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Bladder biomechanics and the use of scaffolds for regenerative medicine in the urinary bladder

  • Review Article
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From Nature Reviews Urology

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Key Points

  • The tissue of the urinary bladder undergoes constant loading and unloading cycles to fulfil its role in normal physiological conditions

  • Insight into bladder biomechanics is important for restoring its functional properties when bladder augmentation is required

  • Biomechanical clinical assessments include whole-organ urodynamics, whereas preclinical assessments that have been used in animal models also include ex vivo tensile tests of bladder tissue

  • Biomechanical qualification of tissue-engineered bladder scaffolds is crucial; however, the biomechanics of scaffolds have been poorly researched compared with their structural appearance and cellular interactions

  • Mathematical and computational modelling based on biomechanical studies can be used to predict the mechanical performance of a tissue-engineered scaffold

  • A comprehensive algorithm is recommended to study engineered scaffolds in order to validate preclinical experiments before clinical use of these materials

Abstract

The urinary bladder is a complex organ with the primary functions of storing urine under low and stable pressure and micturition. Many clinical conditions can cause poor bladder compliance, reduced capacity, and incontinence, requiring bladder augmentation or use of regenerative techniques and scaffolds. To replicate an organ that is under frequent mechanical loading and unloading, special attention towards fulfilling its biomechanical requirements is necessary. Several biological and synthetic scaffolds are available, with various characteristics that qualify them for use in bladder regeneration in vitro and in vivo, including in the treatment of clinical conditions. The biomechanical properties of the native bladder can be investigated using a range of mechanical tests for standardized assessments, as well as mathematical and computational bladder biomechanics. Despite a large body of research into tissue engineering of the bladder wall, some features of the native bladder and the scaffolds used to mimic it need further elucidation. Collection of comparable reference data from different animal models would be a helpful tool for researchers and will enable comparison of different scaffolds in order to optimize characteristics before entering preclinical and clinical trials.

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Figure 1: Bladder anatomy and muscle layers.
Figure 2: The important role of mechanical properties in the design and development of scaffolds for bladder tissue engineering.
Figure 3: Hysteresis and preconditioning cycles.
Figure 4: Typical stress–strain curve of biological soft tissues.
Figure 5: The setup of different mechanical tests.
Figure 6: Computational modelling of an augmentation cystoplasty using a tissue-engineered graft.
Figure 7: A suggested preclinical algorithm to validate scaffolds for bladder augmentation.

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Acknowledgements

This work was supported by grants from the Danish Research Council Foundation (Individual Postdoctoral Grant DFF-4093-00282A and Sapere Aude: DFF-Research Talent 4217-00048A), the Freemason Foundation for Children's Welfare, the Stockholm City Council, and the Swedish Society of Medicine.

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F.A., J.H., I.S.C., and M.F. made substantial contributions to the discussion of content. F.A. and G.L. researched data for the article and wrote the manuscript. All authors reviewed and edited the article before submission.

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Correspondence to Fatemeh Ajalloueian or Magdalena Fossum.

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Glossary

Load-history-dependent behaviour

A characteristic observed in biological soft tissues owing to viscoelasticity. The response of such materials to loading and unloading depends on how quickly the load is applied or removed. This can be considered as time-dependent material behaviour as well.

Hysteresis

The phenomenon in which a body subjected to cyclic loading–unloading exhibits different stress–strain relationships during loading and unloading procedures. The area enclosed by the loading and unloading curve is called the hysteresis loop, which represents the energy dissipated during the deformation and recovery phases.

Stress relaxation

The phenomenon in which a sample is suddenly strained and maintained at a final strain, and its stress gradually decreases with time.

Creep

The phenomenon in which a sample is suddenly stressed, and the load is held for some time. If the sample continues to deform, it is said to be exhibiting creep.

Viscoelasticity

A property of materials that exhibit both viscous and elastic characteristics when experiencing deformation.

Cystometry

The clinical diagnostic procedure that is used to evaluate bladder function and pressure during filling and voiding.

Cystogram

The resulting chart from cystometry. The intravesical volume is plotted against the intravesical pressure, where urinary leakage and patient sensation are also recorded.

Plastoelasticity

A property of materials that exhibit both elastic recovery and plastic (residual) deformation

Anisotropy

A term used in various scientific disciplines to indicate that the material properties vary with the direction from which they are measured.

Areal strain

The 2D change in area caused by deformation.

Lattice contractility assay164

An assay in which different cell types are mixed with the soluble stabilized type I collagen to create a cell-collagen solution. The solution is placed onto a tissue culture plate, maintained for a predefined duration, and mechanically released from the underlying plastic. The relative change in diameter of cell-collagen lattices is calculated by dividing the lattice diameters at 10 min after release by the initial diameters.

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Ajalloueian, F., Lemon, G., Hilborn, J. et al. Bladder biomechanics and the use of scaffolds for regenerative medicine in the urinary bladder. Nat Rev Urol 15, 155–174 (2018). https://doi.org/10.1038/nrurol.2018.5

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