A validated finite element model to reproduce Helmholtz's theory of accommodation: a powerful tool to investigate presbyopia.

PURPOSE: To reproduce human in vivo accommodation numerically. For that purpose, a finite element model specific for a 29-year-old subject was designed. Once the proposed numerical model was validated, the decrease in accommodative amplitude with age was simulated according to data available in the literature. METHODS: In contrast with previous studies, the non-accommodated eye condition was the reference configuration. Consequently, two aspects were specifically highlighted: contraction of the ciliary muscle, which was simulated by a continuum electro-mechanical model and incorporation of initial lens capsule stresses, which allowed the lens to become accommodated after releasing the resting zonular tension. RESULTS: The morphological changes and contraction of the ciliary muscle were calibrated accurately according to the experimental data from the literature. All dynamic optical and biometric lens measurements validated the model. With the proposed numerical model, presbyopia was successfully simulated. CONCLUSIONS: The most widespread theory of accommodation, proposed by Helmholtz, was simulated accurately. Assuming the same initial stresses in the lens capsule over time, stiffening of the lens nucleus is the main cause of presbyopia.

Assessing the role of Ca2+ in skeletal muscle fatigue using a multi-scale continuum model.

The Calcium ion Ca2+ plays a critical role as an initiator and preserving agent of the cross-bridge cycle in the force generation of skeletal muscle. A new multi-scale chemo-mechanical model is presented in order to analyze the role of Ca2+ in muscle fatigue and to predict fatigue behavior. To this end, a cross-bridge kinematic model was incorporated in a continuum based mechanical model, considering a thermodynamic compatible framework. The contractile velocity and the generated active force were directly related to the force-bearing states that were considered for the cross-bridge cycle. In order to determine the values of the model parameters, the output results of an isometric simulation were initially fitted with experimental data obtained for rabbit Extensor Digitorum Longus muscle. Furthermore, a simulated force-velocity curve under concentric contractions was compared with reported experimental results. Finally, by varying the Ca2+ concentration level and its kinetics in the tissue, the model was able to predict the evolution of the active force of an experimental fatigue protocol. The good agreement observed between the simulated results and the experimental outcomes proves the ability of the model to reproduce the fatigue behavior and its applicability for more detailed multidisciplinary investigations related to chemical conditions in muscle performance.

The Effect of Lens Shape, Zonular Insertion and Finite Element Model on Simulated Shape Change of the Eye Lens.

The process of lens shape change in the eye to alter focussing (accommodation) is still not fully understood. Modelling approaches have been used to complement experimental findings in order to determine how constituents in the accommodative process influence the shape change of the lens. An unexplored factor in modelling is the role of the modelling software on the results of simulated shape change. Finite element models were constructed in both Abaqus and Ansys software using biological parameters from measurements of shape and refractive index of two 35-year-old lenses. The effect of zonular insertion on simulated shape change was tested on both 35-year-old lens models and with both types of software. Comparative analysis of shape change, optical power, and stress distributions showed that lens shape and zonular insertion positions affect the results of simulated shape change and that Abaqus and Ansys show differences in their respective models. The effect of the software package used needs to be taken into account when constructing finite element models and deriving conclusions.

Improving early detection of keratoconus by Non Contact Tonometry. A computational study and new biomarkers proposal.

Keratoconus is a progressive ocular disorder affecting the corneal tissue, leading to irregular astigmatism and decreased visual acuity. The architectural organization of corneal tissue is altered in keratoconus, however, data from ex vivo testing of biomechanical properties of keratoconic corneas are limited and it is unclear how their results relate to true mechanical properties in vivo. This study explores the mechanical properties of keratoconic corneas through numerical simulations of non-contact tonometry (NCT) reproducing the clinical test of the Corvis ST device. Three sensitivity analyses were conducted to assess the impact of corneal material properties, size, and location of the pathological area on NCT results. Additionally, novel asymmetry-based indices were proposed to better characterize corneal deformations and improve the diagnosis of keratoconus. Our results show that the weakening of corneal material properties leads to increased deformation amplitude and altered biomechanical response. Furthermore, asymmetry indices offer valuable information for locating the pathological tissue. These findings suggest that adjusting the Corvis ST operation, such as a camera rotation, could enhance keratoconus detection and provide insights into the relative position of the affected area. Future research could explore the application of these indices in detecting early-stage keratoconus and assessing the fellow eye's risk for developing the pathology.

