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• Nonpregnant and pregnant compound-null mice deficient in class i (decorin and biglycan) and class II (lumican) SLRPs demonstrate inappropriate assembly of collagen fibrils and elastic fibers in the cervix. • Decorin and biglycan influence the uniformity of collagen fibril structure and spacing and their loss impacts the mechanical properties of the cervix during pregnancy. • Formation of mature hydroxylysylpyridinoline (HP) collagen cross-links is independent of decorin and biglycan interactions in the cervical ECM. • Synergistic regulatory functions of class I and class II SLRPs ensure ECM homeostasis through all stages of cervical remodeling. The cervix undergoes rapid and dramatic shifts in collagen and elastic fiber structure to achieve its disparate physiological roles of competence during pregnancy and compliance during birth. An understanding of the structure-function relationships of collagen and elastic fibers to maintain extracellular matrix (ECM) homeostasis requires an understanding of the mechanisms executed by non-structural ECM molecules. Small-leucine rich proteoglycans (SLRPs) play key functions in biology by affecting collagen fibrillogenesis and regulating enzyme and growth factor bioactivities. In the current study, we evaluated collagen and elastic fiber structure-function relationships in mouse cervices using mice with genetic ablation of decorin and/or biglycan genes as representative of Class I SLRPs, and lumican gene representative of Class II SLRP. We identified structural defects in collagen fibril and elastic fiber organization in nonpregnant mice lacking decorin, or biglycan or lumican with variable resolution of defects noted during pregnancy. The severity of collagen and elastic fiber defects was greater in nonpregnant mice lacking both decorin and biglycan and defects were maintained throughout pregnancy. Loss of biglycan alone reduced tissue extensibility in nonpregnant mice while loss of both decorin and biglycan manifested in decreased rupture stretch in late pregnancy. Collagen cross-link density was similar in the Class I SLRP null mice as compared to wild-type nonpregnant and pregnant controls. A broader range in collagen fibril diameter along with an increase in mean fibril spacing was observed in the mutant mice compared to wild-type controls. Collectively, these findings uncover functional redundancy and hierarchical roles of Class I and Class II SLRPs as key regulators of cervical ECM remodeling in pregnancy. These results expand our understating of the critical role SLRPs play to maintain ECM homeostasis in the cervix. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Spontaneous preterm birth (sPTB), a major cause of infant morbidity and mortality, must involve premature cervical softening/dilation for a preterm vaginal delivery to occur. Yet, the mechanism behind premature cervical softening/dilation in humans remains unclear. We previously reported the non-pregnant human cervix contains considerably more cervical smooth muscle cells (CSMC) than historically appreciated and the CSMC organization resembles a sphincter. We hypothesize that premature cervical dilation leading to sPTB may be due to (1) an inherent CSMC contractility defect resulting in sphincter failure and/or (2) altered cervical extracellular matrix (ECM) rigidity which influences CSMC contractility. To test these hypotheses, we utilized immunohistochemistry to confirm this CSMC phenotype persists in the human pregnant cervix and then assessed in vitro arrays of contractility (F:G actin ratios, PDMS pillar arrays) using primary CSMC from pregnant women with and without premature cervical failure (PCF). We show that CSMC from pregnant women with PCF do not have an inherent CSMC contractility defect but that CSMC exhibit decreased contractility when exposed to soft ECM. Given this finding, we used UPLC-ESI-MS/MS to evaluate collagen cross-link profiles in the cervical tissue from non-pregnant women with and without PCF and found that women with PCF have decreased collagen cross-link maturity ratios, which correlates to softer cervical tissue. These findings suggest having soft cervical ECM may lead to decreased CSMC contractile tone and a predisposition to sphincter laxity that contributes to sPTB. Further studies are needed to explore the interaction between cervical ECM properties and CSMC cellular behavior when investigating the pathophysiology of sPTB. [ABSTRACT FROM AUTHOR]

Preterm birth is the leading cause of childhood mortality and can lead to health risks in survivors. The mechanical functions of the uterus, feta! membranes, and cervix have dynamic roles to protect the fetus during gestation. To understand their mechanical function and relation to preterm birth, we built a three-dimensional parameterized finite element model of pregnancy. This model is generated by an automated procedure that is informed by maternal ultrasound measurements. A baseline model at 25 weeks of gestation was characterized, and to visualize the impact of cervical structural parameters on tissue stretch, we evaluated the model sensitivity to (1) anterior uterocervical angle, (2) cervical length, (3) posterior cervical offset, and (4) cervical stiffness. We found that cervical tissue stretching is minimal when the cervical canal is aligned with the longitudinal uterine axis, and a softer cervix is more sensitive to changes in the geometric variables tested. [ABSTRACT FROM AUTHOR]

Materials currently used to repair or replace a heart valve are not durable. Their limited durability related to structural degeneration or thrombus formation is attributed to their inadequate mechanical properties and biocompatibility profiles. Our hypothesis is that a biostable material that mimics the structure, mechanical and biological properties of native tissue will improve the durability of these leaflets substitutes and in fine improve the patient outcome. Here, we report the development, optimization, and testing of a biomimetic, multilayered material (BMM), designed to replicate the native valve leaflets. Polycarbonate urethane and polycaprolactone have been processed as film, foam, and aligned fibers to replicate the leaflet's architecture and anisotropy, through solution casting, lyophilization, and electrospinning. Compared to the commercialized materials, our BMMs exhibited an anisotropic behavior and a closer mechanical performance to the aortic leaflets. The material exhibited superior biostability in an accelerated oxidization environment. It also displayed better resistance to protein adsorption and calcification in vitro and in vivo. These results will pave the way for a new class of advanced synthetic material with long-term durability for surgical valve repair or replacement. [Display omitted] • Biostable polymers have been used to fabricate a multilayered leaflet-like structure that mimics native tissue. • Mechanical performance of this multilayered material better resembles native leaflets. • This multilayered material displayed superior biostability in an accelerated oxidization environment. • In vivo subcutaneous model confirmed the superior biocompatibility of this material compared to commercial alternatives. [ABSTRACT FROM AUTHOR]

