Biology subjects

Myers, K. M.

Publications and source records attributed to Myers, K. M..

11 recordsLinked to original sources

bioRxiv2026

A Method for Image-Based Modeling of Uterine Passive Mechanics During Late Pregnancy

PurposeComputational models of the uterus during pregnancy enable analysis of electro-chemo-mechanical pathways to predict labor timing and guide treatment planning. We aim to develop a robust image-based modeling pipeline to investigate uterine passive mechanics during late pregnancy. MethodsA parametric model of the uterus and cervix was created using a patients MRI measurements at 38 weeks of gestation. Inspired by advances in cardiac mechanics models, we created Laplace-Dirichlet solutions to inform tissue domains, fiber structure within the uterus and cervix, and spatially varying Robin boundary conditions. Prior imaging and mechanical testing data were used to fit material parameters. Boundary condition parameters were tuned to match the displacements of a previously established approach that employed contact with surrounding tissue. The tissue mechanical response to a physiologic load was assessed across varying material properties and fiber architectures. ResultsDiscrepancies in nodal displacements between the current approach and the contact-based model were limited to 3.4 {+/-} 1.8 mm, yielding nearly 90 % computational savings. Uterine tensile strains were more sensitive to ground substance elastic modulus (E) compared to fiber properties. Reduced E and fiber stiffness increased cervical strains and compression. Fiber dispersion and architecture modulated the opening of the cervical internal ostium but had a reduced impact on compression. ConclusionWe developed a novel workflow for modeling passive uterine mechanics, informed by patient-specific measurements and in vitro mechanical tests. The robust workflow may prove useful for studying labor progression and conducting longitudinal studies to enhance our understanding of normal and pathological pregnancies.

bioengineering↗

bioRxiv2026

A finite element model of pregnancy derived from maternal sonography: effect of uterine and cervical structural properties on cervical mechanical loading

Identification and treatment of pregnancies at risk for preterm birth is a central challenge in obstetric research. Many of the known causes of preterm birth originate from mechanical failure in reproductive tissues. To better understand the biomechanical environment of the gravid uterus and its potential contribution to preterm birth, this computational study presents a parametric method for modeling maternal reproductive anatomy during the early second trimester. A finite element modeling approach was built using existing sonographic measurements from early second-trimester maternal anatomy and material properties from published mechanical tests. We applied the same physiologically relevant intrauterine pressure to all models and quantified the resulting tissue stretch. The sensitivity of the stretch in the proximal cervix was explored by varying material properties and sonographic maternal anatomy dimensions. Cervical material properties, particularly the fiber stiffness modulus and ground substance Youngs modulus, were found to have the greatest effect on proximal cervix stretch compared to other material properties and sonographic dimensions. Among the sonographic dimension measurements, those defining the region surrounding the proximal cervix had the greatest effect on proximal cervix stretch, including the curvature of the posterior uterine wall and the thickness of the lower uterine segment. The computational modeling approach presented here enables future patient-specific studies of gravid reproductive tissues to elucidate differences between individuals who do and do not deliver preterm. Additionally, this study is foundational for building digital twins to support future virtual clinical studies on diagnostic and therapeutic device design to prevent preterm birth.

bioengineering↗

bioRxiv2025

Spatially Mapping the Mechanical and Structural Properties of the Seedling Uterine Fibroid-Myometrium Interface

Uterine fibroids (leiomyomas) are highly prevalent, noncancerous tumors canonically described as stiff and collagen-dense. Still, the mechanical heterogeneity within uterine fibroids and the alterations that occur at the fibroid-myometrium interface remain poorly understood. This study quantitatively maps the local mechanical, structural, and compositional properties of seedling uterine fibroids (< 1 cm) at the interface region. Relative to patient-matched myometrial tissues, uterine fibroids exhibited increased stiffness, decreased permeability, increased diffusivity, decreased hydration, greater collagen content, and distinct collagen organization. At the fibroid-myometrium interface, a band of aligned myometrial fibers immediately adjacent to the fibroid was observed, and heterogeneous spatial patterns in elastic modulus and permeability were identified. Ultimately, this study establishes foundational knowledge on the mechanics and structure of seedling uterine fibroids, facilitating future developments of clinically translatable detection tools.

