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Vancomycin-Loaded, Nanohydroxyapatite-Based Scaffold for Osteomyelitis Treatment: In Vivo Rabbit Toxicological Tests and In Vivo Efficacy Tests in a Sheep Model

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 sim...

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Autores principales: Alegrete, Nuno, Sousa, Susana R., Padrão, Tatiana, Carvalho, Ângela, Lucas, Raquel, Canadas, Raphael F., Lavrador, Catarina, Alexandre, Nuno, Gärtner, Fátima, Monteiro, Fernando J., Gutierres, Manuel
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9952702/
https://www.ncbi.nlm.nih.gov/pubmed/36829700
http://dx.doi.org/10.3390/bioengineering10020206
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author Alegrete, Nuno
Sousa, Susana R.
Padrão, Tatiana
Carvalho, Ângela
Lucas, Raquel
Canadas, Raphael F.
Lavrador, Catarina
Alexandre, Nuno
Gärtner, Fátima
Monteiro, Fernando J.
Gutierres, Manuel
author_facet Alegrete, Nuno
Sousa, Susana R.
Padrão, Tatiana
Carvalho, Ângela
Lucas, Raquel
Canadas, Raphael F.
Lavrador, Catarina
Alexandre, Nuno
Gärtner, Fátima
Monteiro, Fernando J.
Gutierres, Manuel
author_sort Alegrete, Nuno
collection PubMed
description 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.
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spelling pubmed-99527022023-02-25 Vancomycin-Loaded, Nanohydroxyapatite-Based Scaffold for Osteomyelitis Treatment: In Vivo Rabbit Toxicological Tests and In Vivo Efficacy Tests in a Sheep Model Alegrete, Nuno Sousa, Susana R. Padrão, Tatiana Carvalho, Ângela Lucas, Raquel Canadas, Raphael F. Lavrador, Catarina Alexandre, Nuno Gärtner, Fátima Monteiro, Fernando J. Gutierres, Manuel Bioengineering (Basel) Article 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. MDPI 2023-02-04 /pmc/articles/PMC9952702/ /pubmed/36829700 http://dx.doi.org/10.3390/bioengineering10020206 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Alegrete, Nuno
Sousa, Susana R.
Padrão, Tatiana
Carvalho, Ângela
Lucas, Raquel
Canadas, Raphael F.
Lavrador, Catarina
Alexandre, Nuno
Gärtner, Fátima
Monteiro, Fernando J.
Gutierres, Manuel
Vancomycin-Loaded, Nanohydroxyapatite-Based Scaffold for Osteomyelitis Treatment: In Vivo Rabbit Toxicological Tests and In Vivo Efficacy Tests in a Sheep Model
title Vancomycin-Loaded, Nanohydroxyapatite-Based Scaffold for Osteomyelitis Treatment: In Vivo Rabbit Toxicological Tests and In Vivo Efficacy Tests in a Sheep Model
title_full Vancomycin-Loaded, Nanohydroxyapatite-Based Scaffold for Osteomyelitis Treatment: In Vivo Rabbit Toxicological Tests and In Vivo Efficacy Tests in a Sheep Model
title_fullStr Vancomycin-Loaded, Nanohydroxyapatite-Based Scaffold for Osteomyelitis Treatment: In Vivo Rabbit Toxicological Tests and In Vivo Efficacy Tests in a Sheep Model
title_full_unstemmed Vancomycin-Loaded, Nanohydroxyapatite-Based Scaffold for Osteomyelitis Treatment: In Vivo Rabbit Toxicological Tests and In Vivo Efficacy Tests in a Sheep Model
title_short Vancomycin-Loaded, Nanohydroxyapatite-Based Scaffold for Osteomyelitis Treatment: In Vivo Rabbit Toxicological Tests and In Vivo Efficacy Tests in a Sheep Model
title_sort vancomycin-loaded, nanohydroxyapatite-based scaffold for osteomyelitis treatment: in vivo rabbit toxicological tests and in vivo efficacy tests in a sheep model
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9952702/
https://www.ncbi.nlm.nih.gov/pubmed/36829700
http://dx.doi.org/10.3390/bioengineering10020206
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