{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T21:51:33Z","timestamp":1790373093029,"version":"4.1.0"},"reference-count":54,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2022,1,29]],"date-time":"2022-01-29T00:00:00Z","timestamp":1643414400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100017515","name":"Heidelberger Stiftung Chirurgie","doi-asserted-by":"publisher","award":["2017\/167"],"award-info":[{"award-number":["2017\/167"]}],"id":[{"id":"10.13039\/501100017515","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Basic Clin Pharma Tox"],"published-print":{"date-parts":[[2022,4]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Pancreatic surgery is complicated by untreated fluid leakage, but no tenable techniques exist to detect and close leakage sites during surgery. A novel hydrogel called SmartPAN has been developed to meet this need and is here assessed for safety before trials on human patients. First, resazurin assays were used to test the cytotoxic effects of SmartPAN's active bromothymol blue (BTB) indicator and its solution of phosphate\u2010buffered saline (PBS) on normal (HPDE: human pancreatic duct epithelial) or carcinomic (FAMPAC) human pancreatic cells. Cells incubated with BTB showed no significant reduction in cell viability below threshold safety levels. However, PBS had a mild cytotoxic effect on FAMPAC cells. Second, SmartPAN's pathological effects were evaluated in vivo by applying 4\u2010ml SmartPAN to a porcine (<jats:styled-content style=\"fixed-case\"><jats:italic>Sus scrofa domesticus<\/jats:italic><\/jats:styled-content>) model of pancreatic resection. There were no significant differences in macroscopic and microscopic pathologies between pigs treated with SmartPAN or saline. Third, measurements using HPLC\u2010MS\/MS demonstrate that BTB does not cross into the bloodstream and was eliminated from the body within 2\u00a0days of surgery. Overall, SmartPAN appears safe in the short term and ready for first\u2010in\u2010human trials because its components are either biocompatible or quickly neutralized by dilution and drainage.<\/jats:p>","DOI":"10.1111\/bcpt.13708","type":"journal-article","created":{"date-parts":[[2022,1,18]],"date-time":"2022-01-18T04:29:23Z","timestamp":1642480163000},"page":"542-552","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["SmartPAN: In vitro and in vivo proof\u2010of\u2010safety assessments for an intra\u2010operative predictive indicator of postoperative pancreatic fistula"],"prefix":"10.1111","volume":"130","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6145-3263","authenticated-orcid":false,"given":"Thomas M.","family":"Pausch","sequence":"first","affiliation":[{"name":"Department of General, Visceral, and Transplantation Surgery Heidelberg University Hospital  Heidelberg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marc","family":"Bartel","sequence":"additional","affiliation":[{"name":"Institute of Legal and Traffic Medicine Heidelberg University Hospital  Heidelberg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4203-1406","authenticated-orcid":false,"given":"Jiaqu","family":"Cui","sequence":"additional","affiliation":[{"name":"Department of General, Visceral, and Transplantation Surgery Heidelberg University Hospital  Heidelberg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ophelia","family":"Aubert","sequence":"additional","affiliation":[{"name":"Department of General, Visceral, and Transplantation Surgery Heidelberg University Hospital  Heidelberg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Clara","family":"Mitzscherling","sequence":"additional","affiliation":[{"name":"Department of General, Visceral, and Transplantation Surgery Heidelberg University Hospital  Heidelberg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3796-9520","authenticated-orcid":false,"given":"Xinchun","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of General, Visceral, and Transplantation Surgery Heidelberg University Hospital  Heidelberg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bodil","family":"Gesslein","sequence":"additional","affiliation":[{"name":"Magle Chemoswed  Malm\u00f6 Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter","family":"Schuisky","sequence":"additional","affiliation":[{"name":"Magle