Nanostructured Titanium-Based Support Modulates Endothelial and Mesenchymal Cell Communication Through Extracellular Vesicles
10 affiliations
- 1Department of Medical Sciences, University of Ferrara, 44121 Ferrara, Italy
- 2Department of Biomedical Engineering, Isparta University of Applied Science, 32040 Isparta, Turkey
- 3Biomedical Engineering Program, Middle East Technical University, 06800 Ankara, Turkey
- 4Department of Oral Surgery, University Hospital Düsseldorf, 40225 Düsseldorf, Germany
- 5Department of Orthodontics and Dentofacial Orthopedics, Charité-Universitätsmedizin, 14197 Berlin, Germany
- 6Department of Neuroscience, Dentistry Section, University of Padova, 35128 Padova, Italy
- 7IRCCS Maria Cecilia Hospital, GVM Care & Research, 48033 Cotignola, Italy
- 8Department of Metallurgical and Materials Engineering, İzmir Katip Celebi University, 35620 İzmir, Turkey
- 9Department of Metallurgical and Materials Engineering, Middle East Technical University, 06800 Ankara, Turkey
- 10BIOMATEN, METU Center of Excellence in Biomaterials and Tissue Engineering, 06800 Ankara, Turkey
Abstract
Titanium surface nanotopography can regulate cellular behavior not only through direct cell–material interactions but also by influencing extracellular vesicle (EV)-mediated communication. Here, we investigated how anodized nanostructured Ti–Nb–Ta–Zr–Hf surfaces affect human endothelial cells and human adipose-derived stem cells (hADSCs), as well as the biological activity of EVs released by each cell type. Nanostructuring increased surface roughness and hydrophilicity while maintaining compatibility with both cellular populations. Endothelial cells progressively adapted to the titanium surfaces, maintaining viability and NOS3 expression while reducing inflammatory, proliferative, and angiogenic activation markers. Although surface topography did not substantially affect endothelial EV size or release, EVs generated on nanostructured titanium displayed increased CD81 expression, enhanced recipient-cell and preserved endothelial monolayer organization compared with EVs generated on the bare surface. In hADSCs, the nanostructured interface induced a rounded morphology associated with reduced expression of focal-adhesion and cytoskeletal-tension mediators, including VCL, PTK2, ACTA2, and ROCK1, together with downregulation of the mechanosensitive transcriptional regulators YAP1 and WWTR1/TAZ. This response was accompanied by upregulation of the pro-osteogenic miRNAs miR-21-5p and miR-20a-5p, downregulation of the osteogenesis-inhibitory miRNAs miR-133a-5p and miR-138-5p, and activation of RUNX2, ALPL, BGLAP, and SPARC. hADSC-derived EVs were efficiently internalized by recipient cells and promoted a concordant osteogenic-priming response. Overall, nanostructured titanium modulates direct cellular mechanotransduction and the biological activity of EV-mediated signals in a cell-type-specific manner. Rather than demonstrating osteogenic–angiogenic coupling, these findings reveal parallel endothelial homeostatic and mesenchymal osteogenic responses that may independently support the establishment of a regenerative peri-implant microenvironment.
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BibTeX
@article{cavaleri2026nanostructured,
title = {{Nanostructured Titanium-Based Support Modulates Endothelial and Mesenchymal Cell Communication Through Extracellular Vesicles}},
author = {Maria Pia Cavaleri and Yasar Kemal Erdogan and Luna Ardondi and Giulia Brunello and Lucia Sileo and Ilenia Pia Cappucci and Laura Basile and Francesca Zalunardo and Sivolella Stefano and Gökhan Polat and Batur Ercan and Letizia Ferroni and Barbara Zavan},
journal = {International Journal of Molecular Sciences},
year = {2026},
month = nov,
doi = {10.3390/ijms27219972},
url = {https://www.mdpi.com/1422-0067/27/21/9972},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Nanostructured Titanium-Based Support Modulates Endothelial and Mesenchymal Cell Communication Through Extracellular Vesicles
AU - Maria Pia Cavaleri
AU - Yasar Kemal Erdogan
AU - Luna Ardondi
AU - Giulia Brunello
AU - Lucia Sileo
AU - Ilenia Pia Cappucci
AU - Laura Basile
AU - Francesca Zalunardo
AU - Sivolella Stefano
AU - Gökhan Polat
AU - Batur Ercan
AU - Letizia Ferroni
AU - Barbara Zavan
PY - 2026
DA - 2026/11/06
JO - International Journal of Molecular Sciences
DO - 10.3390/ijms27219972
UR - https://www.mdpi.com/1422-0067/27/21/9972
AB - Titanium surface nanotopography can regulate cellular behavior not only through direct cell–material interactions but also by influencing extracellular vesicle (EV)-mediated communication. Here, we investigated how anodized nanostructured Ti–Nb–Ta–Zr–Hf surfaces affect human endothelial cells and human adipose-derived stem cells (hADSCs), as well as the biological activity of EVs released by each cell type. Nanostructuring increased surface roughness and hydrophilicity while maintaining compatibility with both cellular populations. Endothelial cells progressively adapted to the titanium surfaces, maintaining viability and NOS3 expression while reducing inflammatory, proliferative, and angiogenic activation markers. Although surface topography did not substantially affect endothelial EV size or release, EVs generated on nanostructured titanium displayed increased CD81 expression, enhanced recipient-cell and preserved endothelial monolayer organization compared with EVs generated on the bare surface. In hADSCs, the nanostructured interface induced a rounded morphology associated with reduced expression of focal-adhesion and cytoskeletal-tension mediators, including VCL, PTK2, ACTA2, and ROCK1, together with downregulation of the mechanosensitive transcriptional regulators YAP1 and WWTR1/TAZ. This response was accompanied by upregulation of the pro-osteogenic miRNAs miR-21-5p and miR-20a-5p, downregulation of the osteogenesis-inhibitory miRNAs miR-133a-5p and miR-138-5p, and activation of RUNX2, ALPL, BGLAP, and SPARC. hADSC-derived EVs were efficiently internalized by recipient cells and promoted a concordant osteogenic-priming response. Overall, nanostructured titanium modulates direct cellular mechanotransduction and the biological activity of EV-mediated signals in a cell-type-specific manner. Rather than demonstrating osteogenic–angiogenic coupling, these findings reveal parallel endothelial homeostatic and mesenchymal osteogenic responses that may independently support the establishment of a regenerative peri-implant microenvironment.
SN - 1422-0067
ER -