{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,12]],"date-time":"2026-08-12T06:29:15Z","timestamp":1786516155336,"version":"build-2736575974"},"reference-count":44,"publisher":"IOP Publishing","issue":"4","license":[{"start":{"date-parts":[[2026,8,12]],"date-time":"2026-08-12T00:00:00Z","timestamp":1786492800000},"content-version":"vor","delay-in-days":11,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,8,12]],"date-time":"2026-08-12T00:00:00Z","timestamp":1786492800000},"content-version":"tdm","delay-in-days":11,"URL":"https:\/\/iopscience.iop.org\/info\/page\/text-and-data-mining"}],"funder":[{"name":"Funda\u00e7\u00e3o para a Ci\u00eancia e a Tecnologia","award":["2021.06440.BD"],"award-info":[{"award-number":["2021.06440.BD"]}]}],"content-domain":{"domain":["iopscience.iop.org"],"crossmark-restriction":false},"short-container-title":["Biomed. Mater."],"published-print":{"date-parts":[[2026,8,1]]},"abstract":"Abstract<\/jats:title>\n \n Bacteria-mammalian cell co-cultures can provide information on host-cell responses to biomaterials under bacterial challenge that is not available from separate monocultures. This study established a two-stage osteogenic cell\u2013\n Staphylococcus aureus<\/jats:italic>\n co-culture for assessment of a previously developed dual and sequential drug delivery system (DDS) designed to release gentamicin followed by alendronate. MG-63 cells were initially exposed to\n \n \n \n <\/jats:tex-math>\n \n \n \n \n 10<\/mml:mn>\n 2<\/mml:mn>\n <\/mml:msup>\n <\/mml:mrow>\n \n \u2013<\/mml:mtext>\n <\/mml:mrow>\n \n \n 10<\/mml:mn>\n 5<\/mml:mn>\n <\/mml:msup>\n <\/mml:mrow>\n <\/mml:mrow>\n <\/mml:math>\n <\/jats:inline-formula>\n CFU\/ml of\n S. aureus<\/jats:italic>\n for different periods. An inoculum of\n \n \n \n <\/jats:tex-math>\n \n \n \n \n 10<\/mml:mn>\n 2<\/mml:mn>\n <\/mml:msup>\n <\/mml:mrow>\n <\/mml:mrow>\n <\/mml:math>\n <\/jats:inline-formula>\n CFU\/ml and a 2 h exposure were selected because MG-63 metabolic activity did not differ significantly from the monoculture control at this time point (\n p<\/jats:italic>\n > 0.05). These conditions were subsequently transferred to primary human bone-marrow mesenchymal stromal cells. The DDS-containing co-culture exhibited an increasing resazurin signal over 16 d and maintained adherent cells with an organised F-actin cytoskeleton. On day 25, protein-normalised alkaline phosphatase activity was 40 mol \u00b5g\n \u22121<\/jats:sup>\n protein in the DDS-containing co-culture, compared with 5 mol \u00b5g\n \u22121<\/jats:sup>\n protein in the basal-medium control and 63 mol \u00b5g\n \u22121<\/jats:sup>\n protein in the osteogenic-medium control. The model supports preliminary assessment of mammalian-cell compatibility and osteogenic-associated activity during sequential drug release under an initial bacterial challenge.\n <\/jats:p>","DOI":"10.1088\/1748-605x\/ae934c","type":"journal-article","created":{"date-parts":[[2026,7,31]],"date-time":"2026-07-31T22:52:29Z","timestamp":1785538349000},"page":"045035","update-policy":"https:\/\/doi.org\/10.1088\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Prokaryotic\/eukaryotic co-culture as a model for\n in vitro<\/i>\n functional validation of a dual and sequential drug delivery system with antimicrobial and bone regenerative features"],"prefix":"10.1088","volume":"21","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8391-5860","authenticated-orcid":true,"given":"Miguel A","family":"Rodrigues","sequence":"first","affiliation":[{"name":"University of Porto"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-5888-1100","authenticated-orcid":true,"given":"Giorgia","family":"Barbolini","sequence":"additional","affiliation":[{"name":"University of Porto"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0274-106X","authenticated-orcid":true,"given":"Maria P","family":"Ferraz","sequence":"additional","affiliation":[{"name":"University of Porto, Rua Dr. Roberto Frias s\/n"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3996-6545","authenticated-orcid":true,"given":"Jo\u00e3o P","family":"Borges","sequence":"additional","affiliation":[{"name":"School of Science and Technology, NOVA University Lisbon"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jos\u00e9 D","family":"Santos","sequence":"additional","affiliation":[{"name":"University of Porto"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4105-8148","authenticated-orcid":true,"given":"Maria A","family":"Lopes","sequence":"additional","affiliation":[{"name":"University of Porto"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"266","published-online":{"date-parts":[[2026,8,12]]},"reference":[{"key":"bmmae934cbib1","doi-asserted-by":"publisher","DOI":"10.1016\/j.heliyon.2023.e17488","type":"journal-article","article-title":"Advances in drug delivery systems, challenges and future directions","volume":"9","author":"Ezike","year":"2023","journal-title":"Heliyon"},{"key":"bmmae934cbib2","doi-asserted-by":"publisher","first-page":"71","DOI":"10.1186\/s12951-018-0392-8","type":"journal-article","article-title":"Nano based drug delivery systems: recent developments and future prospects","volume":"16","author":"Patra","year":"2018","journal-title":"J. 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