{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T02:16:23Z","timestamp":1791857783956,"version":"4.3.4"},"reference-count":37,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2023,3,21]],"date-time":"2023-03-21T00:00:00Z","timestamp":1679356800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Adhesys Medical GmbH"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JFB"],"abstract":"<jats:p>Tissue adhesives constitute a great possibility to improve conventional wound closure. In contrast to sutures, they enable nearly immediate hemostasis and can prevent fluid or air leaks. In the present study, a poly(ester)urethane-based adhesive was investigated which already proved to be suitable for different indications, such as reinforcing vascular anastomosis and sealing liver tissue. Using in vitro and in vivo setups, the degradation of the adhesives was monitored over a period of up to 2 years, to evaluate long-term biocompatibility and determine degradation kinetics. For the first time, the complete degradation of the adhesive was documented. In subcutaneous locations, tissue residues were found after 12 months and in intramuscular locations, tissue degradation was complete after about 6 months. A detailed histological evaluation of the local tissue reaction revealed good biocompatibility throughout the different degradation stages. After full degradation, complete remodeling to physiological tissue was observed at the implant locations. In addition, this study critically discusses common issues related to the assessment of biomaterial degradation kinetics in the context of medical device certification. This work highlighted the importance and encouraged the implementation of biologically relevant in vitro degradation models to replace animal studies or at least reduce the number of animals in preclinical testing prior to clinical studies. Moreover, the suitability of frequently used implantation studies based on ISO 10993-6 at standard locations was critically discussed, especially in light of the associated lack of reliable predictions for degradation kinetics at the clinically relevant site of implantation.<\/jats:p>","DOI":"10.3390\/jfb14030168","type":"journal-article","created":{"date-parts":[[2023,3,21]],"date-time":"2023-03-21T02:36:22Z","timestamp":1679366182000},"page":"168","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":23,"title":["Long-Term Degradation Assessment of a Polyurethane-Based Surgical Adhesive\u2014Assessment and Critical Consideration of Preclinical In Vitro and In Vivo Testing"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6418-0245","authenticated-orcid":false,"given":"Lisanne","family":"Bremer","sequence":"first","affiliation":[{"name":"Department of Biohybrid & Medical Textiles, Institute of Applied Medical Engineering, Helmholtz Institute for Biomedical Engineering, RWTH Aachen University, 52074 Aachen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kerstin","family":"Hagemeister","sequence":"additional","affiliation":[{"name":"Adhesys Medical GmbH, 52078 Aachen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michaela","family":"Moss","sequence":"additional","affiliation":[{"name":"Institute for Laboratory Animal Science & Experimental Surgery, University Hospital RWTH Aachen, 52074 Aachen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3808-4222","authenticated-orcid":false,"given":"Lisa","family":"Ernst","sequence":"additional","affiliation":[{"name":"Institute for Laboratory Animal Science & Experimental Surgery, University Hospital RWTH Aachen, 52074 Aachen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ren\u00e9 H.","family":"Tolba","sequence":"additional","affiliation":[{"name":"Institute for Laboratory Animal Science & Experimental Surgery, University Hospital RWTH Aachen, 52074 Aachen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0584-9444","authenticated-orcid":false,"given":"Stefan","family":"Jockenhoevel","sequence":"additional","affiliation":[{"name":"Department of Biohybrid & Medical Textiles, Institute of Applied Medical Engineering, Helmholtz Institute for Biomedical Engineering, RWTH Aachen University, 52074 Aachen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1339-1990","authenticated-orcid":false,"given":"Christian","family":"Apel","sequence":"additional","affiliation":[{"name":"Department of Biohybrid & Medical Textiles, Institute of Applied Medical Engineering, Helmholtz Institute for Biomedical Engineering, RWTH Aachen University, 52074 Aachen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,3,21]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"626","DOI":"10.1002\/jbm.b.33409","article-title":"Adhesive and sealant interfaces for general surgery applications","volume":"104","author":"Scognamiglio","year":"2016","journal-title":"J. Biomed. Mater. Res. B. Appl. Biomater."