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Here, we developed and optimised methods to generate spatial heterogeneity of hydrogel-embedded bioactive signalling molecules within organ-on-a-chip (OOAC) systems, to drive spatiotemporal tissue patterning through controlled stem cell differentiation. As an exemplar application, we spatially patterned bone morphogenetic protein-2 (BMP-2) in both closed-channel and open-chamber OOAC formats. The resulting BMP-2 gradient in 3D heparin methacryloyl\/gelatin methacryloyl, successfully drove spatially divergent differentiation of human bone marrow-derived stem cells into bone-like and cartilage-like regions, mimicking the process of endochondral ossification in the growth plate. The application of hydrogel-embedded morphogens to drive spatial tissue patterning within OOAC systems represents a significant technological advancement and has broad-ranging applicability for a diverse range of tissues and organs, and a wide variety of OOAC platforms.<\/jats:p>","DOI":"10.1177\/20417314251326256","type":"journal-article","created":{"date-parts":[[2025,6,25]],"date-time":"2025-06-25T03:13:20Z","timestamp":1750821200000},"update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":11,"title":["Engineering growth factor gradients to drive spatiotemporal tissue patterning in organ-on-a-chip systems"],"prefix":"10.1177","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0300-8230","authenticated-orcid":false,"given":"Timothy","family":"Hopkins","sequence":"first","affiliation":[{"name":"Centre for Predictive In Vitro Models, Queen Mary University of London, UK"},{"name":"Centre for Bioengineering, School of Engineering and Materials Science, Queen Mary University of London, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Swati","family":"Midha","sequence":"additional","affiliation":[{"name":"Centre for Predictive In Vitro Models, Queen Mary University of London, UK"},{"name":"Centre for Bioengineering, School of Engineering and Materials Science, Queen Mary University of London, UK"},{"name":"School of Biological Sciences, Institute for Life Sciences, University of Southampton, UK"},{"name":"Kennedy Institute of Rheumatology, Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, University of Oxford, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Simon","family":"Grossemy","sequence":"additional","affiliation":[{"name":"Centre for Predictive In Vitro Models, Queen Mary University of London, UK"},{"name":"Centre for Bioengineering, School of Engineering and Materials Science, Queen Mary University of London, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hazel R. 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The fibroblast growth factor receptor, FGFR3, forms gradients of intact and degraded protein across the growth plate of developing bovine ribs. 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