We conducted two experiments to evaluate the effects of errors of omission and commission during alternative reinforcement of compliance in young children. In Experiment 1, we evaluated errors of omission by examining two levels of integrity during alternative reinforcement (20 and 60 %) for child compliance following no treatment (baseline) versus treatment at full (i.e., 100 %) integrity. Results indicated that compliance varied according to the level of integrity in place. In addition, compliance in the 60 % integrity condition was high and stable when it followed baseline, but was substantially lower for one participant and slightly lower for a second participant when it followed the full integrity condition. In Experiment 2, we evaluated errors of commission. For three participants, we compared treatment at full integrity to a condition in which errors of commission were made on every trial (i.e., 0 % integrity). For one of these three participants, we also compared treatment at full integrity to baseline and to a condition in which errors of commission were made on 50 % of trials. Results of all four evaluations again indicate that compliance varied according to the level of integrity in place: compliance was low in both the 0 and 50 % integrity conditions, regardless of the preceding condition. These results suggest that during alternative reinforcement of compliance, the effect of occasional errors of omission may depend on the immediately preceding context but that errors of commission are more detrimental. [ABSTRACT FROM AUTHOR]

Abstract: Objective: Although a short cervix is known to be associated with preterm birth, the patterns of three-dimensional, anatomic changes leading to a short cervix are unknown. Our objective was to (1) construct three-dimensional anatomic models during normal pregnancy and (2) use the models to compare cervical anatomy in the second and third trimester. Study design: A cross-sectional study was performed in a population of patients referred to magnetic resonance imaging (MRI) for a fetal indication. Using magnetic resonance images for guidance, three-dimensional solid models of the following anatomic structures were constructed: amniotic cavity, uterine wall, cervical stroma, cervical mucosa and anterior vaginal wall. To compare cervical anatomy in the second and third trimester, models were matched according the size of the bony pelvis. Results: Fourteen patients were imaged and divided into two groups according to gestational age: 20–24 weeks (n =7)) and 31–36 weeks (n =7). Compared to the second trimester, the third trimester was associated with significant descent of the amniotic sac (p =.02). Descent of the amniotic sac was associated with modified anatomy of the uterocervical junction. These three-dimensional changes were associated with a cervix that appeared shorter in the third trimester. Conclusion: We report a technique for constructing MRI-based, three-dimensional anatomic models during pregnancy. Compared to the second trimester, the third trimester is associated with three-dimensional changes in the cervix and lower uterine segment. [Copyright &y& Elsevier]

Abstract: The Presence and distribution of elastin in the posterior and retrobulbar regions of the mouse eye was investigated. Mice of two strains (C57/BL6 and DBA/2J) were studied at 2 months and 8–12 months of age. Light, confocal, and transmission electron microscopy were used to identify elastin, using immunohistochemical techniques and ultrastructural evaluation. Elastin was found in the following ocular structures: conjunctiva, muscle tendons, sclera, choroid, and meninges. The elastin in the sclera was most dense in a ring surrounding the peripapillary optic nerve head, with its presence in the inner sclera declining with greater distance from the nerve head. Elastin fibers were oriented in the sclera along what would be expected to be the principal stress directions generated from the intraocular pressure, though actual biomechanical measurements have not yet been made in the mouse sclera. Elastin comprises a portion of the mouse sclera and its distribution in the peripapillary area is similar to that in human eyes. [Copyright &y& Elsevier]

The study describes a novel method for tinnitus screening in rats by use of gap detection reflex procedures. The authors hypothesized that if a background acoustic signal was qualitatively similar to the rat's tinnitus, poorer detection of a silent gap in the background would be expected, Rats with prior evidence of tinnitus at 10 kHz (n = 14) exhibited significantly worse gap detection than controls (n = 13) when the gap was embedded in a background similar to their tinnitus. No differences between tinnitus and control rats were found with 16 kHz or broadband noise backgrounds, which helped to rule out explanations related to hearing loss or general performance deficits. The results suggest that gap detection reflex procedures might be effective for rapid tinnitus screening in rats. [ABSTRACT FROM AUTHOR]

To identify children and evaluate patterns of charges for pediatric medical care, by overall health status, severity of illness, and categories of medical service. Enrollment, claims, and charges data from a Washington State health plan. The study population includes all children ages 0 to 18 years during calendar year 1999. Children were classified into clinically defined health status groups and severity levels using Clinical Risk Groups (CRGs). Health plan charges were analyzed according to core health status group, severity level, and category of service. The three secondary data sources were obtained electronically from the health plan and cleaned for unique members and data quality before analysis. Children classified as healthy (85.2 percent) had mean and median annual charges of $485 and $191. Children with one or more chronic conditions (9.5 percent) had mean and median charges increasing by status and severity group from $2,303 to $76,143 and from $1,151 to $19,456, and accounted for 45.2 percent of all charges. Distribution of charges varied across health status groups. Healthy children had 70.6 percent of their charges in outpatient and physician services. Children classified in the complex, catastrophic, and malignancy groups had 67 percent of their charges in inpatient encounters. Children with chronic conditions accounted for 31.8 percent of all physician, 41.8 percent of outpatient, 47.7 percent of pharmacy, 60.7 percent of inpatient, and 75.8 percent of all other charges. Children with chronic conditions account for a disproportionately high percentage of children's health expenditures. They account for different percentages of expenses for different medical services. These percentages vary according to health status and severity. This analysis can be used to identify and track groups of children for various purposes. [ABSTRACT FROM AUTHOR]

Successful pregnancy highly depends on the complex interaction between the uterine body, cervix, and fetal membrane. This interaction is synchronized, usually following a specific sequence in normal vaginal deliveries: (1) cervical ripening, (2) uterine contractions, and (3) rupture of fetal membrane. The complex interaction between the cervix, fetal membrane, and uterine contractions before the onset of labor is investigated using a complete third-trimester gravid model of the uterus, cervix, fetal membrane, and abdomen. Through a series of numerical simulations, we investigate the mechanical impact of (i) initial cervical shape, (ii) cervical stiffness, (iii) cervical contractions, and (iv) intrauterine pressure. The findings of this work reveal several key observations: (i) maximum principal stress values in the cervix decrease in more dilated, shorter, and softer cervices; (ii) reduced cervical stiffness produces increased cervical dilation, larger cervical opening, and decreased cervical length; (iii) the initial cervical shape impacts final cervical dimensions; (iv) cervical contractions increase the maximum principal stress values and change the stress distributions; (v) cervical contractions potentiate cervical shortening and dilation; (vi) larger intrauterine pressure (IUP) causes considerably larger stress values and cervical opening, larger dilation, and smaller cervical length; and (vii) the biaxial strength of the fetal membrane is only surpassed in the cases of the (1) shortest and most dilated initial cervical geometry and (2) larger IUP., (© 2024. The Author(s).)

