TY - JOUR A1 - Knox, Ronald A1 - Bruggemann, Andrea A1 - Gossmann, Matthias A1 - Thomas, Ulrich A1 - Horváth, András A1 - Dragicevic, Elena A1 - Stoelzle-Feix, Sonja A1 - Fertig, Niels A1 - Jung, Alexander A1 - Raman, Aravind Hariharan A1 - Staat, Manfred A1 - Linder, Peter T1 - Combining physiological relevance and throughput for in vitro cardiac contractility measurement JF - Biophysical Journal N2 - Despite increasing acceptance of human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) in safety pharmacology, controversy remains about the physiological relevance of existing in vitro models for their mechanical testing. We hypothesize that existing signs of immaturity of the cell models result from an improper mechanical environment. We cultured hiPSC-CMs in a 96-well format on hyperelastic silicone membranes imitating their native mechanical environment, resulting in physiological responses to compound stimuli.We validated cell responses on the FLEXcyte 96, with a set of reference compounds covering a broad range of cellular targets, including ion channel modulators, adrenergic receptor modulators and kinase inhibitors. Acute (10 - 30 min) and chronic (up to 7 days) effects were investigated. Furthermore, the measurements were complemented with electromechanical models based on electrophysiological recordings of the used cell types.hiPSC-CMs were cultured on freely-swinging, ultra-thin and hyperelastic silicone membranes. The weight of the cell culture medium deflects the membranes downwards. Rhythmic contraction of the hiPSC-CMs resulted in dynamic deflection changes which were quantified by capacitive distance sensing. The cells were cultured for 7 days prior to compound addition. Acute measurements were conducted 10-30 minutes after compound addition in standard culture medium. For chronic treatment, compound-containing medium was replaced daily for up to 7 days. Electrophysiological properties of the employed cell types were recorded by automated patch-clamp (Patchliner) and the results were integrated into the electromechanical model of the system.Calcium channel agonist S Bay K8644 and beta-adrenergic stimulator isoproterenol induced significant positive inotropic responses without additional external stimulation. Kinase inhibitors displayed cardiotoxic effects on a functional level at low concentrations. The system-integrated analysis detected alterations in beating shape as well as frequency and arrhythmic events and we provide a quantitative measure of these. Y1 - 2020 U6 - http://dx.doi.org/10.1016/j.bpj.2019.11.3104 SN - 0006-3495 N1 - Raman, Arayind Hariharan im Artikel unter dem Namen: Raman, Alexander H. VL - 118 IS - Issue 3, Supplement 1 SP - 570a PB - Elsevier CY - Amsterdam ER - TY - JOUR A1 - Rausch, Valentin A1 - Kahmann, Stephanie Lucina A1 - Baltschun, Christoph A1 - Staat, Manfred A1 - Müller, Lars P. A1 - Wegmann, Kilian T1 - Pressure distribution to the distal biceps tendon at the radial tuberosity: a biomechanical study JF - The Journal of Hand Surgery N2 - Purpose Mechanical impingement at the narrow radioulnar space of the tuberosity is believed to be an etiological factor in the injury of the distal biceps tendon. The aim of the study was to compare the pressure distribution at the proximal radioulnar space between 2 fixation techniques and the intact state. Methods Six right arms and 6 left arms from 5 female and 6 male frozen specimens were used for this study. A pressure transducer was introduced at the height of the radial tuberosity with the intact distal biceps tendon and after 2 fixation methods: the suture-anchor and the cortical button technique. The force (N), maximum pressure (kPa) applied to the radial tuberosity, and the contact area (mm²) of the radial tuberosity with the ulna were measured and differences from the intact tendon were detected from 60° supination to 60° pronation in 15° increments with the elbow in full extension and in 45° and 90° flexion of the elbow. Results With the distal biceps tendon intact, the pressures during pronation were similar regardless of extension and flexion and were the highest at 60° pronation with 90° elbow flexion (23.3 ± 53.5 kPa). After repair of the tendon, the mean peak pressure, contact area, and total force showed an increase regardless of the fixation technique. Highest peak pressures were found using the cortical button technique at 45° flexion of the elbow and 60° pronation. These differences were significantly different from the intact tendon. The contact area was significantly larger in full extension and 15°, 30°, and 60° pronation using the cortical button technique. Conclusions Pressures on the distal biceps tendon at the radial tuberosity increase during pronation, especially after repair of the tendon. Clinical relevance Mechanical impingement could play a role in both the etiology of primary distal biceps tendon ruptures and the complications occurring after fixation of the tendon using certain techniques. Y1 - 2020 U6 - http://dx.doi.org/10.1016/j.jhsa.2020.01.006 SN - 0363-5023 VL - 45 IS - 8 SP - 776.e1 EP - 776.e9 PB - Elsevier CY - Amsterdam ER - TY - JOUR A1 - Abel, Alexander A1 - Kahmann, Stephanie Lucina A1 - Mellon, Stephen A1 - Staat, Manfred A1 - Jung, Alexander T1 - An open-source tool for the validation of finite element models using three-dimensional full-field measurements JF - Medical Engineering & Physics N2 - Three-dimensional (3D) full-field measurements provide a comprehensive and accurate validation of finite element (FE) models. For the validation, the result of the model and measurements are compared based on two respective point-sets and this requires the point-sets to be registered in one coordinate system. Point-set registration is a non-convex optimization problem that has widely been solved by the ordinary iterative closest point algorithm. However, this approach necessitates a good initialization without which it easily returns a local optimum, i.e. an erroneous registration. The globally optimal iterative closest point (Go-ICP) algorithm has overcome this drawback and forms the basis for the presented open-source tool that can be used for the validation of FE models using 3D full-field measurements. The capability of the tool is demonstrated using an application example from the field of biomechanics. Methodological problems that arise in real-world data and the respective implemented solution approaches are discussed. Y1 - 2020 U6 - http://dx.doi.org/10.1016/j.medengphy.2019.10.015 SN - 1350-4533 VL - 77 SP - 125 EP - 129 PB - Elsevier CY - Amsterdam ER -