Biomechanical behaviour of ankle ligaments: constitutive formulation and numerical modelling

This study was aimed at the definition of a constitutive formulation of ankle ligaments and of a procedure for the constitutive parameters evaluation, for the biomechanical analysis by means of numerical models. To interpret the typical features of ligaments mechanical response, as anisotropic configuration, geometric non-linearity, non-linear elasticity and time-dependent behaviour, a specific fibre-reinforced visco-hyperelastic model is provided. The identification of constitutive parameters is performed by a stochastic–deterministic procedure that minimises the discrepancy between experimental and computational results. A preliminary evaluation of parameters is performed by analytical models in order to define reference values. Afterwards, solid models are developed to consider the complex histo-morphometric configuration of samples as a basis for the definition of numerical models. The results obtained are adopted for upgrading parameter values by comparison with specific mechanical tests. Assuming the new parameters set, the final numerical results are compared with the overall set of experimental data, to assess the reliability and efficacy of the analysis developed for the interpretation of the mechanical response of ankle ligaments.     

Advances in the understanding of sress urinary incontinence and the promise of stem-cell therapy

The middle urethra and external urethral sphincter are the focus in management of stress urinary incontinence, and recent cellular-therapy research suggests a new paradigm in treatment. Cell-based therapies are most often described as using autologous multipotent stem cells procured from bone marrow in procedures that may be painful, require anesthesia, and yield low numbers of mesenchymal stem cells upon processing. In contrast, muscleand adipose-derived stem cells can be obtained easily in large quantities under local anesthesia. Instead of lifting the urethra with a sling or bulking up the urethral sphincter with collagen, we now have the potential to restore function with the use of autologous stem cells.     

Urethral closure mechanisms during sneezing-induced stress in anesthetized female cats

During stress-induced increase in abdominal pressure, urinary continence is maintained by urethral closure mechanisms. Active urethral response has been studied in dogs and rats. Such an active urethral response is also believed to occur in humans during stress events. We aimed to investigate urethral closure mechanisms during sneezing in cats. Urethral pressures along the urethra (UP1-UP4), with microtip transducer catheters with UP4 positioned in the distal urethra where the external urethral sphincter (EUS) is located, and intravesical pressure were measured, and abdominal wall, anal sphincter (AS), levator ani (LA), and EUS electromyograms (EMGs) were recorded during sneezing under closed-abdomen and open-abdomen conditions in eight anesthetized adult female cats. Proximal and middle urethral response induced by sneezing was not different from bladder response. Distal urethral response was greater compared with proximal and middle urethral and bladder response. In the open-abdomen bladder, proximal and middle urethral responses were similarly decreased and distal urethral response was unchanged compared with the closed-abdomen bladder. Bladder and urethral responses were positively correlated to sneeze strength. EUS, LA, and AS EMGs increased during sneezing. No urine leakage was observed, regardless of the strength of sneeze. In cats urethral closure mechanisms are partly passive in the proximal and middle urethra and involve an active component in the distal urethra that is believed to result from EUS and possibly LA contractions. Because central serotonin exerts similar effects on the lower urinary tract in cats and humans, the cat may represent a relevant model for pharmacological studies on continence mechanisms.     

Evaluation and surgical management of intrinsic sphincter deficiency after radical prostatectomy

Urinary incontinence following prostatectomy is usually due to intrinsic sphincter deficiency and is often referred to as post-prostatectomy incontinence (PPI). The male sling is an effective minimally invasive procedure for low volume PPI. Although the male sling procedure is becoming increasingly popular, the artificial urinary sphincter (AUS) remains the gold standard. Placement of the AUS cuff using the transcorporal technique salvages patients with urethral atrophy as well as prior AUS erosion or infection. As the surgical options for PPI expand, it is important to analyze the outcomes with contemporary surgical techniques and to develop an algorithm for procedure selection.     

Spinning top urethra and lower urinary tract dysfunction in a young female

Spinning top urethra (STU) denotes a particular urethral configuration that is a dilated posterior urethra mainly seen in young girls or women. STU deformity arises secondary to detrusor instability, leading to a rise the intravesical pressure against a closed sphincter. We describe a case of spinning top urethra in a 30-year-old woman who presented with lower urinary tract symptoms and left flank pain.     

