Elucidating the Mechanism of Large-Diameter Titanium Dioxide Nanotubes in Protecting Osteoblasts Under Oxidative Stress Environment: The Role of Fibronectin and Albumin Adsorption

Int J Nanomedicine. 2024 Oct 22:19:10639-10659. doi: 10.2147/IJN.S488154. eCollection 2024.

Abstract

Background: Large-diameter titanium dioxide nanotubes (TNTs) have shown promise in preserving osteoblast function under oxidative stress (OS) in vitro. However, their ability to enhance osteogenesis in vivo under OS conditions and the underlying mechanisms remain unclear.

Purpose: This study aimed to evaluate the osteogenic potential of 110 nm TNTs (TNT110) compared to 30 nm TNTs (TNT30) in an aging rat model exhibiting OS, and to investigate the mechanisms involved.

Methods: Surface properties of TNTs were characterized, and in vitro and in vivo experiments were conducted to assess their osteoinductive effects under OS. Transcriptomic, proteomic analyses, and Western blotting were performed to investigate the protective mechanisms of TNT110 on osteoblasts. Protein adsorption studies focused on the roles of fibronectin (FN) and albumin (BSA) in modulating osteoblast behavior on TNT110.

Results: In both in vitro and in vivo experiments, TNT110 significantly improved new bone formation and supported osteoblast survival under OS conditions. Subsequent ribonucleic acid sequencing results indicated that TNT110 tended to attenuate inflammatory responses and reactive oxygen species (ROS) expression while promoting endoplasmic reticulum (ER) stress and extracellular matrix receptor interactions, all of which are crucial for osteoblast survival and functionality. Further confirmation indicated that the cellular behavior changes of osteoblasts in the TNT110 group could only occur in the presence of serum. Moreover, proteomic analysis under OS conditions revealed the pivotal roles of FN and BSA in augmenting TNT110's resistance to OS. Surface pretreatment of TNT110 with FN/BSA alone could beneficially influence the early adhesion, spreading, ER activity, and ROS expression of osteoblasts, a trend not observed with TNT30.

Conclusion: TNT110 effectively protects osteoblast function in the OS microenvironment by modulating protein adsorption, with FN and BSA synergistically enhancing osteogenesis. These findings suggest TNT110's potential for use in implants for elderly patients.

Keywords: osteogenesis; osteoporosis; oxidative stress; protein adsorption; titania nanotube.

MeSH terms

  • Adsorption / drug effects
  • Animals
  • Cell Survival / drug effects
  • Endoplasmic Reticulum Stress / drug effects
  • Fibronectins* / pharmacology
  • Male
  • Nanotubes* / chemistry
  • Osteoblasts* / drug effects
  • Osteogenesis* / drug effects
  • Oxidative Stress* / drug effects
  • Proteomics / methods
  • Rats
  • Rats, Sprague-Dawley
  • Reactive Oxygen Species / metabolism
  • Serum Albumin, Bovine / chemistry
  • Surface Properties
  • Titanium* / chemistry
  • Titanium* / pharmacology

Substances

  • Titanium
  • titanium dioxide
  • Fibronectins
  • Reactive Oxygen Species
  • Serum Albumin, Bovine

Grants and funding

This work was funded by National Natural Science Foundation of China (82171004), Zhejiang Provincial Science and Technology Project for Public Welfare (LQ23H140001), Wenzhou Municipal Science and Technology Project for Public Welfare (Y20220922), and Wenzhou Medical University Basic Scientific Research Operating Expenses (KYYW202230).