On the Mechanical Role of De Novo Synthesized Elastin in the Urinary Bladder Wall

Abstract

The urinary bladder wall (UBW), which is composed of smooth muscle, collagen, and elastin, undergoes profound remodeling in response to changes in mechanical loading resulting from various pathologies. In our laboratory, we have observed the production of fibrillar elastin in the extracellular matrix (ECM), which makes the UBW a particularly attractive tissue to investigate smooth muscle tissue remodeling. In the present study, we explored the mechanical role that de novo elastin fibers play in altering UBW ECM mechanical behavior using a structural constitutive modeling approach. The mechanical behavior of the collagen fiber component of the UBW ECM was determined from the biaxial stress-stretch response of normal UBW ECM, based on bimodal fiber recruitment that was motivated by the UBW's unique collagen fiber structure. The resulting fiber ensemble model was then combined with an experimentally derived fiber angular distribution to predict the biaxial mechanical behavior of normal and the elastin-rich UBW ECM to elucidate the underlying mechanisms of elastin production. Results indicated that UBW ECM exhibited a distinct structure with highly coiled collagen fiber bundles and visible elastic fibers in the pathological situation. Elastin-rich UBW ECM had a distinct mechanical behavior with higher compliance, attributable to the indirect effect of elastin fibers contracting the collagen fiber network, resulting in a retracted unloaded reference state of the tissue. In conclusion, our results suggest that the urinary bladder responds to prolonged periods of high strain by increasing its effective compliance through the interaction between collagen and de novo synthesized elastic fibers.

Ex vivo deformations of the urinary bladder wall during whole bladder filling: Contributions of extracellular matrix and smooth muscle

“…We also confirmed evidence in the literature that the collagen in the bladder exists in a hierarchy of folding and coiling beyond simple uncrimping in which large coils of collagen fibers are able to accommodate very large strains (Chang et al, 1998). Modeling the mechanical behavior of the bladder ECM, we have demonstrated that collagen fiber recruitment upon loading occurred in a bimodal manner, which was confirmed by histological evidence (Wognum et al, 2009b). In addition, we have shown that the stress relaxation responses of the smooth muscle and extracellular matrix can be considered separate and contribute differently .…”

Towards an in vitro model mimicking the foreign body response: tailoring the surface properties of biomaterials to modulate extracellular matrix

“…Yet, no studies have found and targeted elastin synthesis in a fibrocellular capsule. The trigger for elastin synthesis, however, is not completely understood, but includes exposure to mechanical stress and presence of growth factor such as TGF-β153. In this study, techniques to modified the surface of biomaterials have statistically significantly triggered an increase in both total collagen and elastin production, conceivably due to the observed enhanced production of cytokines, such as TGF-β1 as a key enhancer of collagen production and providing support for elastin secretion505455.…”

Structural stability and sustained release of protein from a multilayer nanofiber/nanoparticle composite

“…properties obtained in the present study suggest that both mono and multilayer nanofibrous scaffold can probably withstand the biomechanical stresses existing in hollow organs including vessels and bladders [53,54]. Further studies will be necessary to optimize the M a n u s c r i p t 15 scaffold characteristics to achieve mechanical properties more similar to hollow organ walls.…”