{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,13]],"date-time":"2026-04-13T07:19:21Z","timestamp":1776064761607,"version":"3.50.1"},"reference-count":42,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2023,2,23]],"date-time":"2023-02-23T00:00:00Z","timestamp":1677110400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceutics"],"abstract":"<jats:p>Hypertrophic scars (HTSs) are aberrant structures that develop where skin is injured complexly and represent the result of a chronic inflammation as a healing response. To date, there is no satisfactory prevention option for HTSs, which is due to the complexity of multiple mechanisms behind the formation of these structures. The present work aimed to propose Biofiber (Biodegradable fiber), an advanced textured electrospun dressing, as a suitable solution for HTS formation in complex wounds. Biofiber has been designed as a 3-day long-term treatment to protect the healing environment and enhance wound care practices. Its textured matrix consists of homogeneous and well-interconnected Poly-L-lactide-co-poly-\u03b5-caprolactone (PLA-PCL) electrospun fibers (size 3.825 \u00b1 1.12 \u00b5m) loaded with Naringin (NG, 2.0% w\/w), a natural antifibrotic agent. The structural units contribute to achieve an optimal fluid handling capacity demonstrated through a moderate hydrophobic wettability behavior (109.3 \u00b1 2.3\u00b0), and a suitable balance between absorbency (389.8 \u00b1 58.16%) and moisture vapor transmission rate (MVTR, 2645 \u00b1 60.43 g\/m2 day). The flexibility and conformability of Biofiber to the body surfaces is due to its innovative circular texture, that also allow it to obtain finer mechanical properties after 72 h in contact with Simulated Wound Fluid (SWF), with an elongation of 352.6 \u00b1 36.10%, and a great tenacity (0.25 \u00b1 0.03 Mpa). The ancillary action of NG results in a prolonged anti-fibrotic effect on Normal Human Dermal Fibroblasts (NHDF), through the controlled release of NG for 3 days. The prophylactic action was highlighted at day 3 with the down regulation of the major factors involved in the fibrotic process: Transforming Growth Factor \u03b21 (TGF-\u03b21), Collagen Type 1 alpha 1 chain (COL1A1), and \u03b1-smooth muscle actin (\u03b1-SMA). No significant anti-fibrotic effect has been demonstrated on Hypertrophic Human Fibroblasts derived from scars (HSF), proving the potential of Biofiber to minimize HTSs in the process of early wound healing as a prophylactic therapy.<\/jats:p>","DOI":"10.3390\/pharmaceutics15030747","type":"journal-article","created":{"date-parts":[[2023,2,24]],"date-time":"2023-02-24T03:01:01Z","timestamp":1677207661000},"page":"747","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":17,"title":["Electrospun Naringin-Loaded Fibers for Preventing Scar Formation during Wound Healing"],"prefix":"10.3390","volume":"15","author":[{"given":"Erika M.","family":"Tottoli","sequence":"first","affiliation":[{"name":"Department of Drug Sciences, University of Pavia, 27100 Pavia, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Laura","family":"Benedetti","sequence":"additional","affiliation":[{"name":"Department of Public Health, Experimental Medicine and Forensic, University of Pavia, 27100 Pavia, Italy"},{"name":"CHT Center for Health Technologies, University of Pavia, 27100 Pavia, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Enrica","family":"Chiesa","sequence":"additional","affiliation":[{"name":"Department of Drug Sciences, University of Pavia, 27100 Pavia, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5396-1601","authenticated-orcid":false,"given":"Silvia","family":"Pisani","sequence":"additional","affiliation":[{"name":"Department of Otolaryngology, IRCCS Policlinico S. Matteo, 27100 Pavia, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1958-2998","authenticated-orcid":false,"given":"Giovanna","family":"Bruni","sequence":"additional","affiliation":[{"name":"Department of Chemistry, Physical-Chemistry Section, University of Pavia, Via Taramelli 16, 27100 Pavia, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5710-0588","authenticated-orcid":false,"given":"Ida","family":"Genta","sequence":"additional","affiliation":[{"name":"Department of Drug Sciences, University of Pavia, 27100 