Tabriz University of Medical Sciences BioImpacts 2228-5652 15 1 2025 01 19 Cell-imprinted substrates as biomimetic platforms for osteoarthritis modeling with mesenchymal stem cells 32628 32628 10.34172/bi.32628 EN Hanieh Sadat Hashemi Motahar https://orcid.org/0009-0005-6019-7321 Mojtaba Tajbakhsh Mahboobeh Tavassoli Shahin Bonakdar https://orcid.org/0000-0001-8759-3790 Mohammad Reza Sadeghi https://orcid.org/0000-0001-6713-5821 Journal Article 10.34172/bi.32628 2025 07 29 2025 11 01 Introduction: The objective of this study is twofold: first, to investigate the relationship between chondrocyte morphology and their own gene and protein expression profiles in healthy and osteoarthritic (OA) cartilage; and second, to assess whether replicating the morphology of OA chondrocytes (OACs) can induce a hypertrophic expression pattern in MSCs. Methods: Polydimethylsiloxane (PDMS) substrates were fabricated to replicate the morphologies of human OACs and healthy chondrocytes (HCs). MSCs were cultured on these imprinted substrates, and differentiation was assessed using real-time PCR, immunocytochemistry, Alcian blue/Safranin O staining, and scanning electron microscopy (SEM). Results: SEM and optical microscopy revealed that OACs had a larger surface area than HCs. Real-time PCR analysis showed morphology-dependent variations in the expression of cartilage- and OA-related markers, with statistically significant differences observed only for SOX9. Immunofluorescence analysis of collagen types I and II supported these findings, though visual inspection of the staining did not indicate any significant changes. Conclusion: The results show that OACs-imprinted substrates can be effectively combined with other methods to improve in vitro models of OA. This offers a useful tool for exploring disease mechanisms and potential therapies.