{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,12]],"date-time":"2026-10-12T15:15:40Z","timestamp":1791818140060,"version":"4.3.4"},"reference-count":50,"publisher":"MDPI AG","issue":"17","license":[{"start":{"date-parts":[[2022,8,25]],"date-time":"2022-08-25T00:00:00Z","timestamp":1661385600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100002858","name":"China Postdoctoral Science Foundation","doi-asserted-by":"publisher","award":["2020M673586XB"],"award-info":[{"award-number":["2020M673586XB"]}],"id":[{"id":"10.13039\/501100002858","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002858","name":"China Postdoctoral Science Foundation","doi-asserted-by":"publisher","award":["2020T130334"],"award-info":[{"award-number":["2020T130334"]}],"id":[{"id":"10.13039\/501100002858","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002858","name":"China Postdoctoral Science Foundation","doi-asserted-by":"publisher","award":["2021M137"],"award-info":[{"award-number":["2021M137"]}],"id":[{"id":"10.13039\/501100002858","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Shandong Traditional Chinese Medicine Science and Technology Project","award":["2020M673586XB"],"award-info":[{"award-number":["2020M673586XB"]}]},{"name":"Shandong Traditional Chinese Medicine Science and Technology Project","award":["2020T130334"],"award-info":[{"award-number":["2020T130334"]}]},{"name":"Shandong Traditional Chinese Medicine Science and Technology Project","award":["2021M137"],"award-info":[{"award-number":["2021M137"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Nanomaterials"],"abstract":"<jats:p>The design and development of novel dressing materials are urgently required for the treatment of chronic wounds caused by diabetic ulcers in clinics. In this study, ursolic acid (UA) extracted from Chinese herbal plants was encapsulated into electrospun nanofibers made from a blend of chitosan (CS) and polyvinyl alcohol (PVA) to generate innovative CS-PVA-UA dressings for diabetic wound treatment. The as-prepared CS-PVA-UA nanofiber mats exhibited randomly aligned fiber morphology with the mean fiber diameters in the range of 100\u2013200 nm, possessing great morphological resemblance to the collagen fibrils which exist in the native skin extracellular matrix (ECM). In addition, the CS-PVA-UA nanofiber mats were found to possess good surface hydrophilicity and wettability, and sustained UA release behavior. The in vitro biological tests showed that the high concentration of UA could lead to slight cytotoxicity. It was also found that the CS-PVA-UA nanofiber dressings could significantly reduce the M1 phenotypic transition of macrophages that was even stimulated by lipopolysaccharide (LPS) and could effectively restore the M2 polarization of macrophages to shorten the inflammatory period. Moreover, the appropriate introduction of UA into CS-PVA nanofibers decreased the release levels of TNF-\u03b1 and IL-6 inflammatory factors, and suppressed oxidative stress responses by reducing the generation of reactive oxygen species (ROS) as well. The results from mouse hepatic hemorrhage displayed that CS-PVA-UA nanofiber dressing possessed excellent hemostatic performance. The in vivo animal experiments displayed that the CS-PVA-UA nanofiber dressing could improve the closure rate, and also promote the revascularization and re-epithelization, as well as the deposition and remodeling of collagen matrix and the regeneration of hair follicles for diabetic wounds. Specifically, the mean contraction rate of diabetic wounds using CS-PVA-UA nanofiber dressing could reach 99.8% after 18 days of treatment. In summary, our present study offers a promising nanofibrous dressing candidate with multiple biological functions, including anti-inflammation, antioxidation, pro-angiogenesis, and hemostasis functions, for the treatment of hard-to-heal diabetic wounds.