{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,19]],"date-time":"2026-08-19T05:33:01Z","timestamp":1787117581856,"version":"build-2736575974"},"reference-count":35,"publisher":"PeerJ","license":[{"start":{"date-parts":[[2025,6,9]],"date-time":"2025-06-09T00:00:00Z","timestamp":1749427200000},"content-version":"unspecified","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"abstract":"<jats:sec>\n               <jats:title>Background<\/jats:title>\n               <jats:p>Bile duct injury (BDI) remains a serious complication of hepatobiliary surgery, particularly in laparoscopic cholecystectomy, often leading to strictures, fibrosis, and long-term morbidity. Although traditional repair techniques such as primary suturing and Roux-en-Y hepaticojejunostomy are widely used, they carry risks of anastomotic complications and bile duct dysfunction. Autologous peritoneum has emerged as a potential alternative graft material due to its biocompatibility and regenerative properties. This study evaluates the efficacy of autologous parietal peritoneum graft in bile duct healing, focusing on fibroblast activity, vascular endothelial growth factor (VEGF), and interleukin-6 (IL-6) expression as indicators of tissue remodeling.<\/jats:p>\n            <\/jats:sec>\n            <jats:sec>\n               <jats:title>Materials and Methods<\/jats:title>\n               <jats:p>This experimental study involved 27 male New Zealand rabbits (<jats:italic>Oryctolagus cuniculus<\/jats:italic>), divided into three groups: group A (primary bile duct closure), group B (gallbladder transplant), and group C (parietal peritoneum transplant). The rabbits were anesthetized using a combination of ketamine, xylazine, isoflurane, and sevoflurane. Postoperative care included antibiotics and pain management. The study employed a post-test-only design. IL-6 and VEGF expression were assessed using enzyme-linked immunosorbent assay (ELISA), and the anastomosis was pathologically evaluated using hematoxylin and eosin (H&amp;E) staining. Statistical analysis was conducted with SPSS 28.0, using one-way analysis of variance (ANOVA) or Kruskal\u2013Wallis tests, with significance set at <jats:italic>p<\/jats:italic>\u00a0&lt;\u00a00.05. Ethical approval was obtained.<\/jats:p>\n            <\/jats:sec>\n            <jats:sec>\n               <jats:title>Results<\/jats:title>\n               <jats:p>On day 3, fibroblast infiltration was significantly lower in the autologous peritoneum group (<jats:italic>p<\/jats:italic>\u00a0=\u00a00.040) compared to other groups, suggesting delayed initial recruitment. By day 7, fibroblast density increased, and by day 14, all groups exhibited well-organized tissue structures with no significant intergroup differences. VEGF (<jats:italic>p<\/jats:italic>\u00a0=\u00a00.788 on day 3, 0.473 on day 7, and 0.586 on day 14) and IL-6 (<jats:italic>p<\/jats:italic>\u00a0=\u00a00.629 on day 3, 0.587 on day 7, and 0.925 on day 14) levels showed no significant variations among the groups, indicating comparable angiogenic and inflammatory responses across treatment conditions.<\/jats:p>\n            <\/jats:sec>\n            <jats:sec>\n               <jats:title>Conclusion<\/jats:title>\n               <jats:p>Autologous peritoneum supports gradual bile duct healing, despite initial delayed fibroblast recruitment, with histological evidence of progressive tissue remodeling. However, the lack of significant differences in VEGF and IL-6 levels suggests that angiogenesis and inflammation were similarly regulated across groups. Given the study\u2019s short follow-up period, further research is needed to assess the long-term integration, functional outcomes, and potential benefits of autologous peritoneum in bile duct reconstruction.<\/jats:p>\n            <\/jats:sec>","DOI":"10.7717\/peerj.19306","type":"journal-article","created":{"date-parts":[[2025,6,9]],"date-time":"2025-06-09T08:05:09Z","timestamp":1749456309000},"page":"e19306","source":"Crossref","is-referenced-by-count":1,"title":["Expression of Vascular Endothelial Growth Factor and Interleukin-6 in bile duct healing with autologous parietal peritoneum: a non-inferiority experimental study in rabbits"],"prefix":"10.7717","volume":"13","author":[{"given":"Anung Noto","family":"Nugroho","sequence":"first","affiliation":[{"name":"Doctoral Program of Medical Sciences, Sebelas Maret University, Surakarta, Central