Collagen networks in soft tissues define their nonlinear mechanics: first the tissue is compliant, then it stiffens sharply. In the uterus, collagen is oriented mainly circumferentially and axially, and its remodeling during aging, disease, or toxic exposure changes how the organ works. However, linking microstructure to organ-level mechanics has remained difficult: histology shows composition but not mechanical consequences. Around this work there are already inflation studies of other hollow organs, such as arteries, vagina, bladder, and intestine, but for the mouse uterus the combination of inflation with inverse material parameter analysis has been applied for the first time. Neighboring papers in the archive follow the same broad line: they also use inflation or inverse analysis for soft tissues, but do not combine them for the uterus.
Six CD-1 mice at 6 months of age yielded 12 segments of uterine horns 15 mm long. Half of the segments were kept for 4 hours in 0.04% glutaraldehyde solution at 4°C to crosslink collagen. Each segment was mounted on a balloon catheter 1 mm in diameter and inflated at a rate of 0.02 mL/min, stepping the volume from 0 to 0.20 mL in increments of 0.025 mL. After each step, an image was taken in a Rigaku CTLab GX130 micro-CT scanner at 10 µm resolution. Pressure was measured with a differential sensor relative to an empty balloon to subtract the catheter's own resistance. From the images, the inner and outer contours of the uterine wall were extracted, converted to polar coordinates, and compared with the predicted contours from the finite element model. The model described the wall as a homogeneous material with two families of collagen fibers according to the Gasser-Ogden-Holzapfel model. Parameters were fitted by two-stage optimization: first differential evolution, then the Nelder-Mead simplex method, minimizing the root-mean-square error between measured and predicted contour radii at four inflation levels.
Inflation revealed a nonlinear pressure-volume relationship: first the tissue is compliant, then it resists sharply. Glutaraldehyde-treated segments required higher pressure at all levels. Inflation work increased, and linear stiffness over the 0.10-0.20 mL range and maximum resistance at 0.20 mL rose significantly (p < 0.001). Inverse analysis yielded model parameters: for untreated tissues, matrix stiffness C10 = 14.6 ± 2.1 kPa, fiber stiffness k1 = 381.9 ± 18.3 kPa, nonlinearity parameter k2 = 9.1 ± 0.6. After treatment, C10 increased 9.2-fold to 133.8 kPa, k1 increased 2.0-fold to 773.2 kPa, and k2 increased 2.7-fold to 24.3. Variability between samples was small: the coefficient of variation for k1 was only 4.8%. Contour fitting error did not exceed 3% for all samples and levels. Sensitivity analysis showed a single minimum of the objective function with no secondary minima, which indicates reliable parameter estimation.
This work differs from neighboring studies in that it is the first to combine inflation of the mouse uterus with inverse finite element analysis to estimate material parameters. Earlier inflation studies of the reproductive tract were limited to thin-walled theory and mean stress, while inverse analysis for the human uterus was done only from indentation and uniaxial tension data. Here, the parameters come from a physiological loading regime, pressure from within, and the method is shown to be sensitive to collagen crosslinking. This opens the way to quantifying the mechanical consequences of tissue remodeling that previously could be seen only in histology.
The method can be extended to study natural remodeling during aging, disease, and toxic exposure, where collagen changes may be smaller than after glutaraldehyde treatment. The next step will be to test the smallest changes in mechanics the method can detect. It is also worth accounting for the layered structure of the uterine wall, active smooth muscle contraction, and viscoelasticity to bring the model closer to living tissue.
The results will be useful in reproductive biomechanics, toxicology, and the development of methods for diagnosing uterine condition from mechanical parameters.
Test the method at lower degrees of crosslinking and on tissues after exposure to real toxins, and also assess how the fixed fiber dispersion parameter affects the results.
In soft tissue biomechanics, the question of how microstructural changes in collagen translate into organ function remains open. This work shows that inverse inflation analysis can link these levels, but a full solution requires accounting for layering, muscle activity, and time-dependent effects.
The balloon catheter used to inflate the mouse uterus is 1 mm in diameter, roughly like a pencil lead.
Not published on arXiv. Here are its page, the PDF and the formalization: you can check it yourself, not only read our account.