The leading cause of perinatal mortality is fetal growth restriction (FGR), defined as in utero fetal growth below the 10th percentile. Insufficient exchange of oxygen and nutrients at the maternal-fetal interface is associated with FGR. This transport occurs through the vasculature of the placenta, particularly in the terminal villi, where the vascular membranes have a large surface area and are the thinnest. Altered structure of the placenta villi is thought to contribute to decreased oxygen exchange efficiency, however, understanding how the three-dimensional microstructure and properties decrease this efficiency remains a challenge. Here, a novel, multiscale workflow is presented to quantify patient-specific biophysical properties, 3D structural features, and blood flow of the villous tissue. Namely, nanoindentation, optical coherence tomography, and ultrasound imaging were employed to measure the time-dependent material properties of placenta tissue, the 3D structure of villous tissue, and blood flow through the villi to characterize the microvasculature of the placenta at increasing length scales. Quantifying the biophysical properties, the 3D architecture, and blood flow in the villous tissue can be used to infer changes in maternal-fetal oxygen transport at the villous membrane. Overall, this multiscale understanding will advance knowledge of how microvascular changes in the placenta ultimately lead to FGR, opening opportunities for diagnosis and intervention., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Cervical remodeling is critical for a healthy pregnancy. Premature tissue changes can lead to preterm birth (PTB), and the absence of remodeling can lead to post-term birth, causing significant morbidity. Comprehensive characterization of cervical material properties is necessary to uncover the mechanisms behind abnormal cervical softening. Quantifying cervical material properties during gestation is challenging in humans. Thus, a nonhuman primate (NHP) model is employed for this study. In this study, cervical tissue samples were collected from Rhesus macaques before pregnancy and at three gestational time points. Indentation and tension mechanical tests were conducted, coupled with digital image correlation (DIC), constitutive material modeling, and inverse finite element analysis (IFEA) to characterize the equilibrium material response of the macaque cervix during pregnancy. Results show, as gestation progresses: (1) the cervical fiber network becomes more extensible (nonpregnant versus pregnant locking stretch: 2.03 ± 1.09 versus 2.99 ± 1.39) and less stiff (nonpregnant versus pregnant initial stiffness: 272 ± 252 kPa versus 43 ± 43 kPa); (2) the ground substance compressibility does not change much (nonpregnant versus pregnant bulk modulus: 1.37 ± 0.82 kPa versus 2.81 ± 2.81 kPa); (3) fiber network dispersion increases, moving from aligned to randomly oriented (nonpregnant versus pregnant concentration coefficient: 1.03 ± 0.46 versus 0.50 ± 0.20); and (4) the largest change in fiber stiffness and dispersion happen during the second trimester. These results, for the first time, reveal the remodeling process of a nonhuman primate cervix and its distinct regimes throughout the entire pregnancy., (Copyright © 2024 by ASME.)

During vaginal delivery, the delivery requires the fetal head to mold to accommodate the geometric constraints of the birth canal. Excessive molding can produce brain injuries and long-term sequelae. Understanding the loading of the fetal brain during the second stage of labor (fully dilated cervix, active pushing, and expulsion of fetus) could thus help predict the safety of the newborn during vaginal delivery. To this end, this study proposes a finite element model of the fetal head and maternal canal environment that is capable of predicting the stresses experienced by the fetal brain at the onset of the second phase of labor. Both fetal and maternal models were adapted from existing studies to represent the geometry of full-term pregnancy. Two fetal positions were compared: left-occiput-anterior and left-occiput-posterior. The results demonstrate that left-occiput-anterior position reduces the maternal tissue deformation, at the cost of higher stress in the fetal brain. In both cases, stress is concentrated underneath the sutures, though the location varies depending on the presentation. In summary, this study provides a patient-specific simulation platform for the study of vaginal delivery and its effect on both the fetal brain and maternal anatomy. Finally, it is suggested that such an approach has the potential to be used by obstetricians to support their decision-making processes through the simulation of various delivery scenarios., (Copyright © 2024 by ASME.)

Birthing mechanics are poorly understood, though many injuries during childbirth are mechanical, like fetal and maternal tissue damage. Several biomechanical simulation models of parturition have been proposed to investigate birth, but many do not include the uterus. Additionally, most solid models rely on segmenting anatomical structures from clinical images to generate patient geometry, which can be time-consuming. This work presents two new parametric solid modeling methods for generating patient-specific, at-term uterine three-dimensional geometry. Building from an established method of modeling the sagittal uterine shape, this work improves the uterine coronal shape, especially where the fetal head joins the lower uterine wall. Solid models of the uterus and cervix were built from five at-term patients' magnetic resonance imaging (MRI) sets. Using anatomy measurements from MRI-segmented models, two parametric models were created-one that employs an averaged coronal uterine shape and one with multiple axial measurements of the coronal uterus. Through finite element analysis, the two new parametric methods were compared to the MRI-segmented high-fidelity method and a previously published elliptical low-fidelity method. A clear improvement in the at-term uterine shape was found using the two new parametric methods, and agreement in principal Lagrange strain directions was observed across all modeling methods. These methods provide an effective and efficient way to generate three-dimensional solid models of patient-specific maternal uterine anatomy, advancing possibilities for future research in computational birthing biomechanics., (Copyright © 2024 by ASME.)

