Design Of Artificial Organs Research Articles

Intrinsically Disordered Synthetic Polymers in Biomedical Applications.

In biology and medicine, intrinsically disordered synthetic polymers bio-mimicking intrinsically disordered proteins, which lack stable three-dimensional structures, possess high structural/conformational flexibility. They are prone to self-organization and can be extremely useful in various biomedical applications. Among such applications, intrinsically disordered synthetic polymers can have potential usage in drug delivery, organ transplantation, artificial organ design, and immune compatibility. The designing of new syntheses and characterization mechanisms is currently required to provide the lacking intrinsically disordered synthetic polymers for biomedical applications bio-mimicked using intrinsically disordered proteins. Here, we present our strategies for designing intrinsically disordered synthetic polymers for biomedical applications based on bio-mimicking intrinsically disordered proteins.

Experimental Demonstration of Compact Polymer Mass Transfer Device Manufactured by Additive Manufacturing with Hydrogel Integration to Bio-Mimic the Liver Functions.

In this paper, we designed and demonstrated a stimuli-responsive hydrogel that mimics the mass diffusion function of the liver. We have controlled the release mechanism using temperature and pH variations. Additive manufacturing technology was used to fabricate the device with nylon (PA-12), using selective laser sintering (SLS). The device has two compartment sections: the lower section handles the thermal management, and feeds temperature-regulated water into the mass transfer section of the upper compartment. The upper chamber has a two-layered serpentine concentric tube; the inner tube carries the temperature-regulated water to the hydrogel using the given pores. Here, the hydrogel is present in order to facilitate the release of the loaded methylene blue (MB) into the fluid. By adjusting the fluid's pH, flow rate, and temperature, the deswelling properties of the hydrogel were examined. The weight of the hydrogel was maximum at 10 mL/min and decreased by 25.29% to 10.12 g for the flow rate of 50 mL/min. The cumulative MB release at 30 °C increased to 47% for the lower flow rate of 10 mL/min, and the cumulative release at 40 °C climbed to 55%, which is 44.7% more than at 30 °C. The MB release rates considerably increased when the pH dropped from 12 to 8, showing that the lower pH had a major impact on the release of MB from the hydrogel. Only 19% of the MB was released at pH 12 after 50 min, and after that, the release rate remained nearly constant. At higher fluid temperatures, the hydrogels lost approximately 80% of their water in just 20 min, compared to a loss of 50% of their water at room temperature. The outcomes of this study may contribute to further developments in artificial organ design.

Cardio-Pulmonary System Quantum Biological Thermodynamics with Finite Speed of the Cardio-Pulmonary System II - Computation of power and the entropy source of the cardio pulmonary system

The paper presents the results of the recent studies and research conducted within the Quantum Biological Thermodynamics with Finite Speed on the calculation and interpretation of the Cardio-Pulmonary System performance. Thus, based on the new PV/Px diagram developed for the Cardio-Respiratory System, an original Scheme for calculating the Mechanical Work and Power of the Heart/Lungs has been developed. The new Calculation Scheme allows to study the variation of the Heart and Lungs parameters for each person, in Quantum States and in Processes with and without Quantum Jump. Based on the values calculated in each Stationary State, for the cases studied, the diagrams of the Mechanical Work, of the total Power and the Entropy Source for the Cardio-Pulmonary System, as functions of the Frequencies of the Heart (FH), and the Lungs (FL), the maximum systolic pressure and body mass of the person were thus constructed. The study and interpretation of these diagrams - which are novel elements - provides information on interactions within the Cardio-Pulmonary System or between it and the entire body, particularly useful in bioengineering for optimized and personalized design of artificial organs.

Development of a globally optimised model of the cerebral arteries

The cerebral arteries are difficult to reproduce from first principles, featuring interwoven territories, and intricate layers of grey and white matter with differing metabolic demand. The aim of this study was to identify the ideal configuration of arteries required to sustain an entire brain hemisphere based on minimisation of the energy required to supply the tissue. The 3D distribution of grey and white matter within a healthy human brain was first segmented from magnetic resonance images. A novel simulated annealing algorithm was then applied to determine the optimal configuration of arteries required to supply brain tissue. The model was validated through comparison of this ideal, entirely optimised, brain vasculature with the structure and properties of real arteries. This analysis established that the human cerebral vasculature is highly optimised; closely resembling the most energy efficient arrangement of vessels. In addition to local adherence to fluid dynamical optimisation principles, the optimised vasculature reproduced expected brain perfusion territories, featuring well-defined boundaries between anterior, middle and posterior regions. This validated brain vascular model and algorithm can be used for patient-specific modelling of stroke and cerebral haemodynamics, identification of sub-optimal conditions associated with vascular disease, and optimising vascular structures for tissue engineering applications and artificial organ design.

