Header

UZH-Logo

Maintenance Infos

Reduced thrombogenicity of surface-treated Nitinol implants steered by altered protein adsorption


Gegenschatz-Schmid, Katharina; Buzzi, Stefano; Grossmann, Jonas; Roschitzki, Bernd; Urbanet, Riccardo; Heuberger, Roman; Glück, Dorothea; Zucker, Arik; Ehrbar, Martin (2022). Reduced thrombogenicity of surface-treated Nitinol implants steered by altered protein adsorption. Acta Biomaterialia, 137:331-345.

Abstract

Blood-contacting medical implants made of Nitinol and other titanium alloys, such as neurovascular flow diverters and peripheral stents, have the disadvantage of being highly thrombogenic. This makes the use of systemic (dual) anti-platelet/anticoagulant therapies inevitable with related risks of device thrombosis, bleeding and other complications. Meeting the urgent clinical demand for a less thrombogenic Nitinol surface, we describe here a simple treatment of standard, commercially available Nitinol that renders its surface ultra-hydrophilic and functionalized with phosphate ions. The efficacy of this treatment was assessed by comparing standard and surface-treated Nitinol disks and braids, equivalent to flow diverters. Static and dynamic (Chandler loop) blood incubation tests showed a drastic reduction of thrombus formation on treated devices. Surface chemistry and proteomic analysis indicated a key role of phosphate and calcium ions in steering blood protein adsorption and avoiding coagulation cascade activation and platelet adhesion. A good endothelialization of the surface confirmed the biocompatibility of the treated surface. STATEMENT OF SIGNIFICANCE: Titanium alloys such as Nitinol are biocompatible and show favorable mechanical properties, which led to their widespread use in medical implants. However, in contact with blood their surface triggers the activation of the intrinsic coagulation cascade, which may result in catastrophic thrombotic events. The presented results showed that a phosphate functionalization of the titanium oxide surface suppresses the activation of both coagulation cascade and platelets, avoiding the subsequent formation of a blood clot. This novel approach has therefore a great potential for mitigating the risks associated to either thrombosis or bleeding complications (due to systemic anticoagulation) in patients with cardiovascular implants.

Abstract

Blood-contacting medical implants made of Nitinol and other titanium alloys, such as neurovascular flow diverters and peripheral stents, have the disadvantage of being highly thrombogenic. This makes the use of systemic (dual) anti-platelet/anticoagulant therapies inevitable with related risks of device thrombosis, bleeding and other complications. Meeting the urgent clinical demand for a less thrombogenic Nitinol surface, we describe here a simple treatment of standard, commercially available Nitinol that renders its surface ultra-hydrophilic and functionalized with phosphate ions. The efficacy of this treatment was assessed by comparing standard and surface-treated Nitinol disks and braids, equivalent to flow diverters. Static and dynamic (Chandler loop) blood incubation tests showed a drastic reduction of thrombus formation on treated devices. Surface chemistry and proteomic analysis indicated a key role of phosphate and calcium ions in steering blood protein adsorption and avoiding coagulation cascade activation and platelet adhesion. A good endothelialization of the surface confirmed the biocompatibility of the treated surface. STATEMENT OF SIGNIFICANCE: Titanium alloys such as Nitinol are biocompatible and show favorable mechanical properties, which led to their widespread use in medical implants. However, in contact with blood their surface triggers the activation of the intrinsic coagulation cascade, which may result in catastrophic thrombotic events. The presented results showed that a phosphate functionalization of the titanium oxide surface suppresses the activation of both coagulation cascade and platelets, avoiding the subsequent formation of a blood clot. This novel approach has therefore a great potential for mitigating the risks associated to either thrombosis or bleeding complications (due to systemic anticoagulation) in patients with cardiovascular implants.

Statistics

Citations

Dimensions.ai Metrics
14 citations in Web of Science®
14 citations in Scopus®
Google Scholar™

Altmetrics

Downloads

34 downloads since deposited on 27 Jan 2022
9 downloads since 12 months
Detailed statistics

Additional indexing

Item Type:Journal Article, refereed, original work
Communities & Collections:04 Faculty of Medicine > University Hospital Zurich > Clinic for Obstetrics
04 Faculty of Medicine > Functional Genomics Center Zurich
Dewey Decimal Classification:570 Life sciences; biology
610 Medicine & health
Scopus Subject Areas:Life Sciences > Biotechnology
Physical Sciences > Biomaterials
Life Sciences > Biochemistry
Physical Sciences > Biomedical Engineering
Life Sciences > Molecular Biology
Language:English
Date:1 January 2022
Deposited On:27 Jan 2022 09:21
Last Modified:16 Jun 2024 03:47
Publisher:Elsevier
ISSN:1742-7061
OA Status:Hybrid
Free access at:Publisher DOI. An embargo period may apply.
Publisher DOI:https://doi.org/10.1016/j.actbio.2021.10.022
PubMed ID:34673227
  • Content: Published Version
  • Licence: Creative Commons: Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0)