{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,26]],"date-time":"2026-09-26T04:46:58Z","timestamp":1790398018813,"version":"4.1.0"},"reference-count":62,"publisher":"American Society for Microbiology","issue":"11","license":[{"start":{"date-parts":[[2016,10,21]],"date-time":"2016-10-21T00:00:00Z","timestamp":1477008000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2016,11,1]],"date-time":"2016-11-01T00:00:00Z","timestamp":1477958400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"funder":[{"name":"Biocomposites, Ltd.","award":["R117796"],"award-info":[{"award-number":["R117796"]}]},{"DOI":"10.13039\/501100000268","name":"Biotechnology and Biological Sciences Research Council (BBSRC)","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000268","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["Antimicrob Agents Chemother"],"published-print":{"date-parts":[[2016,11]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:p>Diabetes has major implications for public health, with diabetic foot ulcers (DFUs) being responsible for significant morbidity and mortality. A key factor in the development of nonhealing ulcers is infection, which often leads to the development of biofilm, gangrene, and amputation. A novel approach to treating DFUs is the local release of antibiotics from calcium sulfate beads. We have developed a novel model system to study and compare the release and efficacy of antibiotics released locally, using collagen as a substrate for biofilm growth and incorporating serum to mimic the biochemical complexity of the wound environment. We found that our soft-tissue model supports the growth of a robust<jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">Pseudomonas aeruginosa<\/jats:named-content>biofilm, and that this was completely eradicated by the introduction of calcium sulfate beads loaded with tobramycin or gentamicin. The model also enabled us to measure the concentration of these antibiotics at different distances from the beads and in simulated wound fluid bathing the collagen matrix. We additionally found that a multidrug-resistant<jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">Staphylococcus aureus<\/jats:named-content>biofilm, nonsusceptible to antibiotics, nonetheless showed an almost 1-log drop in viable counts when exposed to calcium sulfate beads combined with antibiotics. Together, these data suggest that locally applied antibiotics combined with calcium sulfate provide surprising efficacy in diabetic foot infections and offer an effective alternative approach to infection management. Our study additionally establishes our new system as a biochemically and histologically relevant model that may be used to study the effectiveness of a range of therapies locally or systemically for infected DFUs.<\/jats:p>","DOI":"10.1128\/aac.01064-16","type":"journal-article","created":{"date-parts":[[2016,9,13]],"date-time":"2016-09-13T01:59:02Z","timestamp":1473731942000},"page":"6880-6889","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":43,"title":["Development of a Novel Collagen Wound Model To Simulate the Activity and Distribution of Antimicrobials in Soft Tissue during Diabetic Foot Infection"],"prefix":"10.1128","volume":"60","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1843-618X","authenticated-orcid":false,"given":"Bianca L.","family":"Price","sequence":"first","affiliation":[{"name":"Medical Device Biology Group, Faculty of Biology, Medicine and Health, The University of Manchester, Manchester, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew M.","family":"Lovering","sequence":"additional","affiliation":[{"name":"Antimicrobial Reference Laboratory, Microbiology Department, Bristol, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Frank L.","family":"Bowling","sequence":"additional","affiliation":[{"name":"University of Manchester, Manchester Diabetes Centre, Manchester, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Curtis B.","family":"Dobson","sequence":"additional","affiliation":[{"name":"Medical Device Biology Group, Faculty of Biology, Medicine and Health, The University of Manchester, Manchester, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","volume-title":"Diabetic foot problems: prevention and management","author":"Internal Clinical Guidelines Team","year":"2015","unstructured":"Internal Clinical Guidelines Team. 2015. Diabetic foot problems: prevention and management. National Institute for Health and Care Excellence, London, United Kingdom."