{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,19]],"date-time":"2026-08-19T20:00:42Z","timestamp":1787169642616,"version":"build-2736575974"},"reference-count":62,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2024,2,8]],"date-time":"2024-02-08T00:00:00Z","timestamp":1707350400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"The National Recovery and Resilience Plan","award":["ECS00000017"],"award-info":[{"award-number":["ECS00000017"]}]},{"name":"The National Recovery and Resilience Plan","award":["CUP I53C22000780001"],"award-info":[{"award-number":["CUP I53C22000780001"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>It is widely agreed that microbial biofilms play a major role in promoting infection and delaying healing of chronic wounds. In the era of microbial resistance, probiotic strains or their metabolic products are emerging as an innovative approach for the treatment of hard-to-heal (chronic) wounds due to their antimicrobial, healing, and host immune-modulatory effects. In this study, we aimed to investigate the potential of cell-free supernatants (CFS) from Lacticaseibacillus rhamnosus GG against mono- and dual-species biofilms of wound pathogens in a 3D in vitro infection model. Mature biofilms of Pseudomonas aeruginosa and Staphylococcus aureus were obtained on collagen scaffolds in the presence of a simulant wound fluid (SWF) and treated with CFS at different doses and time intervals. At 1:4 dilution in SWF, CFS caused a marked reduction in the colony forming-unit (CFU) numbers of bacteria embedded in mono-species biofilms as well as bacteria released by the biofilms in the supernatant. CFU count and electron microscopy imaging also demonstrated a marked antibiofilm effect against dual-species biofilms starting from 8 h of incubation. Furthermore, CFS exhibited acceptable levels of cytotoxicity at 24 h of incubation against HaCaT cells and, differently from ciprofloxacin, failed to induce resistance after 15 passages at sub-inhibitory concentrations. Overall, the results obtained point to L. rhamnosus GG postbiotics as a promising strategy for the treatment of wound biofilms.<\/jats:p>","DOI":"10.3390\/ijms25042087","type":"journal-article","created":{"date-parts":[[2024,2,8]],"date-time":"2024-02-08T09:00:02Z","timestamp":1707382802000},"page":"2087","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["Strong Activity and No Resistance Induction Exerted by Cell-Free Supernatants from Lacticaseibacillus rhamnosus against Mono-Species and Dual-Species Biofilms of Wound Pathogens in In Vivo-like Conditions"],"prefix":"10.3390","volume":"25","author":[{"given":"Esing\u00fcl","family":"Kaya","sequence":"first","affiliation":[{"name":"Department of Translational Research and New Technologies in Medicine and Surgery, University of Pisa, Via S. Zeno 37, 56123 Pisa, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-6484-2939","authenticated-orcid":false,"given":"Marta","family":"Bianchi","sequence":"additional","affiliation":[{"name":"Department of Translational Research and New Technologies in Medicine and Surgery, University of Pisa, Via S. Zeno 37, 56123 Pisa, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giuseppantonio","family":"Maisetta","sequence":"additional","affiliation":[{"name":"Department of Translational Research and New Technologies in Medicine and Surgery, University of Pisa, Via S. Zeno 37, 56123 Pisa, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4358-5294","authenticated-orcid":false,"given":"Semih","family":"Esin","sequence":"additional","affiliation":[{"name":"Department of Translational Research and New Technologies in Medicine and Surgery, University of Pisa, Via S. Zeno 37, 56123 Pisa, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4448-2385","authenticated-orcid":false,"given":"Giovanna","family":"Batoni","sequence":"additional","affiliation":[{"name":"Department of Translational Research and New Technologies in Medicine and Surgery, University of Pisa, Via S. Zeno 37, 56123 Pisa, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,2,8]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"281","DOI":"10.1089\/wound.2021.0026","article-title":"Human wounds and its burden: Updated 2020 compendium of estimates","volume":"10","author":"Sen","year":"2021","journal-title":"Adv. Wound Care"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"560","DOI":"10.1089\/wound.2015.0635","article-title":"Challenges in the treatment of chronic wounds","volume":"4","author":"Frykberg","year":"2015","journal-title":"Adv. Wound Care"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1016\/j.jval.2017.07.007","article-title":"An economic evaluation of the impact, cost, and medicare policy implications of chronic nonhealing wounds","volume":"21","author":"Nussbaum","year":"2018","journal-title":"Value Health"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"605","DOI":"10.1586\/14787210.2015.1023291","article-title":"Chronic wound infections: The role of Pseudomonas aeruginosa and Staphylococcus aureus","volume":"13","author":"Serra","year":"2015","journal-title":"Expert Rev. Anti Infect. Ther."