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Textilinin-1, a venom-derived Kunitz-type serine protease inhibitor, has previously established its profile as a potent hemostatic agent. However, its potential as a multifunctional biopharmaceutical for wound management remains largely untapped. This study evaluates the pharmacological effects of Textilinin-1 in preclinical models of cutaneous wound repair. Methods: We employed an integrated platform comprising bioinformatics, in vitro cellular assays, and in vivo murine excisional wounds and a pilot porcine proof-of-concept model to assess the wound healing-promoting effects of Textilinin-1 and explore associated cellular responses associated with key stages of the wound healing cascade. Results: Textilinin-1 was associated with multiple cellular responses relevant to tissue repair. It attenuated M1-like inflammatory activation and showed preliminary growth-inhibitory activity against Staphylococcus aureus under the tested conditions. Concurrently, it enhanced the proliferative and migratory capacity of fibroblasts, endothelial cells, and keratinocytes, which are key cellular targets for wound closure. In pre-clinical pilot porcine and rodent models, Textilinin-1 treatment was associated with accelerated wound contraction and improved structural tissue quality. Conclusions: Our findings provide preclinical evidence that Textilinin-1 may promote cutaneous wound repair and modulate cellular responses relevant to key stages of the wound healing cascade. These results support further investigation of Textilinin-1 as a candidate for wound repair applications. Future studies are required to define its precise molecular mechanisms, evaluate its efficacy in chronic or otherwise compromised wound models, and optimize its topical formulation or hydrogel-based delivery.<\/jats:p>","DOI":"10.3390\/pharmaceutics18060762","type":"journal-article","created":{"date-parts":[[2026,6,26]],"date-time":"2026-06-26T05:52:11Z","timestamp":1782453131000},"page":"762","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Textilinin-1, a Snake Venom-Derived Kunitz-Type Protease Inhibitor, Accelerates Wound Healing Through Anti-Inflammatory, Antibacterial, and Pro-Regenerative Activities"],"prefix":"10.3390","volume":"18","author":[{"given":"Zhuo","family":"Chen","sequence":"first","affiliation":[{"name":"Australian Institute for Bioengineering and Nanotechnology, The University of Queensland, Brisbane, QLD 4072, Australia"},{"name":"Centre for Innovation in Pain and Health Research (CIPHeR), School of Health and Rehabilitation Sciences, The University of Queensland, Brisbane, QLD 4072, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2669-2335","authenticated-orcid":false,"given":"Huiwen","family":"Pang","sequence":"additional","affiliation":[{"name":"Australian Institute for Bioengineering and Nanotechnology, The University of Queensland, Brisbane, QLD 4072, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7950-8872","authenticated-orcid":false,"given":"Youzhi","family":"Wu","sequence":"additional","affiliation":[{"name":"Australian Institute for Bioengineering and Nanotechnology, The University of Queensland, Brisbane, QLD 4072, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4993-5101","authenticated-orcid":false,"given":"David M.","family":"Klyne","sequence":"additional","affiliation":[{"name":"Centre for Innovation in Pain and Health Research (CIPHeR), School of Health and Rehabilitation Sciences, The University of Queensland, Brisbane, QLD 4072, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6926-6515","authenticated-orcid":false,"given":"Xuqiang","family":"Nie","sequence":"additional","affiliation":[{"name":"Key Lab of the Basic Pharmacology of the Ministry of Education & Joint International Research Laboratory of Ethnomedicine of Ministry of Education, Zunyi Medical University, Zunyi 563006, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pengfei","family":"Jiang","sequence":"additional","affiliation":[{"name":"Institute of Molecular Virology and Immunology, Department of Microbiology & Immunology, School of Basic Medical Sciences, Wenzhou Medical University, Wenzhou 325035, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-0315-220X","authenticated-orcid":false,"given":"Xinfei","family":"Wu","sequence":"additional","affiliation":[{"name":"Institute of Molecular Virology and Immunology, Department of Microbiology & Immunology, School of Basic Medical Sciences, Wenzhou Medical University, Wenzhou 325035, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kong-Nan","family":"Zhao","sequence":"additional","affiliation":[{"name":"Australian Institute for Bioengineering and Nanotechnology, The University of Queensland, Brisbane, QLD 4072, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7260-5832","authenticated-orcid":false,"given":"Felicity Y.","family":"Han","sequence":"additional","affiliation":[{"name":"Australian Institute for Bioengineering and Nanotechnology, The University of Queensland, Brisbane, QLD 4072, Australia"},{"name":"Centre for Innovation in Pain and Health Research (CIPHeR), School of Health and Rehabilitation Sciences, The University of Queensland, Brisbane, QLD 4072, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,6,22]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"225","DOI":"10.1089\/wound.2014.0581","article-title":"Metalloproteinases and Wound Healing","volume":"4","author":"Caley","year":"2015","journal-title":"Adv. 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