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Dunn Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100006988","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J Biomedical Materials Res"],"published-print":{"date-parts":[[2019,9]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>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 <jats:italic>in vivo<\/jats:italic> models. Therefore, a large cutaneous wound was created in immunosuppressed mice and inoculated with <jats:italic>Aspergillus fumigatus<\/jats:italic>. We fabricated biodegradable polymer microparticles (MPs) that were capable of locally delivering antifungal and characterized <jats:italic>in vitro<\/jats:italic> release kinetics. We compared wound bed size, fungal burden, and histological presence of fungi in mice treated with antifungal\u2010loaded 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\u2010dependent manner. MPs were capable of releasing antifungals at concentrations above <jats:styled-content style=\"fixed-case\"><jats:italic>A. fumigatus<\/jats:italic><\/jats:styled-content> 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, <jats:italic>p<\/jats:italic> = 0.002) and were not significantly different from uninfected controls (64.2% vs. 58.1%, <jats:italic>p<\/jats:italic> = 0.497). This murine model may serve to better understand cutaneous fungal infection and evaluate local biomaterials\u2010based therapies. \u00a9 2019 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 107A: 1867\u20131874, 2019.<\/jats:p>","DOI":"10.1002\/jbm.a.36671","type":"journal-article","created":{"date-parts":[[2019,3,18]],"date-time":"2019-03-18T15:42:40Z","timestamp":1552923760000},"page":"1867-1874","update-policy":"http:\/\/dx.doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["A murine model of cutaneous aspergillosis for evaluation of biomaterials\u2010based local delivery therapies"],"prefix":"10.1002","volume":"107","author":[{"given":"Alexander M.","family":"Tatara","sequence":"first","affiliation":[{"name":"Department of Bioengineering Rice University  Houston Texas"},{"name":"Department of Medicine Massachusetts General Hospital  Boston Massachusetts"},{"name":"Department of Infectious Diseases, Infection Control and Employee Health The University of Texas MD Anderson Cancer Center  Houston 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