Urethral lumen occlusion by artificial sphincteric device: Evaluation of degraded tissues effects

Urinary incontinence can be surgically treated by means of artificial sphincters, based on a cuff that provides a pressure around the urethra to occlude the lumen. Considering the frequent access of elderly patients to this surgical practice, tissue degradation phenomena must be investigated, since they could affect treatment reliability and durability. The potential degradation can be interpreted considering a variation within soft tissue constitutive formulation, by means of a correlation between mechanical properties and tissues ageing. The overall compressibility varies, as characteristics aspect of soft tissue mechanical response with age, as well as the stiffness. The investigation is performed by means of a three dimensional numerical model of the urethral duct. The effects of the interaction phenomenon with a cuff is interpreted considering the changes, within the constitutive models, of the basic parameters that define the potential degradation process. The deformation related to compressibility is recalled, ranging between ten and fifty percent in dependence on the degradation level considered. This parameter, reported mostly as representative of the aging effect, shows a large variation that confirms the relevance of the investigation performed toward a sensitivity of the mechanical response of the urethral duct referred to the lumen occlusion.     

Urethral closure mechanisms under sneeze-induced stress condition in rats: a new animal model for evaluation of stress urinary incontinence

The urethral closure mechanism under a stress condition induced by sneezing was investigated in urethane-anesthetized female rats. During sneezing, while the responses measured by microtip transducer catheters in the proximal and middle parts of the urethra increased, the response in the proximal urethra was almost negligible when the bladder response was subtracted from the urethral response or when the abdomen was opened. In contrast, the response in the middle urethra during sneezing was still observed after subtracting the bladder response or after opening the abdomen. These responses in the middle urethra during sneezing were significantly reduced approximately 80% by bilateral transection of the pudendal nerves and the nerves to the iliococcygeous and pubococcygeous muscles but not by transection of the visceral branches of the pelvic nerves and hypogastric nerves. The sneeze leak point pressure was also measured to investigate the role of active urethral closure mechanisms in maintaining total urethral resistance against sneeze-induced urinary incontinence. In sham-operated rats, no urinary leakage was observed during sneeze, which produced an increase of intravesical pressure up to 37 +/- 2.2 cmH2O. However, in nerve-transected rats urinary leakage was observed when the intravesical pressure during sneezing exceeded 16.3 +/- 2.1 cmH2O. These results indicate that during sneezing, pressure increases elicited by reflex contractions of external urethral sphincter and pelvic floor muscles occur in the middle portion of the urethra. These reflexes in addition to passive transmission of increased abdominal pressure significantly contribute to urinary continence mechanisms under a sneeze-induced stress condition.     

Effects of Materials of Cementless Femoral Stem on the Functional Adaptation of Bone

The objective of this paper is to identify the effects of materials of cementless femoral stem on the functional adaptive behaviors of bone.The remodeling behaviors of a two-dimensional simplified model of cementless hip prosthesis with stiff stem,flexible 'iso-elastic' stem,one-dimensional Functionally Graded Material (FGM) stem and two-dimensional FGM stem for the period of four years after prosthesis replacement were quantified by incorporating the bone remodeling algorithm with finite element analysis.The distributions of bone density,von Mises stress,and interface shear stress were obtained.The results show that two-dimensional FGM stem may produce more mechanical stimuli and more uniform interface shear stress compared with the stems made of other materials,thus the host bone is well preserved.Accordingly,the two-dimensional FGM stem is an appropriate femoral implant from a biomechanical point of view.The numerical simulation in this paper can provide a quantitative computational paradigm for the changes of bone morphology caused by implants,which can help to improve the design of implant to reduce stress shielding and the risk of bone-prosthesis interface failure.     

