[en] [en] BACKGROUND: Cystoscopy-assisted submucosal injections of urethral bulking agents offer a safe and efficient alternative to surgery for treating urinary incontinence in both dogs and women. To address the concern of their transient therapeutic effect, a preclinical study evaluating the biocompatibility, safety, and durability of nanofibrillated cellulose as a bulking agent was designed. Plant-based nanofibrillated cellulose is considered renewable, biocompatible, and non-degradable in vivo. To the best of our knowledge, no studies of nanofibrillated cellulose injected into the urethral wall of experimental animals have been published to date.
METHODS: After assessing the rheological behavior of nanofibrillated cellulose, a biocompatibility study with 50 rats and a durability study with two Beagle dogs were conducted. In anesthesized rats, deposits of either nanofibrillated cellulose or sodium chloride as an inert control were injected into the urethral wall via a caudal laparotomy. The rats were euthanized for histopathological assessment after 7, 30, and 90 days. In dogs, cystoscopy-assisted injections of nanofibrillated cellulose were followed with magnetic resonance imaging at 14 days and at 2, 3, 6, and 12 months.
RESULTS: The rheological studies demonstrated a gel-like behavior under a wide range of shear stress. Nanofibrillated cellulose induced a moderate host tissue response according to the EN ISO 10993-6 standard, consisting primarily of macrophages, foreign body giant cells, lymphocytes, and plasma cells. No significant difference was observed in the tissue response at different time points. In dogs, the bulking agent was visible in 4/5 (80%) injection sites on magnetic resonance imaging at 12 months post-injection. No signs of migration, abscess formation or any major or long-term complications were observed.
CONCLUSIONS: Nanofibrillated cellulose maintains a chronic but stable and tolerable inflammatory response for up to 90 days in the urethral wall of rats. Durability in the urethral wall of dogs indicates a potential long-term effect.
Disciplines :
Veterinary medicine & animal health
Author, co-author :
Peltokallio, Nina M M ; Department of Equine and Small Animal Medicine, Faculty of Veterinary Medicine, University of Helsinki, Finland
Noël, Stéphanie ; Université de Liège - ULiège > Fundamental and Applied Research for Animals and Health (FARAH) > FARAH: Médecine vétérinaire comparée
Bolen, Géraldine ; Université de Liège - ULiège > Fundamental and Applied Research for Animals and Health (FARAH) > FARAH: Médecine vétérinaire comparée
Kuure, Satu ; GM Unit, Helsinki Institute of Life Science/STEMM, Research Program's Unit, Faculty of Medicine, University of Helsinki, Helsinki, Finland
Raussi-Lehto, Eija; Department of Neuroscience and Biomedical Engineering, School of Science, Aalto University, Espoo, Finland
Reyes, Guillermo ; VTT Technical Research Centre of Finland Ltd., Tampere, Finland
Ajdary, Rubina; Department of Bioproducts and Biosystems, School of Chemical Engineering, Aalto University, Espoo, Finland
Kuula, Jani; Department of Neuroscience and Biomedical Engineering, School of Science, Aalto University, Espoo, Finland
Hamaide, Annick ; Université de Liège - ULiège > Fundamental and Applied Research for Animals and Health (FARAH) > FARAH: Médecine vétérinaire comparée
Laitinen-Vapaavuori, Outi M; Department of Equine and Small Animal Medicine, Faculty of Veterinary Medicine, University of Helsinki, Finland
Language :
English
Title :
In vivo biocompatibility and long-term durability of nanofibrillated cellulose as a urethral bulking agent in rats and Beagle dogs.
This study was funded by: Business Finland TUTLI fund, \u201CSolving the Mesh\u201D, Project number 211795, BF 6108/31/2019 (www.businessfinland.fi), received by ER-L and JK. Open access funded by Helsinki University Library, received by NP. The sponsors/funders did not play any role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript. The authors thank Hannu Sariola (Department of Pathology, Faculty of Medicine, University of Helsinki) for expertise in histopathological assessment and Jouni Junnila (EstiMates Oy, Helsinki) in statistical analysis. We also thank Anna Meller, Salla Jalkanen, Kylli Haller, and Raili Heinonen (GM Unit, Laboratory Animal Center, University of Helsinki) for assisting in planning and carrying out the experiments and for animal care; Anna Ahmala and P\u00E4ivi Laitinen (Department of Pathology, Faculty of Medicine, University of Helsinki) for paraffin sectioning and HE staining of tissue samples, and board-certified veterinary internalist Emilie Vangrinsven, ECVIM-CA (Teaching and Clinical Department of Companion Animals, Faculty of Veterinary Medicine, University of Li\u00E8ge), for cystoscopy. This study was carried out with the support of the HiLIFE GM-Unit Core Facility, University of Helsinki, Finland, a member of Biocenter Finland, and in the facilities of the Teaching and Clinical Department of Clinical Sciences of the College of Veterinary Medicine, University of Li\u00E8ge, Belgium.
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