<\/jats:p>","DOI":"10.3390\/nano12172933","type":"journal-article","created":{"date-parts":[[2022,8,26]],"date-time":"2022-08-26T02:04:32Z","timestamp":1661479472000},"page":"2933","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":94,"title":["Electrospun Chitosan\u2013Polyvinyl Alcohol Nanofiber Dressings Loaded with Bioactive Ursolic Acid Promoting Diabetic Wound Healing"],"prefix":"10.3390","volume":"12","author":[{"given":"Hongyu","family":"Lv","sequence":"first","affiliation":[{"name":"College of Basic Medicine, Qingdao University, 308 Ningxia Road, Qingdao 266071, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Meng","family":"Zhao","sequence":"additional","affiliation":[{"name":"College of Nursing, Qingdao University, 308 Ningxia Road, Qingdao 266071, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yiran","family":"Li","sequence":"additional","affiliation":[{"name":"College of Textiles and Clothing, Qingdao University, 308 Ningxia Road, Qingdao 266071, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kun","family":"Li","sequence":"additional","affiliation":[{"name":"College of Textiles and Clothing, Qingdao University, 308 Ningxia Road, Qingdao 266071, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shaojuan","family":"Chen","sequence":"additional","affiliation":[{"name":"College of Textiles and Clothing, Qingdao University, 308 Ningxia Road, Qingdao 266071, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenwen","family":"Zhao","sequence":"additional","affiliation":[{"name":"College of Basic Medicine, Qingdao University, 308 Ningxia Road, Qingdao 266071, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shaohua","family":"Wu","sequence":"additional","affiliation":[{"name":"College of Textiles and Clothing, Qingdao University, 308 Ningxia Road, Qingdao 266071, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yantao","family":"Han","sequence":"additional","affiliation":[{"name":"College of Basic Medicine, Qingdao University, 308 Ningxia Road, Qingdao 266071, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,8,25]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"e2100275","DOI":"10.1002\/advs.202100275","article-title":"Emerging Targets in Type 2 Diabetes and Diabetic Complications","volume":"8","author":"Demir","year":"2021","journal-title":"Adv. Sci."},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Iatcu, C.O., Steen, A., and Covasa, M. (2021). Gut Microbiota and Complications of Type-2 Diabetes. Nutrients, 14.","DOI":"10.3390\/nu14010166"},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Burgess, J.L., Wyant, W.A., Abujamra, B.A., Kirsner, R.S., and Jozic, I. (2021). Diabetic Wound-Healing Science. Medicina, 57.","DOI":"10.3390\/medicina57101072"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"87","DOI":"10.1016\/j.trsl.2021.05.003","article-title":"Cutaneous innervation in impaired diabetic wound healing","volume":"236","author":"Nowak","year":"2021","journal-title":"Transl. Res."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"106","DOI":"10.1080\/07853890.2016.1231932","article-title":"Global epidemiology of diabetic foot ulceration: A systematic review and meta-analysis","volume":"49","author":"Zhang","year":"2017","journal-title":"Ann. Med."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"12687","DOI":"10.1021\/acsnano.1c04206","article-title":"Functional Hydrogels as Wound Dressing to Enhance Wound Healing","volume":"15","author":"Liang","year":"2021","journal-title":"ACS Nano"},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Alven, S., Peter, S., Mbese, Z., and Aderibigbe, B.A. (2022). Polymer-Based Wound Dressing Materials Loaded with Bioactive Agents: Potential Materials for the Treatment of Diabetic Wounds. Polymers, 14.","DOI":"10.3390\/polym14040724"},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Sun, M., Chen, S., Ling, P., Ma, J., and Wu, S. (2021). Electrospun Methacrylated Gelatin\/Poly(L-Lactic Acid) Nanofibrous Hydrogel Scaffolds for Potential Wound Dressing Application. Nanomaterials, 12.","DOI":"10.3390\/nano12010006"},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Li, T., Sun, M., and Wu, S. (2022). State-of-the-Art Review of Electrospun Gelatin-Based Nanofiber Dressings for Wound Healing Applications. Nanomaterials, 12.","DOI":"10.3390\/nano12050784"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"100243","DOI":"10.1016\/j.mtbio.2022.100243","article-title":"Electrospun strong, bioactive, and bioabsorbable silk fibroin\/poly (L-lactic-acid) nanoyarns for constructing advanced nanotextile tissue scaffolds","volume":"14","author":"Liu","year":"2022","journal-title":"Mater. Today Bio"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"91","DOI":"10.1016\/j.actbio.2020.11.042","article-title":"Electrospun conductive nanofiber yarns for accelerating mesenchymal stem cells differentiation and maturation into Schwann cell-like cells under a combination of electrical stimulation and chemical induction","volume":"139","author":"Wu","year":"2022","journal-title":"Acta Biomater."