262 MANIPULATION OF SILK SCAFFOLD FABRICATION PARAMETERS MODULATES IN VIVO MATRIX PERFORMANCE IN A MURINE MODEL OF BLADDER AUGMENTATION

You have accessJournal of UrologyPediatrics: Basic Research1 Apr 2011262 MANIPULATION OF SILK SCAFFOLD FABRICATION PARAMETERS MODULATES IN VIVO MATRIX PERFORMANCE IN A MURINE MODEL OF BLADDER AUGMENTATION Pablo Gomez, Joshua R. Mauney, Danielle Rockwood, Michael Lovett, Jonathan C. Routh, David L. Kaplan, Rosalyn M. Adam, and Carlos R. Estrada Pablo GomezPablo Gomez Boston, MA More articles by this author , Joshua R. MauneyJoshua R. Mauney Boston, MA More articles by this author , Danielle RockwoodDanielle Rockwood Medford, MA More articles by this author , Michael LovettMichael Lovett Medford, MA More articles by this author , Jonathan C. RouthJonathan C. Routh Boston, MA More articles by this author , David L. KaplanDavid L. Kaplan Medford, MA More articles by this author , Rosalyn M. AdamRosalyn M. Adam Boston, MA More articles by this author , and Carlos R. EstradaCarlos R. Estrada Boston, MA More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2011.02.353AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Silk-based biomaterials are an attractive platform for the design of scaffolds capable of overcoming the limitations associated with gastrointestinal segments for bladder augmentation. Silk fabrication methods grant precise control of scaffold geometry, porosity, strength and elasticity by manipulating liquid silk spinning and post-winding parameters. We hypothesize that variations in these methods will generate a 3D matrix with superior properties including biocompatibility, mechanical integrity, porosity and rate of degradation sufficient to support murine bladder regeneration. METHODS Three groups of gel spun silk scaffolds with diverse properties were generated from Bombyx mori silkworm cocoons using various axial slew rates (ASR)[2mm/s and 40mm/s] and post-winding (PW) parameters [methanol (MET) and lyophilization (LYO)] as follows: Group 1: ASR=2mm/s, PW=MET; Group 2: ASR=40mm/s, PW=MET; Group 3: ASR=40mm/s, PW=LYO. Bladder augmentations were performed in CD-1 mice with acellular scaffolds (0.5cm2). After a 10 week follow-up, urodynamic (bladder capacity and compliance) and voiding stain on paper (voided volume and frequency) were performed. We also analyzed the harvested bladders for bladder wall regeneration (smooth muscle and urothelium) using histological (H&E) and immunofluorescence analyses (IF). Unoperated animals were used as controls. Statistical analysis was performed by student's t-test. RESULTS Histological and IF analyses of silk-augmented bladders revealed that all groups contained organized smooth muscle layers with prominent a-actin and SM22a expression within the original defect similar to control levels. Regeneration of multi-layer urothelium was detected in Groups 1 and 3 and was associated with robust pan-uroplakin staining, in contrast to Group 2 where it was thin and underdeveloped. Quantification of residual silk matrix by histological analysis revealed that Group 3 had the highest degree of scaffold degradation after 10 weeks (p<0.05). Functional analysis including mean bladder capacity, voided volume and frequency were similar between all silk groups (p>0.05) while average compliance increased in all augmented animals relative to the control group. CONCLUSIONS Manipulation of structural and mechanical properties of silk scaffolds by adjusting gel-spinning fabrication parameters to include high ASR coupled with LYO PW treatment produces matrices that support functional bladder tissue regeneration in rodents while maximizing the rate of scaffold degradation. © 2011 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 185Issue 4SApril 2011Page: e105-e106 Advertisement Copyright & Permissions© 2011 by American Urological Association Education and Research, Inc.MetricsAuthor Information Pablo Gomez Boston, MA More articles by this author Joshua R. Mauney Boston, MA More articles by this author Danielle Rockwood Medford, MA More articles by this author Michael Lovett Medford, MA More articles by this author Jonathan C. Routh Boston, MA More articles by this author David L. Kaplan Medford, MA More articles by this author Rosalyn M. Adam Boston, MA More articles by this author Carlos R. Estrada Boston, MA More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...