Pavia, Italy"},{"name":"CHT Center for Health Technologies, University of Pavia, 27100 Pavia, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0034-2815","authenticated-orcid":false,"given":"Bice","family":"Conti","sequence":"additional","affiliation":[{"name":"Department of Drug Sciences, University of Pavia, 27100 Pavia, Italy"},{"name":"CHT Center for Health Technologies, University of Pavia, 27100 Pavia, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8576-694X","authenticated-orcid":false,"given":"Gabriele","family":"Ceccarelli","sequence":"additional","affiliation":[{"name":"Department of Public Health, Experimental Medicine and Forensic, University of Pavia, 27100 Pavia, Italy"},{"name":"CHT Center for Health Technologies, University of Pavia, 27100 Pavia, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5774-9547","authenticated-orcid":false,"given":"Rossella","family":"Dorati","sequence":"additional","affiliation":[{"name":"Department of Drug Sciences, University of Pavia, 27100 Pavia, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2023,2,23]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Tottoli, E.M., Dorati, R., Genta, I., Chiesa, E., Pisani, S., and Conti, B. (2020). Skin Wound Healing Process and New Emerging Technologies for Skin Wound Care and Regeneration. Pharmaceutics, 12.","DOI":"10.3390\/pharmaceutics12080735"},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Gushiken, L., Beserra, F., Bastos, J., Jackson, C., and Pellizzon, C. (2021). Cutaneous Wound Healing: An Update from Physiopathology to Current Therapies. Life, 11.","DOI":"10.3390\/life11070665"},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"T\u00e9ot, L., Mustoe, T.A., Middelkoop, E., and Gauglitz, G.G. (2020). Textbook on Scar Management, Springer.","DOI":"10.1007\/978-3-030-44766-3"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"179","DOI":"10.1089\/wound.2021.0061","article-title":"Mechanomodulation of Burn Scarring Via Pressure Therapy","volume":"11","author":"Powell","year":"2022","journal-title":"Adv. Wound Care"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"163","DOI":"10.1016\/j.bjps.2015.11.015","article-title":"Currently known risk factors for hypertrophic skin scarring: A review","volume":"69","author":"Butzelaar","year":"2015","journal-title":"J. Plast. Reconstr. Aesthetic Surg."},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"T\u00e9ot, L., Mustoe, T.A., Middelkoop, E., and Gauglitz, G.G. (2020). Textbook on Scar Management, Springer.","DOI":"10.1007\/978-3-030-44766-3"},{"key":"ref_7","unstructured":"Bowler, P., and Parsons, D. (2016). Microbial Biofilms\u2013Importance and Applications, IN TECH."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"22","DOI":"10.7603\/s40681-015-0022-9","article-title":"Wound dressings\u2014A review","volume":"5","author":"Dhivya","year":"2015","journal-title":"BioMedicine"},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Uhljar, L., and Ambrus, R. (2023). Electrospinning of Potential Medical Devices (Wound Dressings, Tissue Engineering Scaffolds, Face Masks) and Their Regulatory Approach. Pharmaceutics, 15.","DOI":"10.3390\/pharmaceutics15020417"},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Huang, C., Xu, X., Fu, J., Yu, D.-G., and Liu, Y. (2022). Recent Progress in Electrospun Polyacrylonitrile Nanofiber-Based Wound Dressing. Polymers, 14.","DOI":"10.3390\/polym14163266"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"60","DOI":"10.1016\/j.colsurfb.2018.05.011","article-title":"Electrospun polymeric nanofibres as wound dressings: A review","volume":"169","author":"Miguel","year":"2018","journal-title":"Colloids Surf. B Biointerfaces"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"463","DOI":"10.1016\/j.jconrel.2021.03.033","article-title":"Electrospinning for drug delivery applications: A review","volume":"334","author":"Luraghi","year":"2021","journal-title":"J. Control. Release"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"111316","DOI":"10.1016\/j.msec.2020.111316","article-title":"Fabrication and characterization of starch-TPU based nanofibers for wound healing applications","volume":"119","author":"Mistry","year":"2020","journal-title":"Mater. Sci. Eng. C"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"660571","DOI":"10.3389\/fcell.2021.660571","article-title":"Metallic Ions Encapsulated in Electrospun Nanofiber for Antibacterial and Angiogenesis Function to Promote Wound Repair","volume":"9","author":"Zhu","year":"2021","journal-title":"Front. Cell Dev. Biol."