Preclinical Assessment of Tissue Effects by Gastrointestinal Endoscope Tip Temperature.

Background: Endoscope tips are heated by their electrical and illuminating components. During the procedure, they might get in close or even direct contact with intestinal tissues. Objective: To assess endoscope tip and tissue temperature as well as histopathologic changes of gastrointestinal (GI) tissues when exposed to the heated tip of GI endoscopes. Methods: The endoscope tip temperatures of four GI endoscopes were measured for 30 minutes in a temperature-controlled chamber. The temperature of ex vivo porcine GI tissues was measured for 5-, 15-, and 120-minute exposure to endoscope tips within a climate chamber to control environmental factors (simulation of fever as worst-case). Exposed tissues were histopathologically examined afterward. Control samples included untreated mucosa, tissue samples exposed to endoscope tips for 120 minutes, as well as tissue samples thermally coagulated with a bipolar high-frequency probe. Results: Actual endoscope tip temperatures of 59 to 86°C, dependent on the endoscope type, were measured. After 10 to 15 minutes, the maximum temperatures were reached. Maximum tissue temperatures of 44 to 46°C for 5 and 15 minutes, as well as up to 50°C for 120 minutes, were recorded dependent on tissue and endoscope type. No direct heat-induced histopathologic tissue alterations were observed in the 5- and 15-minute samples. Conclusions: Both clinically relevant and a worst-case control were tested. Even though elevated temperatures were recorded, no heat-related tissue alterations were detected. This overall supports the safety profile of GI endoscopy; however, the study findings are limited by the ex vivo setting (no metabolic tissue alterations accessible, no blood flow) and small sample number.

A pilot study on active and passive ex vivo characterisation of the urinary bladder and its impact on three-dimensional modelling.

Insight into the global deformation of the urinary bladder during passive and active phases is crucial for understanding the biomechanics and function of the organ. Therefore, in the present study, the three-dimensional deformations of the porcine urinary bladder were investigated using 10 cameras in ex vivo experiments. Voltages between 20 V and 40 V were applied to induce contraction without outflow (isovolumetric) and against different back pressures (isobaric). The fluid volume in the bladder and the fluid volume pushed out of the bladder in the active state were measured. During filling, a roughly constant pressure of 2.5-4 cmH2O was measured for a large volume range, followed by a steep increase. Overall, the urinary bladder shape changes from elliptical to spherical in the active phase, resulting in a more homogeneous stress field. The active pressure decreases with increasing volume, while the actively generated stress increases up to 65 kPa at the maximum volume examined. Smaller filling volumes and lower back pressures allowed complete emptying, whereas higher back pressures prevent full emptying from larger filling states. Finally, a recently developed three-dimensional model was used to describe the active and passive bladder characteristics in order to qualitatively represent the mechanical properties. Overall, this study provides for the first time a comprehensive experimental data set at organ level that leads to an improved understanding of load transfer mechanisms within the urinary bladder and serves to validate corresponding models.

On multiscale tension-compression asymmetry in skeletal muscle.

Skeletal muscle tissue shows a clear asymmetry with regard to the passive stresses under tensile and compressive deformation, referred to as tension-compression asymmetry (TCA). The present study is the first one reporting on TCA at different length scales, associated with muscle tissue and muscle fibres, respectively. This allows for the first time the comparison of TCA between the tissue and one of its individual components, and thus to identify the length scale at which this phenomenon originates. Not only the passive stress-stretch characteristics were recorded, but also the volume changes during the axial tension and compression experiments. The study reveals clear differences in the characteristics of TCA between fibres and tissue. At tissue level TCA increases non-linearly with increasing deformation and the ratio of tensile to compressive stresses at the same magnitude of strain reaches a value of approximately 130 at 13.5% deformation. At fibre level instead it initially drops to a value of 6 and then rises again to a TCA of 14. At a deformation of 13.5%, the tensile stress is about 6 times higher. Thus, TCA is about 22 times more expressed at tissue than fibre scale. Moreover, the analysis of volume changes revealed little compressibility at tissue scale whereas at fibre level, especially under compressive stress, the volume decreases significantly. The data collected in this study suggests that the extracellular matrix has a distinct role in amplifying the TCA, and leads to more incompressible tissue behaviour. STATEMENT OF SIGNIFICANCE: This article analyses and compares for the first time the tension-compression asymmetry (TCA) displayed by skeletal muscle at tissue and fibre scale. In addition, the volume changes of tissue and fibre specimens with application of passive tensile and compressive loads are studied. The study identifies a key role of the extracellular matrix in establishing the mechanical response of skeletal muscle tissue: It contributes significantly to the passive stress, it is responsible for the major part of tissue-scale TCA and, most probably, prevents/balances the volume changes of muscle fibres during deformation. These new results thus shed light on the origin of TCA and provide new information to be used in microstructure-based approaches to model and simulate skeletal muscle tissue.

