A Review: Biomechanical Aspects of the Fallopian Tube Relevant to its Function in Fertility.

The fallopian tube (FT) plays a crucial role in the reproductive process by providing an ideal biomechanical and biochemical environment for fertilization and early embryo development. Despite its importance, the biomechanical functions of the FT that originate from its morphological aspects, and ultrastructural aspects, as well as the mechanical properties of FT, have not been studied nor used sufficiently, which limits the understanding of fertilization, mechanotrasduction, and mechanobiology during embryo development, as well as the replication of the FT in laboratory settings for infertility treatments. This paper reviews and revives valuable information on human FT reported in medical literature in the past five decades relevant to the biomechanical aspects of FT. In this review, we summarized the current state of knowledge concerning the morphological, ultrastructural aspects, and mechanical properties of the human FT. We also investigate the potential arising from a thorough consideration of the biomechanical functions and exploring often neglected mechanical aspects. Our investigation encompasses both macroscopic measurements (such as length, diameter, and thickness) and microscopic measurements (including the height of epithelial cells, the percentage of ciliated cells, cilia structure, and ciliary beat frequency). Our primary focus has been on healthy women of reproductive age. We have examined various measurement techniques, encompassing conventional metrology, 2D histological data as well as new spatial measurement techniques such as micro-CT.

Poroelastic behavior and water permeability of human skin at the nanoscale.

Topical skin care products and hydrating compositions (moisturizers or injectable fillers) have been used for years to improve the appearance of, for example facial wrinkles, or to increase "plumpness". Most of the studies have addressed these changes based on the overall mechanical changes associated with an increase in hydration state. However, little is known about the water mobility contribution to these changes as well as the consequences to the specific skin layers. This is important as the biophysical properties and the biochemical composition of normal stratum corneum, epithelium, and dermis vary tremendously from one another. Our current studies and results reported here have focused on a novel approach (dynamic atomic force microscopy-based nanoindentation) to quantify biophysical characteristics of individual layers of ex vivo human skin. We have discovered that our new methods are highly sensitive to the mechanical properties of individual skin layers, as well as their hydration properties. Furthermore, our methods can assess the ability of these individual layers to respond to both compressive and shear deformations. In addition, since human skin is mechanically loaded over a wide range of deformation rates (frequencies), we studied the biophysical properties of skin over a wide frequency range. The poroelasticity model used helps to quantify the hydraulic permeability of the skin layers, providing an innovative method to evaluate and interpret the impact of hydrating compositions on water mobility of these different skin layers.

Micro-scale probing of the Rat's oviduct detects its viscoelastic property needed for creating a biologically relevant substrate for In-Vitro- Fertilization.

Techniques used in assisted reproductive technology such as In-Vitro- Fertilization (IVF) process, often only replicate the biomechanical environment for embryo. Despite its importance, the biomechanics of the Oviduct tissue that is usually called Fallopian Tube in Human, the natural site of fertilization, has not been replicated nor sufficiently studied. This work studies the time-independent and time-dependent biomechanics of the oviduct tissue by realizing a viscoelastic model that accurately fit on the experimental indentation data collected on the mucosal epithelial lining of the oviduct tissue of rats. Nano-scale experiments with varying indentation rates ranging from 0.3 to 8 µms were conducted using atomic force microscopy (AFM) resulting in instantaneous elastic modulus ranging from 0.86 MPa to 6.46 MPa correspondingly. This result showed strong time dependency of the mechanical properties of the oviduct. An improved viscoelastic equation based on the fractional viscoelastic model was proposed. This modified relation successfully captured all the experimental data found at different rates (R2 > 0.8). Using the proposed model, the pure elasticity of the oviduct (i.e., about 317.2 kPa) and the viscoelastic parameters were found.

Extracting the elasticity of the human skin in microscale and in-vivo from atomic force microscopy experiments using viscoelastic models.

Detecting mechanical properties of the intact skin in-vivo leads to a novel quantitative method to diagnose skin diseases and to monitor skin conditions in clinical settings. Current research and clinical methods that detect skin mechanics have major limitations. The in-vitro experiments are done in non-physiological conditions and in-vivo clinical methods measurer unwanted mechanics of underneath fat and muscle tissues but report the measurement as skin mechanics. An ideal skin mechanics should be captured at skin scale (i.e., micron-scale) and in-vivo. However, extreme challenges of capturing the in-vivo skin mechanics in micron-scale including skin motion due to heart beep, breathing and movement of the subject, has hindered measurement of skin mechanics in-vivo.This study for the first time captures micro-scale mechanics (elasticity and viscoelasticity) of top layers of skin (i.e., the stratum corneum (SC) and stratum granulosum (SG)) in-vivo. In this study, the relevant literature is reviewed and Atomic Force Microscopy (AFM) was used to capture force-indentation curves on the fingertip skin of four human subjects at a high indentation speed of 40 µm/s. The skin of the same subject were tested in-vitro at 10 different indentation speeds ranging from 0.125 to 40 µm/s by AFM. This study extracts the in-vivo elasticity of SC and SG by detecting time-dependency of tested tissue using a fractional viscoelastic standard linear model developed for indentation. The in-vivo elasticity of SC and SG were smaller in females and in-vitro elasticity were higher than that of in-vivo results. The results were consistent with previous observations.

