Calcium Phosphate Spacers for the Local Delivery of Sitafloxacin and Rifampin to Treat Orthopedic Infections: Efficacy and Proof of Concept in a Mouse Model of Single-Stage Revision of Device-Associated Osteomyelitis
Osteomyelitis is a chronic bone infection that is often treated with adjuvant antibiotic-impregnated poly(methyl methacrylate) (PMMA) cement spacers in multi-staged revisions. However, failure rates remain substantial due to recurrence of infection, which is attributed to the poor performance of the...
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| Format: | Article |
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MDPI AG
2019-02-01
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| Series: | Pharmaceutics |
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| Online Access: | https://www.mdpi.com/1999-4923/11/2/94 |
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| author | Ryan P. Trombetta Mark J. Ninomiya Ihab M. El-Atawneh Emma K. Knapp Karen L. de Mesy Bentley Paul M. Dunman Edward M. Schwarz Stephen L. Kates Hani A. Awad |
| author_facet | Ryan P. Trombetta Mark J. Ninomiya Ihab M. El-Atawneh Emma K. Knapp Karen L. de Mesy Bentley Paul M. Dunman Edward M. Schwarz Stephen L. Kates Hani A. Awad |
| author_sort | Ryan P. Trombetta |
| collection | DOAJ |
| description | Osteomyelitis is a chronic bone infection that is often treated with adjuvant antibiotic-impregnated poly(methyl methacrylate) (PMMA) cement spacers in multi-staged revisions. However, failure rates remain substantial due to recurrence of infection, which is attributed to the poor performance of the PMMA cement as a drug release device. Hence, the objective of this study was to design and evaluate a bioresorbable calcium phosphate scaffold (CaPS) for sustained antimicrobial drug release and investigate its efficacy in a murine model of femoral implant-associated osteomyelitis. Incorporating rifampin and sitafloxacin, which are effective against bacterial phenotypes responsible for bacterial persistence, into 3D-printed CaPS coated with poly(lactic co-glycolic) acid, achieved controlled release for up to two weeks. Implantation into the murine infection model resulted in decreased bacterial colonization rates at 3- and 10-weeks post-revision for the 3D printed CaPS in comparison to gentamicin-laden PMMA. Furthermore, a significant increase in bone formation was observed for 3D printed CaPS incorporated with rifampin at 3 and 10 weeks. The results of this study demonstrate that osteoconductive 3D printed CaPS incorporated with antimicrobials demonstrate more efficacious bacterial colonization outcomes and bone growth in a single-stage revision in comparison to gentamicin-laden PMMA requiring a two-stage revision. |
| first_indexed | 2024-12-10T08:03:33Z |
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| id | doaj.art-d8763242108746ebb52ce337f972b8d9 |
| institution | Directory Open Access Journal |
| issn | 1999-4923 |
| language | English |
| last_indexed | 2024-12-10T08:03:33Z |
| publishDate | 2019-02-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Pharmaceutics |
| spelling | doaj.art-d8763242108746ebb52ce337f972b8d92022-12-22T01:56:43ZengMDPI AGPharmaceutics1999-49232019-02-011129410.3390/pharmaceutics11020094pharmaceutics11020094Calcium Phosphate Spacers for the Local Delivery of Sitafloxacin and Rifampin to Treat Orthopedic Infections: Efficacy and Proof of Concept in a Mouse Model of Single-Stage Revision of Device-Associated OsteomyelitisRyan P. Trombetta0Mark J. Ninomiya1Ihab M. El-Atawneh2Emma K. Knapp3Karen L. de Mesy Bentley4Paul M. Dunman5Edward M. Schwarz6Stephen L. Kates7Hani A. Awad8Department of Biomedical Engineering, University of Rochester, Rochester, NY 14642, USACenter for Musculoskeletal Research, University of Rochester, Rochester, NY 14642, USADepartment of Biomedical Engineering, University of Rochester, Rochester, NY 14642, USACenter for Musculoskeletal Research, University of Rochester, Rochester, NY 14642, USACenter for Musculoskeletal Research, University of Rochester, Rochester, NY 14642, USADepartment of