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Considering that, the present study proposed the development of multi-action polycaprolactone (PCL)\/polyethylene glycol (PEG) electrospun fibers incorporating elastase-targeting peptides, AAPV and WAAPV, via blending. Characterization confirmed WAAPV\u2019s efficacy in regulating proteolytic enzymes by inhibiting HNE. The engineered fibers, particularly those containing PEG, exhibited optimal wettability but an accelerated degradation that was mitigated with the peptide\u2019s inclusion, thus promoting a sustained peptide release over 24 h. Peptide loading was verified indirectly through thermal stability and hydration capacity studies (hydrophobic bonding between PCL and WAAPV and hydrophilic affinities between PCL\/PEG and AAPV) and determined at \u224851.1 \u00b5g\/cm2 and \u224846.0 \u00b5g\/cm2 for AAPV and \u224848.5 \u00b5g\/cm2 and \u224851.3 \u00b5g\/cm2 for WAAPV, respectively, for PCL and PCL\/PEG. Both AAPV and WAAPV effectively inhibited HNE, with PEG potentially enhancing this effect by interacting with the peptides and generating detectable peptide\u2013PEG complexes (\u224810% inhibition with PCL + peptide fibers after 6 h of incubation, and \u224820% with PCL\/PEG + peptide fibers after 4 h incubation). Peptide-loaded fibers demonstrated antibacterial efficacy against Staphylococcus aureus (up to \u224878% inhibition) and Escherichia coli (up to \u224866% inhibition), with peak effectiveness observed after 4 and 2 h of incubation, respectively. This study provides initial insights into the WAAPV\u2019s potential for inhibiting HNE and bacteria activities, showing promise for applications in diabetic ulcer management.<\/jats:p>","DOI":"10.3390\/pharmaceutics16070911","type":"journal-article","created":{"date-parts":[[2024,7,8]],"date-time":"2024-07-08T14:40:50Z","timestamp":1720449650000},"page":"911","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Inhibition of Enzyme and Bacteria Activities in Diabetic Ulcer-like Scenarios via WAAPV-Loaded Electrospun Fibers"],"prefix":"10.3390","volume":"16","author":[{"given":"Ana R. M.","family":"Ribeiro","sequence":"first","affiliation":[{"name":"Centre for Textile Science and Technology (2C2T), University of Minho, Campus of Azur\u00e9m, 4800-058 Guimar\u00e3es, Portugal"}]},{"given":"Catarina S.","family":"Miranda","sequence":"additional","affiliation":[{"name":"Centre for Textile Science and Technology (2C2T), University of Minho, Campus of Azur\u00e9m, 4800-058 Guimar\u00e3es, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7966-1623","authenticated-orcid":false,"given":"Ana Francisca G.","family":"Silva","sequence":"additional","affiliation":[{"name":"Centre of Chemistry (CQ), University of Minho, Campus of Gualtar, 4710-057 Braga, Portugal"}]},{"given":"Filipa D. P.","family":"Mendes","sequence":"additional","affiliation":[{"name":"Centre of Chemistry (CQ), University of Minho, Campus of Gualtar, 4710-057 Braga, Portugal"}]},{"given":"Beatriz M.","family":"Silva","sequence":"additional","affiliation":[{"name":"Centre for Textile Science and Technology (2C2T), University of Minho, Campus of Azur\u00e9m, 4800-058 Guimar\u00e3es, Portugal"}]},{"given":"Bruna A. S.","family":"Oliveira","sequence":"additional","affiliation":[{"name":"Centre for Textile Science and Technology (2C2T), University of Minho, Campus of Azur\u00e9m, 4800-058 Guimar\u00e3es, Portugal"}]},{"given":"Eduardo D.","family":"Paiva","sequence":"additional","affiliation":[{"name":"Centre for Textile Science and Technology (2C2T), University of Minho, Campus of Azur\u00e9m, 4800-058 Guimar\u00e3es, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-7125-6536","authenticated-orcid":false,"given":"S\u00f3nia P.","family":"Gon\u00e7alves","sequence":"additional","affiliation":[{"name":"Centre for Textile Science and Technology (2C2T), University of Minho, Campus of Azur\u00e9m, 4800-058 Guimar\u00e3es, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4310-8292","authenticated-orcid":false,"given":"S\u00edlvia M. M. 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G.","family":"Costa","sequence":"additional","affiliation":[{"name":"Centre of Chemistry (CQ), University of Minho, Campus of Gualtar, 4710-057 Braga, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4354-0256","authenticated-orcid":false,"given":"Helena P.","family":"Felgueiras","sequence":"additional","affiliation":[{"name":"Centre for Textile Science and Technology (2C2T), University of Minho, Campus of Azur\u00e9m, 4800-058 Guimar\u00e3es, Portugal"}]}],"member":"1968","published-online":{"date-parts":[[2024,7,8]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"133","DOI":"10.1016\/j.colsurfb.2017.05.001","article-title":"Functionalization of electrospun polymeric wound dressings with antimicrobial peptides","volume":"156","author":"Felgueiras","year":"2017","journal-title":"Colloids Surf. B Biointerfaces"},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Felgueiras, H.P. (2023). 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