{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,27]],"date-time":"2026-08-27T16:18:48Z","timestamp":1787847528078,"version":"build-2784847793"},"reference-count":39,"publisher":"Ovid Technologies (Wolters Kluwer Health)","content-domain":{"domain":["lww.com","ovid.com"],"crossmark-restriction":true},"short-container-title":[],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background:<\/jats:title>\n                    <jats:p>Diabetic foot ulcer (DFU) is one of serious consequences of diabetes mellitus leading to many complications. Chitosan is a natural polymer used in wound dressings and is effective on healing. Also, arginine is the most important amino acid in wound healing. In this study, the clinical effects of a topical gel containing arginine-releasing chitosan nanofibers on the healing of DFUs was evaluated.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods:<\/jats:title>\n                    <jats:p>\n                      In this randomized controlled clinical trial, patients with grades 1 or 2 DFU were divided to two groups of drug (\n                      <jats:italic toggle=\"yes\">n<\/jats:italic>\n                      = 25) and control (\n                      <jats:italic toggle=\"yes\">n<\/jats:italic>\n                      = 31). For drug and control groups, arginine-releasing chitosan nanofibers gel and a type of novel dressing (Sorbact\n                      <jats:sup>\u00ae<\/jats:sup>\n                      gel dressing) were applied every other day for 14 days. The percentage of change in wound size as well as the rate of complete healing of the ulcer (&gt;90% reduction in the size) at the 7\n                      <jats:sup>th<\/jats:sup>\n                      and 14\n                      <jats:sup>th<\/jats:sup>\n                      days of the intervention was recorded and compared between the groups.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results:<\/jats:title>\n                    <jats:p>\n                      There was significant decrease in the wound size in both groups at the end of weeks 1 and 2 compared to the baseline. However, there was no significant difference between the groups regarding the percentage of decrease in the size. There was no significant difference between the groups in terms of the rate of complete wound healing at the end of the study (9 cases [36%] vs. 7 cases [22.58%], respectively;\n                      <jats:italic toggle=\"yes\">P<\/jats:italic>\n                      = 0.269).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions:<\/jats:title>\n                    <jats:p>Topical gel containing arginine-releasing chitosan nanofibers improves and accelerates the healing of DFUs. However, more studies are required to confirm these effects.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.4103\/ijpvm.ijpvm_41_24","type":"journal-article","created":{"date-parts":[[2026,5,31]],"date-time":"2026-05-31T21:00:07Z","timestamp":1780261207000},"update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":0,"title":["The Effectiveness of Topical Gel Containing Arginine-Releasing Chitosan Nanofibers on the Healing of Diabetic Foot Ulcers: A Randomized Controlled Clinical Trial"],"prefix":"10.4103","volume":"17","author":[{"given":"Razieh","family":"Ramazani","sequence":"first","affiliation":[{"name":"Department of Clinical Pharmacy and Pharmacy Practice, School of Pharmacy and Pharmaceutical Sciences, Isfahan University of Medical Sciences, Isfahan, Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rasool","family":"Soltani","sequence":"additional","affiliation":[{"name":"Department of Clinical Pharmacy and Pharmacy Practice, School of Pharmacy and Pharmaceutical Sciences, Isfahan University of Medical Sciences, Isfahan, Iran"},{"name":"Infectious Diseases and Tropical Medicine Research Center, Isfahan University of Medical Sciences, Isfahan, Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Farzin","family":"Khorvash","sequence":"additional","affiliation":[{"name":"Nosocomial Infection Research Center, Isfahan University of Medical Sciences, Isfahan, Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Azade","family":"Taheri","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutics, School of Pharmacy and Novel Drug Delivery