Electrolyte disorders in the human ventricle. A simulation study.

Ventricular cells are immersed in a bath of electrolytes and these ions are essential for a healthy heart and a regular rhythm. Maintaining physiological concentration of them is fundamental for reducing arrhythmias and risk of sudden cardiac death, especially in haemodialysis patients and in the heart diseases treatments. Models of electrically activity of the heart based on mathematical formulation are a part of the efforts to improve the understanding and prediction of heart behaviour. Modern models incorporate the extensive and ever increasing amounts of experimental data in incorporating biophysically detailed mechanisms to allow the detailed study of molecular and subcellular mechanisms of heart disease. The goal of this project was to simulate the effects of changes in potassium and calcium concentrations in the extracellular space between experimental data and and a description incorpored into two modern biophysically detailed models (Grandi et al. Model; O’Hara Rudy Model). Moreover the task was to analyze the changes in the ventricular electrical activity, in particular by studying the modifications on the simulated electrocardiographic signal. We used the cellular information obtained by the heart models in order to build a 1D tissue description. The fibre is composed by 165 cells, it is divided in four groups to differentiate the cell types that compound human ventricular tissue. The main results are the following: Grandi et al. (GBP) model is not even able to reproduce the correct action potential profile in hyperkalemia. Data from hospitalized patients indicates that the action potential duration (APD) should be shorter than physiological state but in this model we have the opposite. From the potassium point of view the results obtained by using O’Hara model (ORD) are in agreement with experimental data for the single cell action potential in hypokalemia and hyperkalemia, most of the currents follow the data from literature. In the 1D simulations we were able to reproduce ECGs signal in most the potassium concentrations we selected for this study and we collected data that can help physician in understanding what happens in ventricular cells during electrolyte disorder. However the model fails in the conduction of the stimulus under hyperkalemic conditions. The model emphasized the ECG modifications when the K+ is slightly more than physiological value. In the calcium setting using the ORD model we found an APD shortening in hypocalcaemia and an APD lengthening in hypercalcaemia, i.e. the opposite to experimental observation. This wrong behaviour is kept in one dimensional simulations bringing a longer QT interval in the ECG under higher [Ca2+]o conditions and vice versa. In conclusion it has highlighted that the actual ventricular models present in literature, even if they are useful in the original form, they need an improvement in the sensitivity of these two important electrolytes. We suggest an use of the GBP model with modifications introduced by Carro et al. who understood that the failure of this model is related to the Shannon et al. model (a rabbit model) from which the GBP model was built. The ORD model should be modified in the Ca2+ - dependent IcaL and in the influence of the Iks in the action potential for letting it him produce a correct action potential under different calcium concentrations. In the 1D tissue maybe a heterogeneity setting of intra and extracellular conductances for the different cell types should improve a reproduction of the ECG signal.

Design methods and geometric modelling of scaffolds for bone tissue engineering

Every year, thousand of surgical treatments are performed in order to fix up or completely substitute, where possible, organs or tissues affected by degenerative diseases. Patients with these kind of illnesses stay long times waiting for a donor that could replace, in a short time, the damaged organ or the tissue. The lack of biological alternates, related to conventional surgical treatments as autografts, allografts, e xenografts, led the researchers belonging to different areas to collaborate to find out innovative solutions. This research brought to a new discipline able to merge molecular biology, biomaterial, engineering, biomechanics and, recently, design and architecture knowledges. This discipline is named Tissue Engineering (TE) and it represents a step forward towards the substitutive or regenerative medicine. One of the major challenge of the TE is to design and develop, using a biomimetic approach, an artificial 3D anatomy scaffold, suitable for cells adhesion that are able to proliferate and differentiate themselves as consequence of the biological and biophysical stimulus offered by the specific tissue to be replaced. Nowadays, powerful instruments allow to perform analysis day by day more accurateand defined on patients that need more precise diagnosis and treatments.Starting from patient specific information provided by TC (Computed Tomography) microCT and MRI(Magnetic Resonance Imaging), an image-based approach can be performed in order to reconstruct the site to be replaced. With the aid of the recent Additive Manufacturing techniques that allow to print tridimensional objects with sub millimetric precision, it is now possible to practice an almost complete control of the parametrical characteristics of the scaffold: this is the way to achieve a correct cellular regeneration. In this work, we focalize the attention on a branch of TE known as Bone TE, whose the bone is main subject. Bone TE combines osteoconductive and morphological aspects of the scaffold, whose main properties are pore diameter, structure porosity and interconnectivity. The realization of the ideal values of these parameters represents the main goal of this work: here we'll a create simple and interactive biomimetic design process based on 3D CAD modeling and generative algorithmsthat provide a way to control the main properties and to create a structure morphologically similar to the cancellous bone. Two different typologies of scaffold will be compared: the first is based on Triply Periodic MinimalSurface (T.P.M.S.) whose basic crystalline geometries are nowadays used for Bone TE scaffolding; the second is based on using Voronoi's diagrams and they are more often used in the design of decorations and jewellery for their capacity to decompose and tasselate a volumetric space using an heterogeneous spatial distribution (often frequent in nature). In this work, we will show how to manipulate the main properties (pore diameter, structure porosity and interconnectivity) of the design TE oriented scaffolding using the implementation of generative algorithms: "bringing back the nature to the nature".