Chemoswed  Malm\u00f6 Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Felix K. F.","family":"Kommoss","sequence":"additional","affiliation":[{"name":"Institute of Pathology Heidelberg University Hospital  Heidelberg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas","family":"Bruckner","sequence":"additional","affiliation":[{"name":"Institute of Legal and Traffic Medicine Heidelberg University Hospital  Heidelberg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohammad","family":"Golriz","sequence":"additional","affiliation":[{"name":"Department of General, Visceral, and Transplantation Surgery Heidelberg University Hospital  Heidelberg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arianeb","family":"Mehrabi","sequence":"additional","affiliation":[{"name":"Department of General, Visceral, and Transplantation Surgery Heidelberg University Hospital  Heidelberg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7012-1196","authenticated-orcid":false,"given":"Thilo","family":"Hackert","sequence":"additional","affiliation":[{"name":"Department of General, Visceral, and Transplantation Surgery Heidelberg University Hospital  Heidelberg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2022,1,29]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1097\/MOG.0b013e32832e29d2"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1097\/SLA.0b013e31821fd334"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.surg.2005.05.001"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1097\/SLA.0000000000000577"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1097\/SLA.0b013e318158a3e2"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1097\/01.sla.0000251708.70219.d2"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1097\/MD.0000000000006858"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.2147\/CEG.S120217"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1097\/SLA.0000000000002491"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0002-9610(97)00290-0"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1002\/bjs.9185"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2015.07.068"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1021\/acsami.5b11902"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1021\/jacs.7b11014"},{"key":"e_1_2_9_16_1","first-page":"1","article-title":"IDEAL\u2010D: a rational framework for evaluating and regulating the use of medical devices","volume":"353","author":"Sedrakyan A","year":"2016","journal-title":"BMJ"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1097\/SLA.0000000000002794"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1177\/0885328220913057"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.1093\/bjs\/znaa115"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.1111\/bcpt.13492"},{"key":"e_1_2_9_21_1","unstructured":"Deutsches Institut f\u00fcr Normung.Chemical analysis\u2014decision limit detection limit and determination limit under repeatability conditions\u2014terms methods evaluation;2008."},{"key":"e_1_2_9_22_1","first-page":"10993","article-title":"Biological evaluation of medical devices\u2014Part 1: evaluation and testing within a risk management process","author":"International Standard Organization (ISO)","year":"2018","journal-title":"ISO"},{"key":"e_1_2_9_23_1","first-page":"1","article-title":"Biological evaluation of medical devices\u2014Part 5: tests for in vitro cytotoxicity","volume":"2007","author":"International Standard Organization (ISO)","year":"2009","journal-title":"ISO 10993\u201052009"},{"key":"e_1_2_9_24_1","unstructured":"U.S. Department of Health and Human Services \u2010 Food and Drug Administration \u2010 Center for Drug Evaluation and Research.Guidance for industry investigators and reviewers: exploratory IND studies;2006."