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"744","DOI":"10.1111\/wrr.12590","article-title":"Global wound biofilm expert panel. Consensus guidelines for the identification and treatment of biofilms in chronic nonhealing wounds","volume":"25","author":"Schultz","year":"2017","journal-title":"Wound Repair Regen."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"908","DOI":"10.12968\/jowc.2022.31.11.908","article-title":"The antibacterial and antibiofilm activity of Granudacyn in vitro in a 3D collagen wound infection model","volume":"31","author":"Esin","year":"2022","journal-title":"J. Wound Care"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1111\/iwj.12049","article-title":"Bacterial isolates from infected wounds and their antibiotic susceptibility pattern: Some remarks about wound infection","volume":"12","author":"Bessa","year":"2015","journal-title":"Int. Wound J."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"750","DOI":"10.24976\/Discov.Med.202335178.70","article-title":"Therapeutic and unconventional strategies to contrast antimicrobial resistance: A literature review","volume":"35","author":"Vitiello","year":"2023","journal-title":"Discov. Med."},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Chin, J.D., Zhao, L., Mayberry, T.G., Cowan, B.C., Wakefield, M.R., and Fang, Y. (2023). Photodynamic therapy, probiotics, acetic acid, and essential oil in the treatment of chronic wounds infected with Pseudomonas aeruginosa. Pharmaceutics, 15.","DOI":"10.3390\/pharmaceutics15061721"},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"De Almeida, C.V., Antiga, E., and Lulli, M. (2023). Oral and topical probiotics and postbiotics in skincare and dermatological therapy: A concise review. Microorganisms, 11.","DOI":"10.3390\/microorganisms11061420"},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Fijan, S., Frauwallner, A., Langerholc, T., Krebs, B., Ter Haar N\u00e9e Younes, J.A., Heschl, A., Mi\u010deti\u0107 Turk, D., and Rogelj, I. (2019). Efficacy of using probiotics with antagonistic activity against pathogens of wound infections: An integrative review of literature. BioMed. Res. Int., 2019.","DOI":"10.1155\/2019\/7585486"},{"key":"ref_12","unstructured":"Cecchini, M., Langer, J., and Slawomirski, L. (2015). Antimicrobial Resistance in G7 Countries and beyond, Economic Issues, Policies and Options for Action: OECD Report, OECD."},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Batoni, G., Maisetta, G., Kaya, E., and Esin, S. (2022). Lung-directed bacteriotherapy in cystic fibrosis: Could it be an option?. Antibiotics, 11.","DOI":"10.3390\/antibiotics11030326"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"604","DOI":"10.1111\/1541-4337.12872","article-title":"The impacts of antimicrobial and antifungal activity of cell-free supernatants from lactic acid bacteria in vitro and foods","volume":"21","year":"2022","journal-title":"Compr. Rev. Food Sci. Food Saf."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"2117508","DOI":"10.1080\/19490976.2022.2117508","article-title":"The clinical evidence for postbiotics as microbial therapeutics","volume":"14","author":"Mosca","year":"2022","journal-title":"Gut. Microbes"},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Thorakkattu, P., Khanashyam, A.C., Shah, K., Babu, K.S., Mundanat, A.S., Deliephan, A., Deokar, G.S., Santivarangkna, C., and Nirmal, N.P. (2022). Postbiotics: Current trends in food and pharmaceutical industry. Foods, 11.","DOI":"10.3390\/foods11193094"},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Pompilio, A., Kaya, E., Lupetti, V., Catelli, E., Bianchi, M., Maisetta, G., Esin, S., Di Bonaventura, G., and Batoni, G. (2024). Cell-free supernatants from Lactobacillus strains exert antibacterial, antibiofilm, and antivirulence activity against Pseudomonas aeruginosa from cystic fibrosis patients. Microbes Infect., 105301.","DOI":"10.1016\/j.micinf.2024.105301"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"457","DOI":"10.1016\/j.lwt.2019.05.072","article-title":"Characterization and application of