A new method to correlate histology with biomechanical properties in urethral tissue. An in-vitro study using light microscopy and scanning acoustic microscopy

When surveying the classical biomechanical theory of flow and resistance, the passive elastic properties of the urethra seems to be important for the transport of urine though the urethra. The aim of this study was to show that scanning acoustic microscopy (SAM) is a suitable methodology for investigating elastic properties of the urethra, and that it can be used to correlate elastic properties to histological areas. One 40 kg female pig and one 2 kg male rabbit comprised the material. A SAM2000 was used at a working frequency of 1000 MHz. Sections of nominal 3 micrometer thickness fixed urethral tissue were prepared for SAM and stained for light microscopy. The histological layers of the urethra were evident in the SAM image, and showed highly variable values of elastic properties. The layers seen with SAM correlated well with those seen with light microscopy. In conclusion, we have provided the first images of the microelastic properties of the urethra and correlated them to histology.     

Distribution,shape, and immunohistochemical characteristics of serotonin-immunoreactive neuroendocrine cells in the urethra and periurethral genital organs in mice

The aim of this study is to clarify the disibution, shape, and immunohistochemical characteristics of serotonin-immunoreactive neuroendocrine cells (SIR-NECs) in mouse prostate and in the surrounding genital organs by histological and immunohistochemical analysis of the light microscopic serial sections of urethra. We collected lower urinary tracts from 13-week-old mice and observed the distribution pattern and shape of the SIR-NECs by serial light microscopy. The organs on the sections were divided into three anatomical zones to clarify the distribution pattern of SIR-NECs: (1) zone A, the ducts near the prostatic urethra; (2) zone B, the ducts outside the urethral sphincter; and (3) zone C, the acinus areas. Sections were double immune-stained with antibodies against serotonin and one of neuroendocrine-related factors (NRFs), including 10 neural cell markers and eight neurotransmitters, and also 4′,6-diamino-2-phenylindole (DAPI). In addition, SIR-NECs were double immune-stained with antibodies against cytokeratin 5 (CK5) and p63, together with DAPI. SIR-NECs were mostly localized in zone A, and no SIR-NECs were observed in zone C. The proportion of flask-shaped SIR-NECs was approximately 15% in zones A and B. No flask-shaped SIR-NECs were observed in urethral epithelia. The NRFs co-localized with SIR-NEC were calcitonin gene-related peptide, CD56, chromogranin A, neuron-specific enolase, neuron cytoplastic protein 9.5, and synaptophysin (72.3%, 73.2%, 88.9%, 92.3%, 91.7%, and 81.9%, respectively). CK5 and p63 were not co-localized with SIR-NECs.　In this study, SIR-NEC of the urethra and the surrounding genital organs was ubiquitous in the urethra and the ducts near the urethra and co-expressed specific nerve-related NRFs.

     

A biomechanical approach to the analysis of methods and procedures of bariatric surgery

Bariatric surgery includes a variety of procedures that are performed on obese people and aim at decreasing the intake of food and calories. This goal is usually pursued by reducing stomach capacity and/or absorbing capability. Adjustable gastric banding is the most common and successful operation. In general, bariatric surgical procedures are effective, but are often associated with major complications.Surgical procedure and post-surgical conformation of the stomach are usually defined on clinical and surgical basis only. Instead, the optimal configuration should be identified by analyzing the mechanical functionality of the stomach and the surrounding structures, and the relationship between food intake, nutrient adsorption, mechanical stimulation of stomach wall and feeling of satiety.A novel approach to bariatric surgery is required, integrating competences in the areas of biomechanics, physiology and surgery, based on a strong interaction between engineers and clinicians. Preliminary results from coupled experimental and computational investigations are here reported. The analyses aim to develop computational tools for the investigation of stomach mechanical functionality in pre- and post-surgical conformations.     