Java, Indonesia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Soetrisno","family":"Soetrisno","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, Dr. Moewardi Hospital\/Faculty of Medicine, Sebelas Maret University, Surakarta, Central Java, Indonesia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ambar","family":"Mudigdo","sequence":"additional","affiliation":[{"name":"Department of Anatomical Pathology, Dr. Moewardi Hospital\/Faculty of Medicine, Sebelas Maret University, Surakarta, Central Java, Indonesia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kristanto Yuli","family":"Yarso","sequence":"additional","affiliation":[{"name":"Oncology Division, Surgery Department, Sebelas Maret University, Surakarta, Central Java, Indonesia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dono","family":"Indarto","sequence":"additional","affiliation":[{"name":"Department of Physiology and Biomedical Laboratory, Sebelas Maret University, Surakarta, Central Java,  Indonesia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Akmal Zhahir","family":"Wahyudi","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, Sebelas Maret University, Surakarta, Central Java, Indonesia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"4443","published-online":{"date-parts":[[2025,6,9]]},"reference":[{"issue":"6","key":"10.7717\/peerj.19306\/ref-1","doi-asserted-by":"publisher","first-page":"1018","DOI":"10.1016\/S0015-0282(16)58700-7","article-title":"Long-term analysis of peritoneal plasminogen activator activity and adhesion formation after surgical trauma in the rat model","volume":"66","author":"Bakkum","year":"1996","journal-title":"Fertility and Sterility"},{"issue":"1","key":"10.7717\/peerj.19306\/ref-2","doi-asserted-by":"publisher","first-page":"32188","DOI":"10.1038\/srep32188","article-title":"Effects of IL-1\u03b2, IL-6 and IL-8 on erythrocytes, platelets and clot viscoelasticity","volume":"6","author":"Bester","year":"2016","journal-title":"Scientific Reports"},{"issue":"4","key":"10.7717\/peerj.19306\/ref-3","doi-asserted-by":"publisher","first-page":"308","DOI":"10.1080\/00015458.2013.11680935","article-title":"Reconstruction of a common bile duct injury by venous bypass","volume":"113","author":"Biglari","year":"2013","journal-title":"Acta Chirurgica Belgica"},{"issue":"3","key":"10.7717\/peerj.19306\/ref-4","doi-asserted-by":"publisher","first-page":"e33557","DOI":"10.1371\/journal.pone.0033557","article-title":"The peritoneum as a natural scaffold for vascular regeneration. Madeddu P, editor","volume":"7","author":"Bonvini","year":"2012","journal-title":"PLOS ONE"},{"key":"10.7717\/peerj.19306\/ref-5","doi-asserted-by":"publisher","first-page":"529","DOI":"10.1016\/j.redox.2014.02.005","article-title":"Hydrogen peroxide signaling in vascular endothelial cells","volume":"2","author":"Bret\u00f3n-Romero","year":"2014","journal-title":"Redox Biology"},{"issue":"8","key":"10.7717\/peerj.19306\/ref-6","doi-asserted-by":"publisher","first-page":"98","DOI":"10.3390\/antiox7080098","article-title":"Targeting oxidative stress and mitochondrial dysfunction in the treatment of impaired wound healing: a systematic review","volume":"7","author":"Cano Sanchez","year":"2018","journal-title":"Antioxidants"},{"issue":"1","key":"10.7717\/peerj.19306\/ref-7","doi-asserted-by":"publisher","first-page":"e1418","DOI":"10.1590\/0102-672020180001e1418","article-title":"Parietal peritoneum graft for duodenum injuries in an animal model","volume":"32","author":"Castillo","year":"2019","journal-title":"ABCD Arquivos Brasileiros de Cirurgia Digestiva (S\u00e3o Paulo)"},{"issue":"4","key":"10.7717\/peerj.19306\/ref-8","doi-asserted-by":"publisher","first-page":"1220","DOI":"10.1016\/j.bbadis.2017.06.024","article-title":"Pathobiology of biliary epithelia","volume":"1864","author":"Cheung","year":"2018","journal-title":"Biochimica et Biophysica Acta (BBA)\u2014Molecular Basis of Disease"},{"issue":"3","key":"10.7717\/peerj.19306\/ref-9","doi-asserted-by":"publisher","first-page":"69","DOI":"10.14701\/kjhbps.2014.18.3.69","article-title":"Recent classifications of the common bile duct injury","volume":"18","author":"Chun","year":"2014","journal-title":"Korean Journal of Hepato-Biliary-Pancreatic Surgery"},{"issue":"22","key":"10.7717\/peerj.19306\/ref-10","doi-asserted-by":"publisher","first-page":"3512","DOI":"10.3748\/wjg.v12.i22.3512","article-title":"Biliary wound healing, ductular reactions, and IL-6\/gp130 signaling in the development of liver