Layer-dependent role of collagen recruitment during loading of the rat bladder wall
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In this work, we re-evaluated long-standing conjectures as to the source of the exceptionally large compliance of the bladder wall. Whereas these conjectures were based on indirect measures of loading mechanisms, in this work we take advantage of advances in bioimaging to directly assess collagen fibers and wall architecture during biaxial loading. A custom biaxial mechanical testing system compatible with multiphoton microscopy was used to directly measure the layer-dependent collagen fiber recruitment in bladder tissue from 9 male Fischer rats (4 adult and 5 aged). As for other soft tissues, the bladder loading curve was exponential in shape and could be divided into toe, transition and high stress regimes. The relationship between collagen recruitment and loading curves was evaluated in the context of the inner (lamina propria) and outer (detrusor smooth muscle) layers. The large extensibility of the bladder was found to be possible due to folds in the wall (rugae) that provide a mechanism for low resistance flattening without any discernible recruitment of collagen fibers throughout the toe regime. For more extensible bladders, as the loading extended into the transition regime, a gradual coordinated recruitment of collagen fibers between the lamina propria layer and detrusor smooth muscle layer was found. A second important finding was that wall extensibility could be lost by premature recruitment of collagen in the outer wall that cut short the toe region. This change was correlated with age. This work provides, for the first time, a mechanistic understanding of the role of collagen recruitment in determining bladder extensibility and capacitance.
KeywordsBladder compliance Collagen recruitment Multiphoton Extracellular matrix
The authors gratefully acknowledge the NIH National Institute on Aging for funding through 1R56 AG050408-01(PI Birder) as well as the aged rats used in this study. P. Watton acknowledges partial support towards this work from the UK EPSRC (EP/N014642/1). The authors also gratefully acknowledge Mr. Chih Yuan Chuang for performing the immunohistochemistry work to obtain Fig. 5. The authors gratefully acknowledge financial support from the Swanson School of Engineering Office of Research for creation of Fig. 1 by McKenzie Illustrations. The custom biaxial system and some preliminary data for the present work were previously described in the Proceedings of the 5th International Conference on Computational and Mathematical Biomedical Engineering—CMBE2017, Cheng et al. (2017).
Compliance with ethical standards
Human and animal rights
All procedures were approved by the Institutional Animal Care and Use Committee at the University of Pittsburgh, which adheres to NIH Guidelines for the Care and Use of Laboratory Animals. The University of Pittsburgh is accredited by the Association for Assessment and Accreditation of Laboratory Animal Care (AAALAC).
Conflict of interest
Four of the authors (Cheng, Birder, Kullmann, Robertson) received funding from that National Institute on Aging for this work. The authors have no additional conflicts to report.
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