System Research Center, Isfahan University of Medical Sciences, Isfahan, Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mehdi Shahbazi","family":"Azad","sequence":"additional","affiliation":[{"name":"Nosocomial Infection Research Center, Isfahan University of Medical Sciences, Isfahan, Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","published-online":{"date-parts":[[2026,5]]},"reference":[{"issue":"Suppl 1","key":"R1-20260708","doi-asserted-by":"crossref","first-page":"e3273","DOI":"10.1002\/dmrr.3273","article-title":"Guidelines on the classification of diabetic foot ulcers (IWGDF 2019)","volume":"36","author":"Monteiro-Soares","year":"2020","journal-title":"Diabetes Metab Res Rev"},{"key":"R2-20260708","doi-asserted-by":"crossref","first-page":"e0239236","DOI":"10.1371\/journal.pone.0239236","article-title":"Risk factors for lower extremity amputation in patients with diabetic foot ulcers: A meta-analysis","volume":"15","author":"Lin","year":"2020","journal-title":"PLoS One"},{"key":"R3-20260708","doi-asserted-by":"crossref","first-page":"123","DOI":"10.1016\/j.rmu.2017.07.002","article-title":"Association between peripheral arterial disease and diabetic foot ulcers in patients with diabetes mellitus type 2","volume":"19","author":"Tresierra-Ayala","year":"2017","journal-title":"Medicina Universitaria"},{"key":"R4-20260708","doi-asserted-by":"crossref","first-page":"218","DOI":"10.1002\/dmrr.2255","article-title":"Diagnosis and treatment of peripheral arterial disease in diabetic patients with a foot ulcer. A progress report of the International Working Group on the Diabetic Foot","volume":"28","author":"Schaper","year":"2012","journal-title":"Diabetes Metab Res Rev"},{"key":"R5-20260708","doi-asserted-by":"crossref","first-page":"28","DOI":"10.1097\/01.JAA.0000464276.44117.b1","article-title":"Pathogenesis and management of diabetic foot ulcers","volume":"28","author":"Aumiller","year":"2015","journal-title":"JAAPA"},{"key":"R6-20260708","doi-asserted-by":"crossref","first-page":"101909","DOI":"10.1016\/j.foot.2022.101909","article-title":"Health economics of diabetic foot ulcer and recent trends to accelerate treatment","volume":"52","author":"Jodheea-Jutton","year":"2022","journal-title":"Foot (Edinb)"},{"key":"R7-20260708","doi-asserted-by":"crossref","first-page":"342","DOI":"10.3144\/expresspolymlett.2011.34","article-title":"Preparations, properties and applications of chitosan based nanofibers fabricated by electrospinning","volume":"5","author":"Sun","year":"2011","journal-title":"Express Polym Lett"},{"key":"R8-20260708","doi-asserted-by":"crossref","first-page":"3873","DOI":"10.4049\/jimmunol.166.6.3873","article-title":"Biphasic regulation of NF-kappa B activity underlies the pro- and anti-inflammatory actions of nitric oxide","volume":"166","author":"Connelly","year":"2001","journal-title":"J Immunol"},{"key":"R9-20260708","doi-asserted-by":"crossref","first-page":"139","DOI":"10.1023\/A:1006431309841","article-title":"Nitric oxide and angiogenesis","volume":"50","author":"Ziche","year":"2000","journal-title":"J Neurooncol"},{"key":"R10-20260708","doi-asserted-by":"crossref","first-page":"3877","DOI":"10.4049\/jimmunol.144.10.3877","article-title":"Temporal expression of different pathways of 1-arginine metabolism in healing wounds","volume":"144","author":"Albina","year":"1990","journal-title":"J Immunol"},{"key":"R11-20260708","first-page":"224","article-title":"Arginine: An essential amino acid for injured rats","volume":"84","author":"Seifter","year":"1978","journal-title":"Surgery"},{"key":"R12-20260708","doi-asserted-by":"crossref","first-page":"328","DOI":"10.1016\/0022-4804(85)90045-9","article-title":"Intravenous hyperalimentation with high arginine levels improves wound healing and immune function","volume":"38","author":"Barbul","year":"1985","journal-title":"J Surg Res"},{"key":"R13-20260708","doi-asserted-by":"crossref","first-page":"772","DOI":"10.1002\/mabi.201300561","article-title":"Electrospun nanofibers as dressings for chronic wound care: Advances, challenges, and future prospects","volume":"14","author":"Abrigo","year":"2014","journal-title":"Macromol Biosci"},{"key":"R14-20260708","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1016\/j.biopha.2016.06.016","article-title":"Preparation