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PubMedDate not supplied

Hybrid artificial cells: microencapsulation of living cells.

In 1965, the use of artificial cells for the microencapsulation of living cells was demonstrated. At that time, this technique was also proposed for use in immunoisolation of endocrine cells, islets, and hepatocytes as hybrid artificial organs. Progress in the biotechnology of cell culture in the last 10 years has allowed this approach to be extensively investigated by an increasing number of centers. The author's recent studies concentrated on microencapsulation of hepatocytes as a model system. Such cells were implanted to increase the survival of galactosamine induced fulminant hepatic failure rats, or to decrease the high bilirubin levels in Gunn rats and xenografts of microencapsulated rat hepatocytes into mice provided immunoisolation. Furthermore, hepatocyte secreted hepatic stimulating factors (mw 110,000 D) accumulating in the microcapsules helps to increase the viability of the hepatocytes. In addition to these studies, a novel, two step cell encapsulation method was developed to improve immunoisolation and biocompatibility. Microencapsulation of microorganisms was also carried out using a model microorganism to convert serum cholesterol to carbon dioxide.

Animals↗
PubMed1993

Biomaterials in medicine--a bioengineering perspective.

Biomaterials are considered with an emphasis on those used in artificial organs. Attention is drawn to the importance of the polymeric biomaterials and factors which affect their properties. Functions of membranes, sorbents, blood tubing, ventricular diaphragms and cell culture substrates are examined in order to obtain a summary of fundamental properties. Observations are made on the importance of blood compatibility assessment and its association with a biomaterial structure-property relationship. Blood-biomaterial interactions are discussed in terms of an overall relationship between the three components--blood, biomaterial and antithrombotic agent, with examples given of factors influencing each component. Cell-biomaterial interactions are examined in the areas of toxicity evaluation and the promotion of cell attachment and growth, where an overall relationship is described for the cell, growth medium and growth factors, and the biomaterial acting as a substrate.

Animals↗
PubMed1998

Blood compatible polymers in intensive care units: state of the art and current aspects of biomaterials research.

The use of artificial organs in cases of acute renal failure, acute respiratory distress syndrome (ARDS) and multiorgan dysfunction syndrome (MODS) has lead to a significant reduction of mortality. However, the interaction between body and biomaterials results in the activation of the coagulation system and in the induction of systemic inflammatory response syndrome. The necessary anticoagulation may be contraindicated and may even further increase the risk for the patient. This article evaluates the currently applied polymeric materials used in intensive care units (ICU) and gives a possible outlook into future developments. It is emphasized that systematic interdisciplinary research of physicians and biomaterial scientists is essential for the successful development of new polymers with improved biocompatibility. For this purpose a brief overview of analytical techniques for surface characterization is given, and future developments to a fully biocompatible polymer are described.

Artificial Organs↗
PubMed1987

Review of medical biosensors and associated materials problems.

Developers of biosensors as medical devices are using emerging technologies that incorporate chemical assays with fiber optics and semiconductors. These biosensors will eventually become indwelling catheters for monitoring blood analyte concentrations as well as functioning as controlled feedback elements for artificial organs. Materials used in these devices are subject to problems of manufacture and reliability as well as those induced by the human body's response to these "foreign agents." The Division of Mechanics and Materials Science in the Center for Devices and Radiological Health at the Food and Drug Administration has initiated a program to investigate factors that effect sensitivity, selectivity and reliability of sensors used in biological applications. Our group's principle focus is on sensors of chemical processes. This article is an outgrowth of our research efforts and is a review of some of the technologies that are currently available or becoming available for these applications. The goal of our research is to identify factors that will have an impact on the reliability of long-term implanted medical devices with particular attention to sensors used in feedback-controlled therapeutic systems.

Artificial Organs↗
PubMedDate not supplied

Development of a novel intrafascicular nerve electrode.

Artificial organs could be controlled using autonomic neural signals, because they exhibit rapid responses to physical needs similar to those of natural organs. A nerve electrode must satisfy many requirements to measure autonomous neural signals such as a long lifetime, high signal-to-noise ratio, multichannel recording, simple installation into a nerve fascicle, and good manufacturing productivity. The purpose of our study is to propose and evaluate a novel nerve electrode that satisfies these conditions, which to date has not been developed. A novel intrafascicular nerve electrode was designed, fabricated, and evaluated on autonomic nerves. Conventional extrafascicular and intrafascicular nerve electrodes were fabricated and tested for comparison to our novel intrafascicular nerve electrode. The novel intrafascicular nerve electrode had a 3-week lifetime, whereas the conventional extrafascicular nerve electrode had a 2-week lifetime. The signal-to-noise ratio was improved from 1.6 to 2.0 compared with the conventional extrafascicular nerve electrode. The novel intrafascicular nerve electrode was easier to install into a nerve fascicle and had better manufacturing productivity than the conventional intrafascicular nerve electrode. We succeeded in demonstrating the feasibility of our novel intrafascicular nerve electrode.

Animals↗
PubMed1989

Experimental study on the adsorption of excess heparin with anion exchange resin fiber.

