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Background/Aims: Common systems for the quantification of cellular contraction rely on animal-based models, complex experimental setups or indirect approaches. The herein presented CellDrum technology for testing mechanical tension of cellular monolayers and thin tissue constructs has the potential to scale-up mechanical testing towards medium-throughput analyses. Using hiPS-Cardiac Myocytes (hiPS-CMs) it represents a new perspective of drug testing and brings us closer to personalized drug medication. Methods: In the present study, monolayers of self-beating hiPS-CMs were grown on ultra-thin circular silicone membranes and deflect under the weight of the culture medium. Rhythmic contractions of the hiPS-CMs induced variations of the membrane deflection. The recorded contraction-relaxation-cycles were analyzed with respect to their amplitudes, durations, time integrals and frequencies. Besides unstimulated force and tensile stress, we investigated the effects of agonists and antagonists acting on Ca²⁺ channels (S-Bay K8644/verapamil) and Na⁺ channels (veratridine/lidocaine). Results: The measured data and simulations for pharmacologically unstimulated contraction resembled findings in native human heart tissue, while the pharmacological dose-response curves were highly accurate and consistent with reference data. Conclusion: We conclude that the combination of the CellDrum with hiPS-CMs offers a fast, facile and precise system for pharmacological, toxicological studies and offers new preclinical basic research potential.
For pelvic floor disorders that cannot be treated with non-surgical procedures, minimally invasive surgery has become a more frequent and safer repair procedure. More than 20 million prosthetic meshes are implanted each year worldwide. The simple selection of a single synthetic mesh construction for any level and type of pelvic floor dysfunctions without adopting the design to specific requirements increase the risks for mesh related complications. Adverse events are closely related to chronic foreign body reaction, with enhanced formation of scar tissue around the surgical meshes, manifested as pain, mesh erosion in adjacent structures (with organ tissue cut), mesh shrinkage, mesh rejection and eventually recurrence. Such events, especially scar formation depend on effective porosity of the mesh, which decreases discontinuously at a critical stretch when pore areas decrease making the surgical reconstruction ineffective that further augments the re-operation costs. The extent of fibrotic reaction is increased with higher amount of foreign body material, larger surface, small pore size or with inadequate textile elasticity. Standardized studies of different meshes are essential to evaluate influencing factors for the failure and success of the reconstruction. Measurements of elasticity and tensile strength have to consider the mesh anisotropy as result of the textile structure. An appropriate mesh then should show some integration with limited scar reaction and preserved pores that are filled with local fat tissue. This chapter reviews various tissue reactions to different monofilament mesh implants that are used for incontinence and hernia repairs and study their mechanical behavior. This helps to predict the functional and biological outcomes after tissue reinforcement with meshes and permits further optimization of the meshes for the specific indications to improve the success of the surgical treatment.
Limit loads can be calculated with the finite element method (FEM) for any component, defect geometry, and loading. FEM suggests that published long crack limit formulae for axial defects under-estimate the burst pressure for internal surface defects in thick pipes while limit loads are not conservative for deep cracks and for pressure loaded crack-faces. Very deep cracks have a residual strength, which is modelled by a global collapse load. These observations are combined to derive new analytical local and global collapse loads. The global collapse loads are close to FEM limit analyses for all crack dimensions.
Load bearing capacity of thin shell structures made of elastoplastic material by direct methods
(2008)
The load-carrying capacity or the safety against plastic limit states are the central questions in the design of structures and passive components in the apparatus engineering. A precise answer is most simply given by limit and shakedown analysis. These methods can be based on static and kinematic theorems for lower and upper bound analysis. Both may be formulated as optimization problems for finite element discretizations of structures. The problems of large-scale analysis and the extension towards realistic material modelling will be solved in a European research project. Limit and shakedown analyses are briefly demonstrated with illustrative examples.
Limit loads of circumferentially flawed pipes and cylindrical vessels under internal pressure
(2006)
7th International Conference on Reliability of Materials and Structures (RELMAS 2008). June 17 - 20, 2008 ; Saint Petersburg, Russia. pp 354-358. Reprint with corrections in red Introduction Analysis of advanced structures working under extreme heavy loading such as nuclear power plants and piping system should take into account the randomness of loading, geometrical and material parameters. The existing reliability are restricted mostly to the elastic working regime, e.g. allowable local stresses. Development of the limit and shakedown reliability-based analysis and design methods, exploiting potential of the shakedown working regime, is highly needed. In this paper the application of a new algorithm of probabilistic limit and shakedown analysis for shell structures is presented, in which the loading and strength of the material as well as the thickness of the shell are considered as random variables. The reliability analysis problems may be efficiently solved by using a system combining the available FE codes, a deterministic limit and shakedown analysis, and the First and Second Order Reliability Methods (FORM/SORM). Non-linear sensitivity analyses are obtained directly from the solution of the deterministic problem without extra computational costs.
Direct methods comprising limit and shakedown analysis is a branch of computational mechanics. It plays a significant role in mechanical and civil engineering design. The concept of direct method aims to determinate the ultimate load bearing capacity of structures beyond the elastic range. For practical problems, the direct methods lead to nonlinear convex optimization problems with a large number of variables and onstraints. If strength and loading are random quantities, the problem of shakedown analysis is considered as stochastic programming. This paper presents a method so called chance constrained programming, an effective method of stochastic programming, to solve shakedown analysis problem under random condition of strength. In this our investigation, the loading is deterministic, the strength is distributed as normal or lognormal variables.
Limit and shakedown theorems are exact theories of classical plasticity for the direct computation of safety factors or of the load carrying capacity under constant and varying loads. Simple versions of limit and shakedown analysis are the basis of all design codes for pressure vessels and pipings. Using Finite Element Methods more realistic modeling can be used for a more rational design. The methods can be extended to yield optimum plastic design. In this paper we present a first implementation in FE of limit and shakedown analyses for perfectly plastic material. Limit and shakedown analyses are done of a pipe–junction and a interaction diagram is calculated. The results are in good correspondence with the analytic solution we give in the appendix.
Upper and lower bound theorems of limit analyses have been presented in part I of the paper. Part II starts with the finite element discretization of these theorems and demonstrates how both can be combined in a primal–dual optimization problem. This recently proposed numerical method is used to guide the development of a new class of closed-form limit loads for circumferential defects, which show that only large defects contribute to plastic collapse with a rapid loss of strength with increasing crack sizes. The formulae are compared with primal–dual FEM limit analyses and with burst tests. Even closer predictions are obtained with iterative limit load solutions for the von Mises yield function and for the Tresca yield function. Pressure loading of the faces of interior cracks in thick pipes reduces the collapse load of circumferential defects more than for axial flaws. Axial defects have been treated in part I of the paper.
Limit Analysis of Defects
(2000)