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., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Ltd.)

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, the 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., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Published by Elsevier Ltd.)

The fetal membranes are an essential mechanical structure for pregnancy, protecting the developing fetus in an amniotic fluid environment and rupturing before birth. In cooperation with the cervix and the uterus, the fetal membranes support the mechanical loads of pregnancy. Structurally, the fetal membranes comprise two main layers: the amnion and the chorion. The mechanical characterization of each layer is crucial to understanding how each layer contributes to the structural performance of the whole membrane. The in-vivo mechanical loading of the fetal membranes and the amount of tissue stress generated in each layer throughout gestation remains poorly understood, as it is difficult to perform direct measurements on pregnant patients. Finite element analysis of pregnancy offers a computational method to explore how anatomical and tissue remodeling factors influence the load-sharing of the uterus, cervix, and fetal membranes. To aid in the formulation of such computational models of pregnancy, this work develops a fiber-based multilayer fetal membrane model that captures its response to previously published bulge inflation loading data. First, material models for the amnion, chorion, and maternal decidua are formulated, informed, and validated by published data. Then, the behavior of the fetal membrane as a layered structure was analyzed, focusing on the respective stress distribution and thickness variation in each layer. The layered computational model captures the overall behavior of the fetal membranes, with the amnion being the mechanically dominant layer. The inclusion of fibers in the amnion material model is an important factor in obtaining reliable fetal membrane behavior according to the experimental dataset. These results highlight the potential of this layered model to be integrated into larger biomechanical models of the gravid uterus and cervix to study the mechanical mechanisms of preterm birth., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Mammalian pregnancy requires gradual yet extreme remodeling of the reproductive organs to support the growth of the embryos and their birth. After delivery, the reproductive organs return to their non-pregnant state. As pregnancy has traditionally been understudied, there are many unknowns pertaining to the mechanisms behind this remarkable remodeling and repair process which, when not successful, can lead to pregnancy-related complications such as maternal trauma, pre-term birth, and pelvic floor disorders. This study presents the first longitudinal imaging data that focuses on revealing anatomical alterations of the vagina, cervix, and uterine horns during pregnancy and postpartum using the mouse model. By utilizing advanced magnetic resonance imaging (MRI) technology, T1-weighted and T2-weighted images of the reproductive organs of three mice in their in vivo environment were collected at five time points: non-pregnant, mid-pregnant (gestation day: 9-10), late pregnant (gestation day: 16-17), postpartum (24-72 h after delivery) and three weeks postpartum. Measurements of the vagina, cervix, and uterine horns were taken by analyzing MRI segmentations of these organs. The cross-sectional diameter, length, and volume of the vagina increased in late pregnancy and then returned to non-pregnant values three weeks after delivery. The cross-sectional diameter of the cervix decreased at mid-pregnancy before increasing in late pregnancy. The volume of the cervix peaked at late pregnancy before shortening by 24-72 h postpartum. As expected, the uterus increased in cross-sectional diameter, length, and volume during pregnancy. The uterine horns decreased in size postpartum, ultimately returning to their average non-pregnant size three weeks postpartum. The newly developed methods for acquiring longitudinal in vivo MRI scans of the murine reproductive system can be extended to future studies that evaluate functional and morphological alterations of this system due to pathologies, interventions, and treatments., (© 2024. The Author(s).)

Atherosclerosis is a primary precursor of cardiovascular disease (CVD), the leading cause of death worldwide. While proprotein convertase subtilisin/kexin 9 (PCSK9) contributes to CVD by degrading low-density lipoprotein receptors (LDLR) and altering lipid metabolism, PCSK9 also influences vascular inflammation, further promoting atherosclerosis. Here, we utilized a vascular microphysiological system to test the effect of PCSK9 activation or repression on the initiation of atherosclerosis and to screen the efficacy of a small molecule PCSK9 inhibitor. We have generated PCSK9 over-expressed (P+) or repressed (P-) human induced pluripotent stem cells (iPSCs) and further differentiated them to smooth muscle cells (viSMCs) or endothelial cells (viECs). Tissue-engineered blood vessels (TEBVs) made from P+ viSMCs and viECs resulted in increased monocyte adhesion compared to the wild type (WT) or P- equivalents when treated with enzyme-modified LDL (eLDL) and TNF-α. We also found significant viEC dysfunction, such as increased secretion of VCAM-1, TNF-α, and IL-6, in P+ viECs treated with eLDL and TNF-α. A small molecule compound, NYX-1492, that was originally designed to block PCSK9 binding with the LDLR was tested in TEBVs to determine its effect on lowering PCSK9-induced inflammation. The compound reduced monocyte adhesion in P+ TEBVs with evidence of lowering secretion of VCAM-1 and TNF-α. These results suggest that PCSK9 inhibition may decrease vascular inflammation in addition to lowering plasma LDL levels, enhancing its anti-atherosclerotic effects, particularly in patients with elevated chronic inflammation., Competing Interests: Yes, A.K.S. and B.J.E. are employees of Nyrada, Inc. and are listed as inventors on a patent that discloses NYX-1492 and related compounds. B.J.E. has share/stock options in Nyrada Inc. J.B.K. and C.A.G. have field patent applications related to technologies for genome engineering and cell reprogramming. C.A.G. is a co-founder of Tune Therapeutics and Locus Biosciences and is an advisor to Tune Therapeutics, Sarepta Therapeutics, Levo Therapeutics, and Iveric Bio., (© 2023 Author(s).)

