{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,30]],"date-time":"2026-04-30T21:35:44Z","timestamp":1777584944758,"version":"3.51.4"},"reference-count":52,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2023,2,4]],"date-time":"2023-02-04T00:00:00Z","timestamp":1675468800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"FEDER\u2014Fundo Europeu de Desenvolvimento Regional funds","award":["POCI-01-0145-FEDER-007274"],"award-info":[{"award-number":["POCI-01-0145-FEDER-007274"]}]},{"name":"FEDER\u2014Fundo Europeu de Desenvolvimento Regional funds","award":["NORTE-01-0145-FEDER-000012"],"award-info":[{"award-number":["NORTE-01-0145-FEDER-000012"]}]},{"name":"FEDER\u2014Fundo Europeu de Desenvolvimento Regional funds","award":["NORTE-01-0246-FEDER-000018"],"award-info":[{"award-number":["NORTE-01-0246-FEDER-000018"]}]},{"name":"Portuguese funds","award":["POCI-01-0145-FEDER-007274"],"award-info":[{"award-number":["POCI-01-0145-FEDER-007274"]}]},{"name":"Portuguese funds","award":["NORTE-01-0145-FEDER-000012"],"award-info":[{"award-number":["NORTE-01-0145-FEDER-000012"]}]},{"name":"Portuguese funds","award":["NORTE-01-0246-FEDER-000018"],"award-info":[{"award-number":["NORTE-01-0246-FEDER-000018"]}]},{"name":"Project Biotherapies","award":["POCI-01-0145-FEDER-007274"],"award-info":[{"award-number":["POCI-01-0145-FEDER-007274"]}]},{"name":"Project Biotherapies","award":["NORTE-01-0145-FEDER-000012"],"award-info":[{"award-number":["NORTE-01-0145-FEDER-000012"]}]},{"name":"Project Biotherapies","award":["NORTE-01-0246-FEDER-000018"],"award-info":[{"award-number":["NORTE-01-0246-FEDER-000018"]}]},{"name":"HEPHAPC Program RESOLVE, Norte 2020","award":["POCI-01-0145-FEDER-007274"],"award-info":[{"award-number":["POCI-01-0145-FEDER-007274"]}]},{"name":"HEPHAPC Program RESOLVE, Norte 2020","award":["NORTE-01-0145-FEDER-000012"],"award-info":[{"award-number":["NORTE-01-0145-FEDER-000012"]}]},{"name":"HEPHAPC Program RESOLVE, Norte 2020","award":["NORTE-01-0246-FEDER-000018"],"award-info":[{"award-number":["NORTE-01-0246-FEDER-000018"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Bioengineering"],"abstract":"<jats:p>The treatment for osteomyelitis consists of surgical debridement, filling of the dead space, soft tissue coverage, and intravenous administration of antimicrobial (AM) agents for long periods. Biomaterials for local delivery of AM agents, while providing controllable antibiotic release rates and simultaneously acting as a bone scaffold, may be a valuable alternative; thus, avoiding systemic AM side effects. V-HEPHAPC is a heparinized nanohydroxyapatite (nHA)\/collagen biocomposite loaded with vancomycin that has been previously studied and tested in vitro. It enables a vancomycin-releasing profile with an intense initial burst, followed by a sustained release with concentrations above the Minimum Inhibitory Concentration (MIC) for MRSA. In vitro results have also shown that cellular viability is not compromised, suggesting that V-HEPHAPC granules may be a promising alternative device for the treatment of osteomyelitis. In the present study, V-HEPHAPC (HEPHAPC with vancomycin) granules were used as a vancomycin carrier to treat MRSA osteomyelitis. First, in vivo Good Laboratory Practice (GLP) toxicological tests were performed in a rabbit model, assuring that HEPHAPC and V-HEPHAPC have no relevant side effects. Second, V-HEPHAPC proved to be an efficient drug carrier and bone substitute to control MRSA infection and simultaneously reconstruct the bone cavity in a sheep model.