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Published on: February 9, 2015
Impact of Antibiotic-Loaded PMMA Spacers on the Osteogenic Potential of hMSCs
Jakob Hofmann1, Tim Niklas Bewersdorf1, Ulrike Sommer1
1Clinic for Trauma and Reconstructive Surgery, Centre for Orthopedics, Trauma and Reconstructive Surgery and Paraplegiology, University Hospital Heidelberg, Schlierbacher Landstrasse 200a, 69118 Heidelberg, Germany.
Abstract:
Antibiotic-loaded PMMA bone cement is frequently used in modern trauma and orthopedic surgery. Although many of the antibiotics routinely applied are described to have cytotoxic effects in the literature, clinical experience shows no adverse effects for bone healing. To determine the effects of antibiotic-loaded PMMA spacers on osteogenesis in vitro, we cultivated human bone marrow mesenchymal stem cells (BM-hMSCs) in the presence of PMMA spacers containing Gentamicin, Vancomycin, Gentamicin + Clindamycin as well as Gentamicin + Vancomycin in addition to a blank control (agarose) and PMMA containing no antibiotics. The cell number was assessed with DAPI staining, and the osteogenic potential was evaluated by directly measuring the amount of hydroxyapatite synthesized using radioactive 99mTc-HDP labelling as well as measuring the concentration of calcium and phosphate in the cell culture medium supernatant. The results showed that Gentamicin and Vancomycin as well as their combination show a certain amount of cytotoxicity but no negative effect on osteogenic potential. The combination of Gentamicin and Clindamycin, on the other hand, led to a drastic reduction in both the cell count and the osteogenic potential.
Insights
Antibiotic-loaded bone cement with Gentamicin and Vancomycin showed cytotoxicity but did not impair bone healing. However, Gentamicin plus Clindamycin significantly reduced cell count and osteogenic potential in vitro.
Area of Science:
- Orthopedic Surgery
- Biomaterials Science
- Stem Cell Biology
Background:
- Antibiotic-loaded polymethyl methacrylate (PMMA) bone cement is widely used in orthopedic surgery.
- While some antibiotics exhibit cytotoxicity, clinical outcomes suggest no adverse effects on bone healing.
- Investigating the in vitro effects of these cements on osteogenesis is crucial.
Purpose of the Study:
- To evaluate the impact of antibiotic-loaded PMMA spacers on osteogenesis in vitro.
- To assess the effects of Gentamicin, Vancomycin, and their combinations on human bone marrow mesenchymal stem cells (BM-hMSCs).
Main Methods:
- Cultured BM-hMSCs with PMMA spacers containing Gentamicin, Vancomycin, Gentamicin + Clindamycin, Gentamicin + Vancomycin, or no antibiotics (control).
- Assessed cell number via DAPI staining.
- Measured osteogenic potential by hydroxyapatite synthesis (99mTc-HDP labeling) and calcium/phosphate levels in cell culture supernatant.
Main Results:
- Gentamicin and Vancomycin, individually and combined, demonstrated some cytotoxicity but did not negatively affect osteogenic potential.
- The combination of Gentamicin and Clindamycin resulted in a significant decrease in both cell count and osteogenic potential.
- Control groups (agarose and antibiotic-free PMMA) showed no adverse effects.
Conclusions:
- Gentamicin and Vancomycin in PMMA bone cement appear safe for osteogenesis in vitro, despite some cytotoxicity.
- The combination of Gentamicin and Clindamycin should be used with caution due to its detrimental effects on osteogenesis.
- These findings support the clinical observation of good bone healing with certain antibiotic-loaded bone cements.