of asiaticoside-loaded coaxially electrospinning nanofibers and their effect on deep partial-thickness burn injury","volume":"83","author":"Zhu","year":"2016","journal-title":"Biomed Pharmacother"},{"key":"R15-20260708","doi-asserted-by":"crossref","first-page":"747","DOI":"10.1016\/j.msec.2016.05.074","article-title":"Recent advancements in nanotechnological strategies in selection, design and delivery of biomolecules for skin regeneration","volume":"67","author":"Korrapati","year":"2016","journal-title":"Mater Sci Eng C Mater Biol Appl"},{"key":"R16-20260708","doi-asserted-by":"crossref","first-page":"415","DOI":"10.1016\/j.colsurfb.2016.03.052","article-title":"Electrospun tilapia collagen nanofibers accelerating wound healing via inducing keratinocytes proliferation and differentiation","volume":"143","author":"Zhou","year":"2016","journal-title":"Colloids Surf B Biointerfaces"},{"key":"R17-20260708","doi-asserted-by":"crossref","first-page":"3653","DOI":"10.1002\/jps.24610","article-title":"Advanced therapeutic dressings for effective wound healing--A review","volume":"104","author":"Boateng","year":"2015","journal-title":"J Pharm Sci"},{"key":"R18-20260708","doi-asserted-by":"crossref","first-page":"933","DOI":"10.1007\/s10856-005-4428-x","article-title":"Recent development of polymer nanofibers for biomedical and biotechnological applications","volume":"16","author":"Zhang","year":"2005","journal-title":"J Mater Sci Mater Med"},{"key":"R19-20260708","doi-asserted-by":"crossref","first-page":"689","DOI":"10.1177\/0885328217739562","article-title":"Preparation and in vivo evaluation of a novel gel-based wound dressing using arginine-alginate surface-modified chitosan nanofibers","volume":"32","author":"Hoseinpour Najar","year":"2018","journal-title":"J Biomater Appl"},{"key":"R20-20260708","doi-asserted-by":"crossref","first-page":"4314","DOI":"10.1021\/acs.analchem.7b00510","article-title":"Coomassie brilliant blue G-250 dye: An application for forensic fingerprint analysis","volume":"89","author":"Brunelle","year":"2017","journal-title":"Anal Chem"},{"key":"R21-20260708","doi-asserted-by":"crossref","first-page":"64","DOI":"10.1177\/107110078100200202","article-title":"The dysvascular foot: A system for diagnosis and treatment","volume":"2","author":"Wagner","year":"1981","journal-title":"Foot Ankle"},{"key":"R22-20260708","doi-asserted-by":"crossref","first-page":"445","DOI":"10.1016\/j.carbpol.2018.06.114","article-title":"Chitosan based hydrogels and their applications for drug delivery in wound dressings: A review","volume":"199","author":"Hamedi","year":"2018","journal-title":"Carbohydr Polym"},{"key":"R23-20260708","doi-asserted-by":"crossref","first-page":"304","DOI":"10.1016\/j.eurpolymj.2019.05.020","article-title":"Advancements in nanofibers for wound dressing: A review","volume":"117","author":"Ambekar","year":"2019","journal-title":"Eur Polym J"},{"key":"R24-20260708","doi-asserted-by":"crossref","first-page":"715","DOI":"10.1163\/156856209X435844","article-title":"Development of a wound dressing composed of hyaluronic acid sponge containing arginine and epidermal growth factor","volume":"21","author":"Matsumoto","year":"2010","journal-title":"J Biomater Sci Polym Ed"},{"key":"R25-20260708","first-page":"173","article-title":"Local administration of L-Arginine accelerates wound closure","volume":"12","author":"Varedi","year":"2009","journal-title":"Iran J Basic Med Sci"},{"key":"R26-20260708","doi-asserted-by":"crossref","first-page":"832","DOI":"10.1007\/s10350-004-0858-7","article-title":"Treatment of chronic anal fissure by application of L-arginine gel: A phase II study in 15 patients","volume":"48","author":"Gosselink","year":"2005","journal-title":"Dis Colon Rectum"},{"key":"R27-20260708","doi-asserted-by":"crossref","first-page":"624","DOI":"10.1016\/j.jconrel.2015.08.057","article-title":"Nitric oxide-releasing polymer incorporated ointment for cutaneous wound healing","volume":"220","author":"Kang","year":"2015","journal-title":"J Control Release"},{"key":"R28-20260708","doi-asserted-by":"crossref","first-page":"369","DOI":"10.1097\/00000658-200209000-00013","article-title":"Effect of a specialized amino acid mixture on human collagen deposition","volume":"236","author":"Williams","year":"2002","journal-title":"Ann