The collagen fiber alignment and biomechanical behavior of naturally occurring extracellular matrix (ECM) scaffolds are important considerations for the design of medical devices from these materials. Both should be considered in order to produce a device to meet tissue specific mechanical requirements (e.g., tendon vs. urinary bladder), and could ultimately affect the remodeling response in vivo. The present study evaluated the collagen fiber alignment and biaxial mechanical behavior of ECM scaffold material harvested from porcine urinary bladder tunica mucosa and basement membrane (together referred to as urinary bladder matrix (UBM)) and ECM harvested from urinary bladder submucosa (UBS). Since the preparation of UBM allows for control of the direction of delamination, the effect of the delamination method on the mechanical behavior of UBM was determined by delaminating the submucosa and other abluminal layers by scraping along the longitudinal axis of the bladder (apex to neck) (UBML) or along the circumferential direction (UBMC). The processing of UBS does not allow for similar directional control. UBML and UBS had similar collagen fiber distributions, with a preferred collagen fiber alignment along the longitudinal direction. UBMC showed a more homogenous collagen fiber orientation. All samples showed a stiffer mechanical behavior in the longitudinal direction. Despite similar collagen fiber distributions, UBML and UBS showed quite different mechanical behavior for the applied loading patterns with UBS showing a much more pronounced toe region. The mechanical behavior for UBMC in both directions was similar to the mechanical behavior of UBML. There are distinct differences in the mechanical behavior of different layers of ECM from the porcine urinary bladder, and the processing methods can substantially alter the mechanical behavior observed.

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Validation of multiple DIR algorithms on a novel physiological bladder phantom revealed that the structure accuracy was good for most algorithms, but that the spatial accuracy as assessed from markers was low for all algorithms, especially for large deformations. Hence, many of the available algorithms exhibit sufficient accuracy for contour propagation purposes, but possibly not for accurate dose accumulation.

Exogenous cross-linking of soft collagenous tissues is a common method for biomaterial development and medical therapies. To enable improved applications through computational methods, physically realistic constitutive models are required. Yet, despite decades of research, development and clinical use, no such model exists. In this study, we develop the first rigorous full structural model (i.e. explicitly incorporating various features of the collagen fibre architecture) for exogenously cross-linked soft tissues. This was made possible, in-part, with the use of native to cross-linked matched experimental datasets and an extension to the collagenous structural constitutive model so that the uncross-linked collagen fibre responses could be mapped to the cross-linked configuration. This allowed us to separate the effects of cross-linking from kinematic changes induced in the cross-linking process, which in turn allowed the non-fibrous tissue matrix component and the interaction effects to be identified. It was determined that the matrix could be modelled as an isotropic material using a modified Yeoh model. The most novel findings of this study were that: (i) the effective collagen fibre modulus was unaffected by cross-linking and (ii) fibre-ensemble interactions played a large role in stress development, often dominating the total tissue response (depending on the stress component and loading path considered). An important utility of the present model is its ability to separate the effects of exogenous cross-linking on the fibres from changes due to the matrix. Applications of this approach include the utilization in the design of novel chemical treatments to produce specific mechanical responses and the study of fatigue damage in bioprosthetic heart valve biomaterials.

For respiratory-induced motion, the mean ΔMM is small, but for individual patients the absolute difference can be >4 mm. For interfractional position variations, a stent is, on average, a better surrogate fiducial than bony anatomy, but large PTV margins would still be required. Therefore, intratumoral fiducials are recommended for online setup verification for all pancreatic patients scheduled for radiation therapy, including patients with a biliary stent.

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The weighted S-TPS-RPM registration algorithm with additional weight parameter allowed indirect control over structure-specific flexibility in multistructure registrations of bladder and bladder tumor, enabling anatomically coherent registrations. The availability of an anatomically validated deformable registration method opens up the horizon for improvements in IGART for bladder cancer.

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.