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Locally delivering anticancer compounds improves on high local concentrations with more efficient tumour\u2010killing effect, reduced drugs resistance and confined systemic effects. Here, the synthesis of injectable strontium\u2010doped calcium phosphate (SrCPC) scaffold was proposed as drug delivery system to combine bone tissue regeneration and anticancer treatment by controlled release of methotrexate (MTX) and doxorubicin (DOX), coded as SrCPC\u2010MTX and SrCPC\u2010DOX, respectively. The drug\u2010loaded cements were tested in an in vitro model of human OS cell line SAOS\u20102, engineered OS cell line (SAOS\u20102\u2010eGFP) and U2\u2010OS. The ability of doped scaffolds to induce OS cell death and apoptosis was assessed analysing cell proliferation and Caspase\u20103\/7 activities, respectively. To determine if OS cells grown on doped\u2010scaffolds change their migratory ability and invasiveness, a wound\u2010healing assay was performed. In addition, the osteogenic potential of SrCPC material was evaluated using human adipose derived\u2010mesenchymal stem cells. Osteogenic markers such as (i) the mineral matrix deposition was analysed by alizarin red staining; (ii) the osteocalcin (OCN) protein expression was investigated by enzyme\u2010linked immunosorbent assay test, and (iii) the osteogenic process was studied by real\u2010time polymerase chain reaction array. The delivery system induced cell\u2010killing cytotoxic effects and apoptosis in OS cell lines up to Day 7. SrCPC demonstrates a good cytocompatibility and it induced upregulation of osteogenic genes involved in the skeletal development pathway, together with OCN protein expression and mineral matrix deposition. The proposed approach, based on the local, sustained release of anticancer drugs from nanostructured biomimetic drug\u2010loaded cements is promising for future therapies aiming to combine bone regeneration and anticancer local therapy.<\/jats:p>","DOI":"10.1002\/jcp.31256","type":"journal-article","created":{"date-parts":[[2024,4,9]],"date-time":"2024-04-09T12:34:07Z","timestamp":1712666047000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":17,"title":["Osteosarcoma cell death induced by innovative scaffolds doped with chemotherapeutics"],"prefix":"10.1002","volume":"239","author":[{"given":"Carmen","family":"Lanzillotti","sequence":"first","affiliation":[{"name":"Laboratories of Cell Biology and Molecular Genetics, Department of Medical Sciences University of Ferrara Ferrara Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria 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