The cervix is a soft tissue exhibiting time-dependent behavior under mechanical loads. The cervix is a vital mechanical barrier to protect the growing fetus. The remodeling of the cervical tissue, characterized by an increase in time-dependent material properties, is necessary for a safe parturition. The failure of its mechanical function and accelerated tissue remodeling is hypothesized to lead to preterm birth, which is birth before 37 weeks of gestation. To understand the mechanism of the time-dependent behavior of the cervix under compressive states, we employ a porous-viscoelastic material model to describe a set of spherical indentation tests performed on nonpregnant and term pregnant tissue. A genetic algorithm-based inverse finite element analysis is used to fit the force-relaxation data by optimizing the material parameters, and the statistical analysis of the optimized material parameters is conducted on different sample groups. The force response is captured well using the porous-viscoelastic model. The indentation force-relaxation of the cervix is explained by the porous effects and the intrinsic viscoelastic properties of the extracellular matrix (ECM) microstructure. The hydraulic permeability obtained from the inverse finite element analysis agrees with the trend of the value directly measured previously by our group. The nonpregnant samples are found significantly more permeable than the pregnant samples. Within nonpregnant samples, the posterior internal os is found significantly less permeable than the anterior and posterior external os. The proposed model exhibits the superior capability to capture the force-relaxation response of the cervix under indentation, as compared to the conventional quasi-linear viscoelastic framework (range of r 2 of the porous-viscoelastic model 0.88-0.98 vs. quasi-linear model: 0.67-0.89). As a constitutive model with a relatively simple form, the porous-viscoelastic framework has the potential to be used to understand disease mechanisms of premature cervical remodeling, model contact of the cervix with biomedical devices, and interpret force readings from novel in-vivo measurement tools such as an aspiration device., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Fetal membranes have important mechanical and antimicrobial roles in maintaining pregnancy. However, the small thickness (<800 µm) 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., Competing Interests: The authors declare no conflicts of interest., (© 2023 Optica Publishing Group under the terms of the Optica Open Access Publishing Agreement.)

Non-invasive monitoring of atherosclerosis remains challenging. Pulse Wave Imaging (PWI) is a non-invasive technique to measure the local stiffness at diastolic and end-systolic pressures and quantify the hemodynamics. The objective of this study is twofold, namely (1) to investigate the capability of (adaptive) PWI to assess progressive change in local stiffness and homogeneity of the carotid in a high-cholesterol swine model and (2) to assess the ability of PWI to monitor the change in hemodynamics and a corresponding change in stiffness. Nine (n=9) hypercholesterolemic swine were included in this study and followed for up to 9 months. A ligation in the left carotid was used to cause a hemodynamic disturbance. The carotids with detectable hemodynamic disturbance showed a reduction in wall shear stress immediately after ligation (2.12 ± 0.49 to 0.98 ± 0.47 Pa for 40-90% ligation (Group B) and 1.82 ± 0.25 to 0.49 ± 0.46 Pa for >90% ligation (Group C)). Histology revealed subsequent lesion formation after 8-9 months, and the type of lesion formation was dependent on the type of the induced ligation, with more complex plaques observed in the carotids with a more significant ligation (C: >90%). The compliance progression appears differed for groups B and C, with an increase in compliance to 2.09 ± 2.90×10 -10 m 2 Pa -1 for group C whereas the compliance of group B remained low at 8 months (0.95 ± 0.94×10 -10 m 2 Pa -1 ). In summary, PWI appeared capable of monitoring a change in wall shear stress and separating two distinct progression pathways resulting in distinct compliances., (© 2023. The Author(s).)

Despite the advancements in skin bioengineering, 3D skin constructs are still produced as flat tissues with open edges, disregarding the fully enclosed geometry of human skin. Therefore, they do not effectively cover anatomically complex body sites, e.g., hands. Here, we challenge the prevailing paradigm by engineering the skin as a fully enclosed 3D tissue that can be shaped after a body part and seamlessly transplanted as a biological clothing. Our wearable edgeless skin constructs (WESCs) show enhanced dermal extracellular matrix (ECM) deposition and mechanical properties compared to conventional constructs. WESCs display region-specific cell/ECM alignment, as well as physiologic anisotropic mechanical properties. WESCs replace the skin in full-thickness wounds of challenging body sites (e.g., mouse hindlimbs) with minimal suturing and shorter surgery time. This study provides a compelling technology that may substantially improve wound care and suggests that the recapitulation of the tissue macroanatomy can lead to enhanced biological function.

The mechanical function of the uterine cervix is critical for a healthy pregnancy. During pregnancy, the cervix undergoes significant softening to allow for a successful delivery. Abnormal cervical remodeling is suspected to contribute to preterm birth. Material constitutive models describing known biological shifts in pregnancy are essential to predict the mechanical integrity of the cervix. In this work, the material response of human cervical tissue under spherical indentation and uniaxial tensile tests loaded along different anatomical directions is experimentally measured. A deep-learning segmentation tool is applied to capture the tissue deformation during the uniaxial tensile tests. A 3-dimensional, equilibrium anisotropic continuous fiber constitutive model is formulated, considering collagen fiber directionality, fiber bundle dispersion, and the entropic nature of wavy cross-linked collagen molecules. Additionally, the universality of the material model is demonstrated by characterizing previously published mouse cervix mechanical data. Overall, the proposed material model captures the tension-compression asymmetric material responses and the remodeling characteristics of both human and mouse cervical tissue. The pregnant (PG) human cervix (mean locking stretch ζ=2.4, mean initial stiffness ξ=12 kPa, mean bulk modulus κ=0.26 kPa, mean dispersion b=1.0) is more compliant compared with the nonpregnant (NP) cervix (mean ζ=1.3, mean ξ=32 kPa, mean κ=1.4 kPa, mean b=1.4). Creating a validated material model, which describes the role of collagen fiber directionality, dispersion, and crosslinking, enables tissue-level biomechanical simulations to determine which material and anatomical factors drive the cervix to open prematurely. STATEMENT OF SIGNIFICANCE: In this study, we report a 3D anisotropic hyperelastic constitutive model based on Langevin statistical mechanics and successfully describe the material behavior of both human and mouse cervical tissue using this model. This model bridges the connection between the extracellular matrix (ECM) microstructure remodeling and the macro mechanical properties change of the cervix during pregnancy via microstructure-associated material parameters. This is the first model, to our knowledge, to connect the the entropic nature of wavy cross-linked collagen molecules with the mechanical behavior of the cervix. Inspired by microstructure, this model provides a foundation to understand further the relationship between abnormal cervical ECM remodeling and preterm birth. Furthermore, with a relatively simple form, the proposed model can be applied to other fibrous tissues in the future., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Cervical remodeling is critical for a healthy pregnancy. The proper regulation of extracellular matrix (ECM) turnover leads to remodeling throughout gestation, transforming the tissue from a stiff material to a compliant, extensible, viscoelastic tissue prepared for delivery. Small leucine-rich proteoglycans (SLRPs) regulate structural fiber assembly in the cervical ECM and overall tissue material properties. To quantify the SLRPs' mechanical role in the cervix, whole cervix specimens from nonpregnant and late pregnant knockout mice of SLRPs, decorin and biglycan, were subjected to cyclic load-unload, ramp-hold, and load-to-failure mechanical tests. Further, a fiber composite material model, accounting for collagen fiber bundle waviness, was developed to describe the cervix's three-dimensional large deformation equilibrium behavior. In nonpregnant tissue, SLRP knockout cervices have the same equilibrium material properties as wild-type tissue. In contrast, the load-to-failure and ramp-hold tests reveal SLRPs impact rupture and time-dependent relaxation behavior. Loss of decorin in nonpregnant (NP) cervices results in inferior rupture properties. After extensive remodeling, cervical strength is similar between all genotypes, but the SLRP-deficient tissue has a diminished ability to dissipate stress during a ramp-hold. In mice with a combined loss of decorin and biglycan, the pregnant cervix loses its extensibility, compliance, and viscoelasticity. These results suggest that decorin and biglycan are necessary for crucial extensibility and viscoelastic material properties of a healthy, remodeled pregnant cervix., (Copyright © 2022 by ASME.)

