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Elastogenesis in neurogenic urinary bladder

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Bladder Neurological Diagram

The overarching goal of this project is to transform the way we think about synthesis and deposition of new elastin fibers (elastogenesis) in soft tissues by leveraging the unique remodeling process of the neurogenic urinary bladder, triggered by a biomechanical process (i.e., increased stretch) and mediated by inflammation and growth factors. In my group, we are interested in quantifying and modeling the adaptation of the extracellular matrix (ECM) within the urinary bladder wall in type II diabetes and spinal cord injury (two forms of neurogenic bladder dysfunction). In these conditions, there seems to be functional elastin fibers production, which is an exciting observation since normally cells do not produce functional elastin after birth. The overfilling of the bladder in diabetes and spinal cord injury, due to a loss of sensation of fullness resulting from impaired neurological connection, leads to a dramatic increase in stretch of the bladder wall, which can drive adaptive remodeling. Furthermore, in type II diabetes, inflammatory responses and immune system activation appear to play an important role in this process, surprisingly so, since these conditions are normally associated with a decrease rather than an increase in elastin content. In the past two years, my group has focused on quantifying, for the first time, elastin production in the bladder wall of animal models of type II diabetes and characterizing the mechanical and microstructural effects of elastogenesis on the behavior of the bladder wall. The results of this project have been disseminated in six abstracts published in proceedings of international conferences, and a review article in bladder biomechanics was published in a peer reviewed journal. This project also contributed to one invited talk and three invited seminars.

Collaborators: Prof. C. Chan (Chemical Eng. Dept., MSU), Prof. S. DiCarlo (Physiology Dept., MSU), Prof. M. Chancellor, MD (Urology Dept., Beaumont).

Impact. The remodeling of the urinary bladder presents the perfect opportunity to explore, for the first time, one of the few cases of spontaneous deposition of functional elastin fibers in adult tissues. An improved understanding of this process has the potential to transform our thinking about elastogenesis in soft biological tissues. This has the potential to lead to the development of innovative treatments for many diseases that involve elastin degradation and new strategies to improve the manufacture of artificial tissues.

Future Directions. The long-term goal of this project is to formulate a multiscale modeling framework that predicts the dynamic change of the bladder wall mechanical behavior in vivo due to neurogenic bladder dysfunction.

 

Presentations, proceedings, and papers

Roccabianca S. Biomechanics of underactive bladder (UAB). CURE-UAB 5.0. December 5, 2019. East Lansing Marriott at University Place. East Lansing, MI. (Invited talk)

Roccabianca S., Grobbel M.R., Lewis M., Tonson A., Wiseman R. Extracellular matrix remodeling in the urinary bladder wall in two animal models of type 2 diabetes. University of Wisconsin, School of Medicine and Public Health (O’Brien Center for Benign Urologic Research). November 14, 2018. Madison, WI. (Invited talk)

Grobbel M., Roccabianca S. Alterations to mechanical behavior of the rat urinary bladder due to type II diabetes, with and without obesity. Summer Biomechanics, Bioengineering, and Biotransport Conference. June 17-20, 2020. Virtual Conference. (Virtual lightning talk)

Tuttle T., Lujan H., DiCarlo S., Roccabianca S. Validation of a Collagen Fiber Recruitment Model for Uniaxial Loading of the Spinal Cord Injured. Summer Biomechanics, Bioengineering and Biotransport Conference (SB3C). June 17 - June 20, 2020. Virtual Conference

Grobbel M., Lewis M., Tonson A., Wiseman R., Roccabianca S. Extracellular matrix remodeling of the diabetic urinary bladder. 16th International Symposium on Computer Methods in Biomechanics and Biomedical Engineering (CMBBE2019). August 14-16, 2019. New York City, NY. (Podium presentation)

Tuttle T., Lujan H., DiCarlo S., Roccabianca S. Mechanical behavior of the urinary bladder extracellular matrix in an animal model of spinal cord injury. 16th International Symposium on Computer Methods in Biomechanics and Biomedical Engineering (CMBBE2019). August 14-16, 2019. New York City, NY. (Poster presentation)

Grobbel M., Lewis M., Tonson A., Wiseman R., Roccabianca S. Remodeling of the diabetic urinary bladder: a comparison of an obese and a lean animal model of type ii diabetes. Summer Biomechanics, Bioengineering and Biotransport Conference (SB3C). June 25-28, 2019. Seven Spring, PA. (Podium presentation)

Tuttle T., Lujan H., DiCarlo S., Roccabianca S*. Effects of long-term spinal cord injury on the mechanical behavior of the urinary bladder extracellular matrix. Summer Biomechanics, Bioengineering and Biotransport Conference (SB3C). June 25-28, 2019. Seven Spring, PA. (Podium presentation)