Development of a Microfluidic Vascularized Osteochondral Model as a Drug Testing Platform for Osteoarthritis.

drug testing inflammation microfluidics osteoarthritis osteochondral

Journal

Advanced healthcare materials
ISSN: 2192-2659
Titre abrégé: Adv Healthc Mater
Pays: Germany
ID NLM: 101581613

Informations de publication

Date de publication:
06 Oct 2024
Historique:
revised: 17 09 2024
received: 28 06 2024
medline: 7 10 2024
pubmed: 7 10 2024
entrez: 7 10 2024
Statut: aheadofprint

Résumé

Osteoarthritis (OA) is a degenerative joint disease characterized by changes in cartilage and subchondral bone. To date, there are no available drugs that can counteract the progression of OA, partly due to the inadequacy of current models to recapitulate the relevant cellular complexity. In this study, an osteochondral microfluidic model is developed using human primary cells to mimic an OA-like microenvironment and this study validates it as a drug testing platform. In the model, the cartilage compartment is created by embedding articular chondrocytes in fibrin hydrogel while the bone compartment is obtained by embedding osteoblasts, osteoclasts, endothelial cells, and mesenchymal stem cells in a fibrin hydrogel enriched with calcium phosphate nanoparticles. After developing and characterizing the model, Interleukin-1β is applied to induce OA-like conditions. Subsequently, the model potential is evaluated as a drug testing platform by assessing the effect of two anti-inflammatory drugs (Interleukin-1 Receptor antagonist and Celecoxib) on the regulation of inflammation- and matrix degradation-related markers. The model responded to inflammation and demonstrated differences in drug efficacy. Finally, it compares the behavior of the "Cartilage" and "Cartilage+Bone" models, emphasizing the necessity of incorporating both cartilage and bone compartments to capture the complex pathophysiology of OA.

Identifiants

pubmed: 39370575
doi: 10.1002/adhm.202402350
doi:

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

e2402350

Informations de copyright

© 2024 The Author(s). Advanced Healthcare Materials published by Wiley‐VCH GmbH.

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Auteurs

Shima Salehi (S)

Cell and Tissue Engineering Laboratory, IRCCS Istituto Ortopedico Galeazzi, Via Belgioioso 173, Milan, 20157, Italy.

Stefania Brambilla (S)

Cell and Tissue Engineering Laboratory, IRCCS Istituto Ortopedico Galeazzi, Via Belgioioso 173, Milan, 20157, Italy.

Marco Rasponi (M)

Department of Electronics, Information and Bioengineering, Politecnico di Milano, Via Ponzio 34/5, Milan, 20133, Italy.

Silvia Lopa (S)

Cell and Tissue Engineering Laboratory, IRCCS Istituto Ortopedico Galeazzi, Via Belgioioso 173, Milan, 20157, Italy.

Matteo Moretti (M)

Cell and Tissue Engineering Laboratory, IRCCS Istituto Ortopedico Galeazzi, Via Belgioioso 173, Milan, 20157, Italy.
Regenerative Medicine Technologies Lab, Laboratories for Translational Research (LRT), Ente Ospedaliero Cantonale (EOC), Via Chiesa 5, Bellinzona, 6500, Switzerland.
Service of Orthopaedics and Traumatology, Department of Surgery, EOC, Via Tesserete 46, Lugano, 6900, Switzerland.
Euler Institute, Faculty of Biomedical Sciences, Università della Svizzera Italiana (USI), Via Buffi 13, Lugano, 6900, Switzerland.

Classifications MeSH