In vivo efficacy of a refillable intrawound drug delivery device in a sheep model of biofilm-compromised open fracture-related infection
Open fracture-related infection challenges persist in healthcare. From the time open fractures were defined ∼50 years ago, infection rates have gone essentially unchanged. Contributing factors include compromised vasculature, biofilm, and stalled innovations in treatment and prophylaxis. In this stu...
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Elsevier
2025-06-01
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| Series: | Biofilm |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2590207525000103 |
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| author | Dustin Williams David Rothberg Walker Kay Lisa Nehring Robert Falconer Richard Tyler Epperson Brooke Kawaguchi Carolyn Ardizzone Brian Barnum Nicholas Ashton |
| author_facet | Dustin Williams David Rothberg Walker Kay Lisa Nehring Robert Falconer Richard Tyler Epperson Brooke Kawaguchi Carolyn Ardizzone Brian Barnum Nicholas Ashton |
| author_sort | Dustin Williams |
| collection | DOAJ |
| description | Open fracture-related infection challenges persist in healthcare. From the time open fractures were defined ∼50 years ago, infection rates have gone essentially unchanged. Contributing factors include compromised vasculature, biofilm, and stalled innovations in treatment and prophylaxis. In this study, we engineered and tested the efficacy of a refillable drug delivery device, the Purgo Pouch (Pouch), that sustains local, high dose intrawound antibiotic concentrations in wound sites. We hypothesized that it would manage biofilm-compromised open fracture-related infection better than clinical standards of care. Therapies were tested in a unique sheep model of long bone open fracture-related infection with compromised tissue and biofilm inocula of methicillin-resistant Staphylococcus aureus. Sheep (n = 5/group) were treated with IV vancomycin (10 days), gentamicin-loaded CaSO4 beads (single application), or the Pouch (10 days) loaded with gentamicin alone or a triple antibiotic combination. At 21 days, sheep were euthanized and microbiological and histological data collected. Results indicated that the Pouch managed infection more effectively, reducing bioburden to <105 colony forming units (CFU)/sample, which was statistically significant compared to clinical standards, which failed to reduce bioburden to below 105 CFU. The hypothesis was supported. The Pouch received Breakthrough Device Designation by the FDA, is being transitioned toward clinical trials, and is a potential solution to the long-standing problem of open fracture-related infection. |
| format | Article |
| id | doaj-art-52ccfb613378499daf085a1348ed61ca |
| institution | OA Journals |
| issn | 2590-2075 |
| language | English |
| publishDate | 2025-06-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Biofilm |
| spelling | doaj-art-52ccfb613378499daf085a1348ed61ca2025-08-20T02:14:54ZengElsevierBiofilm2590-20752025-06-01910026210.1016/j.bioflm.2025.100262In vivo efficacy of a refillable intrawound drug delivery device in a sheep model of biofilm-compromised open fracture-related infectionDustin Williams0David Rothberg1Walker Kay2Lisa Nehring3Robert Falconer4Richard Tyler Epperson5Brooke Kawaguchi6Carolyn Ardizzone7Brian Barnum8Nicholas Ashton9Department of Orthopaedics, University of Utah, Salt Lake City, UT, USA; Bone and Biofilm Research Lab, University of Utah, Salt Lake City, UT, USA; Department of Biomedical Engineering, University of Utah, Salt Lake City, UT, USA; Department of Pathology, University of Utah, Salt Lake City, UT, USA; Department of Physical Medicine and Rehabilitation, Uniformed Services University, Bethesda, MD, USA; Purgo Scientific, South Jordan, UT, USA; Corresponding author. University of Utah Department of Orthopaedics 590 Wakara Way Salt Lake City, UT, 84108, USA.Department of Orthopaedics, University of Utah, Salt Lake City, UT, USA; Bone and Biofilm Research Lab, University of Utah, Salt Lake City, UT, USA; Purgo Scientific, South Jordan, UT, USANoorda College of Osteopathic Medicine, Provo, UT, USARocky Vista University School of