Immunomodulatory effect of Ti-Cu alloy by surface nanostructure synergistic with Cu2+ release

Xiaotong Zhao; Jiali Hu; Jingjun Nie; Dafu Chen; Gaowu Qin; Erlin Zhang

doi:10.1016/j.colsurfb.2023.113586

Immunomodulatory effect of Ti-Cu alloy by surface nanostructure synergistic with Cu²⁺ release

Colloids Surf B Biointerfaces. 2023 Nov:231:113586. doi: 10.1016/j.colsurfb.2023.113586. Epub 2023 Oct 11.

Authors

Xiaotong Zhao¹, Jiali Hu¹, Jingjun Nie², Dafu Chen³, Gaowu Qin⁴, Erlin Zhang⁵

Affiliations

¹ Key Lab. for Anisotropy and Texture of Materials, Education Ministry of China, School of Materials Science and Engineering, Northeastern University, Shenyang 110819, China.
² Laboratory of Bone Tissue Engineering, Beijing Laboratory of Biomedical Materials, National Center for Orthopaedics, Beijing Research Institute of Traumatology and Orthopaedics, Beijing Jishuitan Hospital, Beijing 100035, China.
³ Laboratory of Bone Tissue Engineering, Beijing Laboratory of Biomedical Materials, National Center for Orthopaedics, Beijing Research Institute of Traumatology and Orthopaedics, Beijing Jishuitan Hospital, Beijing 100035, China. Electronic address: chendafujst@126.com.
⁴ Key Lab. for Anisotropy and Texture of Materials, Education Ministry of China, School of Materials Science and Engineering, Northeastern University, Shenyang 110819, China; Research Center for Metallic Wires, Northeastern University, Shenyang 110819, China.
⁵ Key Lab. for Anisotropy and Texture of Materials, Education Ministry of China, School of Materials Science and Engineering, Northeastern University, Shenyang 110819, China; Research Center for Metallic Wires, Northeastern University, Shenyang 110819, China. Electronic address: zhangel@atm.neu.edu.cn.

PMID: 37837688
DOI: 10.1016/j.colsurfb.2023.113586

Abstract

The inflammatory response induced by implant/macrophage interaction has been considered to be one of the vital factors in determining the success of implantation. In this study, TiCuN_xO_y coating with an immunomodulatory strategy was proposed for the first time, using nanostructured TiCuN_xO_y coating synthesized on Ti-Cu alloy by oxygen and nitrogen plasma-based surface modification. It was found that TiCuN_xO_y coating inhibited macrophage proliferation but stimulated macrophage preferential activation and presented an elongated morphology due to the surface nanostructure. The most encouraging discovery was that TiCuN_xO_y coating promoted the initial pro-inflammatory response of macrophages and then accelerated the M1-to-M2 transition of macrophages via a synergistic effect of fast-to-slow Cu²⁺ release and surface nanostructure, which was considered to contribute to initial infection elimination and tissue healing. As expected, TiCuN_xO_y coating released desirable Cu²⁺ and generated a favorable immune response that facilitated HUVEC recruitment to the coating, and accelerated proliferation, VEGF secretion and NO production of HUVECs. On the other hand, it is satisfying that TiCuN_xO_y coating maintained perfect long-term antibacterial activity (≥99.9%), mainly relying on Cu₂O/CuO contact sterilization. These results indicated that TiCuN_xO_y coating might offer novel insights into the creation of a surface with immunomodulatory effects and long-term bactericidal potential for cardiovascular applications.

Keywords: Cu(2+) release; Endothelialization; Immunomodulatory; Nanostructure; Titanium-copper alloy.

MeSH terms

Alloys / chemistry
Alloys / pharmacology
Anti-Bacterial Agents* / pharmacology
Macrophages
Nanostructures*
Surface Properties
Titanium / chemistry
Titanium / pharmacology

Substances

Ti-Cu alloy
Anti-Bacterial Agents
Alloys
Titanium