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Rat animal model for preclinical testing of microparticle urethral bulking agents
Author(s) -
MannGow Travis K,
Blaivas Jerry G,
King Benjamin J,
ElGhannam Ahmed,
Knabe Christine,
Lam Michael K,
Kida Masatoshi,
Sikavi Cameron S,
Plante Mark K,
Krhut Jan,
Zvara Peter
Publication year - 2015
Publication title -
international journal of urology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.172
H-Index - 67
eISSN - 1442-2042
pISSN - 0919-8172
DOI - 10.1111/iju.12693
Subject(s) - urethra , medicine , biomedical engineering , microparticle , in vivo , urinary system , histology , pathology , animal model , surgery , urology , anatomy , biology , microbiology and biotechnology , astrobiology
Objectives To develop an economic, practical and readily available animal model for preclinical testing of urethral bulking therapies, as well as to establish feasible experimental methods that allow for complete analysis of hard microparticle bulking agents. Methods Alumina ceramic beads suspended in hyaluronic acid were injected into the proximal urethra of 15 female rats under an operating microscope. We assessed overall lower urinary tract function, bulking material intraurethral integrity and local host tissue response over time. Microphotographs were taken during injection and again 6 months postoperatively, before urethral harvest. Urinary flow rate and voiding frequency were assessed before and after injection. At 6 months, the urethra was removed and embedded in resin. Hard tissue sections were cut using a sawing microtome, and processed for histological analysis using scanning electron microscopy, light microscopy and immunohistochemistry. Results Microphotographs of the urethra showed complete volume retention of the bulking agent at 6 months. There was no significant difference between average urinary frequency and mean urinary flow rate at 1 and 3 months postinjection as compared with baseline. Scanning electron microscopy proved suitable for evaluation of microparticle size and integrity, as well as local tissue remodeling. Light microscopy and immunohistochemistry allowed for evaluation of an inflammatory host tissue reaction to the bulking agent. Conclusions The microsurgical injection technique, in vivo physiology and novel hard tissue processing for histology, described in the present study, will allow for future comprehensive preclinical testing of urethral bulking therapy agents containing microparticles made of a hard material.