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"130229","DOI":"10.1016\/j.matlet.2021.130229","article-title":"Developing high strength poly(L-lactic acid) nanofiber yarns for biomedical textile materials: A comparative study of novel nanofiber yarns and traditional microfiber yarns","volume":"300","author":"Liu","year":"2021","journal-title":"Mater. Lett."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"045018","DOI":"10.1088\/1758-5090\/ac2209","article-title":"Combining electrospinning with hot drawing process to fabricate high performance poly (L-lactic acid) nanofiber yarns for advanced nanostructured bio-textiles","volume":"13","author":"Wu","year":"2021","journal-title":"Biofabrication"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"101473","DOI":"10.1016\/j.apmt.2022.101473","article-title":"State-of-the-art review of advanced electrospun nanofiber yarn-based textiles for biomedical applications","volume":"27","author":"Wu","year":"2022","journal-title":"Appl. Mater. Today"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"100944","DOI":"10.1016\/j.mtchem.2022.100944","article-title":"Review of advances in electrospinning-based strategies for spinal cord regeneration","volume":"24","author":"Li","year":"2022","journal-title":"Mater. Today Chem."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"119375","DOI":"10.1016\/j.carbpol.2022.119375","article-title":"Hyaluronic acid\/lactose-modified chitosan electrospun wound dressings\u2013Crosslinking and stability criticalities","volume":"288","author":"Gruppuso","year":"2022","journal-title":"Carbohydr. Polym."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"112","DOI":"10.1134\/S2079978021010052","article-title":"Electrospinning of Polysaccharides for Tissue Engineering Applications","volume":"11","author":"Poshina","year":"2021","journal-title":"Rev. Adv. Chem."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1020","DOI":"10.1016\/j.addr.2009.07.006","article-title":"Electrospinning of polysaccharides for regenerative medicine","volume":"61","author":"Lee","year":"2009","journal-title":"Adv. Drug Deliv. Rev."},{"key":"ref_19","first-page":"82","article-title":"Electrospun chitosan nanofibers for wound healing application","volume":"2","author":"Cui","year":"2021","journal-title":"Eng. Regen."},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Aitcheson, S.M., Frentiu, F.D., Hurn, S.E., Edwards, K., and Murray, R.Z. (2021). Skin Wound Healing: Normal Macrophage Function and Macrophage Dysfunction in Diabetic Wounds. Molecules, 26.","DOI":"10.3390\/molecules26164917"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1528","DOI":"10.1177\/147323000903700531","article-title":"The wound healing process: An overview of the cellular and molecular mechanisms","volume":"37","author":"Velnar","year":"2009","journal-title":"J. Int. Med. Res."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"17","DOI":"10.4049\/jimmunol.1700223","article-title":"Macrophage-Mediated Inflammation in Normal and Diabetic Wound Healing","volume":"199","author":"Boniakowski","year":"2017","journal-title":"J. Immunol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"109","DOI":"10.1016\/j.trsl.2021.05.006","article-title":"Macrophage polarization and diabetic wound healing","volume":"236","author":"Louiselle","year":"2021","journal-title":"Transl. Res."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"259","DOI":"10.1186\/s13287-020-01756-x","article-title":"Melatonin-stimulated MSC-derived exosomes improve diabetic wound healing through regulating macrophage M1 and M2 polarization by targeting the PTEN\/AKT pathway","volume":"11","author":"Liu","year":"2020","journal-title":"Stem Cell Res. Ther."