{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,3]],"date-time":"2026-08-03T11:45:06Z","timestamp":1785757506294,"version":"3.56.0"},"reference-count":44,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2026,8,2]],"date-time":"2026-08-02T00:00:00Z","timestamp":1785628800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Med. Sci.","Medical Sciences"],"abstract":"<jats:p>Chronic venous leg ulcers (VLUs) affect approximately 1% of adults, and up to 30% remain unhealed by 12 months of standard therapy, with rates of recurrence approaching 70%. The chronicity and treatment resistance cannot be explained by the traditional view that venous hypertension alone causes the pathogenesis of VLUs. This narrative review synthesizes evidence from PubMed, Web of Science, and Scopus (2016\u2013April 2026), including original research, systematic reviews, meta-analyses, and clinical trials on the pathophysiology, diagnosis, and treatment of VLU, with a focus on biofilm, inflammation, and microvascular dysfunction. The reviewed studies were critically appraised. The current integrated framework offers a potential mechanistic roadmap for understanding the pathogenesis of VLUs and may help justify integrated therapeutic strategies. This review evaluates the existing evidence, identifies controversies, and highlights areas of knowledge that require further investigation. We analyze emerging data to propose a unified, conceptually distinct framework focused on the reciprocal, self-perpetuating interactions between biofilm, inflammation, and microvascular dysfunction, a triad that may offer a more comprehensive explanation for clinical heterogeneity and therapeutic resistance than venous hypertension alone. Future research should focus on the development of clinically available biofilm diagnostics, rigorous studies of combination therapies and elucidation of molecular links between components of the triad. We suggest that a transition to mechanism-based approaches targeting simultaneously may hold promise for transforming outcomes for millions of people affected by this debilitating condition.<\/jats:p>","DOI":"10.3390\/medsci14040453","type":"journal-article","created":{"date-parts":[[2026,8,3]],"date-time":"2026-08-03T10:24:07Z","timestamp":1785752647000},"page":"453","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["The Vicious Cycle of Biofilm, Host Inflammation and Microvascular Insufficiency in Venous Leg Ulcers"],"prefix":"10.3390","volume":"14","author":[{"given":"Diana","family":"Tatarciuc","sequence":"first","affiliation":[{"name":"Grigore T. Popa University of Medicine and Pharmacy, 700115 Iasi, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Irina Mihaela","family":"Esanu","sequence":"additional","affiliation":[{"name":"Grigore T. Popa University of Medicine and Pharmacy, 700115 Iasi, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Iolanda","family":"Foia","sequence":"additional","affiliation":[{"name":"Grigore T. Popa University of Medicine and Pharmacy, 700115 Iasi, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Teodor Flaviu","family":"Vasilcu","sequence":"additional","affiliation":[{"name":"Grigore T. Popa University of Medicine and Pharmacy, 700115 Iasi, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6304-9950","authenticated-orcid":false,"given":"Ana Maria Raluca","family":"Pauna","sequence":"additional","affiliation":[{"name":"Grigore T. Popa University of Medicine and Pharmacy, 700115 Iasi, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-8292-5443","authenticated-orcid":false,"given":"Ilinca","family":"Foia","sequence":"additional","affiliation":[{"name":"Grigore T. Popa University of Medicine and Pharmacy, 700115 Iasi, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0867-1135","authenticated-orcid":false,"given":"Roxana Ionela","family":"Vasluianu","sequence":"additional","affiliation":[{"name":"Grigore T. Popa University of Medicine and Pharmacy, 700115 Iasi, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-7558-3730","authenticated-orcid":false,"given":"Nicoleta","family":"Ioanid","sequence":"additional","affiliation":[{"name":"Grigore T. Popa University of Medicine and Pharmacy, 700115 Iasi, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marius Constantin","family":"Moraru","sequence":"additional","affiliation":[{"name":"Grigore T. Popa University of Medicine and Pharmacy, 700115 Iasi, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elena-Roxana","family":"Avadanei","sequence":"additional","affiliation":[{"name":"Grigore T. Popa University of Medicine and Pharmacy, 700115 Iasi, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mioara-Florentina","family":"Trandafirescu","sequence":"additional","affiliation":[{"name":"Grigore T. Popa University of Medicine and Pharmacy, 700115 Iasi, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,8,2]]},"reference":[{"key":"ref_1","first-page":"CD011675","article-title":"Wound Cleansing for Treating Venous Leg Ulcers","volume":"3","author":"McLain","year":"2021","journal-title":"Cochrane Database Syst. Rev."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"e70082","DOI":"10.1111\/iwj.70082","article-title":"Virtual Reality as a Promising Method of Pain Relief in Patients with Venous Leg Ulcers","volume":"21","author":"Spyrka","year":"2024","journal-title":"Int. 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