Cardiomyocyte Differentiation of Embryonic Stem Cells on the Surface of Organic Semiconductors

Electrically active supports provide new horizons for bio-sensing and artificial organ design. Cell-based electrochemical biosensors can be used as bio-microactuators, applied to the biorobotics. Microchip-based bioassay systems can provide real-time cell analysis for preclinical drug design or for intelligent drug delivery devices. In regenerative medicine, electrically active supports can be used as bio-reactors to monitor cell activity, optimize the stem cell differentiation and control cell and tissue morphology. Biocompatibility and direct interaction of the electrically active surface with the cell surface is a critical aspect of this technology. In this work embryonic stem cells (AK7 ES) have been cultivated on the surface of thin films achieved through the evaporation of two aromatic compounds (T6 and PDI-8CN2 ) of particular interest for the fabrication of organic field-effect transistors (OFET). One of the potential advantages offered by the application of OFETs as bio-electronic supports is that they represent a powerful tool for the detection of bio-signals because their electrically active surface is an organic film. The cell morphology on T6 and PDI-8CN2 surface shows to be similar to the usual cell appearance, as obtained when standard culture support (petri dish) are employed. Moreover, our experimental results demonstrate that stem cells can be lead to differentiation up to "beating" cardiomyocytes even on these electrically-active organic films. This investigation encourages the perspective to develop OFET-based biosensors in order to accurately characterize stem cells during the cardiac differentiation process and eventually increase their differentiation efficiency.

Effect of Thermal Modulation on the Onset of Electrothermoconvection in a Dielectric Fluid Saturated Porous Medium

An electroconvection in a horizontal dielectric fluid saturated with a densely packed porous layer is investigated under the simultaneous action of vertical electric field and vertical temperature gradient when the walls of the layer are subjected to time periodic temperature modulation. The dielectric constant is assumed to be a linear function of temperature. A regular perturbation method based on small amplitude of applied temperature field is used to compute the critical values of Rayleigh number and wave number. The shift in the critical Rayleigh number is calculated as a function of frequency of modulation, electric Rayleigh number, Prandtl number, and Darcy number, and their effects on the critical Rayleigh number are discussed. The situations which are favorable for the design of artificial organs without the side effect of hemolysis are explained.

Finite element analysis of blood flow characteristics in a Ventricular Assist Device (VAD)

The replacement or augmentation of failing human organs with artificial devices and systems has been an important element in health care for several decades. There are a lot of geometrical and flow considerations in the artificial organs that are developed to perform in contact with the blood particles. For example, preventing the stagnation, high pressure and shear regions is an important consideration in artificial organ design. In this paper, the geometrical and boundary conditions for the blood flow in the HeartSaver Ventricular Assist Device (VAD) are studied using the numerical solution of the governing equations. In order to provide the interaction between the blood and the elastic diaphragm and between the blood and the inlet/outlet valves, the Fluid-Structural Interaction (FSI) approach is used in this study. Arbitrary Lagrangian–Eulerian (ALE) Finite Element Method (FEM) formulation is used for the numerical solution of the flow domain. Blood and the driving fluid are assumed as isothermal, Newtonian, viscose and incompressible fluids. The numerical solution has provided the required characteristics for the evaluation of the performance of the VAD in contact with the realistic flow conditions. Although they present the formation of wakes in the blood chamber, no stagnation points and high shear rate zones are detected in the blood chamber.

Mathematical Models of Blood Coagulation and Platelet Adhesion: Clinical Applications

At present, computer-assisted molecular modeling and virtual screening have become effective and widely-used tools for drug design. However, a prerequisite for design and synthesis of a therapeutic agent is determination of a correct target in the metabolic system, which should be either inhibited or stimulated. Solution of this extremely complicated problem can also be assisted by computational methods. This review discusses the use of mathematical models of blood coagulation and platelet-mediated primary hemostasis and thrombosis as cost-effective and time-saving tools in research, clinical practice, and development of new therapeutic agents and biomaterials. We focus on four aspects of their application: 1) efficient diagnostics, i.e. theoretical interpretation of diagnostic data, including sensitivity of various clotting assays to the changes in the coagulation system; 2) elucidation of mechanisms of coagulation disorders (e.g. hemophilias and thrombophilias); 3) exploration of mechanisms of action of therapeutic agents (e.g. recombinant activated factor VII) and planning rational therapeutic strategy; 4) development of biomaterials with non-thrombogenic properties in the design of artificial organs and implantable devices. Accumulation of experimental knowledge about the blood coagulation system and about platelets, combined with impressive increase of computational power, promises rapid development of this field.