},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1524-475X.2010.00619.x"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.3402\/dfa.v3i0.18409"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(03)13169-8"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejvs.2013.02.014"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1177\/1534734610363459"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1002\/dmrr.2739"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.2174\/157339912800563990"},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.1002\/dmrr.2699"},{"key":"e_1_3_2_11_2","doi-asserted-by":"publisher","DOI":"10.1007\/s13300-012-0004-9"},{"key":"e_1_3_2_12_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1464-5491.2008.02573.x"},{"key":"e_1_3_2_13_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0109848"},{"key":"e_1_3_2_14_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2796.1993.tb01003.x"},{"key":"e_1_3_2_15_2","first-page":"1","article-title":"Current and emerging therapies in the management of diabetic foot ulcers","volume":"32","author":"Karri VV","year":"2015","unstructured":"Karri VV, Kuppusamy G, Talluri SV, Yamjala K, Mannemala SS, Malayandi R. 2015. Current and emerging therapies in the management of diabetic foot ulcers. Curr Med Res Opin 32:1\u201368.","journal-title":"Curr Med Res Opin"},{"key":"e_1_3_2_16_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaad.2013.07.048"},{"key":"e_1_3_2_17_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0002-9610(03)00299-X"},{"key":"e_1_3_2_18_2","doi-asserted-by":"publisher","DOI":"10.1086\/644732"},{"key":"e_1_3_2_19_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijantimicag.2008.09.008"},{"key":"e_1_3_2_20_2","doi-asserted-by":"publisher","DOI":"10.1097\/01.ASW.0000407647.12832.6c"},{"key":"e_1_3_2_21_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.foot.2015.07.002"},{"key":"e_1_3_2_22_2","doi-asserted-by":"publisher","DOI":"10.2337\/dc14-3100"},{"key":"e_1_3_2_23_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-0463.2009.02580.x"},{"key":"e_1_3_2_24_2","first-page":"9","article-title":"Dressings and biofilms: interpreting evidence from in vitro biofilm models","volume":"7","author":"Bourdillon K","year":"2016","unstructured":"Bourdillon K. 2016. Dressings and biofilms: interpreting evidence from in vitro biofilm models. Wounds Int 7:9\u201315.","journal-title":"Wounds Int"},{"key":"e_1_3_2_25_2","doi-asserted-by":"publisher","DOI":"10.1089\/wound.2014.0532"},{"key":"e_1_3_2_26_2","doi-asserted-by":"publisher","DOI":"10.1007\/s12223-015-0401-3"},{"key":"e_1_3_2_27_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1067-2516(96)80125-6"},{"key":"e_1_3_2_28_2","doi-asserted-by":"publisher","DOI":"10.1046\/j.1464-5491.2001.00422.x"},{"key":"e_1_3_2_29_2","doi-asserted-by":"crossref","first-page":"1122","DOI":"10.1128\/9781555816728.ch68","volume-title":"Manual of clinical microbiology","author":"Patel JB","year":"2011","unstructured":"Patel JB, Tenover FC, Turnidge JD, Jorgensen JH. 2011. Susceptibility test methods: dilution and disk diffusion methods, p 1122\u20131143. In Versalovic J, Carroll KC, Jorgensen JG, Funke G, Landry ML, Warnock DW (ed), Manual of clinical microbiology, 10th ed. ASM