postbiotics of Lactobacillus spp. on Listeria monocytogenes in vitro and in food models","volume":"111","author":"Moradi","year":"2019","journal-title":"LWT"},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Maccelli, A., Carradori, S., Puca, V., Sisto, F., Lanuti, P., Crestoni, M.E., Lasalvia, A., Muraro, R., Bysell, H., and Di Sotto, A. (2020). Correlation between the antimicrobial activity and metabolic profiles of cell free supernatants and membrane vesicles produced by Lactobacillus reuteri DSM 17938. Microorganisms, 8.","DOI":"10.3390\/microorganisms8111653"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"2001","DOI":"10.1128\/AEM.66.5.2001-2005.2000","article-title":"Lactic acid permeabilizes gram-negative bacteria by disrupting the outer membrane","volume":"66","author":"Alakomi","year":"2000","journal-title":"Appl. Environ. Microbiol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"39","DOI":"10.29252\/pbr.3.2.39","article-title":"Antibiofilm potential of Lactobacillus plantarum spp. cell free supernatant (CFS) against multidrug resistant bacterial pathogens","volume":"3","author":"Zamani","year":"2017","journal-title":"Pharm. BioMed. Res."},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Batoni, G., Catelli, E., Kaya, E., Pompilio, A., Bianchi, M., Ghelardi, E., Di Bonaventura, G., Esin, S., and Maisetta, G. (2023). Antibacterial and antibiofilm effects of Lactobacilli strains against clinical isolates of Pseudomonas aeruginosa under conditions relevant to cystic fibrosis. Antibiotics, 12.","DOI":"10.3390\/antibiotics12071158"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"472","DOI":"10.1111\/j.1469-0691.2005.01142.x","article-title":"Interference of Lactobacillus plantarum with Pseudomonas aeruginosa in vitro and in infected burns: The potential use of probiotics in wound treatment","volume":"11","author":"Valdez","year":"2005","journal-title":"Clin. Microbiol. Infect."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1110","DOI":"10.1007\/s12602-018-9486-8","article-title":"Potential properties of Lactobacillus plantarum F-10 as a bio-control strategy for wound infections","volume":"11","author":"Onbas","year":"2019","journal-title":"Probiotics Antimicrob. Proteins"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"73","DOI":"10.1111\/j.1742-481X.2008.00577.x","article-title":"Bacteriotherapy with Lactobacillus plantarum in burns","volume":"J6","author":"Peral","year":"2009","journal-title":"Int. Wound"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"281","DOI":"10.1111\/j.1469-0691.2009.02793.x","article-title":"Interleukin-8 production by polymorphonuclear leukocytes from patients with chronic infected leg ulcers treated with Lactobacillus plantarum","volume":"16","author":"Peral","year":"2010","journal-title":"Clin. Microbiol. Infect."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"5773","DOI":"10.1128\/AEM.00861-14","article-title":"Lactobacillus rhamnosus GG inhibits the toxic effects of Staphylococcus aureus on epidermal keratinocytes","volume":"80","author":"Mohammedsaeed","year":"2014","journal-title":"Appl. Environ. Microbiol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"218","DOI":"10.22317\/jcms.v3i10.169","article-title":"Antimicrobial effect of probiotic Lactobacillus spp. on Pseudomonas aeruginosa","volume":"3","author":"Ismeeal","year":"2017","journal-title":"J. Contemp. Med. Sci."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"20538","DOI":"10.1021\/acsami.1c23713","article-title":"Injectable and self-healing probiotics-loaded hydrogel for promoting superbacteria-infected wound healing","volume":"14","author":"Mei","year":"2022","journal-title":"ACS Appl. Mater. Interfaces"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"156","DOI":"10.1111\/j.1600-0463.2009.02580.x","article-title":"An in vitro model of bacterial infections in wounds and other soft tissues","volume":"118","author":"Henriksson","year":"2010","journal-title":"APMIS"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"397","DOI":"10.1007\/978-3-031-08491-1_15","article-title":"Mixed populations and co-infection: Pseudomonas aeruginosa and Staphylococcus aureus","volume":"1386","author":"Camus","year":"2022","journal-title":"Adv. Exp. Med. Biol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"140","DOI":"10.1016\/j.burns.2003.09.030","article-title":"In vitro cytotoxity of silver: Implication for clinical wound care","volume":"30","author":"Poon","year":"2004","journal-title":"Burns"},{"key":"ref_33","doi-asserted-by":"crossref","unstructured":"Fijan, S., Kocbek, P., Steyer, A., Vodi\u010dar, P.M., and