Quantification of human sperm concentration using machine learning-based spectrophotometry.

Spectrophotometry is an indirect non-invasive and quantitative method for specifying materials with unknown contents based on absorption behavior. This paper presents the first application of artificial neural network in spectrophotometry for quantification of human sperm concentration. A well-trained full spectrum neural network (FSNN) model is developed by examining the absorption response of sperm samples from 41 human subjects to different light spectra (wavelength from 390 to 1100 nm). It is shown that this FSNN accurately estimates sperm concentration based on the full absorption spectrum with over 93% prediction accuracy, and provides 100% agreement with clinical assessments in differentiating the samples of healthy donor from patient samples. We suggest the machine learning-based spectrophotometry approach with the trained FSNN model as a rapid, low-cost, and powerful technique to quantify sperm concentration. The performance of this technique is superior to available spectrophotometry methods currently used for semen analysis and will provide novel research and clinical opportunities for tackling male infertility.

A new framework for characterization of poroelastic materials using indentation.

To characterize a poroelastic material, typically an indenter is pressed onto the surface of the material with a ramp of a finite approach velocity followed by a hold where the indenter displacement is kept constant. This leads to deformation of the porous matrix, pressurization of the interstitial fluid and relaxation due to redistribution of fluid through the pores. In most studies the poroelastic properties, including elastic modulus, Poisson ratio and poroelastic diffusion coefficient, are extracted by assuming an instantaneous step indentation. However, exerting step like indentation is not experimentally possible and usually a ramp indentation with a finite approach velocity is applied. Moreover, the poroelastic relaxation time highly depends on the approach velocity in addition to the poroelastic diffusion coefficient and the contact area. Here, we extensively studied the effect of indentation velocity using finite element simulations which has enabled the formulation of a new framework based on a master curve that incorporates the finite rise time. To verify our novel framework, the poroelastic properties of two types of hydrogels were extracted experimentally using indentation tests at both macro and micro scales. Our new framework that is based on consideration of finite approach velocity is experimentally easy to implement and provides a more accurate estimation of poroelastic properties. STATEMENT OF SIGNIFICANCE: Hydrogels, tissues and living cells are constituted of a sponge-like porous elastic matrix bathed in an interstitial fluid. It has been shown that these materials behave according to the theory of 'poroelasticity' when mechanically stimulated in a way similar to that experienced in organs within the body. In this theory, the rate at which the fluid-filled sponge can be deformed is limited by how fast interstitial fluid can redistribute within the sponge in response to deformation. Here, we simulated indentation experiments at different rates and formulated a new framework that inherently captures the effects of stimulation speed on the mechanical response of poroelastic materials. We validated our framework by conducting experiments at different length-scales on agarose and polyacrylamide hydrogels.

Nanoscale Poroelasticity of the Tectorial Membrane Determines Hair Bundle Deflections.

Stereociliary imprints in the tectorial membrane (TM) have been taken as evidence that outer hair cells are sensitive to shearing displacements of the TM, which plays a key role in shaping cochlear sensitivity and frequency selectivity via resonance and traveling wave mechanisms. However, the TM is highly hydrated (97% water by weight), suggesting that the TM may be flexible even at the level of single hair cells. Here we show that nanoscale oscillatory displacements of microscale spherical probes in contact with the TM are resisted by frequency-dependent forces that are in phase with TM displacement at low and high frequencies, but are in phase with TM velocity at transition frequencies. The phase lead can be as much as a quarter of a cycle, thereby contributing to frequency selectivity and stability of cochlear amplification.

Wide bandwidth nanomechanical assessment of murine cartilage reveals protection of aggrecan knock-in mice from joint-overuse.

