scholarly journals Effects of Elastase Digestion on the Murine Vaginal Wall Biaxial Mechanical Response

2018 ◽  
Vol 141 (2) ◽  
Author(s):  
Akinjide R. Akintunde ◽  
Kathryn M. Robison ◽  
Daniel J. Capone ◽  
Laurephile Desrosiers ◽  
Leise R. Knoepp ◽  
...  
Keyword(s):  
Structural Integrity ◽  
Mechanical Response ◽  
Elastic Fiber ◽  
Pelvic Organ ◽  
Vaginal Wall ◽  
Elastic Fibers ◽  
Vaginal Tissue ◽  
Fiber Damage ◽  
Increased Risk ◽  
Before And After

Although the underlying mechanisms of pelvic organ prolapse (POP) remain unknown, disruption of elastic fiber metabolism within the vaginal wall extracellular matrix (ECM) has been highly implicated. It has been hypothesized that elastic fiber fragmentation correlates to decreased structural integrity and increased risk of prolapse; however, the mechanisms by which elastic fiber damage may contribute to prolapse are poorly understood. Furthermore, the role of elastic fibers in normal vaginal wall mechanics has not been fully ascertained. Therefore, the objective of this study is to investigate the contribution of elastic fibers to murine vaginal wall mechanics. Vaginal tissue from C57BL/6 female mice was mechanically tested using biaxial extension–inflation protocols before and after intraluminal exposure to elastase. Elastase digestion induced marked changes in the vaginal geometry, and biaxial mechanical properties, suggesting that elastic fibers may play an important role in vaginal wall mechanical function. Additionally, a constitutive model that considered two diagonal families of collagen fibers with a slight preference toward the circumferential direction described the data reasonably well before and after digestion. The present findings may be important to determine the underlying structural and mechanical mechanisms of POP, and aid in the development of growth and remodeling models for improved assessment and prediction of changes in structure–function relationships with prolapse development.

scholarly journals Effect of vaginal distention on elastic fiber synthesis and matrix degradation in the vaginal wall: potential role in the pathogenesis of pelvic organ prolapse

2008 ◽  
Vol 295 (4) ◽  
pp. R1351-R1358 ◽  
Author(s):  
D. D. Rahn ◽  
J. F. Acevedo ◽  
R. A. Word
Keyword(s):  
Pelvic Organ Prolapse ◽  
Protease Activity ◽  
Potential Role ◽  
Elastic Fiber ◽  
Pelvic Organ ◽  
Vaginal Wall ◽  
Elastic Fibers ◽  
Wild Type ◽  
Fiber Assembly ◽  
Pregnant Mice

Matrix metalloprotease (MMP) activity is increased in the postpartum vagina of wild-type (WT) animals. This degradative activity is also accompanied by a burst in elastic fiber synthesis and assembly. The mechanisms that precipitate these changes are unclear. The goals of this study were to determine how vaginal distention (such as in parturition) affects elastic fiber homeostasis in the vaginal wall and the potential significance of these changes in the pathogenesis of pelvic organ prolapse. Vaginal distention with a balloon simulating parturition resulted in increased MMP-2 and MMP-9 activity in the vaginal wall of nonpregnant and pregnant animals. This was accompanied by visible fragmented and disrupted elastic fibers in the vaginal wall. In nonpregnant animals, the abundant amounts of tropoelastin and fibulin-5 in the vagina were not increased further by distention. In contrast, in pregnant animals, the suppressed levels of both proteins were increased 3-fold after vaginal distention. Distention performed in fibulin-5-deficient ( Fbln5−/−) mice with defective elastic fiber synthesis and assembly induced accelerated pelvic organ prolapse, which never recovered. We conclude that, in pregnant mice, vaginal distention results in increased protease activity in the vaginal wall but also increased synthesis of proteins important for elastic fiber assembly. Distention may thereby contribute to the burst of elastic fiber synthesis in the postpartum vagina. The finding that distention results in accelerated pelvic organ prolapse in Fbln5−/− animals, but not in WT, indicates that elastic fiber synthesis is crucial for recovery of the vaginal wall from distention-induced increases in vaginal protease activity.

scholarly journals Smooth muscle regional contribution to vaginal wall function

2019 ◽  
Vol 9 (4) ◽  
pp. 20190025 ◽  
Author(s):  
Gabrielle L. Clark ◽  
Anastassia P. Pokutta-Paskaleva ◽  
Dylan J. Lawrence ◽  
Sarah H. Lindsey ◽  
Laurephile Desrosiers ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Mechanical Response ◽  
Muscle Tone ◽  
Multiphoton Microscopy ◽  
Treatment Strategies ◽  
Axial Direction ◽  
Pelvic Organ ◽  
Vaginal Wall ◽  
Vaginal Tissue ◽  
Underlying Mechanisms