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1016\/j.etap.2010.03.005","article-title":"Free radical scavenging, antioxidant enzymes and wound healing activities of leaves extracts from Clerodendrum infortunatum L.","volume":"30","author":"Gouthamchandra","year":"2010","journal-title":"Environ. Toxicol. Pharmacol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"961182","DOI":"10.3389\/fnut.2022.961182","article-title":"A Novel Polysaccharide From Chuanminshen violaceum and Its Protective Effect Against Myocardial Injury","volume":"9","author":"He","year":"2022","journal-title":"Front. Nutr."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"3033","DOI":"10.1111\/1541-4337.12972","article-title":"Bioactive polysaccharides and oligosaccharides from garlic (Allium sativum L.): Production, physicochemical and biological properties, and structure-function relationships","volume":"21","author":"Qiu","year":"2022","journal-title":"Compr. Rev. Food Sci. Food Saf."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"195","DOI":"10.1089\/wound.2013.0429","article-title":"Dynamics of Transforming Growth Factor Beta Signaling in Wound Healing and Scarring","volume":"2","author":"Finnson","year":"2013","journal-title":"Adv. Wound Care"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"101542","DOI":"10.1016\/j.apmt.2022.101542","article-title":"Novel bi-layered dressing patches constructed with radially-oriented nanofibrous pattern and herbal compound-loaded hydrogel for accelerated diabetic wound healing","volume":"28","author":"Wu","year":"2022","journal-title":"Appl. Mater. Today"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"512","DOI":"10.1016\/j.metabol.2009.07.040","article-title":"Inhibitory effects of ursolic acid on hepatic polyol pathway and glucose production in streptozotocin-induced diabetic mice","volume":"59","author":"Jang","year":"2010","journal-title":"Metab. Clin. Exp."},{"key":"ref_31","first-page":"683","article-title":"Effects of ursolic acid on glucose metabolism, the polyol pathway and dyslipidemia in non-obese type 2 diabetic mice","volume":"52","author":"Lee","year":"2014","journal-title":"Indian J. Exp. Biol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"877898","DOI":"10.3389\/fphar.2022.877898","article-title":"Ursolic Acid Protects Neurons in Temporal Lobe Epilepsy and Cognitive Impairment by Repressing Inflammation and Oxidation","volume":"13","author":"Liu","year":"2022","journal-title":"Front. Pharmacol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"1643","DOI":"10.1039\/C5FO00083A","article-title":"Ursolic acid inhibits the development of nonalcoholic fatty liver disease by attenuating endoplasmic reticulum stress","volume":"6","author":"Li","year":"2015","journal-title":"Food Funct."},{"key":"ref_34","first-page":"4675","article-title":"Ursolic acid alleviates inflammation and against diabetes-induced nephropathy through TLR4-mediated inflammatory pathway","volume":"18","author":"Li","year":"2018","journal-title":"Mol. Med. Rep."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"1461","DOI":"10.1016\/j.biopha.2017.11.032","article-title":"Ursolic acid ameliorates oxidative stress, inflammation and fibrosis in diabetic cardiomyopathy rats","volume":"97","author":"Wang","year":"2018","journal-title":"Biomed. Pharmacother."},{"key":"ref_36","first-page":"134","article-title":"Effects of ursolic acid on liver injury and its possible mechanism in diabetes mellitus mice","volume":"34","author":"Wang","year":"2018","journal-title":"Chin. J. Physiol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"6679316","DOI":"10.1155\/2021\/6679316","article-title":"Ursolic Acid Regulates Intestinal Microbiota and Inflammatory Cell Infiltration to Prevent Ulcerative Colitis","volume":"2021","author":"Sheng","year":"2021","journal-title":"J. Immunol. Res."