Controlled Release of Vancomycin and Tigecycline from an Orthopaedic Implant Coating Prevents Staphylococcus aureus Infection in an Open Fracture Animal Model.
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2019-01
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Introduction:Treatment of open fractures routinely involves multiple surgeries and delayed definitive fracture fixation because of concern for infection. If implants were made less susceptible to infection, a one-stage procedure with intramedullary nailing would be more feasible, which would reduce morbidity and improve outcomes. Methods:In this study, a novel open fracture mouse model was developed using Staphylococcus aureus (S. aureus) and single-stage intramedullary fixation. The model was used to evaluate whether implants coated with a novel "smart" polymer coating containing vancomycin or tigecycline would be colonized by bacteria in an open fracture model infected with S. aureus. In vivo bioluminescence, ex vivo CFUs, and X-ray images were evaluated over a 42-day postoperative period. Results:We found evidence of a markedly decreased bacterial burden with the local release of vancomycin and tigecycline from the PEG-PPS polymer compared to polymer alone. Vancomycin was released in a controlled fashion and maintained local drug concentrations above the minimum inhibition concentration for S. aureus for greater than 7 days postoperatively. Bacteria were reduced 139-fold from implants containing vancomycin and undetected from the bone and soft tissue. Tigecycline coatings led to a 5991-fold reduction in bacteria isolated from bone and soft tissue and 15-fold reduction on the implants compared to polymer alone. Antibiotic coatings also prevented osteomyelitis and implant loosening as observed on X-ray. Conclusion:Vancomycin and tigecycline can be encapsulated in a polymer coating and released over time to maintain therapeutic levels during the perioperative period. Our results suggest that antibiotic coatings can be used to prevent implant infection and osteomyelitis in the setting of open fracture. This novel open fracture mouse model can be used as a powerful in vivo preclinical tool to evaluate and optimize the treatment of open fractures before further studies in humans.
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Stavrakis, AI, S Zhu, AH Loftin, X Weixian, J Niska, V Hegde, T Segura, NM Bernthal, et al. (2019). Controlled Release of Vancomycin and Tigecycline from an Orthopaedic Implant Coating Prevents Staphylococcus aureus Infection in an Open Fracture Animal Model. BioMed research international, 2019. p. 1638508. 10.1155/2019/1638508 Retrieved from https://hdl.handle.net/10161/22636.
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Tatiana Segura
Tatiana Segura is a Professor of Biomedical Engineering, Neurology, and Dermatology at Duke University. She received her B.S. degree in Bioengineering from the University of California, Berkeley (UC Berkeley) and her doctorate in Chemical Engineering from Northwestern University. She began her career in Biomaterials research during her doctoral work working with Prof. Lonnie Shea. She designed hydrogels for local non-viral gene delivery, a topic that she still works on today. She continued her Biomaterials training during her postdoctoral work with Jeffrey Hubbell. There she worked on the design of hydrogels and self-assembled polysulfides for gene delivery. She began her independent career at the University of California, Los Angeles (UCLA) in the Department of Chemical and Biomolecular Engineering reaching the title of Professor. At UCLA she participated actively in service culminating with her election as department Vice Chair and running the Graduate Program. At Duke she has continued to be heavily involved in service at the department, school, and university level. In only 5 years, she has Chaired 6 committees, and participated in at least 6 more, is the direct mentor to two young assistant professors, is the Co-director of the Center for Biotechnology and Tissue Engineering and serves as MPI of the T32 Biotechnology Training grant. Notably she is currently the Chair of the BME department Diversity Equity and Inclusion Committee.
Prof. Segura’s research is centered on biomaterials and in engineering biomaterial-soft tissue interactions to promote repair and regeneration. Together with her lab members, she designs new biomaterial interventions that can promote brain plasticity after stroke, promote scarless healing in skin wounds, induce tolerance of transplanted skin, and promote constructive immune responses after biomaterial implantation. Currently, her lab has 12 graduate students, 4 postdoctoral scholars, 2 master students, 1 plastic surgery resident, 16 undergraduate students, one high school student, and one research associate.
Professor Segura has received numerous awards and distinctions during her career, including being named a Senior Member of the National Academy of Inventors, receiving the Acta Biomaterialia Silver Medal, a CAREER Award from the National Science Foundation, a Outstanding Young Investigator Award from the American Society of Gene and Cell Therapy, and a National Scientist Development Grant from the American Heart Association. She was also named a Fellow of the American Institute for Medical and Biological Engineers (AIMBE). Professor Segura has published over 100 peer-reviewed papers and reviews and has over 10,000 citations. Her laboratory has been continuously funded since 2008 with several grants from the National Institutes of Health (NIH).
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