Predicting muscle tissue response from calibrated component models and histology-based finite element models.

Skeletal muscle is an anisotropic soft biological tissue composed of muscle fibres embedded in a structurally complex, hierarchically organised extracellular matrix. In a recent work (Kuravi et al., 2021) we have developed 3D finite element models from series of histological sections. Moreover, based on decellularisation of fresh tissue samples, a novel set of experimental data on the direction dependent mechanical properties of collagenous ECM was established (Kohn et al., 2021). Together with existing information on the material properties of single muscle fibres, the combination of these techniques allows computing predictions of the composite tissue response. To this end, an inverse finite element procedure is proposed in the present work to calibrate a constitutive model of the extracellular matrix, and supplementary biaxial tensile tests on fresh and decellularised tissues are performed for model validation. The results of this rigorously predictive and thus unforgiving strategy suggest that the prediction of the tissue response from the individual characteristics of muscle cells and decellularised tissue is only possible within clear limits. While orders of magnitude are well matched, and the qualitative behaviour in a wide range of load cases is largely captured, the existing deviations point at potentially missing components of the model and highlight the incomplete experimental information in bottom-up multiscale approaches to model skeletal muscle tissue.

Location- and layer-dependent biomechanical and microstructural characterisation of the porcine urinary bladder wall.

The knowledge of the mechanical properties of the urinary bladder wall helps to explain its storage and micturition functions in health and disease studies; however, these properties largely remain unknown, especially with regard to its layer-specific characteristics and microstructure. Consequently, this study entails the assessment of the layer-specific differences in the mechanical properties and microstructure of the bladder wall, especially during loading. Accordingly, ninety-two (n=92) samples of porcine urinary bladder walls were mechanically and histologically analysed. Generally, the bladder wall and different tissue layers exhibit a non-linear stress-stretch relationship. In this study, the load transfer mechanisms were not only associated with the wavy structure of muscular and mucosal layers, but also with the entire bladder wall microstructure. Contextually, an interplay between the mucosal and muscular layers could be identified. Therefore, depending on the region and direction, the mucosal layer exhibited a stiffer mechanical response to equi-biaxial loading than that offered by the muscular layer when deformed to stretch levels higher than λ=1.6 to λ=2.2. For smaller stretches, the mucosal layer evinces no significant mechanical reaction, while the muscular layer bears the load. Owing to the orientation of its muscle fibres, the muscular layer shows an increased degree of anisotropy compared to the mucosal layer. Furthermore, the general incompressibility assumption is analysed for different layers by measuring the change in thickness during loading, which indicated a small volume loss.

Biomechanical and microstructural characterisation of the porcine stomach wall: Location- and layer-dependent investigations.

The mechanical properties of the stomach wall help to explain its function of storing, mixing, and emptying in health and disease. However, much remains unknown about its mechanical properties, especially regarding regional heterogeneities and wall microstructure. Consequently, the present study aimed to assess regional differences in the mechanical properties and microstructure of the stomach wall. In general, the stomach wall and the different tissue layers exhibited a nonlinear stress-stretch relationship. Regional differences were found in the mechanical response and the microstructure. The highest stresses of the entire stomach wall in longitudinal direction were found in the corpus (201.5 kPa), where food is ground followed by the antrum (73.1 kPa) and the fundus (26.6 kPa). In contrast, the maximum stresses in circumferential direction were 39.7 kPa, 26.2 kPa, and 15.7 kPa for the antrum, fundus, and corpus, respectively. Independent of the fibre orientation and with respect to the biaxial loading direction, partially clear anisotropic responses were detected in the intact wall and the muscular layer. In contrast, the innermost mucosal layer featured isotropic mechanical characteristics. Pronounced layers of circumferential and longitudinal muscle fibres were found in the fundus only, whereas corpus and antrum contained almost exclusively circumferential orientated muscle fibres. This specific stomach structure mirrors functional differences in the fundus as well as corpus and antrum. Within this study, the load transfer mechanisms, connected with these wavy layers but also in total with the stomach wall's microstructure, are discussed. STATEMENT OF SIGNIFICANCE: This article examines for the first time the layer-specific mechanical and histological properties of the stomach wall attending to the location of the sample. Moreover, both mechanical behaviour and microstructure were explicitly match identifying the heterogeneous characteristics of the stomach. On the one hand, the results of this study contribute to the understanding of stomach mechanics and thus to their functional understanding of stomach motility. On the other hand, they are relevant to the fields of constitutive formulation of stomach tissue, whole stomach mechanics, and stomach-derived scaffolds i.e., tissue-engineering grafts.