bioengineering↗

bioRxiv2025

An Anisotropic Reactive Viscoelastic Model of the Rhesus Macaque Cervix for Studying Cervical Remodeling

The uterine cervix is a soft biological tissue with critical biomechanical functions in pregnancy. It is a mechanical barrier that supports the growing fetus. As pregnancy progresses, the cervix becomes more compliant and eventually opens in late pregnancy to facilitate childbirth. This dual function is facilitated by extensive remodeling of the cervical extracellular matrix (ECM), giving rise to its complex time-dependent material properties. Premature cervical remodeling is known to result in preterm birth, defined as birth before 37 weeks of gestation. While previous work has studied cervical remodeling using various biomechanical methods, it remains unclear how the intrinsic or flow-independent viscoelastic behavior of the cervix is influenced by cervical remodeling. In this study, an anisotropic reactive viscoelastic material model was formulated and investigated under tensile deformation to understand material behavior in cervical remodeling. To calibrate the model, experimental force relaxation data was used from uniaxial tension tests on Rhesus macaque cervical specimens from four gestational time points. The results showed that cervical tissue equilibrium and instantaneous stiffness significantly decreased from the non-pregnant to the late pregnancy status. In addition, cervical tissue in the late third trimester relaxed faster to equilibrium than the other gestational groups, particularly at prescribed tensile strains greater than 30%. This fast relaxation to equilibrium helps the cervix dissipate tensile hoop stresses induced by the fetus during labor, preventing its rupture. This work provides insights into time-dependent cervical remodeling features, which are crucial for developing diagnostic methods and treatments for preterm birth.

bioengineering↗

bioRxiv2024

Time-Dependent Material Properties and Composition of the Nonhuman Primate Uterine Layers Through Gestation

The uterus is central to the establishment, maintenance, and delivery of a healthy pregnancy. Biomechanics is an important contributor to pregnancy success, and alterations to normal uterine biomechanical functions can contribute to an array of obstetric pathologies. Few studies have characterized the passive mechanical properties of the gravid human uterus, and ethical limitations have largely prevented the investigation of mid-gestation periods. To address this key knowledge gap, this study seeks to characterize the structural, compositional, and time-dependent micro-mechanical properties of the nonhuman primate (NHP) uterine layers in nonpregnancy and at three time-points in pregnancy: early 2nd, early 3rd, and late 3rd trimesters. Distinct material and compositional properties were noted across the different tissue layers, with the nonpregnant endometrium and pregnant decidua being the least stiff, most viscous, least diffusible, and most hydrated layers of the NHP uterus. Pregnancy induced notable compositional and structural changes in the decidua and myometrium but had no effect on their micro-mechanical properties. Further comparison to published human data revealed marked similarities across species, with minor differences noted for the perimetrium and nonpregnant endometrium. This work provides insights into the material properties of the NHP uterus and demonstrates the validity of NHPs as a model for studying certain aspects of human uterine biomechanics.