Osteopathic Medicine, St. George, UT, USADepartment of Orthopaedics, University of Utah, Salt Lake City, UT, USA; Bone and Biofilm Research Lab, University of Utah, Salt Lake City, UT, USA; Department of Biomedical Engineering, University of Utah, Salt Lake City, UT, USADepartment of Orthopaedics, University of Utah, Salt Lake City, UT, USA; Bone and Biofilm Research Lab, University of Utah, Salt Lake City, UT, USA; Purgo Scientific, South Jordan, UT, USADepartment of Orthopaedics, University of Utah, Salt Lake City, UT, USA; Bone and Biofilm Research Lab, University of Utah, Salt Lake City, UT, USA; Purgo Scientific, South Jordan, UT, USASchool of Medicine, University of New Mexico, Albuquerque, NM, USAPurgo Scientific, South Jordan, UT, USADepartment of Orthopaedics, University of Utah, Salt Lake City, UT, USA; Bone and Biofilm Research Lab, University of Utah, Salt Lake City, UT, USA; Purgo Scientific, South Jordan, UT, USAOpen fracture-related infection challenges persist in healthcare. From the time open fractures were defined ∼50 years ago, infection rates have gone essentially unchanged. Contributing factors include compromised vasculature, biofilm, and stalled innovations in treatment and prophylaxis. In this study, we engineered and tested the efficacy of a refillable drug delivery device, the Purgo Pouch (Pouch), that sustains local, high dose intrawound antibiotic concentrations in wound sites. We hypothesized that it would manage biofilm-compromised open fracture-related infection better than clinical standards of care. Therapies were tested in a unique sheep model of long bone open fracture-related infection with compromised tissue and biofilm inocula of methicillin-resistant Staphylococcus aureus. Sheep (n = 5/group) were treated with IV vancomycin (10 days), gentamicin-loaded CaSO4 beads (single application), or the Pouch (10 days) loaded with gentamicin alone or a triple antibiotic combination. At 21 days, sheep were euthanized and microbiological and histological data collected. Results indicated that the Pouch managed infection more effectively, reducing bioburden to <105 colony forming units (CFU)/sample, which was statistically significant compared to clinical standards, which failed to reduce bioburden to below 105 CFU. The hypothesis was supported. The Pouch received Breakthrough Device Designation by the FDA, is being transitioned toward clinical trials, and is a potential solution to the long-standing problem of open fracture-related infection.http://www.sciencedirect.com/science/article/pii/S2590207525000103Open fractureInfectionBiofilmOrthopedicSustainable drug deliverySheep model |
| spellingShingle | Dustin Williams David Rothberg Walker Kay Lisa Nehring Robert Falconer Richard Tyler Epperson Brooke Kawaguchi Carolyn Ardizzone Brian Barnum Nicholas Ashton In vivo efficacy of a refillable intrawound drug delivery device in a sheep model of biofilm-compromised open fracture-related infection Biofilm Open fracture Infection Biofilm Orthopedic Sustainable drug delivery Sheep model |
| title | In vivo efficacy of a refillable intrawound drug delivery device in a sheep model of biofilm-compromised open fracture-related infection |
| title_full | In vivo efficacy of a refillable intrawound drug delivery device in a sheep model of biofilm-compromised open fracture-related infection |
| title_fullStr | In vivo efficacy of a refillable intrawound drug delivery device in a sheep model of biofilm-compromised open fracture-related infection |
| title_full_unstemmed | In vivo efficacy of a refillable intrawound drug delivery device in a sheep model of biofilm-compromised open fracture-related infection |
| title_short | In vivo efficacy of a refillable intrawound drug delivery device in a sheep model of biofilm-compromised open fracture-related infection |
| title_sort | in vivo efficacy of a refillable intrawound drug delivery device in a sheep model of biofilm compromised open fracture related infection |
| topic | Open fracture Infection Biofilm Orthopedic Sustainable drug delivery Sheep model |
| url | http://www.sciencedirect.com/science/article/pii/S2590207525000103 |
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