MP30-09 BI-LAYER SILK FIBROIN GRAFTS PROMOTE TISSUE REGENERATION IN A FETAL OVINE MODEL OF BLADDER EXSTROPHY

Abstract

You have accessJournal of UrologyBladder & Urethra: Anatomy, Physiology & Pharmacology II1 Apr 2016MP30-09 BI-LAYER SILK FIBROIN GRAFTS PROMOTE TISSUE REGENERATION IN A FETAL OVINE MODEL OF BLADDER EXSTROPHY Saif Affas, Khalid Algarrahi, Debra Franck, Yeun Goo Chung, Dario Fauza, Maryrose Sullivan, Vivian Cristofaro, Catherine Seager, Ashley Wietsma, Ruth Strakosha, Kyle Costa, Carlos Estrada, and Joshua Mauney Saif AffasSaif Affas More articles by this author , Khalid AlgarrahiKhalid Algarrahi More articles by this author , Debra FranckDebra Franck More articles by this author , Yeun Goo ChungYeun Goo Chung More articles by this author , Dario FauzaDario Fauza More articles by this author , Maryrose SullivanMaryrose Sullivan More articles by this author , Vivian CristofaroVivian Cristofaro More articles by this author , Catherine SeagerCatherine Seager More articles by this author , Ashley WietsmaAshley Wietsma More articles by this author , Ruth StrakoshaRuth Strakosha More articles by this author , Kyle CostaKyle Costa More articles by this author , Carlos EstradaCarlos Estrada More articles by this author , and Joshua MauneyJoshua Mauney More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2016.02.1241AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Patients afflicted with bladder exstrophy (BE) can often develop low capacity and poorly compliant bladders which necessitate bladder augmentation in order to preserve upper urinary tract function. The objective of the current study was to determine the efficacy of acellular, bi-layer silk fibroin (SF) grafts to promote bladder tissue regeneration in a fetal ovine model of BE. Validation of prospective implant designs in large animal models of bladder disease is a crucial step toward clinical translation. METHODS Bi-layer SF implants (4x4 cm2) were fabricated from Bombyx mori silkworm cocoons. BE defects were surgically created in fetal lambs (N=3) at ~95 d of gestation. Bladder defects were repaired by either primary closure (N=1) or anastomosis of SF grafts (N=2) at time of delivery. A nondiseased control lamb was assessed in parallel. Transient suprapubic catheterization was performed in all lambs for 3 wk following birth. Lambs implanted with SF grafts were harvested at 2 and 3 m of age while all other animals were euthanized at 3 m. Control and regenerated bladder tissues were evaluated by histological (hematoxylin and eosin, Masson′s trichrome staining) and immunohistochemical (IHC) analyses for α-smooth muscle actin (α-SMA), urothelial pan-cytokeratins (CK), as well as innervation (synaptophysin) and vascularization (CD31) markers. RESULTS All lambs survived until scheduled euthanasia. Voluntary voiding was observed in all animal subjects following 3 wk of transient suprapubic catheter drainage. At both timepoints, histological and IHC analyses revealed SF grafts supported prominent host tissue ingrowth of α-SMA+ smooth muscle bundles and CK+urothelium throughout the implantation sites. In addition, the density of smooth muscle bundles following 3 m of SF matrix implantation was comparable to the nondiseased control bladder, however primary closure of the bladder exstrophy defect resulted in substantial less smooth muscle formation. De novo innervation and vascularization were also evident in all regenerated tissues supported by SF implants indicated by the presence of synaptophysin+ boutons and vessels lined with CD31 expressing endothelial cells. Primary closure of the bladder exstrophy defect resulted in qualitatively more fibrosis and inflammatory cell infiltrates than observed in the SF matrix group. CONCLUSIONS These preliminary results demonstrate that bi-layer SF grafts are capable of supporting bladder tissue regeneration in a fetal ovine model of BE. © 2016FiguresReferencesRelatedDetails Volume 195Issue 4SApril 2016Page: e414 Advertisement Copyright & Permissions© 2016MetricsAuthor Information Saif Affas More articles by this author Khalid Algarrahi More articles by this author Debra Franck More articles by this author Yeun Goo Chung More articles by this author Dario Fauza More articles by this author Maryrose Sullivan More articles by this author Vivian Cristofaro More articles by this author Catherine Seager More articles by this author Ashley Wietsma More articles by this author Ruth Strakosha More articles by this author Kyle Costa More articles by this author Carlos Estrada More articles by this author Joshua Mauney More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...