bioengineering↗

bioRxiv2024

Equilibrium Tension and Compression Mechanical Properties of the Human Uterus

A successful pregnancy relies on the proper cellular, biochemical, and mechanical functions of the uterus. A comprehensive understanding of uterine mechanical properties during pregnancy is key to understanding different gynecological and obstetric disorders such as preterm birth, placenta accreta, leiomyoma, and endometriosis. This study sought to characterize the macro-scale equilibrium material behaviors of the human uterus in non-pregnancy and late pregnancy under both compressive and tensile loading. Fifty human uterine specimens from 16 patients (8 nonpregnant [NP] and 8 pregnant [PG]) were tested using spherical indentation and uniaxial tension coupled with digital image correlation (DIC). A three-level incremental load-hold protocol was applied to both tests. A microstructurally-inspired material model considering fiber architecture was applied to this dataset. Inverse finite element analysis (IFEA) was then performed to generate a single set of mechanical parameters to describe compressive and tensile behaviors. The freeze-thaw effect on uterine macro mechanical properties was also evaluated. PG tissue exhibits decreased overall stiffness and increased fiber network extensibility compared to NP uterine tissue. Under indentation, ground substance compressibility was similar between NP and PG uterine tissue. In tension, the fiber network of the PG uterus was found to be more extensible and dispersed than in nonpregnancy. Lastly, a single freeze-thaw cycle did not systematically alter the macro-scale material behavior of the human uterus.

bioengineering↗

bioRxiv2023

Evaluation of gelatin bloom strength on gelatin methacryloyl hydrogel properties

Gelatin methacryloyl (GelMA) hydrogels are widely used for a variety of tissue engineering applications. The properties of gelatin can affect the mechanical properties of gelatin gels; however, the role of gelatin properties such as bloom strength on GelMA hydrogels has not yet been explored. Bloom strength is a food industry standard for describing the quality of gelatin, where higher bloom strength is associated with higher gelatin molecular weight. Here, we evaluate the role of bloom strength on GelMA hydrogel mechanical properties. We determined that both bloom strength of gelatin and weight percent of GelMA influenced both stiffness and viscoelastic ratio; however, only bloom strength affected diffusivity, permeability, and pore size. With this library of GelMA hydrogels of varying properties, we then encapsulated Swan71 trophoblast spheroids in these hydrogel variants to assess how bloom strength affects trophoblast spheroid morphology. Overall, we observed a decreasing trend of spheroid area and Feret diameter as bloom strength increased. In identifying clear relationships between bloom strength, hydrogel mechanical properties, and trophoblast spheroid morphology, we demonstrate that bloom strength should considered when designing tissue engineered constructs.

bioengineering↗

bioRxiv2023

Biomechanical Modeling of Cesarean Section Scars and Scar Defects

Uterine rupture is an intrinsically biomechanical process associated with high maternal and fetal mortality. A previous Cesarean section (C-section) is the main risk factor for uterine rupture in a subsequent pregnancy due to tissue failure at the scar region. Finite element modeling of the uterus and scar tissue presents a promising method to further understand and predict uterine ruptures. Using patient dimensions of an at-term uterus, a C-section scar was modeled with an applied intrauterine pressure to study how scars affect uterine stress. The scar positioning and uterine thickness were varied, and a defect was incorporated into the scar region. The modeled stress distributions confirmed clinical observations as the increased regions of stress due to scar positioning, thinning of the uterine walls, and the presence of a defect are consistent with clinical observations of features that increase the risk of uterine rupture.

bioengineering↗

bioRxiv2023

Material Properties of Nonpregnant and Pregnant Human Uterine Layers

The uterus has critical biomechanical functions in pregnancy and undergoes dramatic material growth and remodeling from implantation to parturition. The intrinsic material properties of the human uterus and how they evolve in pregnancy are poorly understood. To address this knowledge gap and assess the heterogeneity of these tissues, the time-dependent material properties of all human uterine layers were measured with nanoindentation. The endometrium-decidua layer was found to be the least stiff, most viscous, and least permeable layer of the human uterus in nonpregnant and third-trimester pregnant tissues. In pregnancy, endometrium-decidua becomes stiffer and less viscous with no material property changes observed in the myometrium or perimetrium. Additionally, uterine material properties did not significantly differ between third-trimester pregnant tissues with and without placenta accreta. The foundational data generated by this study will facilitate the development of physiologically accurate models of the human uterus to investigate gynecologic and obstetric disorders. HighlightsO_LIHuman uterine layers are distinct, heterogeneous and time-dependent C_LIO_LIPregnancy alters the material properties of the maternal-fetal interface C_LIO_LILargest dataset of uterine mechanical properties measured by nanoindentation C_LI Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=61 SRC="FIGDIR/small/551726v3_ufig1.gif" ALT="Figure 1"> View larger version (24K): org.highwire.dtl.DTLVardef@2d347eorg.highwire.dtl.DTLVardef@1d14584org.highwire.dtl.DTLVardef@2b0920org.highwire.dtl.DTLVardef@1642359_HPS_FORMAT_FIGEXP M_FIG C_FIG