<\/jats:p>","DOI":"10.3390\/bioengineering10020206","type":"journal-article","created":{"date-parts":[[2023,2,6]],"date-time":"2023-02-06T02:29:23Z","timestamp":1675650563000},"page":"206","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Vancomycin-Loaded, Nanohydroxyapatite-Based Scaffold for Osteomyelitis Treatment: In Vivo Rabbit Toxicological Tests and In Vivo Efficacy Tests in a Sheep Model"],"prefix":"10.3390","volume":"10","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2382-1106","authenticated-orcid":false,"given":"Nuno","family":"Alegrete","sequence":"first","affiliation":[{"name":"i3S\u2014Instituto de Investiga\u00e7\u00e3o e Inova\u00e7\u00e3o em Sa\u00fade, Universidade do Porto, R. Alfredo Allen 208, 4200-135 Porto, Portugal"},{"name":"FMUP\u2014Faculdade de Medicina, Universidade do Porto, Alameda Prof. Hern\u00e2ni Monteiro, 4200-319 Porto, Portugal"},{"name":"INEB\u2014Instituto de Engenharia Biom\u00e9dica, R. Alfredo Allen 208, 4200-135 Porto, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8018-4310","authenticated-orcid":false,"given":"Susana R.","family":"Sousa","sequence":"additional","affiliation":[{"name":"i3S\u2014Instituto de Investiga\u00e7\u00e3o e Inova\u00e7\u00e3o em Sa\u00fade, Universidade do Porto, R. Alfredo Allen 208, 4200-135 Porto, Portugal"},{"name":"INEB\u2014Instituto de Engenharia Biom\u00e9dica, R. Alfredo Allen 208, 4200-135 Porto, Portugal"},{"name":"Chemical Engineering Department, ISEP\u2014Instituto Superior de Engenharia do Porto, IPP\u2014Instituto Polit\u00e9cnico do Porto, R. Dr. Ant\u00f3nio Bernardino de Almeida 431, 4200-072 Porto, Portugal"}]},{"given":"Tatiana","family":"Padr\u00e3o","sequence":"additional","affiliation":[{"name":"i3S\u2014Instituto de Investiga\u00e7\u00e3o e Inova\u00e7\u00e3o em Sa\u00fade, Universidade do Porto, R. Alfredo Allen 208, 4200-135 Porto, Portugal"},{"name":"INEB\u2014Instituto de Engenharia Biom\u00e9dica, R. Alfredo Allen 208, 4200-135 Porto, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4837-6539","authenticated-orcid":false,"given":"\u00c2ngela","family":"Carvalho","sequence":"additional","affiliation":[{"name":"i3S\u2014Instituto de Investiga\u00e7\u00e3o e Inova\u00e7\u00e3o em Sa\u00fade, Universidade do Porto, R. Alfredo Allen 208, 4200-135 Porto, Portugal"},{"name":"INEB\u2014Instituto de Engenharia Biom\u00e9dica, R. Alfredo Allen 208, 4200-135 Porto, Portugal"}]},{"given":"Raquel","family":"Lucas","sequence":"additional","affiliation":[{"name":"FMUP\u2014Faculdade de Medicina, Universidade do Porto, Alameda Prof. Hern\u00e2ni Monteiro, 4200-319 Porto, Portugal"},{"name":"EPIUnit\u2014Instituto de Sa\u00fade P\u00fablica, Universidade do Porto, Rua das Taipas 135, 4050-600 Porto, Portugal"}]},{"given":"Raphael F.","family":"Canadas","sequence":"additional","affiliation":[{"name":"FMUP\u2014Faculdade de Medicina, Universidade do Porto, Alameda Prof. Hern\u00e2ni Monteiro, 4200-319 Porto, Portugal"},{"name":"Tech4MED\u2122, UPTEC, ASPRELA I, Office-Lab 0.16, Business Campus, R. Alfredo Allen, 455\/461, 4200-135 Porto, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2927-9071","authenticated-orcid":false,"given":"Catarina","family":"Lavrador","sequence":"additional","affiliation":[{"name":"Med, Mediterranean Institute for Agriculture, Environment and Development, University of \u00c9vora, P\u00f3lo da Mitra, Apartado 94, 7006-554 \u00c9vora, Portugal"}]},{"given":"Nuno","family":"Alexandre","sequence":"additional","affiliation":[{"name":"Med, Mediterranean Institute for Agriculture, Environment and Development, University of \u00c9vora, P\u00f3lo da Mitra, Apartado 94, 7006-554 \u00c9vora, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5302-0086","authenticated-orcid":false,"given":"F\u00e1tima","family":"G\u00e4rtner","sequence":"additional","affiliation":[{"name":"i3S\u2014Instituto de Investiga\u00e7\u00e3o e Inova\u00e7\u00e3o em Sa\u00fade, Universidade do Porto, R. Alfredo Allen 208, 4200-135 Porto, Portugal"},{"name":"IPATIMUP\u2014Instituto de Patologia e Imunologia, Universidade do Porto, Rua J\u00falio Amaral de Carvalho 45, 4200-135 Porto, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1361-4605","authenticated-orcid":false,"given":"Fernando J.","family":"Monteiro","sequence":"additional","affiliation":[{"name":"i3S\u2014Instituto de Investiga\u00e7\u00e3o e Inova\u00e7\u00e3o em Sa\u00fade, Universidade do Porto, R. Alfredo Allen 208, 4200-135 Porto, Portugal"},{"name":"INEB\u2014Instituto de Engenharia Biom\u00e9dica, R. Alfredo Allen 208, 4200-135 Porto, Portugal"},{"name":"FEUP\u2014Faculdade de Engenharia, Universidade do Porto, R. 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