{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T17:25:56Z","timestamp":1785432356700,"version":"3.56.0"},"reference-count":46,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2026,4,20]],"date-time":"2026-04-20T00:00:00Z","timestamp":1776643200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004085","name":"Ministry of Education, Science, and Technology","doi-asserted-by":"crossref","award":["NRF-2022R1F1A1074934"],"award-info":[{"award-number":["NRF-2022R1F1A1074934"]}],"id":[{"id":"10.13039\/501100004085","id-type":"DOI","asserted-by":"crossref"}]},{"award":["NRF-2022R1F1A1074934"],"award-info":[{"award-number":["NRF-2022R1F1A1074934"]}],"id":[{"id":"https:\/\/ror.org\/0270k0c71","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Medicina"],"abstract":"<jats:p>Background and Objectives: Postoperative pain and intra-abdominal adhesions are common complications following surgery. Pain delays early mobilization, whereas adhesions can lead to bowel obstruction, chronic pain, or infertility. Current treatments, including systemic analgesics and physical barrier methods, are only partially effective. We hypothesized that combining these modalities would yield superior outcomes. Accordingly, we investigated whether a lidocaine-loaded alginate\u2013carboxymethyl cellulose\u2013polyethylene oxide (ACPE) electrospun film could more effectively reduce both postoperative pain and adhesion formation than either component alone. Materials and Methods: An electrospun nanofiber film composed of ACPE containing lidocaine was prepared. Its effects were evaluated in rats using an incisional pain and a peritoneal adhesion model. Four groups were compared: saline control, free lidocaine, drug-free ACPE film, and lidocaine-loaded ACPE film. Fifteen rats were allocated to each group. The primary outcome was the mechanical withdrawal threshold (MWT) after plantar incision, while secondary outcomes included histological changes and adhesion scores assessed by the Moreno system. Results: The lidocaine\u2013ACPE film significantly increased MWT compared with all other groups, demonstrating a stronger and longer-lasting analgesic effect than free lidocaine. Adhesion scores were also lowest in the film group. Histological analysis confirmed a reduction in inflammatory cell infiltration and collagen deposition. Conclusions: A lidocaine-loaded ACPE nanofiber film effectively reduced both postoperative pain and adhesion formation in a rodent model. The combination of sustained local drug release and physical barrier function provides a promising strategy to address two major postoperative complications. Further preclinical studies are warranted before clinical application.<\/jats:p>","DOI":"10.3390\/medicina62040789","type":"journal-article","created":{"date-parts":[[2026,4,20]],"date-time":"2026-04-20T13:22:47Z","timestamp":1776691367000},"page":"789","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Effects of a Lidocaine-Loaded Alginate\/CMC\/PEO Electrospun Nanofiber Film on Postoperative Pain and Peritoneal Adhesion in a Rat Model"],"prefix":"10.3390","volume":"62","author":[{"given":"Ha-young","family":"Kim","sequence":"first","affiliation":[{"name":"Department of Anesthesiology and Pain Medicine, College of Medicine, Chung-Ang University, Seoul 06911, Republic of Korea"},{"name":"Department of Anesthesiology and Pain Medicine, Chung-Ang University Hospital, Seoul 06973, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7899-3925","authenticated-orcid":false,"given":"Hyo-jin","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology and Pain Medicine, College of Medicine, Chung-Ang University, Seoul 06911, Republic of Korea"},{"name":"Department of Anesthesiology and Pain Medicine, Chung-Ang University Gwangmyeong Hospital, Gwangmyeong 14353, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Geun Joo","family":"Choi","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology and Pain Medicine, College of Medicine, Chung-Ang University, Seoul 06911, Republic of Korea"},{"name":"Department of Anesthesiology and Pain Medicine, Chung-Ang University Hospital, Seoul 06973, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2844-5880","authenticated-orcid":false,"given":"Hyun","family":"Kang","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology and Pain Medicine, College of Medicine, Chung-Ang University, Seoul 06911, Republic of Korea"},{"name":"Department of Anesthesiology and Pain Medicine, Chung-Ang University Hospital, Seoul 06973, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,4,20]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"2287","DOI":"10.2147\/JPR.S144066","article-title":"Poorly controlled postoperative pain: Prevalence, consequences, and prevention","volume":"10","author":"Gan","year":"2017","journal-title":"J. Pain Res."