Surg"},{"key":"R29-20260708","doi-asserted-by":"crossref","first-page":"840","DOI":"10.2174\/1567201815666180220100154","article-title":"Arginine functionalized bacterial cellulose nanofibers containing gel as an effective wound dressing: In vitro and in vivo evaluation","volume":"15","author":"Feizabadi","year":"2018","journal-title":"Curr Drug Deliv"},{"key":"R30-20260708","doi-asserted-by":"crossref","first-page":"21277","DOI":"10.1016\/S0021-9258(19)36601-3","article-title":"Epidermal growth factor suppresses nitric oxide and hydrogen peroxide production by keratinocytes. Potential role for nitric oxide in the regulation of wound healing","volume":"267","author":"Heck","year":"1992","journal-title":"J Biol Chem"},{"key":"R31-20260708","doi-asserted-by":"crossref","first-page":"286","DOI":"10.1046\/j.1523-1747.1998.00268.x","article-title":"Biphasic effect of exogenous nitric oxide on proliferation and differentiation in skin derived keratinocytes but not fibroblasts","volume":"111","author":"Krischel","year":"1998","journal-title":"J Invest Dermatol"},{"key":"R32-20260708","doi-asserted-by":"crossref","first-page":"1198","DOI":"10.1006\/bbrc.1993.1543","article-title":"Nitric oxide promotes DNA synthesis and cyclic GMP formation in endothelial cells from postcapillary venules","volume":"192","author":"Ziche","year":"1993","journal-title":"Biochem Biophys Res Commun"},{"key":"R34-20260708","doi-asserted-by":"crossref","first-page":"271","DOI":"10.1016\/S1072-7515(98)00303-2","article-title":"Up-regulation by human recombinant transforming growth factor beta-1 of collagen production in cultured dermal fibroblasts is mediated by the inhibition of nitric oxide signaling","volume":"188","author":"Chu","year":"1999","journal-title":"J Am Coll Surg"},{"key":"R35-20260708","doi-asserted-by":"crossref","first-page":"253","DOI":"10.1016\/S0006-2952(00)00529-3","article-title":"Angiogenesis: Regulators and clinical applications","volume":"61","author":"Liekens","year":"2001","journal-title":"Biochem Pharmacol"},{"key":"R36-20260708","doi-asserted-by":"crossref","first-page":"2036","DOI":"10.1172\/JCI117557","article-title":"Nitric oxide mediates angiogenesis in vivo and endothelial cell growth and migration in vitro promoted by substance P","volume":"94","author":"Ziche","year":"1994","journal-title":"J Clin Invest"},{"key":"R37-20260708","doi-asserted-by":"crossref","first-page":"142","DOI":"10.1016\/j.biotechadv.2009.11.001","article-title":"Novel chitin and chitosan nanofibers in biomedical applications","volume":"28","author":"Jayakumar","year":"2010","journal-title":"Biotechnol Adv"},{"key":"R38-20260708","doi-asserted-by":"crossref","first-page":"12","DOI":"10.1016\/j.niox.2008.04.003","article-title":"Sustained release nitric oxide releasing nanoparticles: Characterization of a novel delivery platform based on nitrite containing hydrogel\/glass composites","volume":"19","author":"Friedman","year":"2008","journal-title":"Nitric Oxide"},{"key":"R39-20260708","first-page":"113","article-title":"An evaluation of the efficacy of Cutimed\u00aeSorbact\u00aein different types of non-healing wounds","volume":"3","author":"Hampton","year":"2007","journal-title":"Wounds UK"},{"key":"R40-20260708","first-page":"10","article-title":"An investigation of Cutimed\u00aeSorbact\u00aeas an antimicrobial alternative in wound management","volume":"4","author":"Kammerlander","year":"2008","journal-title":"Wounds UK"}],"container-title":["International Journal of Preventive Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.ovid.com\/10.4103\/ijpvm.ijpvm_41_24","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,27]],"date-time":"2026-08-27T15:20:43Z","timestamp":1787844043000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.ovid.com\/10.4103\/ijpvm.ijpvm_41_24"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,5]]},"references-count":39,"URL":"https:\/\/doi.org\/10.4103\/ijpvm.ijpvm_41_24","relation":{},"ISSN":["2008-7802","2008-8213"],"issn-type":[{"value":"2008-7802","type":"print"},{"value":"2008-8213","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,5]]},"assertion":[{"value":"2024-02-06","name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-04-04","name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}}]}}