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The goal of this study was to evaluate the changes in wounds treated with a hypothermically stored amniotic membrane (HSAM). In this prospective single\u2010arm study, 15 female patients with venous leg ulcers were treated with HSAM from male donors and standard of care for 12\u2009weeks. Over the course of the study, wound exudate was collected and evaluated using proteomic microarrays. Biopsies were collected during the course of treatment to detect the presence of HSAM tissue. By 4\u2009weeks, 60% of subjects achieved 50% or greater reduction in wound size, and by 12\u2009weeks, 53% of subjects achieved 100% re\u2010epithelialization. HSAM DNA was detected in 20% of biopsies as determined by the detection <jats:italic>TSPY4<\/jats:italic>, indicating HSAM was no longer present within the wound bed approximately 7\u2009days from the last treatment for the majority of wounds. Proteomic analysis of wound exudate found that wounds on a healing trajectory had significantly higher levels of MMP\u201010, MMP\u20107, and TIMP\u20104 and significantly lower levels of CX3CL1, FLT\u20103\u00a0L, IL\u20101ra, IL\u20101a, IL\u20109, IL\u20102, IL\u20103, MCP\u20101, and TNF\u2010b compared with other wounds.<\/jats:p>","DOI":"10.1111\/iwj.13606","type":"journal-article","created":{"date-parts":[[2021,5,6]],"date-time":"2021-05-06T22:44:07Z","timestamp":1620341047000},"page":"144-155","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["A prospective clinical trial evaluating changes in the wound microenvironment in patients with chronic venous leg ulcers treated with a hypothermically stored amniotic membrane"],"prefix":"10.1111","volume":"19","author":[{"given":"John P.","family":"McQuilling","sequence":"first","affiliation":[{"name":"Organogenesis  Birmingham Alabama USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marissa J.","family":"Carter","sequence":"additional","affiliation":[{"name":"Stategic Solutions Inc.  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