Pelvic organ prolapse is characterized as the descent of the pelvic organs into the vaginal canal. In the USA, there is a 12% lifetime risk for requiring surgical intervention. Although vaginal childbirth is a well-established risk factor for prolapse, the underlying mechanisms are not fully understood. Decreased smooth muscle organization, composition and maximum muscle tone are characteristics of prolapsed vaginal tissue. Maximum muscle tone of the vaginal wall was previously investigated in the circumferential or axial direction under uniaxial loading; however, the vaginal wall is subjected to multiaxial loads. Further, the contribution of vaginal smooth muscle basal (resting) tone to mechanical function remains undetermined. The objectives of this study were to determine the contribution of smooth muscle basal and maximum tone to the regional biaxial mechanical behaviour of the murine vagina. Vaginal tissue from C57BL/6 mice was subjected to extension–inflation protocols ( n = 10) with and without basal smooth muscle tone. Maximum tone was induced with KCl under various circumferential ( n = 5) and axial ( n = 5) loading conditions. The microstructure was visualized with multiphoton microscopy ( n = 1), multiaxial histology ( n = 4) and multiaxial immunohistochemistry ( n = 4). Smooth muscle basal tone decreased material stiffness and increased anisotropy. In addition, maximum vaginal tone was decreased with increasing intraluminal pressures. This study demonstrated that vaginal muscle tone contributed to the biaxial mechanical response of murine vaginal tissue. This may be important in further elucidating the underlying mechanisms of prolapse, in order to improve current preventative and treatment strategies.

scholarly journals Clinical Relevance of Elastin in the Structure and Function of Skin

2021 ◽  
Author(s):  
Leslie Baumann ◽  
Eric F Bernstein ◽  
Anthony S Weiss ◽  
Damien Bates ◽  
Shannon Humphrey ◽  
...  
Keyword(s):  
Wound Healing ◽  
Clinical Relevance ◽  
Structural Integrity ◽  
Elastic Fiber ◽  
Subcutaneous Fat ◽  
Structure And Function ◽  
Fiber Formation ◽  
Elastic Fibers ◽  
Superficial Dermis ◽  
And Function

Abstract Elastin is the main component of elastic fibers, which provide stretch, recoil, and elasticity to the skin. Normal levels of elastic fiber production, organization, and integration with other cutaneous extracellular matrix proteins, proteoglycans, and glycosaminoglycans are integral to maintaining healthy skin structure, function, and youthful appearance. Although elastin has very low turnover, its production decreases after individuals reach maturity and it is susceptible to damage from many factors. With advancing age and exposure to environmental insults, elastic fibers degrade. This degradation contributes to the loss of the skin’s structural integrity; combined with subcutaneous fat loss, this results in looser, sagging skin, causing undesirable changes in appearance. The most dramatic changes occur in chronically sun-exposed skin, which displays sharply altered amounts and arrangements of cutaneous elastic fibers, decreased fine elastic fibers in the superficial dermis connecting to the epidermis, and replacement of the normal collagen-rich superficial dermis with abnormal clumps of solar elastosis material. Disruption of elastic fiber networks also leads to undesirable characteristics in wound healing, and the worsening structure and appearance of scars and stretch marks. Identifying ways to replenish elastin and elastic fibers should improve the skin’s appearance, texture, resiliency, and wound-healing capabilities. However, few therapies are capable of repairing elastic fibers or substantially reorganizing the elastin/microfibril network. This review describes the clinical relevance of elastin in the context of the structure and function of healthy and aging skin, wound healing, and scars and introduces new approaches being developed to target elastin production and elastic fiber formation.

Computational Modeling of Anterior and Posterior Pelvic Organ Prolapse (POP)

2016 ◽  
Author(s):  
Arnab Chanda ◽  
Vinu Unnikrishnan ◽  
Holly E. Richter ◽  
Mark E. Lockhart
Keyword(s):  
Pelvic Organ Prolapse ◽  
Urinary Bladder ◽  
High Stress ◽  
Significant Proportion ◽  
Pelvic Organ ◽  
Vaginal Wall ◽  
Vaginal Tissue ◽  
Bladder Filling ◽  
Vaginal Length ◽  
Vaginal Canal

