Plasma-Activated Coating for Vascular Devices

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Solution Overview

Problem

Current biomaterials used in cardiovascular applications, such as metal alloys, are inherently thrombogenic, leading to high rates of thrombosis and requiring prolonged antiplatelet therapy, while existing methods for enhancing hemocompatibility face challenges in robust attachment and long-term retention of biologically active substrates on complex geometries like stents.

Innovation Solution

A plasma-activated coating process that covalently binds plasmin or other fibrinolytic enzymes to a plasma-polymerized biocompatible surface on metallic, ceramic, or polymeric substrates, providing a non-thrombogenic interface that supports endothelialization and retains bioactivity over time, applicable to various vascular devices.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Strength

If metallic surfaces are used for vascular devices, then structural strength and durability are improved, but thrombogenicity increases requiring prolonged antiplatelet therapy

Engineering Contradiction:
Improvestructural strengthVSAvoidthrombogenicity
Core Design Contradiction:
StrengthVSObject-affected harmful factors

Solution Approach 1:

The invention applies a composite coating structure consisting of plasma-polymerized biocompatible polyhexane or polyacetylene with incorporated nitrogen on the metallic substrate surface. This composite approach combines the structural strength of metal alloys with the biocompatibility and low thrombogenicity of the polymer coating, eliminating the need for prolonged antiplatelet therapy while maintaining mechanical integrity

Inventive Principle:
Principle #40Composite materials

Solution Approach 2:

The invention modifies the surface chemical composition and structure by plasma polymerization with nitrogen incorporation, changing the surface properties from inherently thrombogenic metallic surfaces to biocompatible surfaces that support endothelialization and reduce platelet activation, thereby reducing thrombogenicity without sacrificing structural strength

Inventive Principle:
Principle #35Parameter changes

2Object-affected harmful factors

If existing methods are used to enhance hemocompatibility, then thrombogenicity is reduced, but robust attachment and long-term retention of biologically active substrates on complex geometries like stents is compromised

Engineering Contradiction:
ImprovethrombogenicityVSAvoidattachment retention
Core Design Contradiction:
Object-affected harmful factorsVSReliability

Solution Approach 1:

The plasma-polymerized polyhexane or polyacetylene layer with incorporated nitrogen acts as an intermediary between the metallic substrate and the biological environment. This intermediate layer provides both hemocompatibility and strong adhesion to complex geometries including stents, ensuring robust attachment and long-term retention of the biocompatible surface

Inventive Principle:
Principle #24Intermediary (Mediator)

Solution Approach 2:

The invention applies the plasma-polymerized coating specifically to the blood-contacting surfaces of vascular devices, including complex three-dimensional geometries like stents. This localized application ensures hemocompatibility where needed while maintaining the structural properties of the underlying metal in all regions

Inventive Principle:
Principle #3Local quality

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 solution significantly reduces thrombogenicity, maintains bioactivity, and supports endothelialization, allowing for safe and effective use in vascular applications with reduced risk of thrombosis and bleeding complications, even after storage and rehydration.

Implementation Method 1

plasmin covalently bound thereto

Methodology Applied
Scientific EffectCovalent bonding: Chemical Bonding

Implementation Method 2

plasma polymerized biocompatible polyhexane or polyacetylene having nitrogen incorporated therein

Methodology Applied
Scientific EffectPlasma polymerization: Plasma Enhanced Chemical Vapour Deposition

Implementation Method 3

Plasmin is a 90 kDa, two-chain proteolytic enzyme, capable of degrading multiple proteins in both the plasma and extracellular space, but in particular fibrin

Methodology Applied
Scientific EffectEnzyme catalysis: Enzyme

Data Source

PatentEP3191148B1Medical devices with reduced thrombogenicity
Publication Date: 2020.03.04 HEART RES INST LTD
  • EP3191148B1 patent drawingFigure 1
  • EP3191148B1 patent drawingFigure 2A~2B
  • EP3191148B1 patent drawingFigure 2C~2D

AI summary

A plasma-activated coating (PAC) process covalently binds enzymes in their bioactive state, has low thrombogenicity and can be robustly applied to medical devices, resisting delamination when deployed in vivo. Applying this process to attachment of proteins such as enzymes that inhibit thrombosis and anticoagulants such as heparin or heparin fragments, one can produce medical devices and other materials for use in vascular applications having a number of benefits including covalent attachment, not requiring intermediate linkers or chemistry; substrate independent - works on polymers, metals, ceramics, 3D shapes like stents, valves, etc.; bioactivity is retained; surface may retain greater bioactivity over time in vivo; Simultaneously supports endothelialisation; can be stored for long periods, following freeze drying, and retains effectiveness when rehydrated and; surface is able to bind many fibrinolytic enzymes such as streptokinase, urokinase, tPA, plasmin).