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Within tissue engineering, these scaffolds can be mechanically stimulated to specifically promote cartilage formation. While in vitro experiments are traditionally used to study the influence of scaffold structure on cell differentiation, in silico studies offer a complementary, cost-effective, and powerful approach. This numerical study employs a transient fluid\u2013structure interaction (FSI) model to modify the structural design of a mechanically stimulated hydrogel scaffold for enhanced cartilage cell differentiation. The study involved two key modification steps applied to scaffolds under 5% compression. In the first step, scaffold porosity was adjusted by altering the number of strands per layer. The scaffold designed with 38% porosity, consisting of 9 strands per layer across 9 layers, improved cartilage differentiation by approximately 15%. The second step focused on scaling the selected scaffold from step 1 by adjusting the number of layers while keeping the porosity constant, aiming to optimize pore dimensions. This led to a slight improvement in cartilage differentiation of about 2.3%. The results indicate that porosity exerts a more significant influence on cell differentiation than pore size in the structured scaffolds investigated. The FSI-based model demonstrates strong potential for analyzing the impact of pore architecture on cell differentiation, although manufacturing challenges of hydrogel scaffolds may limit the practical application of these modification strategies.<\/jats:p>","DOI":"10.1007\/s10237-025-01976-1","type":"journal-article","created":{"date-parts":[[2025,6,15]],"date-time":"2025-06-15T11:13:02Z","timestamp":1749985982000},"page":"1417-1433","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Numerical study of the structural design influence on cartilage cell differentiation in mechanically stimulated hydrogel scaffolds using an FSI-based model"],"prefix":"10.1007","volume":"24","author":[{"ORCID":"https:\/\/orcid.org\/0009-0004-3671-271X","authenticated-orcid":false,"given":"Pedram","family":"Azizi","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christoph","family":"Drobek","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3401-0090","authenticated-orcid":false,"given":"Hermann","family":"Seitz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,6,15]]},"reference":[{"key":"1976_CR1","doi-asserted-by":"publisher","first-page":"201","DOI":"10.1016\/j.compbiomed.2018.06.017","volume":"99","author":"D Ali","year":"2018","unstructured":"Ali D, Sen S (2018) Permeability and fluid flow-induced wall shear stress of bone tissue scaffolds: computational fluid dynamic analysis using Newtonian and non-Newtonian blood flow models. 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