title: Systemic and Local Administration of Antimicrobial and Cell Therapies to Prevent Methicillin-Resistant Staphylococcus epidermidis-Induced Femoral Nonunions in a Rat Model.
abstract: S. epidermidis is responsible for biofilm-related nonunions. This study compares the response to S. epidermidis-infected fractures in rats systemically or locally injected with vancomycin or bone marrow mesenchymal stem cells (BMSCs) in preventing the nonunion establishment. The 50% of rats receiving BMSCs intravenously (s-rBMSCs) died after treatment. A higher cytokine trend was measured in BMSCs locally injected rats (l-rBMSCs) at day 3 and in vancomycin systemically injected rats (l-VANC) at day 7 compared to the other groups. At day 14, the highest cytokine values were measured in l-VANC and in l-rBMSCs for IL-10. µCT showed a good bony bridging in s-VANC and excellent both in l-VANC and in l-rBMSCs. The bacterial growth was lower in s-VANC and l-VANC than in l-rBMSCs. Histology demonstrated the presence of new woven bone in s-VANC and a more mature bony bridging was found in l-VANC. The l-rBMSCs showed a poor bony bridging of fibrovascular tissue. Our results could suggest the synergic use of systemic and local injection of vancomycin as an effective treatment to prevent septic nonunions. This study cannot sustain the systemic injection of BMSCs due to high risks, while a deeper insight into local BMSCs immunomodulatory effects is mandatory before developing cell therapies in clinics.
authors.affiliation: Cell and Tissue Engineering Laboratory, IRCCS Galeazzi Orthopaedic Institute, 20161 Milan, Italy.
authors.forename: Arianna B
authors.identifier: 0000-0002-5230-9718
authors.initials: AB
authors.lastname: Lovati
authors.affiliation: Laboratory of Clinical Chemistry and Microbiology, IRCCS Galeazzi Orthopaedic Institute, 20161 Milan, Italy; Department of Biomedical Science for Health, University of Milan, 20133 Milan, Italy.
authors.forename: Lorenzo
authors.initials: L
authors.lastname: Drago
authors.affiliation: Cell and Tissue Engineering Laboratory, IRCCS Galeazzi Orthopaedic Institute, 20161 Milan, Italy; Department of Veterinary Medicine (DiMeVet), University of Milan, 20133 Milan, Italy.
authors.forename: Marta
authors.initials: M
authors.lastname: Bottagisio
authors.affiliation: Cell and Tissue Engineering Laboratory, IRCCS Galeazzi Orthopaedic Institute, 20161 Milan, Italy.
authors.forename: Matilde
authors.initials: M
authors.lastname: Bongio
authors.affiliation: MAP Laboratory, Fondazione Filarete, 20139 Milan, Italy.
authors.forename: Marzia
authors.initials: M
authors.lastname: Ferrario
authors.affiliation: Laboratory of Experimental Biochemistry & Molecular Biology, IRCCS Galeazzi Orthopaedic Institute, 20161 Milan, Italy.
authors.forename: Silvia
authors.initials: S
authors.lastname: Perego
authors.affiliation: Laboratory of Experimental Biochemistry & Molecular Biology, IRCCS Galeazzi Orthopaedic Institute, 20161 Milan, Italy.
authors.forename: Veronica
authors.initials: V
authors.lastname: Sansoni
authors.affiliation: Laboratory of Clinical Chemistry and Microbiology, IRCCS Galeazzi Orthopaedic Institute, 20161 Milan, Italy.
authors.forename: Elena
authors.initials: E
authors.lastname: De Vecchi
authors.affiliation: Department of Reconstructive Surgery of Osteoarticular Infections, CRIO Unit, IRCCS Galeazzi Orthopaedic Institute, 20161 Milan, Italy.
authors.forename: Carlo L
authors.initials: CL
authors.lastname: Romanò
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000627:therapeutic use; D001854:Bone Marrow Cells / Q000166:cytology* / Q000502:physiology; D064987:Cell- and Tissue-Based Therapy / Q000379:methods*; D002478:Cells, Cultured; D004195:Disease Models, Animal; D005264:Femoral Fractures / Q000188:drug therapy* / Q000382:microbiology / Q000628:therapy*; D020136:Hydrogel, Polyethylene Glycol Dimethacrylate / Q000737:chemistry; D007093:Imidazoles / Q000627:therapeutic use; D008297:Male; D016106:Methicillin Resistance; D051381:Rats; D017208:Rats, Wistar; D013212:Staphylococcus epidermidis / Q000187:drug effects / Q000472:pathogenicity*; D013234:Stem Cells / Q000166:cytology / Q000502:physiology; D014640:Vancomycin / Q000737:chemistry / Q000627:therapeutic use
chemical_list: D000900:Anti-Bacterial Agents; D007093:Imidazoles; C050701:atipamezole; D020136:Hydrogel, Polyethylene Glycol Dimethacrylate; D014640:Vancomycin