Research output: Contribution to journal › Article › Academic › peer-review
3D-Printed Gentamicin-Releasing Poly-ε-Caprolactone Composite Prevents Fracture-Related Staphylococcus aureus Infection in Mice. / Guarch-Pérez, Clara; Shaqour, Bahaa; Riool, Martijn et al.
In: Pharmaceutics, Vol. 14, No. 7, 1363, 01.07.2022.Research output: Contribution to journal › Article › Academic › peer-review
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TY - JOUR
T1 - 3D-Printed Gentamicin-Releasing Poly-ε-Caprolactone Composite Prevents Fracture-Related Staphylococcus aureus Infection in Mice
AU - Guarch-Pérez, Clara
AU - Shaqour, Bahaa
AU - Riool, Martijn
AU - Verleije, Bart
AU - Beyers, Koen
AU - Vervaet, Chris
AU - Cos, Paul
AU - Zaat, Sebastian A. J.
N1 - Funding Information: Funding: This work was funded by the research project PRINTAID, within the EU Framework Programme for Research and Innovation Horizon 2020—Marie Skłodowska-Curie Innovative Training Networks under grant agreement No. 722467. Funding Information: This work was funded by the research project PRINTAID, within the EU Framework Programme for Research and Innovation Horizon 2020—Marie Skłodowska-Curie Innovative Training Networks under grant agreement No. 722467. We would like to thank the animal caretakers of the Animal Research Institute AMC (ARIA) for their excellent support during the animal experiments. The animal welfare officer Wouter Florijn (Department of Animal Welfare, Amsterdam UMC, Amsterdam, The Netherlands) is much acknowledged for his suggestions on the mouse studies. We would also like to thank Nicole van der Wel (Electron Microscopy Center Amsterdam (EMCA), Amsterdam UMC) for her technical assistance in the collection of the SEM images. Publisher Copyright: © 2022 by the authors. Licensee MDPI, Basel, Switzerland.
PY - 2022/7/1
Y1 - 2022/7/1
N2 - Bacterial infections are a serious healthcare complication in orthopedic and trauma surgery worldwide. Compared to systemic, local antibiotic prophylaxis has been shown to provide a higher antibiotic dose and bioavailability at the bone site with minimum toxic effects. However, there are still not enough biomaterial and antibiotic combinations available for personalized implant sizes for patients. The aim of this study was to develop a bone fixation plate coating made of a composite of poly-ε-caprolactone, hydroxyapatite and halloysite nanotubes loaded with gentamicin sulphate and fabricated via fused filament fabrication 3D printing technology. The mechanical and thermal properties of the biomaterial were analyzed. The in vitro release kinetics of gentamicin sulphate were evaluated for 14 days showing a burst release during the first two days that was followed by a sustained release of bactericidal concentrations. The composite loaded with 2 and 5% gentamicin sulphate exhibited complete antimicrobial killing of Staphylococcus aureus in an ex vivo mouse femur fixation plate infection model. Moreover, a fixation plate of the composite loaded with 5% of gentamicin sulphate was able to prevent S. aureus infection in the bone and surrounding tissue in an in vivo mouse bone fixation plate infection model 3 days post-surgery. In conclusion, the newly developed composite material successfully prevented infection in vivo. Additionally, the ability to use fused filament fabrication 3D printing to produce patient-specific implants may provide a wider range of personalized solutions for patients.
AB - Bacterial infections are a serious healthcare complication in orthopedic and trauma surgery worldwide. Compared to systemic, local antibiotic prophylaxis has been shown to provide a higher antibiotic dose and bioavailability at the bone site with minimum toxic effects. However, there are still not enough biomaterial and antibiotic combinations available for personalized implant sizes for patients. The aim of this study was to develop a bone fixation plate coating made of a composite of poly-ε-caprolactone, hydroxyapatite and halloysite nanotubes loaded with gentamicin sulphate and fabricated via fused filament fabrication 3D printing technology. The mechanical and thermal properties of the biomaterial were analyzed. The in vitro release kinetics of gentamicin sulphate were evaluated for 14 days showing a burst release during the first two days that was followed by a sustained release of bactericidal concentrations. The composite loaded with 2 and 5% gentamicin sulphate exhibited complete antimicrobial killing of Staphylococcus aureus in an ex vivo mouse femur fixation plate infection model. Moreover, a fixation plate of the composite loaded with 5% of gentamicin sulphate was able to prevent S. aureus infection in the bone and surrounding tissue in an in vivo mouse bone fixation plate infection model 3 days post-surgery. In conclusion, the newly developed composite material successfully prevented infection in vivo. Additionally, the ability to use fused filament fabrication 3D printing to produce patient-specific implants may provide a wider range of personalized solutions for patients.
KW - 3D printing
KW - Staphylococcus aureus
KW - bone-related infection
KW - fused filament fabrication
KW - mouse model
UR - http://www.scopus.com/inward/record.url?scp=85133438893&partnerID=8YFLogxK
U2 - 10.3390/pharmaceutics14071363
DO - 10.3390/pharmaceutics14071363
M3 - Article
C2 - 35890261
VL - 14
JO - Pharmaceutics
JF - Pharmaceutics
SN - 1999-4923
IS - 7
M1 - 1363
ER -
ID: 24984314