@article{65325263689b4963815c8f48407691ec,
title = "A murine model of cutaneous aspergillosis for evaluation of biomaterials-based local delivery therapies",
abstract = "Cutaneous fungal infection is a challenging condition to treat that primarily afflicts immunocompromised patients. Local antifungal therapy may permit the delivery of high concentrations of antifungals directly to wounds while minimizing systemic toxicities. However, the field currently lacks suitable in vivo models. Therefore, a large cutaneous wound was created in immunosuppressed mice and inoculated with Aspergillus fumigatus. We fabricated biodegradable polymer microparticles (MPs) that were capable of locally delivering antifungal and characterized in vitro release kinetics. We compared wound bed size, fungal burden, and histological presence of fungi in mice treated with antifungal-loaded MPs. Mice with a cutaneous defect but no infection, mice with infected cutaneous defect but no treatment, and infected mice treated with blank MPs were used as controls. Infection of large wounds inhibited healing and resulted in tissue invasion in an inoculum-dependent manner. MPs were capable of releasing antifungals at concentrations above A. fumigatus Minimum Inhibitory Concentration (MIC) for at least 6 days. Wounds treated with MPs had significantly decreased size compared with no treatment (64.2% vs. 19.4% wound reduction, p = 0.002) and were not significantly different from uninfected controls (64.2% vs. 58.1%, p = 0.497). This murine model may serve to better understand cutaneous fungal infection and evaluate local biomaterials-based therapies.",
keywords = "Aspergillus, biomaterials, cutaneous, drug delivery, fungi",
author = "Tatara, {Alexander M.} and Emma Watson and Albert, {Nathaniel D.} and Kontoyiannis, {Panayiotis D.} and Kontoyiannis, {Dimitrios P.} and Mikos, {Antonios G.}",
note = "Funding Information: Additional Supporting Information may be found in the online version of this article. †These authors contributed equally to this work. ‡Outstanding Research by a Hospital Intern, Resident, or Clinical Fellow Award for the 2019 Society For Biomaterials Annual Meeting and Exposition, April 3–6, 2019, Seattle, Washington Correspondence to: A. G. Mikos; e-mail: mikos@rice.edu or D. P. Kontoyiannis; e-mail: dkontoyi@mdanderson.org Contract grant sponsor: John S. Dunn Foundation Contract grant sponsor: National Institute of Dental and Craniofacial Research; contract grant number: F31 DE027586 Contract grant sponsor: Texas 4000 Distinguished Professorship for Cancer Research Contract grant sponsor: American Society for Microbiology Contract grant sponsor: Baylor College of Medicine; contract grant number: GM007330 and T32 Contract grant sponsor: National Institute of Dental and Craniofacial Research; contract grant number: DE027586 and F31 Funding Information: This work was supported by the John S. Dunn Foundation. E.W. received support from a Ruth L. Kirschstein Fellowship from The National Institute of Dental and Craniofacial Research (F31 DE027586). A.M.T. and E.W. would like to thank the Baylor College of Medicine Medical Scientist Training Program (NIH T32 GM007330) and A.M.T. would like to thank the Barrow Scholars Program. DPK acknowledges the Texas 4000 Distinguished Professorship for Cancer Research. Information from this work was previously presented in part at the 2016 American Society for Microbiology Microbe Meeting, ID Week 2017 Meeting, and Tissue Engineering and Regenerative Medicine International Society-Americas 2017 Meeting. The authors have no conflicts of interest to report involving this work. Publisher Copyright: {\textcopyright} 2019 Wiley Periodicals, Inc.",
year = "2019",
month = sep,
doi = "10.1002/jbm.a.36671",
language = "English (US)",
volume = "107",
pages = "1867--1874",
journal = "Journal of Biomedical Materials Research - Part A",
issn = "1549-3296",
publisher = "John Wiley and Sons Inc.",
number = "9",
}