Appropriate timing of cervical remodeling (CR) is key to normal term parturition. To date, mechanisms behind normal and abnormal (premature or delayed) CR remain unclear. Recent studies show regional differences exist in human cervical tissue structure. While the entire cervix contains extracellular matrix (ECM), the internal os is highly cellular containing 50-60% cervical smooth muscle (CSM). The external os contains 10-20% CSM. Previously, we reported ECM rigidity and different ECM proteins influence CSM cell function, highlighting the importance of understanding not only how cervical cells orchestrate cervical ECM remodeling in pregnancy, but also how changes in specific ECM proteins can influence resident cellular function. To understand this dynamic process, we utilized a systematic proteomic approach to understand which soluble ECM and cellular proteins exist in the different regions of the human cervix and how the proteomic profiles change from the non-pregnant (NP) to the pregnant (PG) state. We found the human cervix proteome contains at least 4548 proteins and establish the types and relative abundance of cellular and soluble matrisome proteins found in the NP and PG human cervix. Further, we report the relative abundance of proteins involved with elastic fiber formation and ECM organization/degradation were significantly increased while proteins involved in RNA polymerase I/promoter opening, DNA methylation, senescence, immune system, and compliment activation were decreased in the PG compared to NP cervix. These findings establish an initial platform from which we can further comprehend how changes in the human cervix proteome results in normal and abnormal CR., (© 2022. Society for Reproductive Investigation.)

The mechanical function of the uterus is critical for a successful pregnancy. During gestation, uterine tissue grows and stretches to many times its size to accommodate the growing fetus, and it is hypothesized the magnitude of uterine tissue stretch triggers the onset of contractions. To establish rigorous mechanical testing protocols for the human uterus in hopes of predicting tissue stretch during pregnancy, this study measures the anisotropic mechanical properties of the human uterus using optical coherence tomography (OCT), instrumented spherical indentation, and video extensometry. In this work, we perform spherical indentation and digital image correlation to obtain the tissue's force and deformation response to a ramp-hold loading regimen. We translate previously reported fiber architecture, measured via optical coherence tomography, into a constitutive fiber composite material model to describe the equilibrium material behavior during indentation. We use an inverse finite element method integrated with a genetic algorithm (GA) to fit the material model to our experimental data. We report the mechanical properties of human uterine specimens taken across different anatomical locations and layers from one non-pregnant (NP) and one pregnant (PG) patient; both patients had pathological uterine tissue. Compared to NP uterine tissue, PG tissue has a more dispersed fiber distribution and equivalent stiffness material parameters. In both PG and NP uterine tissue, the mechanical properties differ significantly between anatomical locations., (© 2021. Biomedical Engineering Society.)

Background: Randomized-controlled trials and meta-analyses showed nimodipine use after aneurysmal subarachnoid hemorrhage (aSAH) leads to reduction in incidence of cerebral infarction, persistent neurological deficits, and poor outcomes. Trials administered it for 21 days; however, we assessed whether a shorter duration might be reasonable for a subset of patients., Methods: We performed a retrospective single-center study to compare outcomes between patients who received ≤14 days, 15-20 days or ≥21 days of nimodipine. Primary outcome was defined as rate of good functional outcome at final follow-up, assessed using dichotomized modified Rankin Score (mRS). Secondary outcomes included median mRS at follow-up, discharge disposition, and readmission for stroke or vasospasm., Results: 195 patients were included: 101 patients received nimodipine for ≤14 days, 72 patients for 15-20 days, and 22 patients for ≥21 days. There were differences in baseline characteristics of the groups. The shorter duration groups had higher admission GCS score (GCS 15 for ≤14 days, GCS 13 for 15-20 days, GCS 8 for ≥21 days, p = 0.003) and lower Hunt-Hess grade (2 for ≤14 days, 3 for 15-20 days, 4 for ≥21 days, p = 0.001). Of the group of patients that received ≤14 days of nimodipine, 3 patients (3%) were readmitted for concerns for possible stroke or vasospasm, but they did not experience worsening of their functional status related to this., Conclusion: Our data suggests a more limited 14-day course of nimodipine therapy after aSAH may be reasonable and efficacious in patients with higher GCS and lower Hunt-Hess grade on presentation., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Automatic quantification and visualization of 3-D collagen fiber architecture using Optical Coherence Tomography (OCT) has previously relied on polarization information and/or prior knowledge of tissue-specific fiber architecture. This study explores image processing, enhancement, segmentation, and detection algorithms to map 3-D collagen fiber architecture from OCT images alone. 3-D fiber mapping, histogram analysis, and 3-D tractography revealed fiber groupings and macro-organization previously unseen in uterine tissue samples. We applied our method on centimeter-scale mosaic OCT volumes of uterine tissue blocks from pregnant and non-pregnant specimens revealing a complex, patient-specific network of fibrous collagen and myocyte bundles., Competing Interests: The authors declare that there are no conflicts of interest related to this article., (© 2020 Optical Society of America under the terms of the OSA Open Access Publishing Agreement.)

