journal article·2026-01Open access

A Vascularized Microphysiological System Reproducing Endochondral Ossification in Vitro to Study Ewing Sarcoma Proliferation and Migration

Maria Vittoria Colombo, Chiara Arrigoni, Tobias Faehling, Antonietta Verrillo, Viviana Secci, Thomas G. P. Grünewald, Giuseppe Talò, Alexandra Kummer, Jorge Gonzalez, Vincenzo De Rosa, Christian Candrian, Andrea Barbero, Florencia Cidre‐Aranaz, Matteo Moretti

Advanced Functional Materials· Volume 36· Issue 3

Abstract

Abstract Endochondral ossification (ECO) is the process at the basis of long bone development, occurring in children and involving vascularization and subsequent mineralization of a cartilage template. Deregulated bone developmental pathways could correlate with pediatric bone tumors, including Ewing Sarcoma (EwS), an aggressive tumor with a poor prognosis for patients with recurrent or metastatic disease. Considering the limitations of available EwS preclinical models, at developing a microphysiological system recapitulating bone developmental steps are aimed, to investigate their influence on EwS cell proliferation and migratory behavior. This system includes spheroids of mesenchymal stromal cells sequentially differentiated in chondrogenic and hypertrophic stages within a fibrin hydrogel, in the presence or not of vascular cells and mineralized particles. It shows that by modulating system components it is possible to recapitulate hypertrophic ECO stage, in a higher extent with the addition of vascular cells without a mineral component. Hypertrophic conditions foster the proliferation of EwS cells as compared to avascular and mineralized environments and support the migration of highly aggressive EWSR1::FLI1 low cell phenotype, contrarily to empty 3D fibrin gel. Overall, the results support the use of the ECO‐mimicking microphysiological system as a valuable preclinical model to investigate the role of developmental mechanisms in EwS onset and progression.
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Research context

OpenAlex topics: Sarcoma Diagnosis and Treatment · Bone Tumor Diagnosis and Treatments · Osteoarthritis Treatment and Mechanisms

SciVX discovery tags are terminology-based. OpenAlex topics are source-provided classifications.

Affiliations

Regenerative Medicine Division Institute for Translational Research Ente Ospedaliero Cantonale ‐ Università della Svizzera Italiana via F Chiesa 5 Bellinzona 6500 Switzerland

Department of Chemistry Materials and Chemical Engineering G.Natta Politecnico di Milano Piazzale Leonardo da Vinci 32 Milan 20100 Italy

Euler Institute Biomedical Sciences Faculty Università della Svizzera Italiana (USI) via Buffi 13 Lugano 6900 Switzerland

Hopp Children`s Cancer Center Heidelberg (KiTZ) 69120 Heidelberg Germany

Division of Translational Pediatric Sarcoma Research German Cancer Research Center (DKFZ) German Cancer Consortium (DKTK) 69120 Heidelberg Germany

National Center for Tumor Diseases (NCT) NCT Heidelberg, a partnership between DKFZ and Heidelberg University Hospital 69120 Heidelberg Germany

Institute of Pathology Heidelberg University Hospital 69120 Heidelberg Germany

Cell and Tissue Engineering Laboratory IRCCS Istituto Ortopedico Galeazzi Via Cristina Belgioioso, 173 Milan 20161 Italy

Pediatric Institute of Southern Switzerland Ente Ospedaliero Cantonale Bellinzona 6500 Switzerland

Service of Orthopaedics and Traumatology Department of Surgery Ente Ospedaliero Cantonale Via Tesserete 46 Lugano 6900 Switzerland

Department of Biomedicine University Hospital Basel University of Basel Hebelstrasse, 20 Basel 4031 Switzerland

Funding

Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung

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