Sol-gel Chemistry in Medicinal Science

The sol-gel process is an inorganic polymerization process taking place in mild conditions, allowing the association of mineral phases with organic or biological systems. The possibility to immobilize drugs, enzymes, antibodies and even whole cells without loss of their biological activity led to the development of diagnostic tools, drug delivery carriers as well as new hosts for artificial organ design. These systems take profit from the wide variety of chemical compositions, dimensions and forms that can be achieved via sol-gel chemistry. Recent advances involve multi-functional "smart" devices combining biocompatibility, biological activity and stimuli-responsive materials. The design of such novel devices with significant added value when compared to current products is probably a key factor when foreseeing industrial developments of sol-gel materials in medicinal science.

The Digital Human: Towards a Unified Ontology

THE EXPONENTIAL INCREASE in biological data resulting from the latest automated experimental techniques and the accelerated availability of molecular sequences has provided an explosion of empirical data and analysis on the molecular foundations of biological structure and function. The complexity of this kind of analysis has grown to the point where biological systems can best be understood by using modern computers. Computers were essential for sequencing the human genome and will be even more important for understanding how genomes work by developing computer simulations of their functions. These tools can also make it possible to visualize the operation of complex systems—how cells assemble miniature machines or how defects in electrical networks degrade the performance of a heart—and allow one to “see” what happens when these system are altered with drugs, surgeries, or other therapies. The ability to simulate biological systems will give us an extraordinary set of new tools that could increase economic productivity while reducing pollution and our need for natural resources. We have reached a critical juncture where model integration using diverse data derived from various biomedical domains can significantly enhance our understanding of complex phenomenon in normal human function and disease states. Integration of all of this data into a “Digital Human” will help biomedical researchers master the staggering complexity of their discoveries, physicians make effective use of their discoveries to improve health, and engineers imitate biological mechanisms to achieve revolutionary change in computing, for the design of artificial organs, robots, and a variety of other applications. The ultimate goal of the Digital Human is construction of a complete, functioning, accessible simulation of the human body—from the performance of DNA and other molecules within individual cells to the operation of entire organ systems such as the heart, lungs, brain, and musculo-skeletal systems. The following example outlines why cell models are essential for the Digital Human and why the Digital Human is a worthy goal. Investigators working in cardiac modeling and simulation provide a particularly compelling example. Sophisticated models of cellular, tissue and organ systems have been built from a variety of data sources: diagnostic images, electrophysiological measures, biomechanics, bioelectric fields, and ionic studies. The teams have used this model to build sophisticated simulations that provide insight into the physiology of the heart not possible from studies limited to a single level of analysis. The models have, for example, allowed a detailed understanding of the mechanisms of heart disease, such as arrthymias, ischemia and myopathy that allow them to explore a range of potential new strategies for therapies. Cell models, many of which are being developed through the BioSPICE effort, are essential for understanding the structure and function of the heart. For example, investigators have shown that a mutation in the SCN5A gene produces a structurally defective sodium channel that causes cardiac arrhythmia when inserted into an integrated, quantitative computer model of a cardiac cell (Clancy and Rudy, 1999). The Digital Human will represent human biology at all physical scales, from organs to tissues to cells and protein. However, for this technology to be realized, researchers need to develop common knowledge

Modeling and simulation of pulsatile blood flow with a physiologic wave pattern.

This article presents a computational fluid dynamics (CFD) model to analyze pulsatile blood flow in a human artery. The model assumes the vessel as being a straight wall tube, and the blood flow is considered to be incompressible, Newtonian, and axisymmetric. Physiologically realistic resting conditions were adopted for the simulation tests. The main objective was to identify regions where pulsatile effects were significant. Velocity profiles were obtained for both normal and stenosed vessels. The results have shown that, for normal vessels, pulsatile effects prevail close to the vessel wall. The presence of stenosed sections resulted in flow alterations, with flow recirculation areas changing both size and location during the cardiac cycle. These results are especially important in the design of artificial organs. The knowledge of the flow pattern in complex geometries such as artificial hearts, prosthetic valves, and ventricular assist devices can help avoid or minimize thrombogenesis and hemolysis.

Shape memory alloys: Properties and biomedical applications

Shape memory alloys provide new insights for the design of biomaterials in bioengineering for the design of artificial organs and advanced surgical instruments, since they have specific characteristics and unusual properties. This article will examine (a) the four properties of shape memory alloys, (b) medical applications with high potential for improving the present and future quality of life, and (c) concerns regarding the biocom-patibility properties of nickel-titanium alloys. In particular, the long-term challenges of using shape memory alloys will be discussed, regarding corrosion and potential leakage of elements and ions that could be toxic to cells, tissues and organs.

