storage. The porous architecture enables increased NO loading dosages while controlling release rates through pore size and surface chemistry, thereby achieving both high capacity and sustained duration of action

Inventive Principle:
Principle #31Porous materials

4Reliability

If material modifications are made to reduce device complications, then biocompatibility improves, but mechanical properties and structural integrity are altered

Engineering Contradiction:
ImprovebiocompatibilityVSAvoidmaterial mechanical properties
Core Design Contradiction:
ReliabilityVSStrength

Solution Approach 1:

The patent applies segmentation by separating the structural function (provided by the base device material) from the therapeutic function (provided by the MOF coating). This functional segmentation allows the underlying device to maintain its mechanical integrity while the surface coating provides biocompatibility enhancements through nitric oxide release without compromising structural strength

Inventive Principle:
Principle #1Segmentation

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 modular biomaterials provide sustained nitric oxide release, reducing thrombosis, inflammation, and cell proliferation, while maintaining mechanical properties, thus enhancing the longevity and safety of medical devices and reducing healthcare costs.

Implementation Method 1

incorporating nitric oxide-releasing functional groups, such as S-nitrosothiols or diazeniumdiolates, to create stable and biocompatible coatings

Methodology Applied
Scientific EffectNitric oxide release: Decomposition (biological)

Implementation Method 2

Metal-organic compounds have open spaces and pores that allow for the absorption and/or chemical reaction with small molecules, such as nitric oxide

Methodology Applied
Scientific EffectAdsorption: Adsorption

Data Source

PatentEP2519467B1Modular biocompatible materials for medical devices and uses thereof
Publication Date: 2020.09.09 COLORADO STATE UNIV RES FOUND
  • EP2519467B1 patent drawingFigure 1~2
  • EP2519467B1 patent drawingFigure 3a~3b
  • EP2519467B1 patent drawingFigure 4~5

AI summary

The present disclosure is directed to a method of producing nitric oxide comprising (i) providing a composition comprising a metal-organic framework, and (ii) exposing the composition to a nitric oxide-releasing compound. The disclosure also is directed to compositions, coatings, and medical devices comprising a metal-organic framework.