Evidence map›Paper›PMID 40943403›Full record

ArticleInternational journal of molecular sciences2025

Formation of 3D Human Osteoblast Spheroids Incorporating Extracellular Matrix-Mimetic Phage Peptides as a Surrogate Bone Tissue Model.

Maria Giovanna Rizzo, Dario Morganti, Antonella Smeriglio, Emanuele Luigi Sciuto, Massimo Orazio Spata, Domenico Trombetta, Barbara Fazio, Salvatore Pietro Paolo Guglielmino, Sabrina Conoci

Abstract read
In one paragraph

Article in International journal of molecular sciences, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.

0numbers the graph read from it
0cells of the map it votes in
4citing 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

4 citing papers in PubMed.

  1. Article
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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

9 authors.

Maria Giovanna RizzoDepartment of Chemical, Biological, Pharmaceutical and Environmental Sciences, University of Messina, Viale Ferdinando Stagno d'Alcontres, 31, 98166 Messina, Italy.ORCID 0000-0001-6781-6387
Dario MorgantiCNR-IMM, Institute for Microelectronics and Microsystems, Viale F. Stagno D'Alcontres 31, 98166 Messina, Italy.ORCID 0000-0003-1682-1092
Antonella SmeriglioDepartment of Chemical, Biological, Pharmaceutical and Environmental Sciences, University of Messina, Viale Ferdinando Stagno d'Alcontres, 31, 98166 Messina, Italy.ORCID 0000-0002-9756-304X
Emanuele Luigi SciutoDepartment of Chemical, Biological, Pharmaceutical and Environmental Sciences, University of Messina, Viale Ferdinando Stagno d'Alcontres, 31, 98166 Messina, Italy.ORCID 0000-0003-4972-9874
Massimo Orazio SpataDepartment of Mathematics and Computer, University of Catania, Viale A. Doria 6, 95125 Catania, Italy.ORCID 0000-0001-6704-7485
Domenico TrombettaDepartment of Chemical, Biological, Pharmaceutical and Environmental Sciences, University of Messina, Viale Ferdinando Stagno d'Alcontres, 31, 98166 Messina, Italy.ORCID 0000-0003-4358-5224
Barbara FazioCNR-IMM, Institute for Microelectronics and Microsystems, Viale F. Stagno D'Alcontres 31, 98166 Messina, Italy.ORCID 0000-0002-1947-1123
Salvatore Pietro Paolo GuglielminoDepartment of Chemical, Biological, Pharmaceutical and Environmental Sciences, University of Messina, Viale Ferdinando Stagno d'Alcontres, 31, 98166 Messina, Italy.
Sabrina ConociDepartment of Chemical, Biological, Pharmaceutical and Environmental Sciences, University of Messina, Viale Ferdinando Stagno d'Alcontres, 31, 98166 Messina, Italy.

Funding

European Union (NextGeneration EU), through the MUR-PNRR Project SAMOTHRACE ECS00000022
6 · The paper itself

Abstract

Cell-cell communication and extracellular matrix (ECM) organization in a bone microenvironment are essential to replicate the bone microenvironment accurately. In this study, the extracellular matrix (ECM) was emulated by incorporating M13 phages, selected through phage display for displaying engineered peptides that mimic bone matrix proteins, into human osteoblast cultures to develop a three-dimensional bone model (3D BMP-Phage). Comprehensive analysis was performed to investigate: (i) the morphological development of spheroids, assessed by optical microscopy and quantified via fractal dimension analysis using box-counting algorithms; (ii) the biochemical composition of the extracellular matrix, evaluated by Raman spectroscopy; (iii) ECM protein deposition, analyzed through immunofluorescence staining; (iv) matrix mineralization, assessed by Alizarin Red staining and alkaline phosphatase (ALP) activity assay; and (v) osteogenic gene expression, measured by quantitative RT-PCR. The findings demonstrate that the 3D BMP-Phage model, facilitated by a cocktail of bone-mimicking peptides, enhances structural integrity, ECM complexity, mineralization, and osteogenic pathways compared to the control. This novel approach replicates key aspects of the bone microenvironment, providing a valuable platform for advanced physiological and regenerative medicine research under controlled conditions.

Indexed as

Bone and BonesExtracellular MatrixOsteoblastsPeptidesSpheroids, CellularBacteriophage M13HumansModels, BiologicalOsteogenesisTissue EngineeringPeptides3D bone tissue modelbone physiologycell–cell interactioncell communicationextracellular matrixregenerative medicine

Identifiers

PMID40943403
PMCPMC12428906

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Registered trials

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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 OpenQuestion graph.