Locational and Directional Dependencies of Smooth Muscle Properties in Pig Urinary Bladder.

The urinary bladder is a distensible hollow muscular organ, which allows huge changes in size during absorption, storage and micturition. Pathological alterations of biomechanical properties can lead to bladder dysfunction and loss in quality of life. To understand and treat bladder diseases, the mechanisms of the healthy urinary bladder need to be determined. Thus, a series of studies focused on the detrusor muscle, a layer of urinary bladder made of smooth muscle fibers arranged in longitudinal and circumferential orientation. However, little is known about whether its active muscle properties differ depending on location and direction. This study aimed to investigate the porcine bladder for heterogeneous (six different locations) and anisotropic (longitudinal vs. circumferential) contractile properties including the force-length-(FLR) and force-velocity-relationship (FVR). Therefore, smooth muscle tissue strips with longitudinal and circumferential direction have been prepared from different bladder locations (apex dorsal, apex ventral, body dorsal, body ventral, trigone dorsal, trigone ventral). FLR and FVR have been determined by a series of isometric and isotonic contractions. Additionally, histological analyses were conducted to determine smooth muscle content and fiber orientation. Mechanical and histological examinations were carried out on 94 and 36 samples, respectively. The results showed that maximum active stress (pact ) of the bladder strips was higher in the longitudinal compared to the circumferential direction. This is in line with our histological investigation showing a higher smooth muscle content in the bladder strips in the longitudinal direction. However, normalization of maximum strip force by the cross-sectional area (CSA) of smooth muscle fibers yielded similar smooth muscle maximum stresses (165.4 ± 29.6 kPa), independent of strip direction. Active muscle properties (FLR, FVR) showed no locational differences. The trigone exhibited higher passive stress (ppass ) than the body. Moreover, the bladder exhibited greater ppass in the longitudinal than circumferential direction which might be attributed to its microstructure (more longitudinal arrangement of muscle fibers). This study provides a valuable dataset for the development of constitutive computational models of the healthy urinary bladder. These models are relevant from a medical standpoint, as they contribute to the basic understanding of the function of the bladder in health and disease.

Foot internal stress distribution during impact in barefoot running as function of the strike pattern.

The aim of the present study is to examine the impact absorption mechanism of the foot for different strike patterns (rearfoot, midfoot and forefoot) using a continuum mechanics approach. A three-dimensional finite element model of the foot was employed to estimate the stress distribution in the foot at the moment of impact during barefoot running. The effects of stress attenuating factors such as the landing angle and the surface stiffness were also analyzed. We characterized rear and forefoot plantar sole behavior in an experimental test, which allowed for refined modeling of plantar pressures for the different strike patterns. Modeling results on the internal stress distributions allow predictions of the susceptibility to injury for particular anatomical structures in the foot.

Location-dependent correlation between tissue structure and the mechanical behaviour of the urinary bladder.

The mechanical properties of the urinary bladder wall are important to understand its filling-voiding cycle in health and disease. However, much remains unknown about its mechanical properties, especially regarding regional heterogeneities and wall microstructure. The present study aimed to assess the regional differences in the mechanical properties and microstructure of the urinary bladder wall. Ninety (n=90) samples of porcine urinary bladder wall (ten samples from nine different locations) were mechanically and histologically analysed. Half of the samples (n=45) were equibiaxially tested within physiological conditions, and the other half, matching the sample location of the mechanical tests, was frozen, cryosectioned, and stained with Picro-Sirius red to differentiate smooth muscle cells, extracellular matrix, and fat. The bladder wall shows a non-linear stress-stretch relationship with hysteresis and softening effects. Regional differences were found in the mechanical response and in the microstructure. The trigone region presents higher peak stresses and thinner muscularis layer compared to the rest of the bladder. Furthermore, the ventral side of the bladder presents anisotropic characteristics, whereas the dorsal side features perfect isotropic behaviour. This response matches the smooth muscle fibre bundle orientation within the tunica muscularis. This layer, comprising approximately 78% of the wall thickness, is composed of two fibre bundle arrangements that are cross-oriented, one with respect to the other, varying the angle between them across the organ. That is, the ventral side presents a 60°/120° cross-orientation structure, while the muscle bundles were oriented perpendicular in the dorsal side. STATEMENT OF SIGNIFICANCE: In the present study, we demonstrate that the mechanical properties and the microstructure of the urinary bladder wall are heterogeneous across the organ. The mechanical properties and the microstructure of the urinary bladder wall within nine specific locations matching explicitly the mechanical and structural variations have been examined. On the one hand, the results of this study contribute to the understanding of bladder mechanics and thus to their functional understanding of bladder filling and voiding. On the other hand, they are relevant to the fields of constitutive formulation of bladder tissue, whole bladder mechanics, and bladder-derived scaffolds i.e., tissue-engineering grafts.