Biomechanical Study on the Novel Biomimetic Hemi-Pelvis Prosthesis

A pelvic endoprosthesis is the primary means of pelvic reconstruction after internal hemipelvectomy. In this study, a novel biomimetic hemipelvic prosthesis, including an artificial ilium, an artificial acetabulum, and an artificial pubis, was developed. A Finite Element Method （FEM） was carried out to investigate the biomechanical performance of a pelvis reconstructed with biomimetic hemipelvic prosthesis. Two models, including the reconstructed pelvis and the original pelvis （control model）, were established according to the geometry from CT data of a human male patient with pelvic bone sarcomas. The FE models predict that the biomeehanical function of the pelvic ring can be reestablished using this prosthesis. Results show that the body force loaded on the S 1 vertebra is restored and transferred towards the sacro-iliac joint, and along the ilium onto the bearing surface of the artificial ilium, then to the artificial acetabulum and pubis. Von Mises stresses observed in this reconstructed pelvis model are still within a low and elastic range below the yielding strength of cortical bone and Ti6A14V. The values of deformation and strain of the reconstructed pelvis are close to the data obtained in the original pelvis. With the partial replacement of the pubis, little influence is found towards the pubis symphysis. However, the interface between the prosthesis and pelvic bone may become the critical part of the reconstructed pelvis due to the discontinuity in the material properties, which results in stress shielding and deformation constraining. So a biomimetic flexible connection or inter layer to release the deformation of pelvis is suggested in future designing.     

Systematic review and meta-analysis of the biomechanical properties of the human dura mater applicable in computational human head models

Accurate biomechanical properties of the human dura mater are required for computational models and to fabricate artificial substitutes for transplantation and surgical training purposes. Here, a systematic literature review was performed to summarize the biomechanical properties of the human dura mater that are reported in the literature. Furthermore, anthropometric data, information regarding the mechanically tested samples, and specifications with respect to the used mechanical testing setup were extracted. A meta-analysis was performed to obtain the pooled mean estimate for the elastic modulus, ultimate tensile strength, and strain at maximum force. A total of 17 studies were deemed eligible, which focused on human cranial and spinal dura mater in 13 and 4 cases, respectively. Pooled mean estimates for the elastic modulus (n?=?448), the ultimate tensile strength (n?=?448), and the strain at maximum force (n?=?431) of 68.1 MPa, 7.3 MPa and 14.4% were observed for native cranial dura mater. Gaps in the literature related to the extracted data were identified and future directions for mechanical characterizations of human dura mater were formulated. The main conclusion is that the most commonly used elastic modulus value of 31.5 MPa for the simulation of the human cranial dura mater in computational head models is likely an underestimation and an oversimplification given the morphological diversity of the tissue in different brain regions. Based on the here provided meta-analysis, a stiffer linear elastic modulus of 68 MPa was observed instead. However, further experimental data are essential to confirm its validity.

     

Effect of a 5-HT1A receptor agonist (8-OH-DPAT) on external urethral sphincter activity in a rat model of pudendal nerve injury

Although serotonergic agents have been used to treat patients with stress urinary incontinence, the characteristics of the external urethral sphincter (EUS) activity activated by 5-HT receptors have not been extensively studied. This study examined the effects of the 5-HT(1A) receptor agonist, 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT), on the EUS-electromyography and resistance of the urethra in a rat model with bilateral pudendal nerve injury (BPNI). Two measurements were utilized to assess the effects of the drug on bladder and urethral functions: the simultaneous recordings of transvesical pressure under isovolumetric conditions [isovolumetric intravesical pressure (IVP)] and urethral perfusion pressure, and the simultaneous recordings of IVP during continuously isotonic transvesical infusion with an open urethra (isotonic IVP) and EUS-electromyography. This study also evaluated the urethral continence using leak point pressure testing. The urethral perfusion pressure and leak point pressure measurements of BPNI rats reveal that 8-OH-DPAT significantly increased urethral resistance during the bladder storage phase, yet decreased resistance during the voiding phase. The entire EUS burst period was significantly prolonged, within which the average silent period increased and the frequency of burst discharges decreased. 8-OH-DPAT also improved the voiding efficiency, as evidenced by the detection of decreases in the contraction amplitude and residual volume, with increases in contraction duration and voided volume. These findings suggest that 8-OH-DPAT not only improved continence function, but also elevated the voiding function in a BPNI rat model.     

