Although mechanical alterations to pelvic floor ligaments, such as the cardinal and uterosacral ligaments, are one contributing factor to the development and progression of pelvic floor disorders, very little research has examined their mechanical properties. In this study, the first biaxial elastic and viscoelastic tests were performed on uterosacral and cardinal ligament complexes harvested from adult female swine. Biaxial elastic testing revealed that the ligaments undergo large strains and are anisotropic. The direction normal to the upper vagina was typically stiffer than the transverse direction. Stress relaxation tests showed that the relaxation was the same in both directions, and that more relaxation occurred when the tissue was stretched to lower initial strains. In order to describe the experimental findings, a three-dimensional constitutive model based on the Pipkin-Rogers integral series was formulated and the parameters of such model were determined by fitting the model to the experimental data. In formulating the model, it was assumed that the tissues consist of a ground substance with two embedded families of fibers oriented in two directions and that the ligaments are incompressible. The model accounts for finite strains, anisotropy, and strain-dependent stress relaxation behavior. This study provides information about the mechanical behavior of female pelvic floor ligaments, which should be considered in the development of new treatment methods for pelvic floor disorders. / Master of Science

The uterosacral ligament (USL) and the cardinal ligament (CL) are two major suspensory tissues that provide structural support to the vagina/cervix/uterus complex. These ligaments have been studied mainly due for their role in the surgical repair for pelvic organ prolapse (POP). POP, which is the descent of a pelvic organ from its normal place towards the vaginal walls and into the vaginal cavity, affects an estimated 3.3 million women in the United States annually. Despite their important mechanical function, little is known about the elastic and viscoelastic properties of the USL and CL due to ethical concerns with in vivo testing of human tissues and the lack of accepted animal models. The goal of this first study is to help establish an appropriate animal model for studying the mechanics of these pelvic supportive ligaments. To achieve this, the first rigorous comparison of histological and planar equi-biaxial mechanical properties of the swine and human USLs was completed. Relative collagen, smooth muscle, and elastin contents were quantified from histological sections and the USL was found to have similar components in both species, with a comparable relative collagen content. Using the digital image correlation (DIC) method to calculate the in-plane Lagrangian strain, no differences in the peak strain during precon- ditioning/cyclic loading tests, secant modulus of the pre-creep/elastic response, and strain at the end of creep tests were detected in the USLs from the two species along both axial loading directions (the main in vivo loading direction and the direction that is perpendicular to it). Because these ligaments are subjected to repeated constant loads in vivo, the effect of re- peated biaxial loads at three different load levels (1 N, 2 N, or 3 N) on elastic and creep properties of the swine CL was investigated. The results showed that CL was elastically anisotropic, as statistical differences were found between the mean strains along the two axial loading directions for specimens at all three different load levels. The increase in strain over time by the end of the 3rd creep test was comparable along the axial loading direc- tions. The greatest mean normalized strain (or, equivalently, the largest increase in strain over time) was measured at the end of the 1st creep test, regardless of the equi-biaxial load magnitude or loading direction. Overall, these experimental findings validate the use of swine as an appropriate animal model and offer new knowledge of the mechanical properties of the USL and CL that can guide the development of better treatment methods such as surgical reconstruction for POP. / Ph. D.