Aggrecan loss in human and animal cartilage precedes clinical symptoms of osteoarthritis, suggesting that aggrecan loss is an initiating step in cartilage pathology. Characterizing early stages of cartilage degeneration caused by aging and overuse is important in the search for therapeutics. In this study, atomic force microscopy (AFM)-based force-displacement micromechanics, AFM-based wide bandwidth nanomechanics (nanodynamic), and histologic assessments were used to study changes in distal femur cartilage of wildtype mice and mice in which the aggrecan interglobular domain was mutated to make the cartilage aggrecanase-resistant. Half the animals were subjected to voluntary running-wheel exercise of varying durations. Wildtype mice at three selected age groups were compared. While histological assessment was not sensitive enough to capture any statistically significant changes in these relatively young populations of mice, micromechanical assessment captured changes in the quasi-equilibrium structural-elastic behavior of the cartilage matrix. Additionally, nanodynamic assessment captured changes in the fluid-solid poroelastic behavior and the high frequency stiffness of the tissue, which proved to be the most sensitive assessment of changes in cartilage associated with aging and joint-overuse. In wildtype mice, aging caused softening of the cartilage tissue at the microscale and at the nanoscale. Softening with increased animal age was found at high loading rates (frequencies), suggesting an increase in hydraulic permeability, with implications for loss of function pertinent to running and impact-injury. Running caused substantial changes in fluid-solid interactions in aggrecanase-resistant mice, suggestive of tissue degradation. However, higher nanodynamic stiffness magnitude and lower hydraulic permeability was observed in running aggrecanase-resistant mice compared to running wildtype controls at the same age, thereby suggesting protection from joint-overuse.

High-bandwidth AFM-based rheology is a sensitive indicator of early cartilage aggrecan degradation relevant to mouse models of osteoarthritis.

Murine models of osteoarthritis (OA) and post-traumatic OA have been widely used to study the development and progression of these diseases using genetically engineered mouse strains along with surgical or biochemical interventions. However, due to the small size and thickness of murine cartilage, the relationship between mechanical properties, molecular structure and cartilage composition has not been well studied. We adapted a recently developed AFM-based nano-rheology system to probe the dynamic nanomechanical properties of murine cartilage over a wide frequency range of 1 Hz to 10 kHz, and studied the role of glycosaminoglycan (GAG) on the dynamic modulus and poroelastic properties of murine femoral cartilage. We showed that poroelastic properties, highlighting fluid-solid interactions, are more sensitive indicators of loss of mechanical function compared to equilibrium properties in which fluid flow is negligible. These fluid-flow-dependent properties include the hydraulic permeability (an indicator of the resistance of matrix to fluid flow) and the high frequency modulus, obtained at high rates of loading relevant to jumping and impact injury in vivo. Utilizing a fibril-reinforced finite element model, we estimated the poroelastic properties of mouse cartilage over a wide range of loading rates for the first time, and show that the hydraulic permeability increased by a factor ~16 from knormal=7.80×10(-16)±1.3×10(-16) m(4)/N s to kGAG-depleted=1.26×10(-14)±6.73×10(-15) m(4)/N s after GAG depletion. The high-frequency modulus, which is related to fluid pressurization and the fibrillar network, decreased significantly after GAG depletion. In contrast, the equilibrium modulus, which is fluid-flow independent, did not show a statistically significant alteration following GAG depletion.

Evaluating vibrotactile dimensions for the design of tactons.

Vibrotactile stimuli are defined in terms of their amplitude, frequency, waveform and temporal profile all of which have been varied to create tactons. A number of approaches have been adopted to design tactons including multidimensional scaling, iterative empirical methods and using perceptual processing models. The objective of the present set of experiments was to create sets of tactons based on the properties of the dimensions of vibrotactile stimuli. An absolute identification paradigm was used in which each of nine tactons was presented eight times using a tactor mounted on either the index finger or forearm. It was found that tactons created by varying the frequency, amplitude and temporal profile of the vibrotactile stimuli were correctly identified on 73-83 percent of the trials, with a mean information transfer of 2.41 bits. The latter metric indicates that for these sets of nine tactons between five and six could be reliably identified. The vibrotactile stimuli delivered in the experiments were identified as consistently on the forearm as the hand and the IT values were similar at the two locations. This suggests that sites other than the hand can be used effectively in tactile communication systems and that it is channel capacity that ultimately determines performance on this type of task.

Towards a bio-inspired leg design for high-speed running.

High-speed terrestrial locomotion inevitably involves high acceleration and extensive loadings on the legs. This imposes a challenging trade-off between weight and strength in leg design. This paper introduces a new design paradigm for a robotic leg inspired by musculoskeletal structures. The central hypothesis is that employing a tendon-bone co-location architecture not only provides compliance in the leg, but can also reduce bone stresses caused by bending on structures. This hypothesis is applied to a leg design, and verified by simulations and the experiments on a prototype. In addition, we also present an optimization scheme to maximize the strength to weight ratio. Using the tendon-bone co-location architecture, the stress on the bone during a stride is reduced by up to 59%. A new foam-core prototyping technique enables creating structural characteristics similar to mammalian bones in the robotic leg. This method allows us to use lighter polymeric structures that are cheaper and quicker to fabricate than conventional fabrication methods, and can eventually greatly shorten the design iteration cycle time.