Strauss, M. (2022). The Antimicrobial effect of various single-strain and multi-strain probiotics, dietary supplements or other beneficial microbes against common clinical wound pathogens. Microorganisms, 10.","DOI":"10.3390\/microorganisms10122518"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"350","DOI":"10.3109\/13880209.2014.920037","article-title":"Compounds from Lactobacillus plantarum culture supernatants with potential pro-healing and anti-pathogenic properties in skin chronic wounds","volume":"53","author":"Ramos","year":"2015","journal-title":"Pharm. Biol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"28","DOI":"10.1159\/000494757","article-title":"Influence of laboratory culture media on in vitro growth, adhesion, and biofilm formation of Pseudomonas aeruginosa and Staphylococcus aureus","volume":"28","author":"Wijesinghe","year":"2019","journal-title":"Med. Princ. Pract."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"874","DOI":"10.1016\/j.ultramic.2009.03.042","article-title":"Effects of substrates on biofilm formation observed by atomic force microscopy","volume":"109","author":"Oh","year":"2009","journal-title":"Ultramicroscopy"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"027102","DOI":"10.1088\/1752-7155\/9\/2\/027102","article-title":"Real-time monitoring of hydrogen cyanide (HCN) and ammonia (NH3) emitted by Pseudomonas aeruginosa","volume":"9","author":"Neerincx","year":"2015","journal-title":"J. Breath Res."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"174","DOI":"10.1111\/wrr.12125","article-title":"The effects of pH on wound healing, biofilms, and antimicrobial efficacy","volume":"22","author":"Percival","year":"2014","journal-title":"Wound Repair. Regen."},{"key":"ref_39","unstructured":"Gethin, G. (2007). The Significance of Surface pH in Chronic Wounds, Wounds."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"711","DOI":"10.1002\/adhm.201500553","article-title":"Flexible pH-sensing hydrogel fibers for epidermal applications","volume":"5","author":"Tamayol","year":"2016","journal-title":"Adv. Healthc. Mater."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"415","DOI":"10.12968\/jowc.1999.8.8.25904","article-title":"The role of honey in the management of wounds","volume":"8","author":"Molan","year":"1999","journal-title":"J. Wound Care"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"84","DOI":"10.1016\/0305-4179(85)90032-4","article-title":"Topical acidification promotes healing of experimental deep partial burns\u2014A randonized double-blind preliminary study","volume":"12","author":"Kaufman","year":"1985","journal-title":"Burns"},{"key":"ref_43","doi-asserted-by":"crossref","unstructured":"Sim, P., Strudwick, X.L., Song, Y., Cowin, A.J., and Garg, S. (2022). Influence of acidic pH on wound healing in vivo: A novel perspective for wound treatment. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms232113655"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"460","DOI":"10.30699\/ijp.2022.551202.2863","article-title":"Topical treatment of second-degree burn wounds with Lactobacillus plantarum supernatant: Phase I Trial","volume":"17","author":"Momeni","year":"2022","journal-title":"Iran. J. Pathol."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"1044","DOI":"10.1016\/j.bbamem.2015.10.013","article-title":"Antimicrobial peptides and their interaction with biofilms of medically relevant bacteria","volume":"1858","author":"Batoni","year":"2016","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_46","doi-asserted-by":"crossref","unstructured":"Omar, A., Wright, J.B., Schultz, G., Burrell, R., and Nadworny, P. (2017). Microbial biofilms and chronic wounds. Microorganisms, 5.","DOI":"10.3390\/microorganisms5010009"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"4462","DOI":"10.1038\/ncomms5462","article-title":"Dispersed cells represent a distinct stage in the transition from bacterial biofilm to planktonic lifestyles","volume":"5","author":"Chua","year":"2014","journal-title":"Nat. Commun."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"e00846-17","DOI":"10.1128\/AAC.00846-17","article-title":"Susceptibility of Pseudomonas aeruginosa dispersed cells to antimicrobial agents is dependent on the dispersion cue and class of the antimicrobial agent used","volume":"61","author":"Chambers","year":"2017","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"4718","DOI":"10.1128\/IAI.02198-14","article-title":"Synergistic interactions of Pseudomonas aeruginosa and Staphylococcus aureus in an in vitro wound model","volume":"82","author":"DeLeon","year":"2014","journal-title":"Infect. Immun."