Purpose: A topical corneal cross-linking solution that can be used as an adjunct or replacement to standard photochemical cross-linking (UV-riboflavin) methods remain an attractive possibility. Optimal concentration and delivery method for such topical corneal stabilization in the living rabbit eye were developed., Methods: A series of experiments were carried out using Dutch-belted rabbits (3 months old, weighing 1.0-1.5 kg) and topical cross-linking solutions (sodium hydroxymethylglycinate) (10-250 mM) delivered via corneal reservoir. The application regimen included a one-time 30-minute application (10-40 mM sodium hydroxymethylglycinate) as well as a once per week 5-minute application (250 mM sodium hydroxymethylglycinate) for 7 weeks. Animals were evaluated serially for changes in IOP, pachymetry, epithelial integrity, and endothelial cell counts. Keratocyte changes were identified using intravital laser scanning confocal microscopy. Post mortem efficacy was evaluated by mechanical inflation testing., Results: Overall, there were very few differences observed in right eye treated versus left eye controls with respect to intraocular pressure, pachymetry, and endothelial cell counts, although 30-minute cross-linking techniques did cause transient increases in thickness resolving within 7 days. Epithelial damage was noted in all of the 30-minute applications and fully resolved within 72 hours. Keratocyte changes were significant, showing a wound healing pattern similar to that after riboflavin UVA photochemical cross-linking in rabbits and humans. Surprisingly, post mortem inflation testing showed that the lower concentration of 20 mM delivered over 30 minutes showed the most profound stiffening/strengthening effect., Conclusions: Topical cross-linking conditions that are safe and can increase corneal stiffness/strength in the living rabbit eye have been identified., Translational Relevance: A topical corneal cross-linking solution delivered via corneal reservoir is shown to be both safe and effective at increasing tissue strength in living rabbit eyes and could now be tested in patients suffering from keratoconus and other conditions marked by corneal tissue weakness., Competing Interests: Disclosure: M. Zyablitskaya, None; C. Jayyosi, None; A. Takaoka, None; K.M. Myers, None; L.H. Suh, None; T. Nagasaki, None; S.L. Trokel, None; D.C. Paik, None, (Copyright 2020 The Authors.)

The uterine cervix undergoes a complex remodelling process during pregnancy, characterized by dramatic changes in both extracellular matrix (ECM) structure and mechanical properties. Understanding the cervical remodelling process in a term or preterm birth will aid efforts for the prevention of preterm births (PTBs), which currently affect 14.8 million babies annually worldwide. Animal models of pregnancy, particularly rodents, continue to provide valuable insights into the cervical remodelling process, through the study of changes in ECM structure and mechanical properties at defined gestation time points. Currently, there is a lack of a collective, quantitative framework to relate the complex, nonlinear mechanical behaviour of the rodent cervix to changes in ECM structure. This review aims to fill this gap in knowledge by outlining the current understanding of cervical remodelling during pregnancy in rodent models in the context of solid biomechanics. Here we highlight the collective contribution of multiple mechanical studies which give evidence that cervical softening coincides with known ECM changes throughout pregnancy. Taken together, mechanical tests on tissue from pregnant rodents reveal the cervix's remarkable ability to soften dramatically during gestation to allow for a compliant tissue that can withstand damage and can dissipate mechanical loads., Competing Interests: The authors have no competing interests to disclose.

The cervix is essential to a healthy pregnancy as it must bear the increasing load caused by the growing fetus. Preterm birth is suspected to be caused by the premature softening and mechanical failure of the cervix. The objective of this paper is to measure the anisotropic mechanical properties of human cervical tissue using indentation and video extensometry. The human cervix is a layered structure, where its thick stromal core contains preferentially aligned collagen fibers embedded in a soft ground substance. The fiber composite nature of the tissue provides resistance to the complex three-dimensional loading environment of pregnancy. In this work, we detail an indentation mechanical test to obtain the force and deformation response during loading which closely matches in vivo conditions. We postulate a constitutive material model to describe the equilibrium material behavior to ramp-hold indentation, and we use an inverse finite element method based on genetic algorithm (GA) optimization to determine best-fit material parameters. We report the material properties of human cervical slices taken at different anatomical locations from women of different obstetric backgrounds. In this cohort of patients, the anterior internal os (the area where the cervix meets the uterus) of the cervix is stiffer than the anterior external os (the area closest to the vagina). The anatomic anterior and posterior quadrants of cervical tissue are more anisotropic than the left and right quadrants. There is no significant difference in material properties between samples of different parities (number of pregnancies reaching viable gestation age).

