Immunomodulatory response of layered small intestinal submucosa in a rat bladder regeneration model. Issue 6 (6th December 2018)

• Record Type: Journal Article
• Authors: Xia, Ding; Yang, Qing; Fung, Kar‐Ming; Towner, Rheal A.; Smith, Nataliya; Saunders, Debra; Greenwood‐Van Meerveld, Beverley; Kropp, Bradley P.; Madihally, Sundararajan V.; Lin, Hsueh‐Kung
• Is Part Of: Journal of biomedical materials research. Volume 107:Issue 6(2019)
• Page Start: 1960
• Page End: 1969
• Publication Date: 2018-12-06
• Subjects: bladder augmentation -- small intestinal submucosa -- inflammation -- macrophages -- urothelial differentiation -- multilayer; Biomedical materials -- Periodicals; 610.28
• DOI: 10.1002/jbm.b.34289
• Languages: English
• ISSNs: 1552-4973

Abstract

Abstract: Based on the hypothesis that bioscaffold permeability is a major factor in determining the outcome of histologically complete and functional bladder regeneration, we evaluated regeneration processes of four‐layer porcine small intestinal submucosa (SIS) construct; and compared results between rat bladders augmented with single‐layer SIS bioscaffolds. Sprague–Dawley female rats were subjected to hemi‐cystectomy followed by anastomosis of a patch of either single‐ or four‐layer porcine SIS. Permeability was analyzed in situ using magnetic resonance imaging (MRI) at post‐operative days 7 and 14. Bladder sections excised at days 7, 14, 28, and 56 post‐operation Samples were assessed by H&E and Masson's trichrome stains. Urothelial differentiation was analyzed using cytokeratin AE1/AE3, and uroplakin III (UPIII). In addition, quantitative and qualitative evaluations of neutrophils, mast cells, eosinophils, and macrophages were performed using anti‐myeloperoxidase, Alcian blue, Giemsa stain, and anti‐CD68 staining methods, respectively. Four‐layer SIS was consistently impermeable as evidenced by the absence of intravesical administered gadolinium with diethylenetriaminepentacetate (Gd‐DTPA) contrast signal in peripheral regions of augmented bladders compared with single‐layer SIS bioscaffold. Elevated and sustained eosinophil and neutrophil infiltrations were prominent in four‐layered SIS‐augmented bladders compared with single‐layer SIS with comparable impermeability. Delayed but consistent urothelial regeneration and differentiation were observed in four‐layer SIS‐augmented bladders; and urothelial differentiation was observed at day 56 post‐augmentation. In conclusion, four‐layer SIS enacts an elevated inflammatory response along with extended urothelial regeneration. Four‐layer SIS may activate a different but yet to be identified mechanism for inflammatory responses. © 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater 107B: 1960–1969, 2019.