Pelvic Organ Prolapse (POP) is a condition of the female pelvic system suffered by a significant proportion of women in the U.S. and more across the globe, every year. POP is caused by the weakening of the pelvic floor muscles and musculo-connective tissues due to child birth, menopause and morbid obesity. Prolapse of the pelvic organs namely the urinary bladder, uterus, and rectum into the vaginal canal can cause vaginal discomfort, strained urination or defecation, and sexual dysfunction. To date, success rates of native tissue POP surgeries vary from 50–70% depending on the definition of cure and time-point of assessment. A better understanding of the mechanics of prolapse may lead to improvement in surgical outcomes. In the current work, the mechanics of progression of anterior and posterior vaginal prolapse were modeled to understand the effect of bladder fill and posterior vaginal stresses using computational approaches. A realistic and full-scale female pelvic system model, comprised of the urinary bladder, vaginal canal, uterus, rectum, and fascial connective tissue, was developed using image segmentation methods. All of the relevant loads and boundary conditions were applied based on a comprehensive study of the anatomy and functional morphology of the female pelvis. Hyperelastic material models were adopted to characterize all pelvic tissues, and a non-linear analysis was invoked. In the first set of simulations, a realistic bladder filling and vaginal tissue stiffening in prolapse were modeled and their effects on the anterior vaginal wall (AVW) were estimated in terms of the induced stresses, strains and displacements. The degree of bladder filling was found to be a strong indicator of stress build-up on the AVW. Also, vaginal tissue stiffening was found to increase the size of the high stress zone on the AVW. The second simulation consisted of modeling the different degrees of posterior vaginal wall (PVW) prolapse, in the presence of an average abdominal pressure. The vaginal length was segmented into four sections to study the localized stresses and strains. Also, a clinically well-known phenomena known as the kneeling effect was observed with the PVW in which the vaginal wall displaces away from the rectum and downward towards the vaginal hiatus. All of these results have relevant clinical implications and may provide important perspective for better understanding the mechanics of POP pathophysiology.

scholarly journals Elastic Fibers and Large Artery Mechanics in Animal Models of Development and Disease

2018 ◽  
Vol 140 (2) ◽  
Author(s):  
Maria Gabriela Espinosa ◽  
Marius Catalin Staiculescu ◽  
Jungsil Kim ◽  
Eric Marin ◽  
Jessica E. Wagenseil
Keyword(s):  
Animal Models ◽  
Mechanical Behavior ◽  
Computational Models ◽  
Mechanical Response ◽  
Elastic Fiber ◽  
High Stress ◽  
Elastic Fibers ◽  
Large Artery ◽  
Fiber Network ◽  
Pulsatile Pressure

Development of a closed circulatory system requires that large arteries adapt to the mechanical demands of high, pulsatile pressure. Elastin and collagen uniquely address these design criteria in the low and high stress regimes, resulting in a nonlinear mechanical response. Elastin is the core component of elastic fibers, which provide the artery wall with energy storage and recoil. The integrity of the elastic fiber network is affected by component insufficiency or disorganization, leading to an array of vascular pathologies and compromised mechanical behavior. In this review, we discuss how elastic fibers are formed and how they adapt in development and disease. We discuss elastic fiber contributions to arterial mechanical behavior and remodeling. We primarily present data from mouse models with elastic fiber deficiencies, but suggest that alternate small animal models may have unique experimental advantages and the potential to provide new insights. Advanced ultrastructural and biomechanical data are constantly being used to update computational models of arterial mechanics. We discuss the progression from early phenomenological models to microstructurally motivated strain energy functions for both collagen and elastic fiber networks. Although many current models individually account for arterial adaptation, complex geometries, and fluid–solid interactions (FSIs), future models will need to include an even greater number of factors and interactions in the complex system. Among these factors, we identify the need to revisit the role of time dependence and axial growth and remodeling in large artery mechanics, especially in cardiovascular diseases that affect the mechanical integrity of the elastic fibers.

scholarly journals Progressive Microstructural Deterioration Dictates Evolving Biomechanical Dysfunction in the Marfan Aorta

2021 ◽  
Vol 8 ◽  
Author(s):  
Cristina Cavinato ◽  
Minghao Chen ◽  
Dar Weiss ◽  
Maria Jesús Ruiz-Rodríguez ◽  
Martin A. Schwartz ◽  
...  
Keyword(s):  
Structural Integrity ◽  
Ex Vivo ◽  
Elastic Fiber ◽  
Three Dimensional ◽  
Microstructural Characterization ◽  
Aortic Aneurysms ◽  
Elastic Fibers ◽  
Cell Phenotype ◽  
Medial Degeneration ◽  
Fibrillin 1