disease","volume":"12","author":"Demetris","year":"2006","journal-title":"World Journal of Gastroenterology"},{"issue":"7","key":"10.7717\/peerj.19306\/ref-11","doi-asserted-by":"publisher","first-page":"304","DOI":"10.1097\/01.ASW.0000416006.55218.d0","article-title":"Acute and impaired wound healing","volume":"25","author":"Demidova-Rice","year":"2012","journal-title":"Advances in Skin and Wound Care"},{"issue":"12","key":"10.7717\/peerj.19306\/ref-12","doi-asserted-by":"publisher","first-page":"2563","DOI":"10.3390\/ijms18122563","article-title":"Cellular and oxidative mechanisms associated with interleukin-6 signaling in the vasculature","volume":"18","author":"Didion","year":"2017","journal-title":"International Journal of Molecular Sciences"},{"issue":"9","key":"10.7717\/peerj.19306\/ref-13","doi-asserted-by":"publisher","first-page":"1540","DOI":"10.1007\/s11605-017-3485-z","article-title":"Reconstruction of bile duct injury and defect with the round ligament","volume":"21","author":"Dokmak","year":"2017","journal-title":"Journal of Gastrointestinal Surgery"},{"issue":"1","key":"10.7717\/peerj.19306\/ref-14","doi-asserted-by":"publisher","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":"International Wound Journal"},{"issue":"9","key":"10.7717\/peerj.19306\/ref-15","doi-asserted-by":"publisher","first-page":"690","DOI":"10.17235\/reed.2019.6245\/2019","article-title":"The role of endoscopic retrograde cholangiopancreatography in the management of iatrogenic bile duct injury after cholecystectomy","volume":"111","author":"Garc\u00e9s-Albir","year":"2019","journal-title":"Revista Espa\u00f1ola de Enfermedades Digestivas"},{"issue":"6","key":"10.7717\/peerj.19306\/ref-16","doi-asserted-by":"publisher","first-page":"1133","DOI":"10.1016\/j.suc.2010.08.003","article-title":"Wound healing primer","volume":"90","author":"Goldberg","year":"2010","journal-title":"Surgical Clinics of North America"},{"issue":"3","key":"10.7717\/peerj.19306\/ref-17","doi-asserted-by":"publisher","first-page":"121","DOI":"10.14744\/less.2018.71224","article-title":"Autologous mesenteric vein and peritoneum for repair of portal vein and hepatic artery injuries accompanying bile duct injury following laparoscopic cholecystectomy","volume":"25","author":"Ince","year":"2018","journal-title":"Laparoscopic Endoscopic Surgical Science"},{"issue":"5","key":"10.7717\/peerj.19306\/ref-18","doi-asserted-by":"publisher","first-page":"101","DOI":"10.3390\/biomedicines8050101","article-title":"The role of IL-6 in skin fibrosis and cutaneous wound healing","volume":"8","author":"Johnson","year":"2020","journal-title":"Biomedicines"},{"issue":"12","key":"10.7717\/peerj.19306\/ref-19","doi-asserted-by":"publisher","first-page":"1157","DOI":"10.1177\/000313480907501201","article-title":"Article commentary: management of bile duct injuries: a practical approach","volume":"75","author":"Kapoor","year":"2009","journal-title":"American Surgeon"},{"issue":"5","key":"10.7717\/peerj.19306\/ref-20","doi-asserted-by":"publisher","first-page":"625","DOI":"10.1182\/blood-2013-09-512749","article-title":"Oxidative stress in angiogenesis and vascular disease","volume":"123","author":"Kim","year":"2014","journal-title":"Blood"},{"issue":"14","key":"10.7717\/peerj.19306\/ref-21","doi-asserted-by":"publisher","first-page":"5405","DOI":"10.7150\/ijbs.75876","article-title":"The role of IL-6 in fibrotic diseases: molecular and cellular mechanisms","volume":"18","author":"Li","year":"2022","journal-title":"International Journal of Biological Sciences"},{"issue":"3","key":"10.7717\/peerj.19306\/ref-22","doi-asserted-by":"publisher","first-page":"100251","DOI":"10.1016\/j.jhepr.2021.100251","article-title":"New insights on the role of vascular endothelial growth factor in biliary pathophysiology","volume":"3","author":"Mariotti","year":"2021","journal-title":"JHEP Reports"},{"key":"10.7717\/peerj.19306\/ref-23","doi-asserted-by":"publisher","first-page":"1134661","DOI":"10.3389\/fimmu.2023.1134661","article-title":"NF-\u03baB in monocytes and macrophages\u2014an inflammatory master regulator in multitalented immune cells","volume":"14","author":"Mussbacher","year":"2023","journal-title":"Frontiers in Immunology"},{"issue":"36","key":"10.7717\/peerj.19306\/ref-24","doi-asserted-by":"publisher","first-page":"6741","DOI":"10.3748\/wjg.v23.i36.6741","article-title":"Pedicled omental patch as a bridging procedure for iatrogenic bile duct injury","volume":"23","author":"Ng","year":"2017","journal-title":"World