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"A3787","DOI":"10.1164\/ajrccm.2025.211.Abstracts.A3787","article-title":"Factors Impacting Early Mobilization of Patients Undergoing Thoracic Surgery","volume":"211","author":"Montoya","year":"2025","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1713","DOI":"10.1007\/s11605-017-3488-9","article-title":"Postoperative Abdominal Adhesions: Clinical Significance and Advances in Prevention and Management","volume":"21","author":"Moris","year":"2017","journal-title":"J. Gastrointest. Surg."},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Ghobrial, S., Ott, J., and Parry, J.P. (2023). An Overview of Postoperative Intraabdominal Adhesions and Their Role on Female Infertility: A Narrative Review. J. Clin. Med., 12.","DOI":"10.3390\/jcm12062263"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"101","DOI":"10.17085\/apm.25211","article-title":"Optimizing maternal recovery: Insights into enhanced recovery after Cesarean delivery","volume":"20","author":"Na","year":"2025","journal-title":"Anesth. Pain Med."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"34","DOI":"10.1016\/j.bjae.2019.10.002","article-title":"Basic pharmacology of local anaesthetics","volume":"20","author":"Taylor","year":"2020","journal-title":"BJA Educ."},{"key":"ref_7","first-page":"100115","article-title":"Gynecologic postoperative anti-adhesion barriers: From biomaterials to barrier development","volume":"19","author":"MacPhee","year":"2025","journal-title":"Biomater. Biosyst."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"266","DOI":"10.17085\/apm.24159","article-title":"Comparison of intraoperative intravenous lidocaine infusion and transversus abdominis plane block for postoperative analgesia following laparoscopic cholecystectomy: A randomized controlled trial","volume":"20","author":"Sheikh","year":"2025","journal-title":"Anesth. Pain Med."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"252","DOI":"10.17085\/apm.25264","article-title":"Comparative effectiveness of bupivacaine and lidocaine-bupivacaine mixtures in brachial plexus block: A systematic review and meta-analysis","volume":"20","author":"Cansian","year":"2025","journal-title":"Anesth. Pain Med."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"e2105152","DOI":"10.1002\/advs.202105152","article-title":"Bioactive Materials Promote Wound Healing through Modulation of Cell Behaviors","volume":"9","author":"Li","year":"2022","journal-title":"Adv. Sci."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"5298","DOI":"10.1021\/acs.chemrev.8b00593","article-title":"Electrospinning and Electrospun Nanofibers: Methods, Materials, and Applications","volume":"119","author":"Xue","year":"2019","journal-title":"Chem. Rev."},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"El-Ghoul, Y., Altuwayjiri, A.S., and Alharbi, G.A. (RSC Adv., 2024). Synthesis and characterization of new electrospun medical scaffold-based modified cellulose nanofiber and bioactive natural propolis for potential wound dressing applications, RSC Adv., In press.","DOI":"10.1039\/D4RA04231J"},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Jalalah, M., Ahmad, A., Saleem, A., Qadir, M.B., Khaliq, Z., Khan, M.Q., Nazir, A., Faisal, M., Alsaiari, M., and Irfan, M. (2022). Electrospun Nanofiber\/Textile Supported Composite Membranes with Improved Mechanical Performance for Biomedical Applications. Membranes, 12.","DOI":"10.3390\/membranes12111158"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"e37852","DOI":"10.1002\/jbm.a.37852","article-title":"Dual-Polymer Carboxymethyl Cellulose and Poly(Ethylene Oxide)-Based Gels for the Prevention of Postsurgical Adhesions","volume":"113","author":"DSouza","year":"2025","journal-title":"J. Biomed. Mater. Res. A"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"102733","DOI":"10.1016\/j.amsu.2021.102733","article-title":"Molecular mechanisms of lidocaine","volume":"69","author":"Karnina","year":"2021","journal-title":"Ann. Med. Surg."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"320","DOI":"10.1213\/ANE.0000000000001934","article-title":"Effects of a Lidocaine-Loaded Poloxamer\/Alginate\/CaCl2 Mixture on Postoperative Pain and Adhesion in a Rat Model of Incisional Pain","volume":"125","author":"Choi","year":"2017","journal-title":"Anesth. Analg."