Evidence map›Paper›PMID 41898580›Full record

ArticleInternational journal of molecular sciences2026

Apple-Derived Vesicles Orchestrate Bone Regeneration:

Giulia Brunello, Ilaria Vitali, Luna Ardondi, Maria Pia Cavaleri, Lucia Sileo, Marta Degasperi, Francesca Zalunardo, Kathrin Becker, Beryl Schwarz-Herzke, Stefano Sivolella and 3 more

Abstract read
In one paragraph

Article in International journal of molecular sciences, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

0 citing papers in PubMed.

No citing paper in PubMed yet.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

13 authors.

Giulia BrunelloDepartment of Oral Surgery, University Hospital of Düsseldorf, 40225 Düsseldorf, Germany.
Ilaria VitaliDepartment of Medical Sciences, University of Ferrara, 44121 Ferrara, Italy.
Luna ArdondiDepartment of Medical Sciences, University of Ferrara, 44121 Ferrara, Italy.
Maria Pia CavaleriDepartment of Medical Sciences, University of Ferrara, 44121 Ferrara, Italy.
Lucia SileoDepartment of Medical Sciences, University of Ferrara, 44121 Ferrara, Italy.
Marta DegasperiResearch and Development Melinda Institute, Cles, 38023 Trento, Italy.
Francesca ZalunardoDepartment of Neurosciences, Dentistry Section, University of Padova, 35122 Padova, Italy.
Kathrin BeckerDepartment of Orthodontics and Dentofacial Orthopedics, Charité-Universitätsmedizin Berlin, 14197 Berlin, Germany.
Beryl Schwarz-HerzkeInstitute of Anatomy II, Medical Faculty, Heinrich Heine University, 40225 Düsseldorf, Germany.
Stefano SivolellaDepartment of Neurosciences, Dentistry Section, University of Padova, 35122 Padova, Italy.
Luca LovattiResearch and Development Melinda Institute, Cles, 38023 Trento, Italy.
Letizia FerroniMaria Cecilia Hospital, GVM Care and Research, 48033 Cotignola, Italy.
Barbara ZavanDepartment of Medical Sciences, University of Ferrara, 44121 Ferrara, Italy.ORCID 0000-0002-4779-4456

Funding

Ministry of Enterprises and Made in Italy Ministry of Enterprises and Made in Italy (Agevolazioni ex DM 09/12/2024) Project Melinda CDS001000 "MeByC", Grant number CUP C77B24000000008 of 10 March 2022.
6 · The paper itself

Abstract

The immune microenvironment critically influences bone healing, particularly in the oral cavity where inflammation and microbial biofilms can compromise regeneration. Plant-derived extracellular vesicles (PDEVs) offer a biocompatible means to modulate immune responses, and apple-derived extracellular vesicles (ADEVs) have shown antioxidant and anti-inflammatory activity, although their osteoregenerative potential remains unclear. Here, we investigate the indirect effects of ADEVs on bone regeneration by assessing how their immunomodulatory action on macrophages influences the osteogenic commitment of human dental pulp stem cells (DPSCs). ADEVs were isolated, characterized, and applied to THP-1-derived macrophages to evaluate polarization via morphology and immunofluorescence for M1 (iNOS) and M2 (ARG1) markers. Then, the extracellular vesicles (EVs) from untreated and ADEV-treated macrophages were isolated and applied to DPSCs. All EVs were efficiently internalized by both macrophages and DPSCs. Treated macrophages shifted toward an M2-like phenotype, and macrophage-derived EVs (MDEVs) promoted stem cell morphological features consistent with osteogenic activation. These findings suggest that ADEVs promote osteoregeneration indirectly by influencing macrophage polarization and modifying the osteoactive cargo of MDEVs, thereby supporting their potential in cell-free, immunomodulatory approaches for oral bone regeneration.

Indexed as

Bone RegenerationExtracellular VesiclesCell DifferentiationCells, CulturedDental PulpHumansMacrophagesMesenchymal Stem CellsOsteogenesisStem Cellsapple-derived extracellular vesiclesbone regenerationexosomesmesenchymal stem cellsplant-derived extracellular vesicles

Identifiers

PMID41898580
PMCPMC13026273

What Socratic holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.