{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,9]],"date-time":"2026-09-09T11:13:53Z","timestamp":1788952433504,"version":"build-2803163510"},"reference-count":50,"publisher":"Wiley","license":[{"start":{"date-parts":[[2026,9,9]],"date-time":"2026-09-09T00:00:00Z","timestamp":1788912000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,9,9]],"date-time":"2026-09-09T00:00:00Z","timestamp":1788912000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["febs.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["FEBS Open Bio"],"abstract":"<jats:p>\n                    This systematic review evaluates the therapeutic efficacy and biological mechanisms of Lactoferrin (Lf) in the wound healing process. The objective was to synthesize evidence regarding its multifunctional role in cellular regeneration, gene modulation, and antimicrobial protection. From an initial screening of 1846 records, 11\n                    <jats:italic>in vitro<\/jats:italic>\n                    studies (2001\u20132023) met the eligibility criteria. The synthesized data demonstrate that Lf significantly accelerates the migration and proliferation of human keratinocytes and fibroblasts. At the molecular level, Lf upregulates critical regenerative genes, specifically\n                    <jats:italic>HAS2<\/jats:italic>\n                    (hyaluronan synthesis) and\n                    <jats:italic>COL1A1<\/jats:italic>\n                    (collagen type I). Furthermore, Lf exhibits potent inhibitory effects against biofilm formation and bacterial growth, with high efficacy reported against\n                    <jats:italic>Staphylococcus aureus<\/jats:italic>\n                    and\n                    <jats:italic>Escherichia coli<\/jats:italic>\n                    . Thus, Lf acts as a pivotal bioactive agent that bridges regenerative stimulus with antimicrobial defense across all healing phases. Its ability to modulate the extracellular matrix and suppress pathogens suggests it to be a candidate for advanced wound care and regenerative therapies. These findings establish a robust biological rationale for transitioning toward clinical\u2010stage bioprospecting.\n                  <\/jats:p>","DOI":"10.1002\/2211-5463.70298","type":"journal-article","created":{"date-parts":[[2026,9,9]],"date-time":"2026-09-09T10:32:22Z","timestamp":1788949942000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Exploring the influence of lactoferrin on wound healing and related signaling pathways: a systematic review"],"prefix":"10.1002","author":[{"given":"Morgana L\u00fcdtke","family":"Azevedo","sequence":"first","affiliation":[{"name":"Graduate Program in Biochemistry and Bioprospecting (PPGBBio) Federal University of Pelotas  Pelotas RS Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"K\u00e1tia Cristiane","family":"Hall","sequence":"additional","affiliation":[{"name":"Graduate Program in Dentistry (PPGO) Federal University of Pelotas  Pelotas RS Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matheus","family":"dos Santos Fernandez","sequence":"additional","affiliation":[{"name":"Graduate Program in Dentistry (PPGO) Federal University of Pelotas  Pelotas RS Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Geovanna Peter","family":"Corr\u00eaa","sequence":"additional","affiliation":[{"name":"Graduate Program in Materials Science and Engineering (PPGCEM) Federal University of Pelotas  Pelotas RS Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1006-3809","authenticated-orcid":false,"given":"Rafael Guerra","family":"Lund","sequence":"additional","affiliation":[{"name":"Graduate Program in Biochemistry and Bioprospecting (PPGBBio) Federal University of Pelotas  Pelotas RS Brazil"},{"name":"Graduate Program in Dentistry (PPGO) Federal University of Pelotas  Pelotas RS Brazil"},{"name":"Graduate Program in Materials Science and Engineering (PPGCEM) Federal University of Pelotas  Pelotas RS Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,9,9]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0281913","article-title":"MicroRNAs expressed during normal wound healing and their associated pathways: a systematic review and bioinformatics analysis","volume":"18","author":"Azevedo ML","year":"2023","journal-title":"PLoS One"},{"key":"e_1_2_9_3_1","doi-asserted-by":"crossref","first-page":"599","DOI":"10.1038\/s41580-024-00715-1","article-title":"Cellular and molecular mechanisms of skin wound healing","volume":"25","author":"Pe\u00f1a OA","year":"2024","journal-title":"Nat Rev Mol Cell Biol"},{"key":"e_1_2_9_4_1","doi-asserted-by":"crossref","DOI":"10.3390\/ijms23094928","article-title":"Chronic inflammation in non\u2010healing skin wounds and promising natural bioactive compounds 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