Journal of Gastroenterology"},{"key":"10.7717\/peerj.19306\/ref-25","doi-asserted-by":"publisher","first-page":"5","DOI":"10.1016\/j.sopen.2025.01.006","article-title":"Innovative strategies in bile duct repair: assessing efficacy and safety across varied graft techniques\u2014a systematic review","volume":"24","author":"Nugroho","year":"2025","journal-title":"Surgery Open Science"},{"key":"10.7717\/peerj.19306\/ref-26","doi-asserted-by":"crossref","DOI":"10.5772\/intechopen.81731","article-title":"Regulatory mechanisms and chemical signaling of mediators involved in the inflammatory phase of cutaneous wound healing","author":"Pereira\u00a0Beserra","year":"2019","journal-title":"Wound healing\u2014current perspectives"},{"key":"10.7717\/peerj.19306\/ref-27","doi-asserted-by":"publisher","first-page":"121","DOI":"10.2147\/CEG.S169492","article-title":"Iatrogenic bile duct injury: impact and management challenges","volume":"12","author":"Pesce","year":"2019","journal-title":"Clinical and Experimental Gastroenterology"},{"issue":"3","key":"10.7717\/peerj.19306\/ref-28","doi-asserted-by":"publisher","first-page":"490","DOI":"10.1097\/SLA.0b013e3182a1b25b","article-title":"Improved outcomes of bile duct injuries in the 21st century","volume":"258","author":"Pitt","year":"2013","journal-title":"Annals of Surgery"},{"issue":"1","key":"10.7717\/peerj.19306\/ref-29","doi-asserted-by":"publisher","first-page":"665","DOI":"10.1152\/physrev.00067.2017","article-title":"Wound healing: a cellular perspective","volume":"99","author":"Rodrigues","year":"2019","journal-title":"Physiological Reviews"},{"key":"10.7717\/peerj.19306\/ref-30","doi-asserted-by":"publisher","first-page":"104529","DOI":"10.1016\/j.amsu.2022.104529","article-title":"Locally injected Mesenchymal Stem Cells optimize angiogenesis by regulating VEGF and CD31 expression in duodenal perforation","volume":"82","author":"Setiawan","year":"2022","journal-title":"Annals of Medicine and Surgery"},{"issue":"12","key":"10.7717\/peerj.19306\/ref-31","doi-asserted-by":"publisher","first-page":"1673","DOI":"10.3390\/biom10121673","article-title":"Structural basis for vascular endothelial growth factor receptor activation and implications for disease therapy","volume":"10","author":"Shaik","year":"2020","journal-title":"Biomolecules"},{"issue":"1","key":"10.7717\/peerj.19306\/ref-32","doi-asserted-by":"publisher","first-page":"64","DOI":"10.3390\/ijms24010641","article-title":"Acute inflammation in tissue healing","volume":"24","author":"Soliman","year":"2023","journal-title":"International Journal of Molecular Sciences"},{"issue":"6","key":"10.7717\/peerj.19306\/ref-33","doi-asserted-by":"publisher","first-page":"696","DOI":"10.6002\/ect.2016.0309","article-title":"Repair of bile duct injury with autologous vein graft and stent","volume":"16","author":"Xie","year":"2018","journal-title":"Experimental and Clinical Transplantation"},{"issue":"1","key":"10.7717\/peerj.19306\/ref-34","doi-asserted-by":"publisher","first-page":"8","DOI":"10.1186\/s12893-023-02301-2","article-title":"Post-cholecystectomy bile duct injuries: a retrospective cohort study","volume":"24","author":"Zidan","year":"2024","journal-title":"BMC Surgery"},{"issue":"12","key":"10.7717\/peerj.19306\/ref-35","doi-asserted-by":"publisher","first-page":"1350","DOI":"10.1177\/000313481908501228","article-title":"Hepaticojejunostomy for Benign disease: long-term stricture rate and management","volume":"85","author":"Zielsdorf","year":"2019","journal-title":"American Surgeon"}],"container-title":["PeerJ"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/peerj.com\/articles\/19306.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/peerj.com\/articles\/19306.xml","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/peerj.com\/articles\/19306.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/peerj.com\/articles\/19306.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,6,9]],"date-time":"2025-06-09T08:05:12Z","timestamp":1749456312000},"score":1,"resource":{"primary":{"URL":"https:\/\/peerj.com\/articles\/19306"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,6,9]]},"references-count":35,"alternative-id":["10.7717\/peerj.19306"],"URL":"https:\/\/doi.org\/10.7717\/peerj.19306","archive":["CLOCKSS","LOCKSS","Portico"],"relation":{},"ISSN":["2167-8359"],"issn-type":[{"value":"2167-8359","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,6,9]]},"article-number":"e19306"}}