Micro/Nanostructured Titanium Oxide Coating for Stent Biocompatibility

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Solution Overview

Problem

Conventional medical devices, particularly vascular stents, face issues with restenosis, thrombosis, and bacterial infections due to inadequate biocompatibility, leading to complications such as platelet activation, smooth muscle cell proliferation, and bacterial adhesion, which are not effectively addressed by existing pharmacological means or surface modifications.

Innovation Solution

A method involving electrochemical anodisation combined with atmospheric pressure plasma and ultraviolet radiation is used to create micro and nanostructured titanium oxide surfaces on titanium and titanium alloys, reducing platelet and bacterial adhesion while promoting endothelial cell growth, thereby enhancing biocompatibility and reducing the risk of thrombosis and infection.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If conventional bare-metal stents are used, then the device provides structural support and restores blood flow, but it triggers restenosis and thrombosis due to inadequate biocompatibility

Engineering Contradiction:
ImprovebiocompatibilityVSAvoidplatelet activation and thrombosis
Core Design Contradiction:
ReliabilityVSObject-affected harmful factors

Solution Approach 1:

The invention changes the surface parameters of the stent by creating micro and nano structured titanium oxide surfaces through electrochemical anodisation. This transforms the smooth metal surface into a hierarchical micro/nano structure with specific morphology (flower-like structures), which fundamentally alters the biological response of platelets and cells to the stent surface, reducing thrombogenicity while maintaining structural integrity

Inventive Principle:
Principle #35Parameter changes

Solution Approach 2:

The invention creates a composite surface structure consisting of titanium oxide coating on titanium alloy substrate. The multi-layered structure comprises a titanium oxide layer with micro and nano structures formed through controlled anodisation, combining the mechanical strength of titanium alloy with the biocompatible, anti-thrombogenic properties of structured titanium oxide surface

Inventive Principle:
Principle #40Composite materials

2Reliability

If drug-eluting stents are used to prevent restenosis, then smooth muscle cell proliferation is inhibited, but endothelial cell growth is suppressed and late-stage thrombosis may occur

Engineering Contradiction:
Improverestenosis preventionVSAvoidendothelial cell suppression and late thrombosis
Core Design Contradiction:
ReliabilityVSObject-affected harmful factors

Solution Approach 1:

The invention replaces the pharmacological approach (chemical drugs) with a physical approach (micro/nano surface structures). The structured titanium oxide surface physically interacts with cells through contact guidance and topographical cues, promoting endothelial cell growth and preventing smooth muscle cell proliferation without using drugs that cause immunosuppression or late thrombosis

Inventive Principle:
Principle #28Mechanics substitution (Replace mechanical system)

Solution Approach 2:

The invention creates locally differentiated surface properties at the micro and nano scale. The flower-like micro structures contain nanostructured features that provide different biological signals to different cell types: promoting endothelial cell adhesion and proliferation while inhibiting smooth muscle cell growth, achieving cell-specific responses through local surface architecture rather than uniform drug coating

Inventive Principle:
Principle #3Local quality

3Ease of manufacture

If conventional stent surfaces are used, then manufacturing is simple, but bacterial adhesion and infection risk are high

Engineering Contradiction:
Improvesurface fabricationVSAvoidbacterial adhesion
Core Design Contradiction:
Ease of manufactureVSObject-affected harmful factors

Solution Approach 1:

The invention changes the surface parameters through electrochemical anodisation, transforming the surface morphology into micro and nano structured titanium oxide. This process is achieved through controlled electrolysis in specific electrolyte solutions at controlled temperatures, creating anti-bacterial surface structures that prevent bacterial adhesion while maintaining manufacturing feasibility through a single-step anodisation process

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 method significantly reduces platelet activation and bacterial adhesion, improving hemocompatibility and antibacterial properties, leading to reduced risks of thrombosis and extended device longevity, even on aged samples, by forming a stable micro/nanostructured titanium oxide layer with flower-like morphology.

Implementation Method 1

depositing of a micro/nanostructured titanium oxide layer on the surface of the metal medical device by means of an electrochemical anodisation, whereby an electrode generates atmospheric pressure plasma, to allow creating active species in the liquid

Methodology Applied
Scientific EffectAtmospheric pressure plasma: Plasma

Implementation Method 2

treating the metal medical device by ultraviolet radiation (UV), wherein the UV source preferably emits a wavelength of 365 nm or below with an aerial power density of 3 to 6 mW cm-2

Methodology Applied
Scientific EffectUltraviolet radiation: Photo-oxidation

Implementation Method 3

depositing of a micro/nanostructured titanium oxide layer on the surface of the metal medical device by means of an electrochemical anodisation

Methodology Applied
Scientific EffectElectrochemical anodisation: Oxidation

Data Source

PatentEP4467167A1Method for coating a medical device, especially for fabrication of antithrombogenic and antibacterial titanium materials and their alloys
Publication Date: 2024.11.27 INSTITUT JOZEF STEFAN
  • EP4467167A1 patent drawingFigure 1
  • EP4467167A1 patent drawingFigure 2
  • EP4467167A1 patent drawingFigure 3

AI summary

The method for treatment of Ti and Ti alloys used for implants, especially vascular stents, is provided. The method comprises of two steps, where the first step is based on electrochemical anodisation with atmospheric plasma electrode in environment friendly liquid and the second step where UV irradiation of the substrate is used to activate the surface. In the first step, the surface of titanium and titanium alloys is oxidised and micro/nanostructured and it the second step surface is activated to assure more optimal biological response. The methods of invention enable formation of nanostructured titanium oxide layer on the surface of titanium and titanium alloys with improved biocompatibility/hemocompatibility against state of the art. This innovative approach reduces adhesion and activation of platelets and at the same time reduces bacterial adhesion.