Press, Washington, DC.","edition":"10"},{"key":"e_1_3_2_30_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0065-2164(09)69004-3"},{"key":"e_1_3_2_31_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.03676-14"},{"key":"e_1_3_2_32_2","doi-asserted-by":"publisher","DOI":"10.1002\/jor.1100140511"},{"key":"e_1_3_2_33_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.37.5.1132"},{"key":"e_1_3_2_34_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.addr.2003.08.007"},{"key":"e_1_3_2_35_2","doi-asserted-by":"publisher","DOI":"10.5402\/2011\/290851"},{"key":"e_1_3_2_36_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.01490-08"},{"key":"e_1_3_2_37_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijantimicag.2008.06.029"},{"key":"e_1_3_2_38_2","doi-asserted-by":"publisher","DOI":"10.1089\/sur.2013.162"},{"key":"e_1_3_2_39_2","doi-asserted-by":"publisher","DOI":"10.1002\/jcph.296"},{"key":"e_1_3_2_40_2","doi-asserted-by":"publisher","DOI":"10.1093\/jac\/dkt267"},{"key":"e_1_3_2_41_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.47.1.371-374.2003"},{"key":"e_1_3_2_42_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.49.10.4368-4371.2005"},{"key":"e_1_3_2_43_2","doi-asserted-by":"publisher","DOI":"10.1093\/jac\/dkq109"},{"key":"e_1_3_2_44_2","doi-asserted-by":"publisher","DOI":"10.1093\/jac\/dkh412"},{"key":"e_1_3_2_45_2","doi-asserted-by":"publisher","DOI":"10.1093\/jac\/dkp230"},{"key":"e_1_3_2_46_2","doi-asserted-by":"publisher","DOI":"10.1093\/jac\/31.4.581"},{"key":"e_1_3_2_47_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1574-695X.1999.tb01398.x"},{"key":"e_1_3_2_48_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.50.4.1372-1375.2006"},{"key":"e_1_3_2_49_2","doi-asserted-by":"publisher","DOI":"10.1007\/s11892-006-0076-x"},{"key":"e_1_3_2_50_2","doi-asserted-by":"publisher","DOI":"10.1155\/2014\/153586"},{"key":"e_1_3_2_51_2","doi-asserted-by":"publisher","DOI":"10.1053\/j.semvascsurg.2012.04.008"},{"key":"e_1_3_2_52_2","doi-asserted-by":"publisher","DOI":"10.1111\/ijcp.12347"},{"key":"e_1_3_2_53_2","doi-asserted-by":"publisher","DOI":"10.2337\/db15-0597"},{"key":"e_1_3_2_54_2","doi-asserted-by":"publisher","DOI":"10.2337\/dc14-0769"},{"key":"e_1_3_2_55_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.mcna.2011.03.008"},{"key":"e_1_3_2_56_2","doi-asserted-by":"publisher","DOI":"10.1086\/593185"},{"key":"e_1_3_2_57_2","first-page":"45","article-title":"Neuromuscular blocking activity of aminoglycoside antibiotics","volume":"2","author":"Paradelis AG","year":"1980","unstructured":"Paradelis AG, Triantaphyllidis C, Giala MM. 1980. Neuromuscular blocking activity of aminoglycoside antibiotics. Methods Find Exp Clin Pharmacol 2:45\u201351.","journal-title":"Methods Find Exp Clin Pharmacol"},{"key":"e_1_3_2_58_2","doi-asserted-by":"publisher","DOI":"10.1002\/dmrr.2246"},{"key":"e_1_3_2_59_2","doi-asserted-by":"publisher","DOI":"10.1007\/s40257-014-0081-9"},{"key":"e_1_3_2_60_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1464-5491.2006.01785.x"},{"key":"e_1_3_2_61_2","doi-asserted-by":"publisher","DOI":"10.1517\/17425240902997919"},{"key":"e_1_3_2_62_2","doi-asserted-by":"publisher","DOI":"10.2337\/dc06-1792"},{"key":"e_1_3_2_63_2","doi-asserted-by":"publisher","DOI":"10.1002\/jbm.b.33247"}],"container-title":["Antimicrobial Agents and Chemotherapy"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/AAC.01064-16","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/AAC.01064-16","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,7,8]],"date-time":"2022-07-08T06:06:30Z","timestamp":1657260390000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.asm.org\/doi\/10.1128\/AAC.01064-16"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2016,11]]},"references-count":62,"journal-issue":{"issue":"11","published-print":{"date-parts":[[2016,11]]}},"alternative-id":["10.1128\/AAC.01064-16"],"URL":"https:\/\/doi.org\/10.1128\/aac.01064-16","relation":{},"ISSN":["0066-4804","1098-6596"],"issn-type":[{"value":"0066-4804","type":"print"},{"value":"1098-6596","type":"electronic"}],"subject":[],"published":{"date-parts":[[2016,11]]},"assertion":[{"value":"2016-05-20","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2016-08-20","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2016-10-21","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}