bioengineering↗

bioRxiv2023

Optical coherence tomography of human fetal membrane sub-layers during dynamic loading

Fetal membranes have important mechanical and antimicrobial roles in maintaining pregnancy. However, the small thickness (<800 m) of fetal membranes places them outside the resolution limits of most ultrasound and magnetic resonance systems. Optical imaging methods like optical coherence tomography (OCT) have the potential to fill this resolution gap. Here, OCT and machine learning methods were developed to characterize the ex vivo properties of human fetal membranes under dynamic loading. A saline inflation test was incorporated into an OCT system, and tests were performed on n=33 and n=32 human samples obtained from labored and C-section donors, respectively. Fetal membranes were collected in near-cervical and near-placental locations. Histology, endogenous two photon fluorescence microscopy, and second harmonic generation microscopy were used to identify sources of contrast in OCT images of fetal membranes. A convolutional neural network was trained to automatically segment fetal membrane sub-layers with high accuracy (Dice coefficients >0.8). Intact amniochorion bilayer and separated amnion and chorion were individually loaded, and the amnion layer was identified as the load-bearing layer within intact fetal membranes for both labored and C-section samples, consistent with prior work. Additionally, the rupture pressure and thickness of the amniochorion bilayer from the near-placental region were greater than those of the near-cervical region for labored samples. This location-dependent change in fetal membrane thickness was not attributable to the load-bearing amnion layer. Finally, the initial phase of the loading curve indicates that amniochorion bilayer from the near-cervical region is strain-hardened compared to the near-placental region in labored samples. Overall, these studies fill a gap in our understanding of the structural and mechanical properties of human fetal membranes at high resolution under dynamic loading events.

biophysics↗

bioRxiv2020

Longitudinal ultrasonic dimensions and parametric solid models of the gravid uterus and cervix

Tissue mechanics is central to pregnancy, during which maternal anatomic structures undergo continuous remodeling to serve a dual function to first protect the fetus in utero while it develops and then facilitate its passage out. In this study of normal pregnancy using biomechanical solid modeling, we used standard clinical ultrasound images to obtain measurements of structural dimensions of the gravid uterus and cervix throughout gestation. 2-dimensional ultrasound images were acquired from the uterus and cervix in 30 pregnant subjects in supine and standing positions at four time points during pregnancy (8-14, 14-16, 22-24, and 32-34 weeks). Offline, three observers independently measured from the images of multiple anatomic regions. Statistical analysis was performed to evaluate inter-observer variance, as well as effect of gestational age, gravity, and parity on maternal geometry. A parametric solid model developed in the Solidworks computer aided design (CAD) software was used to convert ultrasonic measurements to a 3-dimensional solid computer model, from which estimates of uterine and cervical volumes were made. This parametric model was compared against previous 3-dimensional solid models derived from magnetic resonance frequency images in pregnancy. In brief, we found several anatomic measurements easily derived from standard clinical imaging are reproducible and reliable, and provide sufficient information to allow biomechanical solid modeling. This structural dataset is the first, to our knowledge, to provide key variables to enable future computational calculations of tissue stress and stretch in pregnancy, making it possible to characterize the biomechanical milieu of normal pregnancy. This vital dataset will be the foundation to understand how the uterus and cervix malfunction in pregnancy leading to adverse perinatal outcomes.

bioengineering↗