Implant Science of Artificial Organ: Design for Success

Although many artificial organs have come to be used clinically, there still remain many problems such as thrombus formation, calcification, infection, malfunction, etc., that sometimes expose the patient to danger. One of the causes of these damages is that we do not know the true mechanisms of these phenomena. In other words, the design criteria of implant devices have not yet been established under scientific basis. It is very important that we artificial organ researchers and manufacturers establish the implant science of artificial organs. In this paper, mention is made of the kinds of factors we should consider for the design of artificial organs and how we should approach them scientifically. Also introduced is our approach method for an implantable total artificial heart.

N‐acetylglucosamine and adenosine derivatized surfaces for cell culture: 3T3 fibroblast and chicken hepatocyte response

3T3 fibroblasts and primary chicken hepatocytes were cultured on derivatized polystyrene surfaces to examine the effect of cell-specific ligands on cellular morphology and growth. Surfaces were prepared by derivatizing chloromethylated polystyrene with N-acetylglucosamine (GlcNAc; recognized by the chicken asialoglycoprotein receptor) and adenosine (not recognized by adult hepatocytes). These surfaces were compared with tissue culture polystyrene (TCPS), acid-cleaned glass, and the unmodified chloromethylated polystyrene. The spreading, cytoskeletal structure and growth of the fibroblasts following attachment to these surfaces were examined. The extent of attachment, total protein levels, and DNA contents for surfaces-attached chicken hepatocytes were also measured. Fibroblast spreading was greatest on polymer surfaces derivatized with GlcNAc, whereas cytoskeletal structure and growth rate were independent of surface chemistry. Although chicken hepatocytes attached most efficiently to the GlcNAc derivatized polymer, the total protein and DNA levels of the surface-attached cells were not affected. In anticipation of the application of these polymers for cell culture and hybrid artificial organ design, the GlcNAc-derivatized polystryrene was fabricated into porous microcarriers. Fibroblasts grew avidly on the microcarriers, whereas chicken hepactocytes adhered well to the formed large aggregates around the microcarriers.

Mechanical Test Methods for Biomedical Membranes

It is important to estimate the mechanical characteristics and strength of biomedical membrane. For this purpose, previously we have proposed several mechanical test methods for biomedical membranes. To establish the safety design for biomedical membrane, such as cellophane membrane for hemodialysis, it is important to estimate the viscoelastic characteristics of these materials. On the other hand, artificial biomedical membrane such as tympanic membrane, are subjected to noncontact internal air pressure under the membranous state. To estimate mechanical characteristics of such membrane, it is necessary to develop a well-simulated test under the gaseous pressure and the other mechanical test under the membranous state. In this paper, several test methods for these purposes were shown. Furthermore, results obtained by these methods were shown and related to clinical problems. These proposed test methods are quite different from the axial tensile test. But they are also important to estimate the mechanical property of biomedical membrane. Each result obtained by these test methods has its own significance. By selection of the most suitable test method for each purpose and revealing these mutual relations, safety design of artificial organs can be performed from the viewpoint of the strength.

Significance of Biomechanics in the Design of Artificial Organs and Biomaterials

Significance of Biomechanics in the Design of Artificial Organs and Biomaterials

Analysis of Interfacial Phenomena of Proteins for Design of Artificial Organs

Analysis of Interfacial Phenomena of Proteins for Design of Artificial Organs

Information and Control in Organ Systems

DESIGNERS of artificial internal organs face many difficult physical and physiological requirements. In order to correct for an organic malfunction, it is necessary for these prosthetic devices to carry out certain physicochemical operations under the control of both specific and not-so-specific signals that originate inside the body and/or in the outside world. This task calls for the establishment of adequate information-matching procedures. The devices must be prepared to deal with control signals in the form of spatiotemporal patterns of electrical, mechanical, or even chemical activity. Appropriate coding (including the necessary redundancy) must insure the transmission of the information-bearing elements, or ``distinctive features,'' of these paterns in the presence of various types of interference, or ``noise.'' In many instances, our knowledge of the control circuits for the various organs is still incomplete. Neuro-physiological research during the last decade has, for instance, focused on elucidating the role of the less specific ascending and descending pathways in the nervous system, in contrast with the better-known (``classical'') afferent pathways. <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">1</sup> Designers of artificial organs are thus often faced with specifications that lack some of the most important data. Another difficulty that stands in the way of establishing rational procedures for the design of artificial organs is our inability to agree upon the evaluation of the performance of a device that has multiple inputs and multiple outputs and that only too often fulfills multiple functions. Under such circumstances, it is not reasonable to hope for a simple, unambiguous figure of merit or of efficiency.