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"3009","DOI":"10.1021\/acs.biomac.7b00969","article-title":"Degradable Adhesives for Surgery and Tissue Engineering","volume":"18","author":"Bhagat","year":"2017","journal-title":"Biomacromolecules"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"464","DOI":"10.1002\/jctb.1771","article-title":"Adhesive biomaterials for tissue reconstruction","volume":"83","author":"Lauto","year":"2008","journal-title":"J. Chem. Technol. Biotechnol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"271","DOI":"10.1615\/CritRevBiomedEng.2014011676","article-title":"Clinical applications of surgical adhesives and sealants","volume":"42","author":"Sanders","year":"2014","journal-title":"Crit. Rev. Biomed. Eng."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"310","DOI":"10.1038\/s41578-019-0171-7","article-title":"Overcoming the translational barriers of tissue adhesives","volume":"5","author":"Taboada","year":"2020","journal-title":"Nat. Rev. Mater."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1031","DOI":"10.1016\/j.progpolymsci.2011.12.003","article-title":"Surgical adhesives: Systematic review of the main types and development forecast","volume":"37","author":"Duarte","year":"2012","journal-title":"Progress. Polym. Sci."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1922","DOI":"10.1002\/jbm.b.35049","article-title":"A polyurethane-based surgical adhesive for sealing blood vessel anastomoses-A feasibility study in pigs","volume":"110","author":"Schulten","year":"2022","journal-title":"J. Biomed. Mater. Res. B. Appl. Biomater."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"13598","DOI":"10.1038\/s41598-021-92998-z","article-title":"Mechanical strength and hydrostatic testing of VIVO adhesive in sutureless microsurgical anastomoses: An ex vivo study","volume":"11","author":"Heitzer","year":"2021","journal-title":"Sci. Rep."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"151782","DOI":"10.1016\/j.aanat.2021.151782","article-title":"Microvascular anastomosis techniques using the medical adhesive VIVO and expandable micro-stents in a rat carotid artery model","volume":"238","author":"Heitzer","year":"2021","journal-title":"Ann. Anat."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"255","DOI":"10.1159\/000517173","article-title":"Efficacy of a Novel Medical Adhesive for Sealing Lung Parenchyma: An in vitro Study in Rabbit Lungs","volume":"62","author":"Kalverkamp","year":"2021","journal-title":"Eur. Surg. Res."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"423","DOI":"10.1177\/1553350617720993","article-title":"Efficacy of the Novel Medical Adhesive, MAR-VIVO-107, in an Acute Porcine Liver Resection Model","volume":"24","author":"Tanaka","year":"2017","journal-title":"Surg. Innov."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"48","DOI":"10.1159\/000481818","article-title":"Hemostatic Efficacy and Safety of the Novel Medical Adhesive, MAR VIVO-107, in a Rabbit Liver Resection Model","volume":"59","author":"Fukushima","year":"2018","journal-title":"Eur. Surg. Res."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1030","DOI":"10.4254\/wjh.v9.i24.1030","article-title":"Novel synthetic adhesive as an effective alternative to Fibrin based adhesives","volume":"9","author":"Srinivasan","year":"2017","journal-title":"World J. Hepatol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"251","DOI":"10.1177\/0023677219871585","article-title":"Severity assessment in pigs after partial liver resection: Evaluation of a score sheet","volume":"54","author":"Hagemeister","year":"2020","journal-title":"Lab. Anim."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"233","DOI":"10.1080\/08941939.2020.1833261","article-title":"Two Polyurethane Adhesives for PVDF Fixation Show Superior Biocompatibility in a Rat Model","volume":"35","author":"Heise","year":"2022","journal-title":"J. Invest. Surg."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"121","DOI":"10.1080\/00202967.2018.1450209","article-title":"Biomedical applications of polyurethane materials and coatings","volume":"96","author":"Joseph","year":"2018","journal-title":"Trans. IMF"},{"key":"ref_17","first-page":"377","article-title":"A long-term in vitro biocompatibility study of a biodegradable polyurethane and its degradation products","volume":"76","author":"Stegenga","year":"2006","journal-title":"J. Biomed. Mater. Res. A"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1083","DOI":"10.1016\/j.bioactmat.2020.10.002","article-title":"Biobased polyurethanes for biomedical applications","volume":"6","author":"Wendels","year":"2021","journal-title":"Bioact. Mater."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"6034","DOI":"10.1016\/j.biomaterials.2011.04.048","article-title":"Biodegradation and in vivo biocompatibility of a degradable, polar\/hydrophobic\/ionic polyurethane for tissue engineering applications","volume":"32","author":"McBane","year":"2011","journal-title":"Biomaterials"},{"key":"ref_20","unstructured":"Heckroth, H., Eggert, C., Hofmann, J., and Lorenz, K. (2013). Isocyanate-Functional Prepolymer for Biologically Degradable Adhesives. (WO2013092504A1), Patent."