},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Grumezescu, A.M., Stoica, A.E., Dima-B\u0103lcescu, M., Chircov, C., Gharbia, S., Balt\u0103, C., Ro\u0219u, M., Herman, H., Holban, A.M., and Ficai, A. (2019). Electrospun Polyethylene Terephthalate Nanofibers Loaded with Silver Nanoparticles: Novel Approach in Anti-Infective Therapy. J. Clin. Med., 8.","DOI":"10.3390\/jcm8071039"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"122073","DOI":"10.1016\/j.ijpharm.2022.122073","article-title":"BioFiber: An advanced fibrous textured dressing to manage exudate in severe wounds","volume":"625","author":"Tottoli","year":"2022","journal-title":"Int. J. Pharm."},{"key":"ref_17","unstructured":"Inventor, R., Dorati, B., Conti, I., and Genta, I. (2020). University of Pavia. 3D-Patterned Fiber Material for the Topical Delivery of Nucleic acid and the Process for its Preparation. (17\/766,082), U.S. Patent."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"500","DOI":"10.1111\/jcmm.12994","article-title":"Naringin in Ganshuang Granule suppresses activation of hepatic stellate cells for anti-fibrosis effect by inhibition of mammalian target of rapamycin","volume":"21","author":"Shi","year":"2016","journal-title":"J. Cell. Mol. Med."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"66","DOI":"10.3892\/etm.2020.9498","article-title":"Naringin attenuates renal interstitial fibrosis by regulating the TGF-\u03b2\/Smad signaling pathway and inflammation","volume":"21","author":"Wang","year":"2020","journal-title":"Exp. Ther. Med."},{"key":"ref_20","first-page":"169","article-title":"Design and fabrication of an instrument to evaluate characteristics of fluid handling capacity of wound care dressings","volume":"45","author":"Vadodaria","year":"2020","journal-title":"Indian J. Fibre Text. Res."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"24596","DOI":"10.1038\/srep24596","article-title":"Controlled water vapor transmission rate promotes wound-healing via wound re-epithelialization and contraction enhancement","volume":"6","author":"Xu","year":"2016","journal-title":"Sci. Rep."},{"key":"ref_22","unstructured":"(2017). ASTM E 96 Standard Test Methods for Water Vapor Transmission of Materials (Standard No. ASTM E 96. S1)."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.emc.2006.12.002","article-title":"Soft Tissue Wounds and Principles of Healing","volume":"25","author":"Jones","year":"2007","journal-title":"Emerg. Med. Clin. N. Am."},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Dorati, R., Chiesa, E., Rosalia, M., Pisani, S., Genta, I., Bruni, G., Modena, T., and Conti, B. (2021). Tubular Electrospun Vancomycin-Loaded Vascular Grafts: Formulation Study and Physicochemical Characterization. Polymers, 13.","DOI":"10.3390\/polym13132073"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1596","DOI":"10.1016\/j.xphs.2017.02.031","article-title":"Gentamicin-Loaded Thermosetting Hydrogel and Moldable Composite Scaffold: Formulation Study and Biologic Evaluation","volume":"106","author":"Dorati","year":"2017","journal-title":"J. Pharm. Sci."},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Chiesa, E., Tottoli, E.M., Giglio, A., Conti, B., Rosalia, M., Rizzi, L.G., Dorati, R., and Genta, I. (2022). Graphene Nanoplatelets-Based Textured Polymeric Fibrous Fabrics for the Next-Generation Devices. Polymers, 14.","DOI":"10.3390\/polym14245415"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"2025","DOI":"10.1039\/C8BM00518D","article-title":"Biocompatibility of polymer-based biomaterials and medical devices\u2014Regulations, in vitro screening and risk-management","volume":"6","author":"Bernard","year":"2018","journal-title":"Biomater. Sci."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"2205","DOI":"10.1177\/1528083716654470","article-title":"Design parameters for electrospun biodegradable vascular grafts","volume":"47","author":"Enis","year":"2016","journal-title":"J. Ind. Text."