Investigation of crystalline lens overshooting: ex vivo experiment and optomechanical simulation results.

Introduction: Crystalline lens overshooting refers to a situation in which the lens momentarily shifts too much from its typical location immediately after stopping the rotational movement of the eye globe. This movement can be observed using an optical technique called Purkinje imaging. Methods: In this work, an experimental setup was designed to reproduce this effect ex vivo using a fresh porcine eye. The sample was rotated 90° around its centroid using a high-velocity rotation stage, and the Purkinje image sequences were recorded, allowing us to quantify the overshooting effect. The numerical part of the study consisted of developing a computational model of the eye, based on the finite element method, that allowed us to understand the biomechanical behavior of the different tissues in this dynamic scenario. A 2D fluid-structure interaction model of the porcine eye globe, considering both the solid parts and humors, was created to reproduce the experimental outcomes. Results: Outputs of the simulation were analyzed using an optical simulation software package to assess whether the mechanical model behaves optically like the real ex vivo eye. The simulation predicted the experimental results by carefully adjusting the mechanical properties of the zonular fibers and the damping factor. Conclusion: This study effectively demonstrates the importance of characterizing the dynamic mechanical properties of the eye tissues to properly comprehend and predict the overshooting effect.

Mechanical response of the herniated human abdomen to the placement of different prostheses.

This paper describes a method designed to model the repaired herniated human abdomen just after surgery and examine its static mechanical response to the maximum intra-abdominal pressure provoked by a physiological movement (standing cough). The model is based on the real geometry of the human abdomen bearing a large incisional hernia with several anatomical structures differentiated by MRI. To analyze the outcome of hernia repair, the surgical procedure was simulated by modeling a prosthesis placed over the hernia. Three surgical meshes with different mechanical properties were considered: an isotropic heavy-weight mesh (Surgipro®), a slightly anisotropic light-weight mesh (Optilene®), and a highly anisotropic medium-weight mesh (Infinit®). Our findings confirm that anisotropic implants need to be positioned such that the most compliant axis of the mesh coincides with the craneo-caudal direction of the body.

A detailed methodology to model the Non Contact Tonometry: a Fluid Structure Interaction study.

Understanding the corneal mechanical properties has great importance in the study of corneal pathologies and the prediction of refractive surgery outcomes. Non-Contact Tonometry (NCT) is a non-invasive diagnostic tool intended to characterize the corneal tissue response in vivo by applying a defined air-pulse. The biomarkers inferred from this test can only be considered as indicators of the global biomechanical behaviour rather than the intrinsic biomechanical properties of the corneal tissue. A possibility to isolate the mechanical response of the corneal tissue is the use of an inverse finite element method, which is based on accurate and reliable modelling. Since a detailed methodology is still missing in the literature, this paper aims to construct a high-fidelity finite-element model of an idealized 3D eye for in silico NCT. A fluid-structure interaction (FSI) simulation is developed to virtually apply a defined air-pulse to a 3D idealized eye model comprising cornea, limbus, sclera, lens and humors. Then, a sensitivity analysis is performed to examine the influence of the intraocular pressure (IOP) and the structural material parameters on three biomarkers associated with corneal deformation. The analysis reveals the requirements for the in silico study linked to the correct reproduction of three main aspects: the air pressure over the cornea, the biomechanical properties of the tissues, and the IOP. The adoption of an FSI simulation is crucial to capture the correct air pressure profile over the cornea as a consequence of the air-jet. Regarding the parts of the eye, an anisotropic material should be used for the cornea. An important component is the sclera: the stiffer the sclera, the lower the corneal deformation due to the air-puff. Finally, the fluid-like behavior of the humors should be considered in order to account for the correct variation of the IOP during the test which will, otherwise, remain constant. The development of a strong FSI tool amenable to model coupled structures and fluids provides the basis to find the biomechanical properties of the corneal tissue in vivo.

Muscular and Tendon Degeneration after Achilles Rupture: New Insights into Future Repair Strategies.