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"104735","DOI":"10.1016\/j.fitote.2020.104735","article-title":"Ursolic acid: A systematic review of its pharmacology, toxicity and rethink on its pharmacokinetics based on PK-PD model","volume":"147","author":"Sun","year":"2020","journal-title":"Fitoterapia"},{"key":"ref_39","doi-asserted-by":"crossref","unstructured":"Luo, M., Wang, Y., Xie, C., and Lei, B. (2022). Multiple Coordination-Derived Bioactive Hydrogel with Proangiogenic Hemostatic Capacity for Wound Repair. Adv. Healthc. Mater., e2200722.","DOI":"10.1002\/adhm.202200722"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"16950","DOI":"10.1021\/acsami.6b05199","article-title":"Fabrication of Aligned Nanofiber Polymer Yarn Networks for Anisotropic Soft Tissue Scaffolds","volume":"8","author":"Wu","year":"2016","journal-title":"ACS Appl. Mater. Interfaces"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"174","DOI":"10.1080\/10717544.2021.2021319","article-title":"Electrospun multifunctional nanofibrous mats loaded with bioactive anemoside B4 for accelerated wound healing in diabetic mice","volume":"29","author":"Zhang","year":"2022","journal-title":"Drug Deliv."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"6425","DOI":"10.1002\/jcp.26429","article-title":"Macrophage plasticity, polarization, and function in health and disease","volume":"233","author":"Mohammadian","year":"2018","journal-title":"J. Cell. Physiol."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"3439","DOI":"10.4049\/jimmunol.1201168","article-title":"SOCS3 deficiency promotes M1 macrophage polarization and inflammation","volume":"189","author":"Qin","year":"2012","journal-title":"J. Immunol."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"89","DOI":"10.1111\/iwj.12557","article-title":"Reactive oxygen species (ROS) and wound healing: The functional role of ROS and emerging ROS-modulating technologies for augmentation of the healing process","volume":"14","author":"Dunnill","year":"2017","journal-title":"Int. Wound J."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"8852759","DOI":"10.1155\/2021\/8852759","article-title":"The Role of Oxidative Stress and Antioxidants in Diabetic Wound Healing","volume":"2021","author":"Deng","year":"2021","journal-title":"Oxid. Med. Cell. Longev."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"S337","DOI":"10.4103\/ccd.ccd_435_18","article-title":"Neovascular Pattern in Wound Healing after Zinc Oxide and Curcuma longa Rhizome Extract Dressing Application","volume":"9","author":"Faiga","year":"2018","journal-title":"Contemp. Clin. Dent."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"599","DOI":"10.1007\/s12325-017-0478-y","article-title":"Chronic Wound Healing: A Review of Current Management and Treatments","volume":"34","author":"Han","year":"2017","journal-title":"Adv. Ther."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"69","DOI":"10.1007\/s12272-013-0284-2","article-title":"Therapeutic applications of electrospun nanofibers for drug delivery systems","volume":"37","author":"Son","year":"2014","journal-title":"Arch. Pharmacal Res."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"1037","DOI":"10.1016\/j.lfs.2013.04.001","article-title":"Neovascularization in diabetes and its complications. Unraveling the angiogenic paradox","volume":"92","author":"Costa","year":"2013","journal-title":"Life Sci."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"106","DOI":"10.1016\/j.expneurol.2018.09.013","article-title":"Post-stroke neovascularization and functional outcomes differ in diabetes depending on severity of injury and sex: Potential link to hemorrhagic transformation","volume":"311","author":"Li","year":"2019","journal-title":"Exp. Neurol."}],"container-title":["Nanomaterials"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2079-4991\/12\/17\/2933\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T00:15:28Z","timestamp":1760141728000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2079-4991\/12\/17\/2933"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,8,25]]},"references-count":50,"journal-issue":{"issue":"17","published-online":{"date-parts":[[2022,9]]}},"alternative-id":["nano12172933"],"URL":"https:\/\/doi.org\/10.3390\/nano12172933","relation":{},"ISSN":["2079-4991"],"issn-type":[{"value":"2079-4991","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,8,25]]}}}