Increased renal ENaC subunits and sodium retention in rats with chronic heart failure

The goal of this study was to examine acute morphological changes, edema, muscle damage, inflammation, and hypoxia in urethral and vaginal tissues with increasing duration of vaginal distension (VD) in a rat model. Twenty-nine virgin Sprague-Dawley rats underwent VD under anesthesia with the use of a modified Foley catheter inserted into the vagina and filled with saline for 0, 1, 4, or 6 h. Control animals were anesthetized for 4 h without catheter placement. Urogenital organs were harvested after intracardiac perfusion of fixative. Tissues were embedded, sectioned, and stained with Masson's trichrome or hematoxylin and eosin stains. Regions of hypoxia were measured by hypoxyprobe-1 immunohistochemistry. Within 1 h of VD, the urethra became vertically elongated and displaced anteriorly. Edema was most prominent in the external urethral sphincter (EUS) and urethral/vaginal septum within 4 h of VD, while muscle disruption and fragmentation of the EUS occurred after 6 h. Inflammatory damage was characterized by the presence of polymorphonuclear leukocytes in vessels and tissues after 4 h of VD, with the greatest degree of infiltration occurring in the EUS. Hypoxia localized mostly to the vaginal lamina propria, urethral smooth muscle, and EUS within 4 h of VD. Increasing duration of VD caused progressively greater tissue edema, muscle damage, and morphological changes in the urethra and vagina. The EUS underwent the greatest insult, demonstrating its vulnerability to childbirth injury.     

Ontogeny of the male urethra: theory of endodermal differentiation

The most widely accepted mechanism of male urethral development proposes that the urethral plate is elevated by urethral folds which fuse ventrally in a proximal-to-distal sequence. Unlike its proximal counterpart, the urethra which forms within the glans is lined by a stratified squamous epithelium and has a more controversial development. One theory supports the idea that fusion of the urethral folds extends all the way to the tip of the glans. Another theory suggests that a solid ectodermal in-growth of epidermis canalizes the glandar urethra. We hypothesized that the use of immunohistochemical staining and tissue recombinant grafting would delineate the epithelia involved and lend clues to their origin. Thirty-six human fetal phallic specimens of gestational ages 5-22 weeks were sectioned and stained immunohistochemically with antibodies raised against different cytokeratins. Evaluation of the sections showed that the urethral plate, an extension of the urogenital sinus, extended to the tip of the phallus and maintained patency and continuity throughout the process of urethral development. The entire urethra, including the glans portion, was formed by dorsal extension and disintegration of the urethral plate combined with ventral growth and fusion of the urethral folds. Sections of the distal glandar urethra showed no evidence of a solid ectodermal ingrowth. Rather, immunostaining results at different ages suggested differentiation of the endodermal urethral plate into a stratified squamous epithelium. To determine whether urothelium could be induced to express a stratified squamous phenotype, mouse fetal bladder epithelium was combined with rat fetal genital tubercle mesenchyme and grown under the renal capsule of athymic mice. The bladder epithelium differentiated into a stratified squamous epithelium. Thus, proper mesenchymal signaling may induce differentiation of urothelium into a stratified squamous phenotype, such as during development of the urethra of the glans penis.     

Sex-Related Differences in Urethra Development in Human Embryos

Virtually no information on the chronology of prenatal development of the human urinary tract and the sex-related differences in the emergence of urinary tract topography during embryonic development is presently available. The aim of our work was to study sex-related differences in urethra development in human embryos and early fetuses. Forty-nine preparations of human embryos and early fetuses without external signs of anatomical abnormalities were studied in order to achieve the aim and fulfill the objectives of the study. Embryos and early fetuses were divided into six groups according to gestational age and parietococcygeal length. The complex of adequate methods of morphological research used in the study included preparation and microscopy of serial histological and anatomical sections of human embryos, including female and male urinary tracts, preparation of 3D-reconstruction models, and morphometry. The formation of prostatic urethra, a derivative of the urogenital sinus, was shown to occur at the beginning of the ninth week of embryogenesis, and the primordium of the internal sphincter of the urinary tract was formed at the end of the tenth week. Formation of the terminal part of spongy urethra took place during weeks 10–11 and involved funnel-like protrusion of the ectoderm from the top of the balanus towards the urethra lumen. The secondary ventral displacement of the urethral opening does not occur in female fetuses, and, therefore, only the prostatic urethra is a homolog of the female urinary tract. The pelvic part of the urogenital sinus was transformed into the prostatic urethra and the membranous urethra of the male at the end of the first stage of fetal development. Elongation of the genital tubercle (a penis primordium) and formation of the urethral ridge walls that involved the urogenital folds occurred at the same time.     