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"5267","DOI":"10.1128\/JB.187.15.5267-5277.2005","article-title":"Cystic fibrosis sputum supports growth and cues key aspects of Pseudomonas aeruginosa physiology","volume":"187","author":"Palmer","year":"2005","journal-title":"J. Bacteriol."},{"key":"ref_51","doi-asserted-by":"crossref","unstructured":"Hotterbeekx, A., Kumar-Singh, S., Goossens, H., and Malhotra-Kumar, S. (2017). In vivo and in vitro interactions between Pseudomonas aeruginosa and Staphylococcus spp.. Front. Cell Infect. Microbiol., 7.","DOI":"10.3389\/fcimb.2017.00106"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"2717","DOI":"10.1128\/JCM.00501-08","article-title":"Distribution, organization, and ecology of bacteria in chronic wounds","volume":"46","author":"Jensen","year":"2008","journal-title":"J. Clin. Microbiol."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"4084","DOI":"10.1128\/JCM.01395-09","article-title":"Nonrandom distribution of Pseudomonas aeruginosa and Staphylococcus aureus in chronic wounds","volume":"47","author":"Fazli","year":"2009","journal-title":"J. Clin. Microbiol."},{"key":"ref_54","doi-asserted-by":"crossref","unstructured":"Gounani, Z., \u015een Karaman, D., Venu, A.P., Cheng, F., and Rosenholm, J.M. (2020). Coculture of P. aeruginosa and S. aureus on cell derived matrix\u2014An in vitro model of biofilms in infected wounds. J. Microbiol. Methods, 175.","DOI":"10.1016\/j.mimet.2020.105994"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"pdb-prot087163","DOI":"10.1101\/pdb.prot087163","article-title":"Measuring cell death by propidium iodide uptake and flow cytometry","volume":"2016","author":"Crowley","year":"2016","journal-title":"Cold Spring Harb. Protoc."},{"key":"ref_56","unstructured":"(2009). Biological Evaluation of Medical Devices\u2014Part 5: Tests for In Vitro Cytotoxicity (Standard No. ISO 10993-5:2009). Available online: https:\/\/www.iso.org\/obp\/ui\/#iso:std:iso:10993:-5:ed-3:v1:en."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"1065","DOI":"10.1099\/jmm.0.057521-0","article-title":"Normal and tumour cervical cells respond differently to vaginal lactobacilli, independent of pH and lactate","volume":"62 Pt 7","author":"Motevaseli","year":"2013","journal-title":"J. Med. Microbiol."},{"key":"ref_58","doi-asserted-by":"crossref","unstructured":"Xing, J., Wang, G., Zhang, Q., Liu, X., Gu, Z., Zhang, H., Chen, Y.Q., and Chen, W. (2015). Determining antioxidant activities of lactobacilli cell-free supernatants by cellular antioxidant assay: A comparison with traditional methods. PLoS ONE, 10.","DOI":"10.1371\/journal.pone.0119058"},{"key":"ref_59","doi-asserted-by":"crossref","unstructured":"Piras, A.M., Maisetta, G., Sandreschi, S., Gazzarri, M., Bartoli, C., Grassi, L., Esin, S., Chiellini, F., and Batoni, G. (2015). Chitosan nanoparticles loaded with the antimicrobial peptide temporin B exert a long-term antibacterial activity in vitro against clinical isolates of Staphylococcus epidermidis. Front. Microbiol., 6.","DOI":"10.3389\/fmicb.2015.00372"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"115094","DOI":"10.1016\/j.carbpol.2019.115094","article-title":"Evaluation and characterization of some protective culture metabolites in free and nano-chitosan-loaded forms against common contaminants of Egyptian cheese","volume":"223","author":"Sharaf","year":"2019","journal-title":"Carbohydr. Polym."},{"key":"ref_61","doi-asserted-by":"crossref","unstructured":"Bekiaridou, A., Karlafti, E., Oikonomou, I.M., Ioannidis, A., and Papavramidis, T.S. (2021). Probiotics and their effect on surgical wound healing: A systematic review and new insights into the role of nanotechnology. Nutrients, 13.","DOI":"10.3390\/nu13124265"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"300","DOI":"10.4103\/joacp.JOACP_349_15","article-title":"Action and resistance mechanisms of antibiotics: A guide for clinicians","volume":"33","author":"Kapoor","year":"2017","journal-title":"J. Anaesthesiol. Clin. Pharmacol."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/25\/4\/2087\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T13:57:20Z","timestamp":1760104640000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/25\/4\/2087"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,2,8]]},"references-count":62,"journal-issue":{"issue":"4","published-online":{"date-parts":[[2024,2]]}},"alternative-id":["ijms25042087"],"URL":"https:\/\/doi.org\/10.3390\/ijms25042087","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,2,8]]}}}