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"120198","DOI":"10.1016\/j.ijpharm.2021.120198","article-title":"Electrospun tubular vascular grafts to replace damaged peripheral arteries: A preliminary formulation study","volume":"596","author":"Dorati","year":"2021","journal-title":"Int. J. Pharm."},{"key":"ref_30","unstructured":"Labib, A.M., and Winters, R. (2022). Complex Wound Management, StatPearls Publishing."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1111\/iwj.13761","article-title":"The performance of gelling fibre wound dressings under clinically relevant robotic laboratory tests","volume":"19","author":"Lustig","year":"2022","journal-title":"Int. Wound J."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"452","DOI":"10.12968\/jowc.2016.25.8.452","article-title":"Comparative evaluation of the functional properties of superabsorbent dressings and their effect on exudate management","volume":"25","author":"Browning","year":"2016","journal-title":"J. Wound Care"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"tkac024","DOI":"10.1093\/burnst\/tkac024","article-title":"Commercial wound dressings for the treatment of exuding wounds: An in-depth physico-chemical comparative study","volume":"10","author":"Minsart","year":"2022","journal-title":"Burn. Trauma"},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"Kordestani, S.S. (2019). Atlas of Wound Healing, Elsevier.","DOI":"10.1016\/B978-0-323-67968-8.00003-3"},{"key":"ref_35","doi-asserted-by":"crossref","unstructured":"Hinz, B., and Lagares, D. (2021). Myofibroblasts: Methods and Protocols, Springer US.","DOI":"10.1007\/978-1-0716-1382-5"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"16611","DOI":"10.1039\/C5NR05367F","article-title":"Melt electrospinning of poly(lactic acid) and polycaprolactone microfibers by using a hand-operated Wimshurst generator","volume":"7","author":"Qin","year":"2015","journal-title":"Nanoscale"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"682","DOI":"10.1515\/epoly-2020-0068","article-title":"Structural design toward functional materials by electrospinning: A review","volume":"20","author":"Yang","year":"2020","journal-title":"E-Polymers"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"101268","DOI":"10.1016\/j.coco.2022.101268","article-title":"Composite fibrous membrane comprising PLA and PCL fibers for biomedical application","volume":"34","author":"Zhang","year":"2022","journal-title":"Compos. Commun."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"661","DOI":"10.1016\/j.ajps.2019.11.008","article-title":"Recent trends on wound management: New therapeutic choices based on polymeric carriers","volume":"15","author":"Okur","year":"2020","journal-title":"Asian J. Pharm. Sci."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"1291","DOI":"10.1016\/j.biopha.2018.06.103","article-title":"Naringin suppresses the growth and motility of hypertrophic scar fibroblasts by inhibiting the kinase activity of Akt","volume":"105","author":"Song","year":"2018","journal-title":"Biomed. Pharmacother."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"704","DOI":"10.1080\/08923973.2022.2077217","article-title":"The antifibrotic effects of naringin in a hypochlorous acid (HOCl)-induced mouse model of skin fibrosis","volume":"44","author":"Mohammadi","year":"2022","journal-title":"Immunopharmacol. Immunotoxicol."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"419","DOI":"10.3109\/13880209.2015.1038755","article-title":"Wound healing potential of naringin ointment formulation via regulating the expression of inflammatory, apoptotic and growth mediators in experimental rats","volume":"54","author":"Kandhare","year":"2015","journal-title":"Pharm. Biol."}],"container-title":["Pharmaceutics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1999-4923\/15\/3\/747\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T18:40:31Z","timestamp":1760121631000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1999-4923\/15\/3\/747"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,2,23]]},"references-count":42,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2023,3]]}},"alternative-id":["pharmaceutics15030747"],"URL":"https:\/\/doi.org\/10.3390\/pharmaceutics15030747","relation":{},"ISSN":["1999-4923"],"issn-type":[{"value":"1999-4923","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,2,23]]}}}