Bioresorbable Stent with NO-Releasing Nanoparticles

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Solution Overview

Problem

Conventional stents fail to inhibit overgrowth of smooth muscle and extracellular matrix, leading to vessel narrowing, and cause complications like post-implementation syndrome and incomplete endothelialization, due to their permanent presence and material-related inflammation, despite advancements in drug-eluting and biodegradable stents.

Innovation Solution

A bioresorbable stent with a scaffold and polymeric coating containing nitric oxide (NO)-releasing nanoparticles, made from different polymers, where the scaffold degrades more slowly than the coating, providing controlled and sustained NO release, inhibiting smooth muscle proliferation, promoting endothelial recovery, and reducing thrombosis.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Strength

If conventional permanent stents are used to maintain vascular patency, then structural support is provided, but late complications including stenosis and inflammation occur due to permanent presence

Engineering Contradiction:
Improvestructural supportVSAvoidinflammation and stenosis
Core Design Contradiction:
StrengthVSObject-affected harmful factors

Solution Approach 1:

The stent material transitions from permanent to bioresorbable, changing the temporal parameter of stent presence. The scaffold degrades over time (complete resorption within 2-3 years) while providing initial structural support, thereby eliminating long-term inflammation and stenosis risks associated with permanent stents.

Inventive Principle:
Principle #35Parameter changes

Solution Approach 2:

The bioresorbable scaffold is designed to be temporarily present and then naturally degraded by the body. The scaffold provides necessary structural support during the critical healing period and is subsequently absorbed, eliminating the need for permanent foreign material and associated late complications.

Inventive Principle:
Principle #34Discarding and recovering

2Object-affected harmful factors

If biodegradable stents are used to avoid permanent presence, then late complications are reduced, but incomplete endothelialization and thrombosis risk increase

Engineering Contradiction:
Improvelate complicationsVSAvoidendothelialization completeness
Core Design Contradiction:
Object-affected harmful factorsVSReliability

Solution Approach 1:

The scaffold surface is pre-coated with nitric oxide-releasing nanoparticles before implantation. This preliminary action ensures immediate release of nitric oxide upon deployment, which promotes endothelial cell adhesion and proliferation from the outset, preventing thrombosis and ensuring complete endothelialization before the scaffold degrades.

Inventive Principle:
Principle #10Preliminary action

Solution Approach 2:

Nitric oxide acts as an intermediary substance that mediates between the bioresorbable scaffold and the endothelial cells. The NO-releasing nanoparticles facilitate endothelialization and inhibit thrombosis during the scaffold degradation process, bridging the gap between temporary structural support and complete vascular healing.

Inventive Principle:
Principle #24Intermediary (Mediator)

3Object-affected harmful factors

If antiproliferative drugs are incorporated into stents to inhibit smooth muscle overgrowth, then stenosis is prevented, but endothelial cell regrowth is also inhibited leading to incomplete healing

Engineering Contradiction:
Improvesmooth muscle overgrowthVSAvoidendothelial healing
Core Design Contradiction:
Object-affected harmful factorsVSReliability

Solution Approach 1:

The patent extracts the harmful side effect of antiproliferative drugs by replacing them with nitric oxide-releasing nanoparticles. Nitric oxide selectively inhibits smooth muscle proliferation while promoting endothelialization, thereby preventing stenosis without compromising endothelial healing, unlike conventional antiproliferative drugs that inhibit both cell types.

Inventive Principle:
Principle #2Taking out (Extraction)

4Ease of manufacture

If single-layer stent design is used for simplicity, then manufacturing is easier, but controlled sustained drug release over extended periods cannot be achieved

Engineering Contradiction:
Improvestent fabricationVSAvoiddrug release duration
Core Design Contradiction:
Ease of manufactureVSDuration of action of moving object

Solution Approach 1:

The stent employs a nested structure where nitric oxide-releasing nanoparticles are incorporated within the scaffold matrix itself. This nested design allows the scaffold to serve dual functions: providing structural support and delivering sustained NO release over 2-3 years as it degrades, eliminating the need for separate coating layers while achieving prolonged therapeutic effect.

Inventive Principle:
Principle #7Nested doll (Nesting)

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 stent achieves sustained NO release for up to 24 months, offering immediate and prolonged vascular dilatation, anti-inflammatory effects, and anti-thrombotic properties, while bioresorbing naturally, thus addressing stenosis and inflammation issues.

Implementation Method 1

nitric oxide (NO)-releasing nanoparticles incorporated into the polymeric coating, and into the scaffold

Methodology Applied
Scientific EffectNitric oxide release:

Implementation Method 2

The polymers are subjected to hydrolysis and/or enzymatic degradation in the body

Methodology Applied
Scientific EffectHydrolysis degradation: Hydrolysis

Implementation Method 3

The polymers are subjected to hydrolysis and/or enzymatic degradation in the body

Methodology Applied
Scientific EffectHydrolysis: Hydrolysis

Implementation Method 4

The polymers are subjected to hydrolysis and/or enzymatic degradation in the body

Methodology Applied
Scientific EffectEnzymatic degradation: Enzyme

Data Source

PatentEP3085395B1Novel nitric oxide-eluting bioresorable stents for percutaneous coronary interventions
Publication Date: 2018.12.26 HEART BIOTECH
  • EP3085395B1 patent drawingFigure 1(a)~2(b)
  • EP3085395B1 patent drawingFigure 3(a)~4(b)

AI summary

Disclosed herein are bioresorbable stents which elute nitric oxide (NO). The stent is comprised of three main key design elements: a bioresorbable scaffold, a bioresorbable polymeric coating layer(s), and NO-releasing nanoparticles incorporated in the bioresorbable polymeric coating layer, and optionally also in the scaffold. The NO-releasing nanoparticles are made of nontoxic biocompatible and biodegradable materials; for example a chitosan polymer and optionally a sugar.