Vancomycin-Loaded, Nanohydroxyapatite-Based Scaffold for Osteomyelitis Treatment: In Vivo Rabbit Toxicological Tests and In Vivo Efficacy Tests in a Sheep Model
Bioengineering, 2023
Vancomycin-Loaded, Nanohydroxyapatite-Based Scaffold for Osteomyelitis Treatment: In Vivo Rabbit Toxicological Tests and In Vivo Efficacy Tests in a Sheep Model
Nuno Alegrete 1, 2, 3, *, Susana R. Sousa 1, 3, 4, Tatiana Padrão 1, 3, Ângela Carvalho 1, 3,
Raquel Lucas 2, 5, Raphael F. Canadas 2, 6, Catarina Lavrador 7, Nuno Alexandre 7,
Fátima Gärtner 1, 8, Fernando J. Monteiro 1, 3, 9 and Manuel Gutierres 2, 10
1 i3S—Instituto de Investigação e Inovação em Saúde, Universidade do Porto, R. Alfredo Allen 208, 4200-135 Porto, Portugal
Raquel Lucas 2, 5, Raphael F. Canadas 2, 6, Catarina Lavrador 7, Nuno Alexandre 7,
Fátima Gärtner 1, 8, Fernando J. Monteiro 1, 3, 9 and Manuel Gutierres 2, 10
1 i3S—Instituto de Investigação e Inovação em Saúde, Universidade do Porto, R. Alfredo Allen 208, 4200-135 Porto, Portugal
2 FMUP—Faculdade de Medicina, Universidade do Porto, Alameda Prof. Hernâni Monteiro, 4200-319 Porto, Portugal
3 INEB—Instituto de Engenharia Biomédica, R. Alfredo Allen 208, 4200-135 Porto, Portugal
4 Chemical Engineering Department, ISEP—Instituto Superior de Engenharia do Porto, IPP—Instituto Politécnico do Porto, R. Dr. António Bernardino de Almeida 431, 4200-072 Porto, Portugal
5 EPIUnit—Instituto de Saúde Pública, Universidade do Porto, Rua das Taipas 135, 4050-600 Porto, Portugal
6 Tech4MED™, UPTEC, ASPRELA I, Office-Lab 0.16, Business Campus, R. Alfredo Allen, 455/461, 4200-135 Porto, Portugal
7 Med,Mediterranean Institute for Agriculture, Environment and Development, University of Évora, Pólo daMitra, Apartado 94, 7006-554 Évora, Portugal
8 IPATIMUP—Instituto de Patologia e Imunologia, Universidade do Porto, Rua Júlio Amaral de Carvalho 45, 4200-135 Porto, Portugal
9 FEUP—Faculdade de Engenharia, Universidade do Porto, R. Dr. Roberto Frias, 4200-465 Porto, Portugal
10 CHUSJ—Centro Hospitalar Universitário S. João, Alameda Prof. Hernâni Monteiro, 4200-319 Porto, Portugal
* Correspondence: nuno.alegrete@ineb.up.pt
Abstract: 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 vancomycinreleasing 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.
Keywords: drug delivery; nanohydroxyapatite; osteomyelitis; vancomycin
Keywords: drug delivery; nanohydroxyapatite; osteomyelitis; vancomycin
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