Construction of Mussel-Inspired Dopamine–Zn2+ Coating on Titanium Oxide Nanotubes to Improve Hemocompatibility, Cytocompatibility, and Antibacterial Activity

Abstract

Zinc ions (Zn2+) are a highly potent bioactive factor with a broad spectrum of physiological functions. In situ continuous and controllable release of Zn2+ from the biomaterials can effectively improve the biocompatibility and antibacterial activity. In the present study, inspired by the adhesion and protein cross-linking in the mussel byssus, with the aim of improving the biocompatibility of titanium, a cost-effective one-step metal–catecholamine assembly strategy was developed to prepare a biomimetic dopamine–Zn2+ (DA-Zn2+) coating by immersing the titanium oxide nanotube (TNT) arrays on the titanium surface prepared by anodic oxidation into an aqueous solution containing dopamine (DA) and zinc ions (Zn2+). The DA-Zn2+ coatings with the different zinc contents exhibited excellent hydrophilicity. Due to the continuous release of zinc ions from the DA-Zn2+ coating, the coated titanium oxide nanotubes displayed excellent hemocompatibility characterized by platelet adhesion and activation and hemolysis assay. Moreover, the DA-Zn2+-coated samples exhibited an excellent ability to enhance endothelial cell (EC) adhesion and proliferation. In addition, the DA-Zn2+ coating can also enhance the antibacterial activity of the nanotubes. Therefore, long-term in situ Zn2+-releasing coating of the present study could serve as the bio-surfaces for long-term prevention of thrombosis, improvement of cytocompatibility to endothelial cells, and antibacterial activity. Due to the easy operation and strong binding ability of the polydopamine on various complicated shapes, the method of the present study can be further applied to other blood contact biomaterials or implantable medical devices to improve the biocompatibility.

Unravelling Surface Modification Strategies for Preventing Medical Device‐Induced Thrombosis

“…[63] One advantage of TNTs is the ability to be introduced further treatments, for example, plasma treatment, hemocompatible factors doping [96] or coating. [97,98] Aside from titanium dioxide coatings, titanium nitride (TiN) has long been used as a coating on medical devices such as heart valves, heart assist devices, and heart pumps. TiN surfaces considerably lower the likelihood of thrombus formation, much like TiO 2 coatings, however they are less wear resistant.…”

“…[ 63 ] One advantage of TNTs is the ability to be introduced further treatments, for example, plasma treatment, hemocompatible factors doping [ 96 ] or coating. [ 97,98 ]…”

Micro-arc oxidation (MAO) and its potential for improving the performance of titanium implants in biomedical applications

“…Zn is an essential trace element for the human body and an important component of superoxide dismutase (Siddiqi et al, 2018). Studies have shown that the incorporation of Zn onto the surface of Ti and its alloys has been shown to not only act as an effective antimicrobial agent but also improve cytocompatibility (Hu et al, 2022;Qin et al, 2022). It was reported that TiO2 coatings significantly inhibited bacterial growth without causing cytotoxicity at concentrations of Zn ions between 10 −5 and 10 −4 M (Zhang et al, 2016).…”

Nano selenium-doped TiO2 nanotube arrays on orthopedic implants for suppressing osteosarcoma growth

“…The preparation of TiO 2 nanotube arrays on the implant surface and the loading of drugs or bioactive substances into the unique hollow structure of TiO 2 nanotubes can promote the adhesion and growth of biological tissues in contact with the implant, and also realize the controlled release of drugs or bioactive substances, endowing the multiple functions of implants ( Ayon et al, 2007 ; Brammer et al, 2009 ; Kodama et al, 2009 ; von Wilmowsky et al, 2009 ; Gultepe et al, 2010 ; Zhang et al, 2023 ). Furthermore, various surface modifications are applied to TiO 2 nanotube arrays (TNA) to further improve the biological properties of TNA, such as inducing the generation of an apatite layer on the surface of TiO 2 nanotubes ( Oh and Jin, 2006 ; Kunze et al, 2008 ; Wang et al, 2008 ; Xiao et al, 2008 ; Kodama et al, 2009 ; Chen et al, 2019 ; Alvi et al, 2020 ; Wu et al, 2021 ), modulating the surface physicochemical properties of TiO 2 nanotubes ( Balaur et al, 2005 ; Lai et al, 2010 ; Vasilev et al, 2010 ), elemental doping ( Yang et al, 2019 ; Hu et al, 2022 ), and alkali treatment ( Oh et al, 2005 ). Although many studies show that appropriate surface modification of TNA can improve the biocompatibility and achieve multifunctionality, these studies mainly focus on the bone integration, and anti-tumor effect is still in its infancy, which urgently need more studies ( Brammer et al, 2010 ; Kang et al, 2010 ; Lai et al, 2010 ; Vasilev et al, 2010 ; Zhao et al, 2010 ).…”