Microbiology and Immunology, University of Rochester, Rochester, NY 14642, USADepartment of Biomedical Engineering, University of Rochester, Rochester, NY 14642, USACenter for Musculoskeletal Research, University of Rochester, Rochester, NY 14642, USADepartment of Biomedical Engineering, University of Rochester, Rochester, NY 14642, USAOsteomyelitis is a chronic bone infection that is often treated with adjuvant antibiotic-impregnated poly(methyl methacrylate) (PMMA) cement spacers in multi-staged revisions. However, failure rates remain substantial due to recurrence of infection, which is attributed to the poor performance of the PMMA cement as a drug release device. Hence, the objective of this study was to design and evaluate a bioresorbable calcium phosphate scaffold (CaPS) for sustained antimicrobial drug release and investigate its efficacy in a murine model of femoral implant-associated osteomyelitis. Incorporating rifampin and sitafloxacin, which are effective against bacterial phenotypes responsible for bacterial persistence, into 3D-printed CaPS coated with poly(lactic co-glycolic) acid, achieved controlled release for up to two weeks. Implantation into the murine infection model resulted in decreased bacterial colonization rates at 3- and 10-weeks post-revision for the 3D printed CaPS in comparison to gentamicin-laden PMMA. Furthermore, a significant increase in bone formation was observed for 3D printed CaPS incorporated with rifampin at 3 and 10 weeks. The results of this study demonstrate that osteoconductive 3D printed CaPS incorporated with antimicrobials demonstrate more efficacious bacterial colonization outcomes and bone growth in a single-stage revision in comparison to gentamicin-laden PMMA requiring a two-stage revision.https://www.mdpi.com/1999-4923/11/2/94osteomyelitis<i>Staphylococcus aureus</i>sitafloxacinrifampincalcium phosphate3D printingdrug delivery1-stage revisionPMMA |
| spellingShingle | Ryan P. Trombetta Mark J. Ninomiya Ihab M. El-Atawneh Emma K. Knapp Karen L. de Mesy Bentley Paul M. Dunman Edward M. Schwarz Stephen L. Kates Hani A. Awad Calcium Phosphate Spacers for the Local Delivery of Sitafloxacin and Rifampin to Treat Orthopedic Infections: Efficacy and Proof of Concept in a Mouse Model of Single-Stage Revision of Device-Associated Osteomyelitis Pharmaceutics osteomyelitis <i>Staphylococcus aureus</i> sitafloxacin rifampin calcium phosphate 3D printing drug delivery 1-stage revision PMMA |
| title | Calcium Phosphate Spacers for the Local Delivery of Sitafloxacin and Rifampin to Treat Orthopedic Infections: Efficacy and Proof of Concept in a Mouse Model of Single-Stage Revision of Device-Associated Osteomyelitis |
| title_full | Calcium Phosphate Spacers for the Local Delivery of Sitafloxacin and Rifampin to Treat Orthopedic Infections: Efficacy and Proof of Concept in a Mouse Model of Single-Stage Revision of Device-Associated Osteomyelitis |
| title_fullStr | Calcium Phosphate Spacers for the Local Delivery of Sitafloxacin and Rifampin to Treat Orthopedic Infections: Efficacy and Proof of Concept in a Mouse Model of Single-Stage Revision of Device-Associated Osteomyelitis |
| title_full_unstemmed | Calcium Phosphate Spacers for the Local Delivery of Sitafloxacin and Rifampin to Treat Orthopedic Infections: Efficacy and Proof of Concept in a Mouse Model of Single-Stage Revision of Device-Associated Osteomyelitis |
| title_short | Calcium Phosphate Spacers for the Local Delivery of Sitafloxacin and Rifampin to Treat Orthopedic Infections: Efficacy and Proof of Concept in a Mouse Model of Single-Stage Revision of Device-Associated Osteomyelitis |
| title_sort | calcium phosphate spacers for the local delivery of sitafloxacin and rifampin to treat orthopedic infections efficacy and proof of concept in a mouse model of single stage revision of device associated osteomyelitis |
| topic | osteomyelitis <i>Staphylococcus aureus</i> sitafloxacin rifampin calcium phosphate 3D printing drug delivery 1-stage revision PMMA |
| url | https://www.mdpi.com/1999-4923/11/2/94 |
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