{
  "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.",
  "abstract_shown": true,
  "affiliations": [
    "Department of Medical Sciences, University of Ferrara, 44121 Ferrara, Italy",
    "Department of Biomedical Engineering, Isparta University of Applied Science, 32040 Isparta, Turkey",
    "Biomedical Engineering Program, Middle East Technical University, 06800 Ankara, Turkey",
    "Department of Oral Surgery, University Hospital Düsseldorf, 40225 Düsseldorf, Germany",
    "Department of Orthodontics and Dentofacial Orthopedics, Charité-Universitätsmedizin, 14197 Berlin, Germany",
    "Department of Neuroscience, Dentistry Section, University of Padova, 35128 Padova, Italy",
    "IRCCS Maria Cecilia Hospital, GVM Care & Research, 48033 Cotignola, Italy",
    "Department of Metallurgical and Materials Engineering, İzmir Katip Celebi University, 35620 İzmir, Turkey",
    "Department of Metallurgical and Materials Engineering, Middle East Technical University, 06800 Ankara, Turkey",
    "BIOMATEN, METU Center of Excellence in Biomaterials and Tissue Engineering, 06800 Ankara, Turkey"
  ],
  "article_type": null,
  "arxiv": null,
  "author_total": 13,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Maria Pia Cavaleri"
    },
    {
      "affs": [
        1,
        2
      ],
      "name": "Yasar Kemal Erdogan",
      "orcid": "0000-0002-5662-5398"
    },
    {
      "affs": [
        0
      ],
      "name": "Luna Ardondi",
      "orcid": "0000-0001-5406-5422"
    },
    {
      "affs": [
        3,
        4,
        5
      ],
      "name": "Giulia Brunello",
      "orcid": "0000-0003-1436-0085"
    },
    {
      "affs": [
        0
      ],
      "name": "Lucia Sileo"
    },
    {
      "affs": [
        6
      ],
      "name": "Ilenia Pia Cappucci"
    },
    {
      "affs": [
        6
      ],
      "name": "Laura Basile",
      "orcid": "0009-0008-8631-8031"
    },
    {
      "affs": [
        5
      ],
      "name": "Francesca Zalunardo"
    },
    {
      "affs": [
        5
      ],
      "name": "Sivolella Stefano"
    },
    {
      "affs": [
        7
      ],
      "name": "Gökhan Polat"
    },
    {
      "affs": [
        2,
        8,
        9
      ],
      "name": "Batur Ercan",
      "orcid": "0000-0003-1657-1142"
    },
    {
      "affs": [
        6
      ],
      "name": "Letizia Ferroni"
    },
    {
      "affs": [
        0,
        6
      ],
      "name": "Barbara Zavan",
      "orcid": "0000-0002-4779-4456"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/7nc6z15hrrmgs.bib",
  "cited_by": 0,
  "doi": "10.3390/ijms27219972",
  "fulltext_url": null,
  "id": "7nc6z15hrrmgs",
  "issns": [
    "1422-0067"
  ],
  "landing_url": "https://www.mdpi.com/1422-0067/27/21/9972",
  "language": null,
  "licence": "CC-BY-4.0",
  "licence_label": "CC BY 4.0",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [],
  "openalex": null,
  "pdf_url": null,
  "pmcid": null,
  "pmid": null,
  "published": "2026-11-06",
  "publisher": "MDPI AG",
  "ris": "https://research.draconitic.com/paper/7nc6z15hrrmgs.ris",
  "sources": [
    {
      "first_seen": "2026-11-10T00:21:27Z",
      "native_id": "10.3390/ijms27219972",
      "source": "crossref",
      "url": "https://www.mdpi.com/1422-0067/27/21/9972"
    }
  ],
  "subjects": [
    {
      "field": "biochemistry",
      "origin": "issn:1422-0067",
      "subfield": "general"
    }
  ],
  "title": "Nanostructured Titanium-Based Support Modulates Endothelial and Mesenchymal Cell Communication Through Extracellular Vesicles",
  "title_text": "Nanostructured Titanium-Based Support Modulates Endothelial and Mesenchymal Cell Communication Through Extracellular Vesicles",
  "type": "peer-reviewed",
  "updated_at": "2026-11-10T00:21:27Z",
  "url": "https://research.draconitic.com/paper/7nc6z15hrrmgs",
  "venue": "International Journal of Molecular Sciences",
  "versions": []
}