The uterosacral ligament (USL) and cardinal ligament (CL) are the two major suspensory tissues of the uterus, cervix, and vagina. These supportive structures can be weakened or damaged, leading to the development of pelvic floor disorders (PFDs) such as urinary incontinence, fecal incontinence, and pelvic organ prolapse. In the surgical treatment for PFDs, the USL and CL are extensively used as anchor structures to restore the normal position of the prolapsed organs. Therefore, the mechanical properties of the USL and CL may be critical for the development of new surgical reconstruction strategies for PFDs. In chapter 1, we present the first histo-mechanical characterization of the swine USL and CL using histological analysis, scanning electron microscopy and quasi-static uniaxial tensile tests. Our results suggest that the histological and uniaxial tensile properties of the swine CL and USL are very similar to those in humans. The swine is found to be a suitable animal model for studying the mechanical properties of these ligaments. To capture both the active and passive mechanical responses of biological tissues containing SMCs such as the USL and CL, a new structural constitutive model is proposed in chapter 2. The deformation of the active component in such tissues during isometric and isotonic contractions is described using an evolution law. This model is tested with published active and passive, uniaxial and biaxial, experimental data on pig arteries due to lack of data on the active properties of the USL and CL. Subjected to constant forces in-vivo, the structure and length of the USL and CL are sig- nificantly altered over time. In chapter 3, we present the first rigorous characterization of the fiber microstructure and creep properties of the USL/CL complex by using scanning electron microscopy and planar biaxial testing. Fibers are found to be oriented primarily along the main in-vivo loading direction. In such direction, the creep proceeds significantly faster under lower load. Overall, our experimental findings advance our knowledge about the passive elastic and viscoelastic properties of the USL/CL complex. The novel structural constitutive model proposed enhances our understanding of the active mechanical behavior of biological tissues containing SMCs. Knowledge about the mechanical behavior of the USL and CL from experimental and theoretical studies such as those presented here will help to improve, in the long term, the medical treatment for PFDs. / Ph. D.

Le col de l'utérus et l'apex vaginal sont soutenus par le ligament utérosacral (LUS) et cardinal (LC). Le LUS s'étend de la région autour des vertèbres sacrées S2-S4 vers la face dorsale du col de l'utérus et/ou du tiers supérieur de la paroi vaginale postérieure. Il contient plus de fibres nerveuses que le LC. Ce dernier est défini comme le fourreau peri-vasculaire s'insérant au niveau proximal autour de l'origine de l'artère iliaque interne, et au niveau du col et/ou le vagin en distal. L'étude de la géométrie spatiale des ligaments chez la femme vivante à l'IRM et après reconstruction 3D a permis d'identifier le LC sous la forme d'un maillage fibreux centré autour de l'axe des vaisseaux iliaques internes, partant dans une direction crânio­caudale vers l'utérus, le col, la vessie et le tiers supérieur du vagin. Les fibres du LC et du LUS convergent vers le col de l'utérus et le tiers supérieur du vagin. La reconstruction 3D a confirmé que le LC fonctionne dans une direction crânio­caudale et le LUS dans une direction dorso-ventrale. L'angle moyen entre le LC et l'axe corporel est de 18°, alors que l'angle moyen entre le LUS et l'axe corporel est de 92°. Le LC est plus long et plus courbé que le LUS. La tension théorique calculée au niveau du LC est de 52% plus importante que celle au niveau du LUS. En cas de prolapsus, il existe une élongation ligamentaire significativement plus importante lors de la manœuvre de Valsalva Des distorsions géométriques majeures sont constatées après cure de prolapsus par promontofixation, et sont plus marquées pour le LC / The uterine cervix and vaginal apex are supported by the uterosacral (USL) and cardinal (CL) ligaments. The USL extends from the presacral fascia between sacral vertebrae S2-S4 towards the dorsal margin of the uterine cervix and the superior third of the posterior vaginal wall. It contains more nervous fibers than the CL. The latter is defined as the perivascular sheath around the internai iliac artery, inserting distally into the cervix and the vagina The geometrical study of the ligaments in living women using MRI and 3D reconstruction shows the CL as a web-like structure around the internai iliac vessels, and going in a cranial to caudal direction towards the cervix and upper third vagina where fibers ofboth the CL and USL mingle together. The USL operates in a dorsal to ventral direction. The mean angles between the body axis and the CL and USL are respectively at 18° and 92°. The CL is longer and more curved than the USL. Theoretical calculated tension on the CL is 52% larger than on the USL. In case of pelvic organ prolapse, significant ligament elongation is observed during Valsalva maneuver. Major geometrical distortions exist after prolapse surgery by sacrocolpopexy, specially for the CL