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Purpose <p>The aim of this study was to evaluate the cytocompatibility of micro- and nano-scale commercially pure Titanium (cpTi) particles in contact with fibroblasts and keratinocytes and the penetration of cpTi particles across keratinocytes' layers.</p> Method <p>Commercially pure titanium (cp-Ti) particles with 50-nm or 1-µm size were chemically and morphologically characterized using a Field Emission Guns Electron Microscopy (FEGSEM), Scanning Transmission Electron Microscope (STEM), and Energy Dispersion Spectrometry (EDAX). Then, the cytotoxic profile of the particles was monitored in contact with murine L929 fibroblasts and TR146 keratinocytes for 1, 4, and 7 days. Further permeability assays were performed across a TR146 monolayer via Transwell<sup>TM</sup> model.</p> Results <p>Physicochemical characterization of cpTi nano-scale particles (cpTi NPs) revealed a mean size at 70&#xa0;nm and a specific surface area at around ~ 17.2 m<sup>2</sup>/g, while micro-scale particles (cpTi MP) size ranged from 0.3 up to 5.3&#xa0;μm with a mean size of 1.4&#xa0;μm at dry conditions. The optimized de-agglomeration of nanoparticles resulted in an increased specific surface area up to 57.3 m<sup>2</sup>/g. The metabolic activity of fibroblasts decreased against 50 or 100&#xa0;µg/ml cpTi over 3 days cell culture while keratinocytes were not affected. Moreover, cpTi NP were internalized and steadily translocated into keratinocyte monolayers, showing an apparent permeability coefficient of 6.65 × 10<sup>−6</sup> cm/s for 50&#xa0;µg/mL and 3.96 × 10<sup>−6</sup> cm/s for 100&#xa0;µg/mL.</p> Conclusions <p>Altogether, nano-scale titanium particles decreased the viability of fibroblasts although a significant viability of keratinocytes has been detected by standard cell culture assays. However, nano-scale titanium particles were found into keratinocytes and even trespassed the cells' layers that could reach other cells and blood vessels in an in vivo scenario. Thus, toxicity of titanium particles depends on their particle size, exposure time, content, and interaction with the surrounding media.</p> Graphical Abstract <p></p>

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Response of murine fibroblasts or human keratinocytes to micro- and nano-scale titanium particles: the permeability of particles across keratinocytes' monolayers

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年9月30日

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  • Catarina Pacheco,
  • Redouane Messous,
  • Rui P Moura,
  • Andreia Almeida,
  • Patrícia Silva,
  • Bruno Sarmento,
  • Hassan Bousbaa,
  • Júlio C. M. Souza

摘要

Purpose

The aim of this study was to evaluate the cytocompatibility of micro- and nano-scale commercially pure Titanium (cpTi) particles in contact with fibroblasts and keratinocytes and the penetration of cpTi particles across keratinocytes' layers.

Method

Commercially pure titanium (cp-Ti) particles with 50-nm or 1-µm size were chemically and morphologically characterized using a Field Emission Guns Electron Microscopy (FEGSEM), Scanning Transmission Electron Microscope (STEM), and Energy Dispersion Spectrometry (EDAX). Then, the cytotoxic profile of the particles was monitored in contact with murine L929 fibroblasts and TR146 keratinocytes for 1, 4, and 7 days. Further permeability assays were performed across a TR146 monolayer via TranswellTM model.

Results

Physicochemical characterization of cpTi nano-scale particles (cpTi NPs) revealed a mean size at 70 nm and a specific surface area at around ~ 17.2 m2/g, while micro-scale particles (cpTi MP) size ranged from 0.3 up to 5.3 μm with a mean size of 1.4 μm at dry conditions. The optimized de-agglomeration of nanoparticles resulted in an increased specific surface area up to 57.3 m2/g. The metabolic activity of fibroblasts decreased against 50 or 100 µg/ml cpTi over 3 days cell culture while keratinocytes were not affected. Moreover, cpTi NP were internalized and steadily translocated into keratinocyte monolayers, showing an apparent permeability coefficient of 6.65 × 10−6 cm/s for 50 µg/mL and 3.96 × 10−6 cm/s for 100 µg/mL.

Conclusions

Altogether, nano-scale titanium particles decreased the viability of fibroblasts although a significant viability of keratinocytes has been detected by standard cell culture assays. However, nano-scale titanium particles were found into keratinocytes and even trespassed the cells' layers that could reach other cells and blood vessels in an in vivo scenario. Thus, toxicity of titanium particles depends on their particle size, exposure time, content, and interaction with the surrounding media.

Graphical Abstract