{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,25]],"date-time":"2026-10-25T03:52:44Z","timestamp":1792900364698,"version":"4.5.0"},"reference-count":299,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2026,4,13]],"date-time":"2026-04-13T00:00:00Z","timestamp":1776038400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01AI165958"],"award-info":[{"award-number":["R01AI165958"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R21AI171932"],"award-info":[{"award-number":["R21AI171932"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"award":["R01AI165958"],"award-info":[{"award-number":["R01AI165958"]}],"id":[{"id":"https:\/\/ror.org\/045p44t13","id-type":"ROR","asserted-by":"publisher"}]},{"award":["R21AI171932"],"award-info":[{"award-number":["R21AI171932"]}],"id":[{"id":"https:\/\/ror.org\/045p44t13","id-type":"ROR","asserted-by":"publisher"}]},{"DOI":"10.13039\/100002280","name":"Plastic Surgery Foundation","doi-asserted-by":"publisher","award":["831458"],"award-info":[{"award-number":["831458"]}],"id":[{"id":"10.13039\/100002280","id-type":"DOI","asserted-by":"publisher"}]},{"award":["831458"],"award-info":[{"award-number":["831458"]}],"id":[{"id":"https:\/\/ror.org\/00dky2106","id-type":"ROR","asserted-by":"publisher"}]},{"name":"IUSoM-PU Engineering in Medicine"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Antibiotics"],"abstract":"<jats:p>Bacterial biofilms are structured microbial communities enclosed within a self-produced extracellular polymeric substance matrix composed of polysaccharides, proteins, extracellular DNA, and lipids. This matrix promotes adhesion, structural stability, and the development of heterogeneous microenvironments that restrict antimicrobial penetration and shield bacteria from host immune responses. As a result, biofilms are major contributors to chronic, recurrent, device-related, and difficult-to-treat infections, posing a major challenge for clinical management and antimicrobial stewardship. This review summarizes current understandings of biofilm biology, its clinical relevance, including the stages of biofilm development, the composition and protective roles of the matrix, and the physiological heterogeneity that arises during maturation. It also examines key mechanisms underlying biofilm tolerance and resistance, such as limited antibiotic diffusion, and sequestration, enzymatic inactivation, efflux pump upregulation, persister cell formation, and horizontal gene transfer. In addition, it highlights important clinical settings in which biofilms are implicated, including cystic fibrosis, chronic wounds, osteomyelitis, implant- or device-associated infections, and breast implant illness, in which persistent implant-associated biofilms and the resulting chronic inflammatory milieu have been hypothesized to contribute to local and systemic manifestations in a subset of patients. The review further discusses conventional and emerging approaches for biofilm detection alongwith real-time monitoring. Biofilm-associated infections remain difficult to eradicate because persistence is driven by multiple interconnected protective mechanisms. Effective management therefore requires integrated strategies that combine accurate detection with multifaceted therapies, including antibiotics alongside matrix-disrupting enzymes, quorum-sensing inhibitors, bacteriophages, metabolic reactivators, and nanotechnology-based delivery systems. Advances in multi-omics and system-level modeling will be essential for developing next-generation strategies to prevent, monitor, and treat biofilm-associated disease.<\/jats:p>","DOI":"10.3390\/antibiotics15040396","type":"journal-article","created":{"date-parts":[[2026,4,13]],"date-time":"2026-04-13T11:38:26Z","timestamp":1776080306000},"page":"396","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":22,"title":["Detection to Disruption: A Comprehensive Review of Bacterial Biofilms and Therapeutic Advances"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5172-7395","authenticated-orcid":false,"given":"Pranay Amruth","family":"Maroju","sequence":"first","affiliation":[{"name":"Department of Surgery, Indiana University School of Medicine, Indianapolis, IN 46202, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-9825-8964","authenticated-orcid":false,"given":"Angad S.","family":"Sidhu","sequence":"additional","affiliation":[{"name":"Department of Surgery, Indiana University School of Medicine, Indianapolis, IN 46202, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amogh R.","family":"Motaganahalli","sequence":"additional","affiliation":[{"name":"Department of Surgery, Indiana University School of Medicine, Indianapolis, IN 46202, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7070-6832","authenticated-orcid":false,"given":"Robert E.","family":"Minto","sequence":"additional","affiliation":[{"name":"Department of Chemistry and Chemical Biology, Indiana University, Indianapolis, IN 46202, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fatih","family":"Zor","sequence":"additional","affiliation":[{"name":"Department of Surgery, Indiana University School of Medicine, Indianapolis, IN 46202, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2871-2662","authenticated-orcid":false,"given":"Christine","family":"Kelley-Patteson","sequence":"additional","affiliation":[{"name":"Meridian Plastic Surgeons, Indianapolis, IN 46290, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rahim","family":"Rahimi","sequence":"additional","affiliation":[{"name":"School of Materials Engineering, Purdue University, West Lafayette, IN 47907, USA"},{"name":"Birck Nanotechnology Center, Purdue University, West Lafayette, IN 47907, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0966-7851","authenticated-orcid":false,"given":"Aladdin H.","family":"Hassanein","sequence":"additional","affiliation":[{"name":"Department of Surgery, Indiana University School of Medicine, Indianapolis, IN 46202, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9222-1921","authenticated-orcid":false,"given":"Mithun","family":"Sinha","sequence":"additional","affiliation":[{"name":"Department of Surgery, Indiana University School of Medicine, Indianapolis, IN 46202, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,4,13]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"e0104225","DOI":"10.1128\/jcm.01042-25","article-title":"Biofilms in clinical infection: Pathophysiology, diagnosis, and the evolving therapeutic landscape","volume":"64","author":"Domouchtsidou","year":"2026","journal-title":"J. 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