},{"key":"ref_21","unstructured":"Baxter (2019). TISSEEL Package Insert, Baxter Healthcare Corporation."},{"key":"ref_22","unstructured":"Pignatello, R. (2013). Advances in Biomaterials Science and Biomedical Applications, IntechOpen. [1st ed.]. Chapter 3 Degradation of Polyurethanes for Cardiovascular Applications."},{"key":"ref_23","unstructured":"Baxter (2020). TISSEEL Thrombin Solution Safety Data Sheet, Baxter Healthcare Corporation."},{"key":"ref_24","unstructured":"Baxter (2021). TISSEEL Sealer Protein Solution Safety Data Sheet, Baxter Healthcare Corporation."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"3666","DOI":"10.1002\/jbm.a.35492","article-title":"In vivo degradation of polyurethane foam with 55 wt % polyethylene glycol","volume":"103","author":"Broekema","year":"2015","journal-title":"J. Biomed. Mater. Res. A"},{"key":"ref_26","unstructured":"(2022, June 03). New Zealand White Rabbit Data Sheet. Available online: https:\/\/www.criver.com\/sites\/default\/files\/resource-files\/RM-NZW-rabbit-information-sheet.pdf."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"101049","DOI":"10.1016\/j.nantod.2020.101049","article-title":"Tissue Adhesives: From Research to Clinical Translation","volume":"36","author":"Cecen","year":"2021","journal-title":"Nano Today"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"7457","DOI":"10.1016\/j.biomaterials.2005.05.079","article-title":"Understanding the biodegradation of polyurethanes: From classical implants to tissue engineering materials","volume":"26","author":"Santerre","year":"2005","journal-title":"Biomaterials"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"531","DOI":"10.1016\/j.pnsc.2014.08.009","article-title":"Influence of HEPES buffer on the local pH and formation of surface layer during in vitro degradation tests of magnesium in DMEM","volume":"24","author":"Dezfuli","year":"2014","journal-title":"Progress. Nat. Sci. Mater. Int."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"109","DOI":"10.1007\/978-981-15-3262-7_8","article-title":"In Vivo Evaluation of the Biocompatibility of Biomaterial Device","volume":"1250","author":"Frazao","year":"2020","journal-title":"Adv. Exp. Med. Biol."},{"key":"ref_31","first-page":"115","article-title":"Polyurethane Degradation in the Biological Milieu","volume":"19","author":"Mathew","year":"2006","journal-title":"Trends Biomater. Artif. Organs"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"927","DOI":"10.1002\/jbm.a.35958","article-title":"The pathology of the foreign body reaction against biomaterials","volume":"105","author":"Klopfleisch","year":"2017","journal-title":"J. Biomed. Mater. Res. A"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"R1","DOI":"10.1088\/1748-6041\/1\/1\/R01","article-title":"A review on macrophage responses to biomaterials","volume":"1","author":"Xia","year":"2006","journal-title":"Biomed. Mater."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"5671","DOI":"10.3390\/ma8095269","article-title":"Macrophages, Foreign Body Giant Cells and Their Response to Implantable Biomaterials","volume":"8","author":"Sheikh","year":"2015","journal-title":"Materials"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"2335","DOI":"10.1016\/S0142-9612(00)00101-0","article-title":"Synthetic biodegradable polymers as orthopedic devices","volume":"21","author":"Middleton","year":"2000","journal-title":"Biomaterials"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"435","DOI":"10.1163\/156856294X00428","article-title":"The effect of site of implantation and animal age on properties of polydioxanone pins","volume":"6","author":"Bhatia","year":"1994","journal-title":"J. Biomater. Sci. Polym. Ed."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"783","DOI":"10.1016\/j.actbio.2008.02.010","article-title":"Non-invasive monitoring of tissue scaffold degradation using ultrasound elasticity imaging","volume":"4","author":"Kim","year":"2008","journal-title":"Acta Biomater."}],"container-title":["Journal of Functional Biomaterials"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2079-4983\/14\/3\/168\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T18:59:22Z","timestamp":1760122762000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2079-4983\/14\/3\/168"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,3,21]]},"references-count":37,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2023,3]]}},"alternative-id":["jfb14030168"],"URL":"https:\/\/doi.org\/10.3390\/jfb14030168","relation":{},"ISSN":["2079-4983"],"issn-type":[{"value":"2079-4983","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,3,21]]}}}