{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T19:26:18Z","timestamp":1792697178787,"version":"4.5.0"},"reference-count":66,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,6,2]],"date-time":"2026-06-02T00:00:00Z","timestamp":1780358400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Pharmacol."],"abstract":"<jats:p>Osteosarcoma remains a lethal paediatric malignancy when it metastasises to lung, yet therapeutic progress has stalled for decades, in part because preclinical models poorly capture patient specific tumor microenvironments. Here, patient- derived osteosarcoma (PDOS) cells are assembled into uniform, matrix-free organoids and then embedded into photocrosslinkable extracellular matrices with independently tuneable stiffness and composition: collagen-rich gelatin methacryloyl (GelMA) or basement membrane protein-enriched lung decellularized extracellular matrix (dECM) methacryloyl (LungMA), each tuneable to soft (approximately 1 kPa) or stiff (approximately 4 kPa) conditions. Embedding converts otherwise compact organoids into invasive, expanding structures and increases resistance to doxorubicin relative to both 2D cultures and matrix-free organoids. Matrix identity influenced early invasion kinetics and treatment response, with LungMA promoting more aggressive invasion shortly after embedding and greater chemoresistance than GelMA, particularly under stiffer conditions. Image-based segmentation of core and invasive compartments revealed a critical divergence between metabolic viability readouts and functional invasion inhibition under chemotherapy, exposing limitations of conventional screening endpoints. These findings establish stiffness-controlled, tissue-derived extracellular matrix (ECM) organoid systems as a tuneable platform to interrogate microenvironment-driven osteosarcoma aggressiveness and to advance patient-specific assessment of therapeutic vulnerability in metastatic niche-like contexts.<\/jats:p>","DOI":"10.3389\/fphar.2026.1831729","type":"journal-article","created":{"date-parts":[[2026,6,2]],"date-time":"2026-06-02T05:41:57Z","timestamp":1780378917000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":2,"title":["Matrix type influences embedded patient-derived osteosarcoma organoid invasion and response to treatment"],"prefix":"10.3389","volume":"17","author":[{"given":"Luke","family":"Hipwood","sequence":"first","affiliation":[{"name":"Faculty of Health, School of Biomedical Sciences, Queensland University of Technology , , QLD","place":["Brisbane, Australia"]},{"name":"Centre for Biomedical Technologies, 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