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Research Papers

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

[+] Author and Article Information
Silvia Wognum, David E. Schmidt

Engineered Tissue Mechanics and Mechanobiology Laboratory, Department of Bioengineering, Swanson School of Engineering, McGowan Institute, School of Medicine, University of Pittsburgh, Pittsburgh, PA 15219

Michael S. Sacks1

Engineered Tissue Mechanics and Mechanobiology Laboratory, Department of Bioengineering, Swanson School of Engineering, McGowan Institute, School of Medicine, University of Pittsburgh, Pittsburgh, PA 15219msacks@pitt.edu

1

Corresponding author.

J Biomech Eng 131(10), 101018 (Oct 14, 2009) (11 pages) doi:10.1115/1.4000182 History: Received December 19, 2008; Revised September 04, 2009; Posted September 09, 2009; Published October 14, 2009

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.

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Copyright © 2009 by American Society of Mechanical Engineers
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Figures

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Figure 1

Schematic of all possible different reference states (Ω) encountered during biaxial mechanical testing. Ω0 represents the free floating decellularized tissue specimen, Ω1 represents the state where the specimen is mounted in the biaxial testing device, and Ω2 represents the state where a tare-load is applied to the specimen and from which the specimen is preconditioned. After this, the specimen is unloaded, which is represented by Ω3 (postpreconditioned unloaded reference state). Before testing, a tare-load is applied, which is represented by Ω4 (tare-loaded references state). The deformation between the different states is defined by the deformation gradient tensor Fαβ. Relative dimensions of the squares are representative of average specimen dimensions as measured. Initial specimen dimensions in Ω0 were 12.7×9.76×0.832 mm3, which are also depicted by the dashed lines in the other reference states.

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Figure 2

Cross sections of intact bladder specimens filled at 25% or 100% capacity with 10% formalin and stained with Picro-Sirius red stain. Red is collagen, yellow is SM, and yellow disks are red blood cells. The more intense the red staining, the denser the collagen structure. Collage fibers appear in a highly supercoiled configuration in tissue under low stretch, and collagen supercoils uncoil at higher stretches. The scale bar is 50 μm. Insets show close ups of representative coiling structures.

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Figure 3

Structure of normal and post-SCI bladder ECM. (a) Cross section of normal decellularized bladder visualized by SEM (magnification 500×, scale bar is 10 μm). Different layers are visible and collagen fibers appear in highly coiled configuration. (b) A close-up showing the collagen coils and individual fibers in the coils (magnification 3700×, scale bar is 1 μm). Other visible structures are salt crystals from PBS. (c) En-face section of post-SCI decellularized bladder stained with the Verhoef van Gieson stain to visualize elastin (black). Arrows point at examples of elastic fibers, and arrow heads point at collagen coils. Some remnants of SM tissue are visible. (d) En-face section of post-SCI decellularized bladder stained with elastic trichrome stain to visualize elastin. Arrows point at examples of elastic fibers. Images in (c) and (d) were enhanced to better visualize the black elastic fibers; scale bar is 50 μm.

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Figure 4

Stress-stretch results of biaxial mechanical testing of normal decellularized bladder specimens (mean±SEM,n=7), with respect to two different reference states. P represents the first Piola–Kirchhoff stress, and λ is stretch. Closed circles are circumferential data (C), and open circles are longitudinal (L). (a) Data referenced to Ω4. (b) The same data, referenced to the stress-free state Ω3, showing that bladder ECM is more compliant in the circumferential direction.

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Figure 5

(a) Comparing equibiaxial stress data of normal and postinjury decellularized UBW, referenced to Ω4 (mean±SEM, n=4 for each group). P represents first Piola–Kirchhoff stress, and λ is stretch. Open circles are normal, and closed triangles are postinjury. Both normal and postinjury UBW ECM specimens were more compliant in circumferential (C) direction than in longitudinal (L) direction. B) Average stress (P11,P22) versus areal strain showing that bladder ECM was significantly more compliant than normal bladder ECM.

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Figure 6

Model fitting results of one representative normal bladder ECM specimen (referenced to Ω3). (a) Representative error space plot (μ2 versus σ2) of the fiber ensemble model with bimodal recruitment showing a smooth and convex error surface with one clear minimum (black dot). The contour lines represent the values of the error function. (b) Representative fit of fiber ensemble stress-strain data of one bladder ECM specimen showing an excellent fit (r2=0.995). The upper bound strain and stress are indicated (Eub=0.34,Sub=18.8), and MTM is defined as the slope of the line fit through the data points beyond Eub(MTM=495 kPa). The fiber effective modulus found from the fit is η=1.11 MPa. (c) Representative recruitment function and cumulative distribution function, of the same specimen, showing two (denoted by *) peaks.

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Figure 7

(a) Average recruitment function of six samples (average±SEM) (referenced to Ω4). The parameters are given in Table 3. (b) Combining average fitting result of fiber ensemble function, with a fiber distribution function R(θ), with σθ=41 deg, predicted the equibiaxial stretch data very well.

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Figure 8

(a) Prediction of equibiaxial stress data of postinjury decellularized bladder by an average fiber ensemble function plus R(θ) with σθ=34 deg. (b) Prediction of effective fiber ensemble behavior of normal and SCI bladder ECM, using average model parameters from normal tissue and modified parameters for postinjury tissue.

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Figure 9

Schematic showing the effects of SCI on organ-level storage function and UBW compliance. SCI induces overfilling of the bladder and increasing tissue strain, which stimulates elastin production. Elastin fibers pull in existing collagen and make the structure more supercoiled, which, in turn, decreases the reference state dimensions. De novo produced collagen is deposited in a more coiled configuration. This increases tissue compliance and overall extensibility, and eventually decreases the effective tissue strain.

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