Achilles tendon rupture is a frequent injury with an increasing incidence. After clinical surgical repair, aimed at suturing the tendon stumps back into their original position, the repaired Achilles tendon is often plastically deformed and mechanically less strong than the pre-injured tissue, with muscle fatty degeneration contributing to function loss. Despite clinical outcomes, pre-clinical research has mainly focused on tendon structural repair, with a lack of knowledge regarding injury progression from tendon to muscle and its consequences on muscle degenerative/regenerative processes and function. Here, we characterize the morphological changes in the tendon, the myotendinous junction and muscle belly in a mouse model of Achilles tendon complete rupture, finding cellular and fatty infiltration, fibrotic tissue accumulation, muscle stem cell decline and collagen fiber disorganization. We use novel imaging technologies to accurately relate structural alterations in tendon fibers to pathological changes, which further explain the loss of muscle mechanical function after tendon rupture. The treatment of tendon injuries remains a challenge for orthopedics. Thus, the main goal of this study is to bridge the gap between clinicians' knowledge and research to address the underlying pathophysiology of ruptured Achilles tendon and its consequences in the gastrocnemius. Such studies are necessary if current practices in regenerative medicine for Achilles tendon ruptures are to be improved.

Effect of Cryopreserved Amniotic Membrane on the Mechanical Properties of Skeletal Muscle after Strabismus Surgery in Rabbits.

PURPOSE: To study the functional recovery of the superior rectus muscle (SRM) after its partial resection in a rabbit model with and without cryopreserved amniotic membrane (AM). MATERIAL AND METHODS: Resection of the right and left SRMs of 30 rabbits was performed. On the left eyes, a single sheet of equine cryopreserved AM was placed covering the muscle edge sutured. Active and passive mechanical properties of muscles operated with and without AM were monitored over time at 30 (n = 10), 60 (n = 10), and 90 (n = 10) days after surgery. Muscle samples were extracted and electrically stimulated to register the force exerted by the samples, characterizing its active behavior. They were, then, subjected to stretching test to obtain its resistance to deformation, known as passive behavior. Moreover, right and left eyes of a control group (n = 5) were equally subjected to active and passive tests to characterize the physiological behavior of SRM muscles. RESULTS: On active function examination, statistically significant differences were documented between the following: control vs AM and no AM at 30 days (p = 0.002 and p = 0.04, respectively). All other comparisons were insignificant (p > 0.05). On passive function analysis, significant differences were only found between control vs. no AM at 30 days (p = 0.004) and between AM vs. no AM at 30 days (p = 0.002). Indeed, muscle operated without AM did not recover a normal passive function until 60 days after surgery. CONCLUSION: Cryopreserved AM is effective in accelerating recovery of SRM passive function in rabbits. Nevertheless, AM produced no significant effect on recovery of SRM active function..

Influence of high-frequency cyclical stimulation on the bone fracture-healing process: mathematical and experimental models.

Mechanical stimulation affects the evolution of healthy and fractured bone. However, the effect of applying cyclical mechanical stimuli on bone healing has not yet been fully clarified. The aim of the present study was to determine the influence of a high-frequency and low-magnitude cyclical displacement of the fractured fragments on the bone-healing process. This subject is studied experimentally and computationally for a sheep long bone. On the one hand, the mathematical computational study indicates that mechanical stimulation at high frequencies can stimulate and accelerate the process of chondrogenesis and endochondral ossification and consequently the bony union of the fracture. This is probably achieved by the interstitial fluid flow, which can move nutrients and waste from one place to another in the callus. This movement of fluid modifies the mechanical stimulus on the cells attached to the extracellular matrix. On the other hand, the experimental study was carried out using two sheep groups. In the first group, static fixators were implanted, while, in the second one, identical devices were used, but with an additional vibrator. This vibrator allowed a cyclic displacement with low magnitude and high frequency (LMHF) to be applied to the fractured zone every day; the frequency of stimulation was chosen from mechano-biological model predictions. Analysing the results obtained for the control and stimulated groups, we observed improvements in the bone-healing process in the stimulated group. Therefore, in this study, we show the potential of computer mechano-biological models to guide and define better mechanical conditions for experiments in order to improve bone fracture healing. In fact, both experimental and computational studies indicated improvements in the healing process in the LMHF mechanically stimulated fractures. In both studies, these improvements could be associated with the promotion of endochondral ossification and an increase in the rate of cell proliferation and tissue synthesis.