Preterm birth is a leading cause of morbidity and mortality in newborns. Babies born prematurely are at increased risk of lifelong health problems, including neurodevelopmental abnormalities. Cervical shortening precedes preterm birth in many women. Cervical shortening is caused, in part, by excessive softening of the extracellular matrix (ECM) of the cervical stroma. In clinical obstetrics, cervical shortening prompts treatment with supplemental progesterone to prevent preterm birth. However, progesterone-mediated effects on the cervical ECM are not well understood. This research sought to study progesterone-mediated remodeling of ECM produced by human cervical fibroblasts in vitro . A previously developed three-dimensional (3D) engineered model of the cervical ECM was used for experiments. Cervical fibroblasts were seeded on porous scaffolds and cultured in spinner flasks to promote ECM synthesis. Scaffolds were exposed to two conditions: 10 -8 M estradiol versus 10 -8 M estradiol +10 -6 M progesterone for 4 weeks. To measure ECM strength, two scaffolds were mounted end-to-end on a wire and cultured such that ECM filled the gap between the scaffolds. The force required to pull the scaffolds apart was measured. Collagen content and collagen crosslinks were measured with ultra performance liquid chromatography-electrospray ionization tandem mass spectrometry. Whole-transcriptome RNA sequencing (RNA-seq) was used to quantify gene expression between the two experimental conditions. Zymography was used to study the quantity and activity of matrix metalloproteinase-2 (MMP2) in the scaffolds. The study found that exposure to progesterone increased tissue softness of the engineered ECM over 28 days. Increased tissue softness correlated with decreased collagen content. With RNA-seq, progesterone exposure resulted in gene expression changes consistent with known progesterone effects. Pathway analysis of the RNA-seq data suggested MMPs were significantly dysregulated in progesterone-exposed engineered ECM. Increased expression of active MMP2 was confirmed in the progesterone-exposed engineered ECM. In summary, progesterone increased the softness of the ECM, which was correlated with decreased collagen production and altered histology. These results are important for deciphering the role of progesterone in preventing preterm birth.

Solid electrolytes are crucial for the development of solid state batteries. Among different types of solid electrolytes, poly(ethylene oxide) (PEO)-based polymer electrolytes have attracted extensive attention owing to their excellent flexibility and easiness for processing. However, their relatively low ionic conductivities and electrochemical instability above 4 V limit their applications in batteries with high energy density. Herein, we prepared poly(vinylidene fluoride) (PVDF) polymer electrolytes with an organic plasticizer, which possesses compatibility with 4 V cathode and high ionic conductivity (1.2 × 10 -4 S/cm) at room temperature. We also revealed the importance of plasticizer content to the ionic conductivity. To address weak mechanical strength of the PVDF electrolyte with plasticizer, we introduced palygorskite ((Mg,Al) 2 Si 4 O 10 (OH)) nanowires as a new ceramic filler to form composite solid electrolytes (CPE), which greatly enhances both stiffness and toughness of PVDF-based polymer electrolyte. With 5 wt % of palygorskite nanowires, not only does the elastic modulus of PVDF CPE increase from 9.0 to 96 MPa but also its yield stress is enhanced by 200%. Moreover, numerical modeling uncovers that the strong nanowire-polymer interaction and cross-linking network of nanowires are responsible for such significant enhancement in mechanically robustness. The addition of 5% palygorskite nanowires also enhances transference number of Li + from 0.21 to 0.54 due to interaction between palygorskite and ClO 4 - ions. We further demonstrate full cells based on Li(Ni 1/3 Mn 1/3 Co 1/3 )O 2 (NMC111) cathode, PVDF/palygorskite CPE, and lithium anode, which can be cycled over 200 times at 0.3 C, with 97% capacity retention. Moreover, the PVDF matrix is much less flammable than PEO electrolytes. Our work illustrates that the PVDF/palygorskite CPE is a promising electrolyte for solid state batteries.

Spontaneous preterm birth (SPTB), defined as delivery before 37 weeks' gestation, remains a significant obstetric dilemma even after decades of research in this field. Although trends from 2007 to 2014 showed the rate of preterm birth slightly decreased, the CDC recently reported the rate of preterm birth has increased for two consecutive years since 2014. Currently, 1 in 10 pregnancies in the US still end prematurely. In this chapter, we focus on the "compartment" of the cervix. The goal is to outline the current knowledge of normal cervical structure and function in pregnancy and the current knowledge of how the cervix malfunctions lead to SPTB. We review the mechanisms by which our current interventions are hypothesized to work. Finally, we outline gaps in knowledge and future research directions that may lead to novel and effective interventions to prevent premature cervical failure and SPTB., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

The cervix shortens and softens as its collagen microstructure remodels in preparation for birth. Altered cervical tissue collagen microstructure can contribute to a mechanically weak cervix and premature cervical dilation and delivery. To investigate the local microstructural changes associated with anatomic location and pregnancy, we used second-harmonic generation microscopy to quantify the orientation and spatial distribution of collagen throughout cervical tissue from 4 pregnant and 14 non-pregnant women. Across patients, the alignment and concentration of collagen within the cervix was more variable near the internal os and less variable near the external os. Across anatomic locations, the spatial distribution of collagen within a radial zone adjacent to the inner canal of the cervix was more homogeneous than that of a region comprising the middle and outer radial zones. Two regions with different collagen distribution characteristics were found. The anterior and posterior sections in the outer radial zone were characterized by greater spatial heterogeneity of collagen than that of the rest of the sections. Our findings suggest that the microstructural alignment and distribution of collagen varies with anatomic location within the human cervix. These observed differences in collagen microstructural alignment may reflect local anatomic differences in cervical mechanical loading and function. Our study deepens the understanding of specific microstructural cervical changes in pregnancy and informs investigations of potential mechanisms for normal and premature cervical remodeling., (© 2018 Society for Reproduction and Fertility.)

The mechanical integrity of the soft tissue structures supporting the fetus may play a role in maintaining a healthy pregnancy and triggering the onset of labor. Currently, the level of mechanical loading on the uterus, cervix, and fetal membranes during pregnancy is unknown, and it is hypothesized that the over-stretch of these tissues contributes to the premature onset of contractility, tissue remodeling, and membrane rupture, leading to preterm birth. The purpose of this review article is to introduce and discuss engineering analysis tools to evaluate and predict the mechanical loads on the uterus, cervix, and fetal membranes. Here we will explore the potential of using computational biomechanics and finite element analysis to study the causes of preterm birth and to develop a diagnostic tool that can predict gestational outcome. We will define engineering terms and identify the potential engineering variables that could be used to signal an abnormal pregnancy. We will discuss the translational ability of computational models for the better management of clinical patients. We will also discuss the process of model validation and the limitations of these models. We will explore how we can borrow from parallel engineering fields to push the boundary of patient care so that we can work toward eliminating preterm birth., (Copyright © 2017 Elsevier Inc. All rights reserved.)