Medial deterioration leading to thoracic aortic aneurysms arises from multiple causes, chief among them mutations to the gene that encodes fibrillin-1 and leads to Marfan syndrome. Fibrillin-1 microfibrils associate with elastin to form elastic fibers, which are essential structural, functional, and instructional components of the normal aortic wall. Compromised elastic fibers adversely impact overall structural integrity and alter smooth muscle cell phenotype. Despite significant progress in characterizing clinical, histopathological, and mechanical aspects of fibrillin-1 related aortopathies, a direct correlation between the progression of microstructural defects and the associated mechanical properties that dictate aortic functionality remains wanting. In this paper, age-matched wild-type, Fbn1C1041G/+, and Fbn1mgR/mgR mouse models were selected to represent three stages of increasing severity of the Marfan aortic phenotype. Ex vivo multiphoton imaging and biaxial mechanical testing of the ascending and descending thoracic aorta under physiological loading conditions demonstrated that elastic fiber defects, collagen fiber remodeling, and cell reorganization increase with increasing dilatation. Three-dimensional microstructural characterization further revealed radial patterns of medial degeneration that become more uniform with increasing dilatation while correlating strongly with increased circumferential material stiffness and decreased elastic energy storage, both of which comprise aortic functionality.

Mismatches in Stiffness Between the Vagina and Transvaginal Mesh Lead to Stress Concentrations Near an Anterior Wall Incision

2013 ◽  
Author(s):  
James Thunes ◽  
Siladitya Pal ◽  
Pamela Moalli ◽  
Steve Abramowitch ◽  
Spandan Maiti
Keyword(s):  
Pelvic Organ ◽  
Anterior Wall ◽  
Synthetic Mesh ◽  
Vaginal Wall ◽  
Common Complication ◽  
Stress Concentrations ◽  
Vaginal Tissue ◽  
Additional Surgery ◽  
High Incidence ◽  
Trans Vaginal Mesh

Trans-vaginal synthetic meshes have been commonly used to treat pelvic organ prolapse. Recently however, concerns related to the use of trans-vaginal mesh have arisen due to the high incidence of complications. The FDA received more than 3000 reports of complications related to these procedures between 2008 and 2010. Of the women who undergo this procedure, approximately 30% will require additional surgery within 4 years [1]. The most common complication reported was an erosion of the vaginal wall [2]. We hypothesize that mismatch between the mechanical properties of the vaginal tissue and the synthetic mesh lead to higher stresses in the vaginal tissue and subsequently to a higher risk of mesh erosion.

scholarly journals Changes of Pelvic Organ Prolapse Symptoms and Quality of Life One Year After Pessary Fitting

2021 ◽  
Author(s):  
Tahereh Eftekhar ◽  
Zinat Ghanbari ◽  
Leila Pourali ◽  
Maryam Deldar Pesikhani ◽  
Soodabeh Darvish ◽  
...  
Keyword(s):  
Pelvic Organ Prolapse ◽  
Pelvic Floor ◽  
Significant Proportion ◽  
Pelvic Organ ◽  
Vaginal Wall ◽  
Sexually Active ◽  
Sexual Symptoms ◽  
Before And After ◽  
Prolapse Symptoms ◽  
One Year

Pelvic organ prolapse (POP) is the descend of pelvic organs, including the uterus, bladder, and rectum, to the vaginal wall. Patients with POP may present with symptoms such as vaginal bulging with other symptoms like urinary, defecatory, or sexual dysfunction. This study was conducted to evaluate the changes of POP symptoms one year after pessary fitting. Patients with symptomatic pelvic organ prolapse who presented to the pelvic floor clinic of an academic hospital between August 2016 and April 2019 were considered. Pelvic organ prolapse symptoms, including urinary, defecatory, sexual, and bulging symptoms, were recorded before and one year after pessary fitting. Pelvic floor distress inventory (PFDI)-20 and pelvic floor impact questionnaire-7 (PFIQ-7) were evaluated before and after treatment for all subjects. We analyzed the characteristics of 110 patients who used the pessary for 12 months. At the baseline, the most common prolapse symptoms were vaginal bulging and pelvic pressure. All urinary, defecatory, and sexual symptoms significantly improved one year after regular pessary use (P<0.001). Changes in PFDI-20 and PFIQ-7 before and after pessary use showed a significant improvement in both frequency and satisfaction of sexual function (P<0.001). The study showed significant improvement in bulging, urinary, and defecatory symptoms. Although the majority of patients were not sexually active, a significant proportion of sexually active patients reported an increase in sexual satisfaction.

scholarly journals Biomechanical properties of the vaginal wall: effect of pregnancy, elastic fiber deficiency, and pelvic organ prolapse

2008 ◽  
Vol 198 (5) ◽  
pp. 590.e1-590.e6 ◽  
Author(s):  
David D. Rahn ◽  
Matthew D. Ruff ◽  
Spencer A. Brown ◽  
Harry F. Tibbals ◽  
R. Ann Word
Keyword(s):  
Pelvic Organ Prolapse ◽  
Elastic Fiber ◽  
Biomechanical Properties ◽  
Pelvic Organ ◽  
Vaginal Wall ◽  
Wall Effect
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