Experimental validation of a finite element model of the proximal femur using digital image correlation and a composite bone model

Computational biomechanical models are useful tools for supporting orthopedic implant design and surgical decision making, but because they are a simplification of the clinical scenario they must be carefully validated to ensure that they are still representative. The goal of this study was to assess the validity of the generation process of a structural finite element model of the proximal femur employing the digital image correlation (DIC) strain measurement technique. A finite element analysis model of the proximal femur subjected to gait loading was generated from a CT scan of an analog composite femur, and its predicted mechanical behavior was compared with an experimental model. Whereas previous studies have employed strain gauging to obtain discreet point data for validation, in this study DIC was used for full field quantified comparison of the predicted and experimentally measured strains. The strain predicted by the computational model was in good agreement with experimental measurements, with R(2) correlation values from 0.83 to 0.92 between the simulation and the tests. The sensitivity and repeatability of the strain measurements were comparable to or better than values reported in the literature for other DIC tests on tissue specimens. The experimental-model correlation was in the same range as values obtained from strain gauging, but the DIC technique produced more detailed, full field data and is potentially easier to use. As such, the findings supported the validity of the model generation process, giving greater confidence in the model's predictions, and digital image correlation was demonstrated as a useful tool for the validation of biomechanical models.     

Cell lineage analysis demonstrates an endodermal origin of the distal urethra and perineum

Congenital malformations of anorectal and genitourinary (collectively, anogenital) organs occur at a high frequency in humans, however the lineage of cells that gives rise to anogenital organs remains poorly understood. The penile urethra has been reported to develop from two cell populations, with the proximal urethra developing from endoderm and the distal urethra forming from an apical ectodermal invagination, however this has never been tested by direct analysis of cell lineage. During gut development, endodermal cells express Sonic hedgehog (Shh), which is required for normal patterning of digestive and genitourinary organs. We have taken advantage of the properties of Shh expression to genetically label and follow the fate of posterior gut endoderm during anogenital development. We report that the entire urethra, including the distal (glandar) region, is derived from endoderm. Cloacal endoderm also gives rise to the epithelial linings of the bladder, rectum and anterior region of the anus. Surprisingly, the lineage map also revealed an endodermal origin of the perineum, which is the first demonstration that endoderm differentiates into skin. In addition, we fate mapped genital tubercle ectoderm and show that it makes no detectable contribution to the urethra. In males, formation of the urethral tube involves septation of the urethral plate by continued growth of the urorectal septum. Analysis of cell lineage following disruption of androgen signaling revealed that the urethral plate of flutamide-treated males does not undergo this septation event. Instead, urethral plate cells persist to the ventral margin of the tubercle, mimicking the pattern seen in females. Based on these spatial and temporal fate maps, we present a new model for anogenital development and suggest that disruptions at specific developmental time points can account for the association between anorectal and genitourinary defects.     

Pathologic guidelines for orthotopic urinary diversion in women with bladder cancer: a review of the literature

Orthotopic lower urinary tract reconstruction to the native intact urethra following radical cystectomy for bladder cancer was slower to gain clinical acceptance for women than for men. Until the 1990s, little was known about the natural history of urethral involvement by urothelial carcinoma in women with primary bladder cancer. The increasing availability of pathologic data to define the incidence of and risks for urethral involvement in women sparked an increasing interest in orthotopic diversion in female patients. Pathologic guidelines have been suggested to identify women suitable for orthotopic diversion. Preoperative involvement of the bladder neck is a significant risk factor for secondary tumor of the urethra, but is not an absolute contraindication, as long as full-thickness, intraoperative frozen-section analysis demonstrates no tumor involvement of the proximal urethra. Although less common, anterior vaginal wall tumor involvement may be a significant risk factor for urethral tumor involvement. Other pathologic parameters, including tumor multifocality, carcinoma in situ of the bladder, and tumor grade and stage, do not seem to be absolute contraindications. Long-term follow-up is critical for all patients. Women undergoing orthotopic reconstruction, if appropriately selected, should be assured of an oncologically sound operation and good function with their neobladder.