},{"key":"e_1_2_9_25_1","doi-asserted-by":"publisher","DOI":"10.1055\/s-2002-32228"},{"key":"e_1_2_9_26_1","doi-asserted-by":"publisher","DOI":"10.1038\/bjc.2012.69"},{"issue":"4","key":"e_1_2_9_27_1","first-page":"369","article-title":"Comparative safety and efficacy of topical hemostatic agents in a rat neurosurgical model","volume":"63","author":"Ereth MH","year":"2008","journal-title":"Neurosurgery"},{"key":"e_1_2_9_28_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00270-014-0966-2"},{"key":"e_1_2_9_29_1","doi-asserted-by":"publisher","DOI":"10.1177\/0284185117694510"},{"key":"e_1_2_9_30_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM199404283301706"},{"key":"e_1_2_9_31_1","doi-asserted-by":"publisher","DOI":"10.1001\/archsurg.1961.01300150149020"},{"key":"e_1_2_9_32_1","doi-asserted-by":"publisher","DOI":"10.1002\/bjs.5316"},{"key":"e_1_2_9_33_1","doi-asserted-by":"publisher","DOI":"10.1097\/MOT.0b013e32835c6f0f"},{"key":"e_1_2_9_34_1","doi-asserted-by":"publisher","DOI":"10.1111\/ajt.13303"},{"key":"e_1_2_9_35_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tiv.2012.02.006"},{"key":"e_1_2_9_36_1","volume-title":"Assay Guidance Manual","author":"Riss TL","year":"2004"},{"key":"e_1_2_9_37_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0002-9440(10)64800-6"},{"key":"e_1_2_9_38_1","doi-asserted-by":"publisher","DOI":"10.1002\/cncr.20193"},{"key":"e_1_2_9_39_1","doi-asserted-by":"publisher","DOI":"10.1177\/1553350610395032"},{"key":"e_1_2_9_40_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.surg.2016.11.014"},{"key":"e_1_2_9_41_1","doi-asserted-by":"publisher","DOI":"10.1111\/hpb.12293"},{"key":"e_1_2_9_42_1","doi-asserted-by":"publisher","DOI":"10.1097\/00000658-199201000-00007"},{"key":"e_1_2_9_43_1","first-page":"392","article-title":"VALISTAT\u2014software for method validation in forensic toxicology","volume":"78","author":"Schmitt G","year":"2011","journal-title":"Toxichem Krimtech"},{"key":"e_1_2_9_44_1","unstructured":"OJ L 276 20.10.2010.Directive 2010\/63\/EU of the European Parliament and of the Council of 22 September 2010 on the Protection of Animals Used for Scientific Purposes Text with EEA Relevance. European Union;2010:33\u201379.https:\/\/eur-lex.europa.eu\/eli\/dir\/2010\/63\/oj"},{"key":"e_1_2_9_45_1","unstructured":"PauschT.SmartPAN: in vitro and in vivo proof\u2010of\u2010safety assessments for an intra\u2010operative predictive indicator of postoperative pancreatic fistula[dataset]. Mendeley Data2021;V1. doi:10.17632\/jvxzstwfry.1"},{"key":"e_1_2_9_46_1","doi-asserted-by":"publisher","DOI":"10.2165\/00003088-199631030-00006"},{"issue":"2","key":"e_1_2_9_47_1","first-page":"S6","article-title":"Spherex (degradable starch microspheres) chemo\u2010occlusion\u2013enhancement of tumor drug concentration and therapeutic efficacy: an overview","volume":"24","author":"H\u00e5kansson L","year":"1997","journal-title":"Semin Oncol"},{"key":"e_1_2_9_48_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcp.20445"},{"key":"e_1_2_9_49_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10495-006-0328-x"},{"key":"e_1_2_9_50_1","doi-asserted-by":"publisher","DOI":"10.1140\/epjp\/i2015-15064-x"},{"key":"e_1_2_9_51_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bpj.2016.05.011"},{"key":"e_1_2_9_52_1","doi-asserted-by":"publisher","DOI":"10.1096\/fj.06-5930fje"},{"key":"e_1_2_9_53_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0028492"},{"key":"e_1_2_9_54_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-019-50198-w"},{"key":"e_1_2_9_55_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1471-0528.2006.01028.x"}],"container-title":["Basic &amp; Clinical Pharmacology &amp; Toxicology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/bcpt.13708","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/bcpt.13708","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/bcpt.13708","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,8,22]],"date-time":"2023-08-22T18:39:29Z","timestamp":1692729569000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/bcpt.13708"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,1,29]]},"references-count":54,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2022,4]]}},"alternative-id":["10.1111\/bcpt.13708"],"URL":"https:\/\/doi.org\/10.1111\/bcpt.13708","archive":["Portico"],"relation":{},"ISSN":["1742-7835","1742-7843"],"issn-type":[{"value":"1742-7835","type":"print"},{"value":"1742-7843","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,1,29]]},"assertion":[{"value":"2021-09-17","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2022-01-12","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2022-01-29","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}