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"20152","DOI":"10.1021\/acsomega.3c00341","article-title":"Antiadhesive Nanofibrous Materials for Medicine: Preventing Undesirable Tissue Adhesions","volume":"8","author":"Klicova","year":"2023","journal-title":"ACS Omega"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"318","DOI":"10.1016\/j.jconrel.2017.06.020","article-title":"Advances in biomaterials for preventing tissue adhesion","volume":"261","author":"Wu","year":"2017","journal-title":"J. Control. Release"},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Percie du Sert, N., Hurst, V., Ahluwalia, A., Alam, S., Avey, M.T., Baker, M., Browne, W.J., Clark, A., Cuthill, I.C., and Dirnagl, U. (2020). The ARRIVE guidelines 2.0: Updated guidelines for reporting animal research. PLoS Biol., 18.","DOI":"10.1371\/journal.pbio.3000410"},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Baek, S., Park, H., Park, Y., Kang, H., and Lee, D. (2020). Development of a Lidocaine-Loaded Alginate\/CMC\/PEO Electrospun Nanofiber Film and Application as an Anti-Adhesion Barrier. Polymers, 12.","DOI":"10.3390\/polym12030618"},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Athnaiel, O., Cantillo, S., Paredes, S., and Knezevic, N.N. (2023). The Role of Sex Hormones in Pain-Related Conditions. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms24031866"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"493","DOI":"10.1016\/0304-3959(95)01441-1","article-title":"Characterization of a rat model of incisional pain","volume":"64","author":"Brennan","year":"1996","journal-title":"Pain"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"e588","DOI":"10.1097\/PR9.0000000000000588","article-title":"Postoperative pain-from mechanisms to treatment","volume":"2","author":"Segelcke","year":"2017","journal-title":"Pain Rep."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"560","DOI":"10.1016\/j.jss.2014.07.056","article-title":"Inhibition of thrombin-activated fibrinolysis inhibitor decreases postoperative adhesion","volume":"193","author":"Kim","year":"2015","journal-title":"J. Surg. Res."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"129","DOI":"10.1159\/000100109","article-title":"Instillation of taurolidine\/heparin after laparotomy reduces intraperitoneal tumour growth in a colon cancer rat model","volume":"39","author":"Opitz","year":"2007","journal-title":"Eur. Surg. Res."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"56","DOI":"10.4174\/astr.2026.110.1.56","article-title":"Effectiveness of atorvastatin, methylene blue, and lidocaine as chemical antiadhesion agents in preventing postoperative remote adhesions: A randomized controlled experimental study in a rat model","volume":"110","author":"Kim","year":"2026","journal-title":"Ann. Surg. Treat. Res."},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Lin, L.X., Yuan, F., Zhang, H.H., Liao, N.N., Luo, J.W., and Sun, Y.L. (2017). Evaluation of surgical anti-adhesion products to reduce postsurgical intra-abdominal adhesion formation in a rat model. PLoS ONE, 12.","DOI":"10.1371\/journal.pone.0172088"},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"Giusto, G., Vercelli, C., Iussich, S., Audisio, A., Morello, E., Odore, R., and Gandini, M. (2017). A pectin-honey hydrogel prevents postoperative intraperitoneal adhesions in a rat model. BMC Vet. Res., 13.","DOI":"10.1186\/s12917-017-0965-z"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1016\/j.jss.2009.09.025","article-title":"An assessment of the effects of a hyaluronan-based solution on reduction of postsurgical adhesion formation in rats: A comparative study of hyaluronan-based solution and two film barriers","volume":"168","author":"Park","year":"2011","journal-title":"J. Surg. Res."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"17448069221124925","DOI":"10.1177\/17448069221124925","article-title":"Lidocaine reduces pain behaviors by inhibiting the expression of Nav1.7 and Nav1.8 and diminishing sympathetic sprouting in SNI rats","volume":"18","author":"Li","year":"2022","journal-title":"Mol. Pain"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"e19898","DOI":"10.1097\/MD.0000000000019898","article-title":"A review of the mechanism of the central analgesic effect of lidocaine","volume":"99","author":"Yang","year":"2020","journal-title":"Medicine"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"e39574","DOI":"10.1097\/MD.0000000000039574","article-title":"The mechanism of perioperative intravenous lidocaine in regulating