Non-linear finite element model to assess the effect of tendon forces on the foot-ankle complex.

A three-dimensional foot finite element model with actual geometry and non-linear behavior of tendons is presented. The model is intended for analysis of the lower limb tendon forces effect in the inner foot structure. The geometry of the model was obtained from computational tomographies and magnetic resonance images. Tendon tissue was characterized with the first order Ogden material model based on experimental data from human foot tendons. Kinetic data was employed to set the load conditions. After model validation, a force sensitivity study of the five major foot extrinsic tendons was conducted to evaluate the function of each tendon. A synergic work of the inversion-eversion tendons was predicted. Pulling from a peroneus or tibialis tendon stressed the antagonist tendons while reducing the stress in the agonist. Similar paired action was predicted for the Achilles tendon with the tibialis anterior. This behavior explains the complex control motion performed by the foot. Furthermore, the stress state at the plantar fascia, the talocrural joint cartilage, the plantar soft tissue and the tendons were estimated in the early and late midstance phase of walking. These estimations will help in the understanding of the functional role of the extrinsic muscle-tendon-units in foot pronation-supination.

Structural and material properties of human foot tendons.

BACKGROUNDS: The aim of this study was to assess the mechanical properties of the main balance tendons of the human foot in vitro reporting mechanical structural properties and mechanical material properties separately. Tendon structural properties are relevant for clinical applications, for example in orthopedic surgery to elect suitable replacements. Tendon material properties are important for engineering applications such as the development of refined constitutive models for computational simulation or in the design of synthetic materials. METHODS: One hundred uniaxial tensile tests were performed to obtain the mechanical response of the main intrinsic and extrinsic human foot tendons. The specimens were harvested from five frozen cadaver feet including: Extensor and Flexor tendons of all toes, Tibialis Anterior and Posterior tendons and Peroneus Brevis and Longus tendons. FINDINGS: Cross-sectional area, load and strain failure, Young's modulus and ultimate tensile stress are reported as a reference of foot tendon mechanical properties. Two different behaviors could be differentiated. Tibialis and Peroneus tendons exhibited higher values of strain failure compared to Flexor and Extensor tendons which had higher Young's modulus and ultimate tensile stress. Stress-strain tendon curves exhibited proportionality between regions. The initial strain, the toe region and the yield point corresponded to the 15, 30 and 70% of the strain failure respectively. INTERPRETATION: Mechanical properties of the lesser-studied human foot tendons are presented under the same test protocol for different engineering and clinical applications. The tendons that work at the inversion/eversion plane are more deformable at the same stress and strain rate than those that work at the flexion/extension plane.

Influence of first proximal phalanx geometry on hallux valgus deformity: a finite element analysis.

Hallux abducto valgus (HAV), one of the most common forefoot deformities, occurs primarily in elderly women. HAV is a complex disease without a clearly identifiable cause for its higher prevalence in women compared with men. Several studies have reported various skeletal parameters related to HAV. This study examined the geometry of the proximal phalanx of the hallux (PPH) as a potential etiologic factor in this deformity. A total of 43 cadaver feet (22 males and 21 females) were examined by means of cadaveric dissection. From these data, ten representative PPHs for both genders were selected, corresponding to five percentiles for males (0, 25, 50, 75, and 100%) and five for females. These ten different PPHs were modeled and inserted in ten foot models. Stress distribution patterns within these ten PPH models were qualitatively compared using finite element analysis. In the ten cases analyzed, tensile stresses were larger on the lateral side, whereas compressive stresses were larger on the medial side. The bones of males were larger than female bones for each of the parameters examined; however, the mean difference between lateral and medial sides of the PPH (mean ± SD) was larger in women. Also the shallower the concavity at the base of the PPH, the larger the compressive stresses predicted. Internal forces on the PPH, due to differences in length between its medial and lateral sides, may force the PPH into a less-stressful position. The geometry of the PPH is a significant factor in HAV development influencing the other reported skeletal parameters and, thus, should be considered during preoperative evaluation. Clinical assessment should evaluate the first ray as a whole and not as isolated factors.