the inflammatory response: A review","volume":"103","author":"Wang","year":"2024","journal-title":"Medicine"},{"key":"ref_33","doi-asserted-by":"crossref","unstructured":"Fernandez-Martinez, A., Garcia, J.G., and Lopez-Picado, A. (2025). Anti-Inflammatory and Immunomodulatory Effects of Intravenous Lidocaine in Surgery: A Narrative Review. J. Clin. Med., 14.","DOI":"10.3390\/jcm14113883"},{"key":"ref_34","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_35","doi-asserted-by":"crossref","first-page":"1367","DOI":"10.1038\/s41467-021-21438-3","article-title":"Degradable polymeric vehicles for postoperative pain management","volume":"12","author":"Brigham","year":"2021","journal-title":"Nat. Commun."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1186\/s11671-019-3241-2","article-title":"Advances of Nano-Structured Extended-Release Local Anesthetics","volume":"15","author":"He","year":"2020","journal-title":"Nanoscale Res. Lett."},{"key":"ref_37","doi-asserted-by":"crossref","unstructured":"Reddy, V.S., Tian, Y., Zhang, C., Ye, Z., Roy, K., Chinnappan, A., Ramakrishna, S., Liu, W., and Ghosh, R. (2021). A Review on Electrospun Nanofibers Based Advanced Applications: From Health Care to Energy Devices. Polymers, 13.","DOI":"10.3390\/polym13213746"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"7312","DOI":"10.1039\/D2RA06023J","article-title":"Electrospun nanofibres in drug delivery: Advances in controlled release strategies","volume":"13","author":"Gaydhane","year":"2023","journal-title":"RSC Adv."},{"key":"ref_39","doi-asserted-by":"crossref","unstructured":"Castro, I., Carvalho, P., Vale, N., Monjardino, T., and Mour\u00e3o, J. (2023). Systemic Anti-Inflammatory Effects of Intravenous Lidocaine in Surgical Patients: A Systematic Review and Meta-Analysis. J. Clin. Med., 12.","DOI":"10.3390\/jcm12113772"},{"key":"ref_40","doi-asserted-by":"crossref","unstructured":"Fatehi Hassanabad, A., Zarzycki, A.N., Jeon, K., Deniset, J.F., and Fedak, P.W.M. (2021). Post-Operative Adhesions: A Comprehensive Review of Mechanisms. Biomedicines, 9.","DOI":"10.3390\/biomedicines9080867"},{"key":"ref_41","first-page":"387","article-title":"Prevention strategies of postoperative adhesion in soft tissues by applying biomaterials: Based on the mechanisms of occurrence and development of adhesions","volume":"26","author":"Liao","year":"2023","journal-title":"Bioact. Mater."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"zrac075","DOI":"10.1093\/bjsopen\/zrac075","article-title":"Barrier materials for prevention of surgical adhesions: Systematic review","volume":"6","author":"Waldron","year":"2022","journal-title":"BJS Open"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"1183","DOI":"10.1016\/j.ijbiomac.2019.08.228","article-title":"Chitosan-collagen based film for controlled delivery of a combination of short life anesthetics","volume":"140","author":"Drannikov","year":"2019","journal-title":"Int. J. Biol. Macromol."},{"key":"ref_44","doi-asserted-by":"crossref","unstructured":"Lee, K.K., Jeong, W., and Chae, M. (2025). Hydrogel Drug Delivery Systems and Liposomal Bupivacaine: Innovations and Future Perspectives in Pain Management. J. Clin. Med., 14.","DOI":"10.3390\/jcm14217824"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"110918","DOI":"10.1016\/j.jclinane.2022.110918","article-title":"The effect of lidocaine patch for postoperative pain: A meta-analysis of randomized controlled trials","volume":"81","author":"Koo","year":"2022","journal-title":"J. Clin. Anesth."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"113996","DOI":"10.1016\/j.biopha.2022.113996","article-title":"Therapeutic applications of electrospun nanofibers impregnated with various biological macromolecules for effective wound healing strategy\u2014A review","volume":"157","author":"Sethuram","year":"2023","journal-title":"Biomed. Pharmacother."}],"container-title":["Medicina"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1648-9144\/62\/4\/789\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,22]],"date-time":"2026-04-22T04:19:19Z","timestamp":1776831559000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1648-9144\/62\/4\/789"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,4,20]]},"references-count":46,"journal-issue":{"issue":"4","published-online":{"date-parts":[[2026,4]]}},"alternative-id":["medicina62040789"],"URL":"https:\/\/doi.org\/10.3390\/medicina62040789","relation":{},"ISSN":["1648-9144"],"issn-type":[{"value":"1648-9144","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,4,20]]}}}