Anion exchange resin fiber (Ionex) was used as a heparin adsorbent. Ionex has the adsorption capacity of 70 mg/g (weight by desiccation) for heparin, and was used in an attempt to remove the heparin from blood-perfused artificial organs, before the blood was transfused back into the patients. In the ex vivo study, the 5 systemically heparinized dogs (500 U/kg) were treated with a 35-40 g column of Ionex, by direct hemoperfusion (DHP). The concentration of heparin was significantly reduced, within 15 to 60 minutes, using the Ionex. This suggested the possibility of removing excess heparin from the living body. In in vitro, the relationship between the amount of heparin by Ionex and the blood-flow volume were evaluated. Whole blood taken from dogs was added to 5 U/ml of heparin. This was then introduced into a small column containing 0.9 g Ionex, at blood-flow rates of 0.8, 1.6, and 3.2 ml/min. A good adsorption capacity was shown at the blood-flow rate of 0.8 ml/min. One possible explanation for this is that the heparin dispersed in the blood cells gradually was passed on into the plasma and, so, did not have time to be adsorbed at the faster flow rates.

Adsorption↗
PubMed2003

Shear stress related blood damage in laminar couette flow.

Artificial organs within the blood stream are generally associated with flow-induced blood damage, particularly hemolysis of red blood cells. These damaging effects are known to be dependent on shear forces and exposure times. The determination of a correlation between these flow-dependent properties and actual hemolysis is the subject of this study. For this purpose, a Couette device has been developed. A fluid seal based on fluorocarbon is used to separate blood from secondary external damage effects. The shear rate within the gap is controlled by the rotational speed of the inner cylinder, and the exposure time by the amount of blood that is axially pumped through the device per given time. Blood damage is quantified by the index of hemolysis (IH), which is calculated from photometric plasma hemoglobin measurements. Experiments are conducted at exposure times from texp=25 - 1250 ms and shear rates ranging from tau=30 up to 450 Pa ensuring Taylor-vortex free flow characteristics. Blood damage is remarkably low over a broad range of shear rates and exposure times. However, a significant increase in blood damage can be observed for shear stresses of tau>or= 425 Pa and exposure times of texp>or= 620 ms. Maximum hemolysis within the investigated range is IH=3.5%. The results indicate generally lower blood damage than reported in earlier studies with comparable devices, and the measurements clearly indicate a rather abrupt (i.e., critical levels of shear stresses and exposure times) than gradual increase in hemolysis, at least for the investigated range of shear rates and exposure times.

Animals↗
PubMed1997

Kidney failure and transplantation in China.

The incidence of chronic renal failure in China is approximately 120,000 cases per year; the vast majority of these new cases will die within a very short time because of the shortage of funds, dialysis machines, and organs for transplantation. This paper focuses on the reasons behind the organ shortage and the strategies proposed by the Chinese medical profession to increase the supply of transplantable kidneys. The data were gathered on multiple trips to China, Hong Kong and Taiwan between August 1993 and January 1995. During these trips the author spoke formally with nephrologists, urologists, dialysis and transplant nurses, and other individuals active in the field of organ procurement, and informally with others familiar with general hospital practice. The author also draws heavily on articles published in leading Chinese journals. The kidney shortage in China is produced by the same sorts of problems as exist in other countries, but the shortage is aggravated by certain beliefs and practices specific to Chinese populations. Live donation is hampered by traditional beliefs about the function of the kidney, while cadaver donation is hampered by reluctance to cut a body and a host of beliefs about ghosts, labeled "feudal superstitions" by the authorities. Cadaver donation is further restrained by the lack of legal recognition of "brain death". In response to the organ shortage, the Chinese medical community has expanded the range of eligible sources to include those condemned to death as criminals, a practice itself usually condemned by the wider international community. At the same time it has advocated: (1) enhancing corpse donation through propaganda work, administrative work, legal work, and incentives; (2) encouraging live donation; (3) familiarizing the public with the benefits of organ transplantation, and (4) pursuing the development of artificial organs.

Attitude to Death↗
PubMed2002

A new haptic interface for VR medical training.

Successful applications of haptic displays are limited to tool-based interfaces that simulate haptic effects on surgical and other medical instruments. However, no satisfactory haptic display exist so far, that enable the simulation of high fidelity palpation of human tissue or body segments. Existing approaches developed for medical training fail due to unrealistic haptic effects, time-consuming donning and doffing, and inconvenient use (e.g., mechatronic tactile and kinesthetic displays) or due to restricted function and adjustability (e.g., passive mannequins). The key idea of the new haptic interface is to attach artificial organs or segments (e.g. a plastic leg) to a force actuating mechatronic unit (e.g. robot). A set of different materials combined in certain layers yield components that look and feel like real objects. When the user touches the artificial object the contact forces and position changes are measured and fed into a model-based controller. Thus, the actuator moves the object so that the user gets the impression that he had induced the movement. The new haptic display has been verified with a setup developed for the training of functional joint evaluation after knee injuries. Compared to classical approaches, this display is convenient to use, provides realistic tactile properties and can be partly adjusted to different system properties (e.g. pathological joint properties). This kind of new interface can be applied to many different medical applications, where the clinician directly touches human limbs or tissue, such as in obstetrics, reanimation, organ palpation, etc.

Artificial Organs↗
PubMed1992

Hepatocyte culture systems for artificial liver support: implications for critical care medicine (bioartificial liver support).

OBJECTIVE: The primary purpose of this review article is to familiarize critical care practitioners with newly developing techniques of hybrid artificial liver support. Implantable and extracorporeal hepatocyte culture systems are emphasized based on their current experimental and clinical status. DATA SOURCES: Data used to prepare this document were obtained from the authors' personal files, as well as the computerized MEDLINE database. Medical headings used include: liver, artificial organs, cell culture, growth hormones, extracellular matrix, and transplantation. Only articles published in English have been cited. STUDY SELECTION: All studies are discussed in which hepatocyte culture systems have been used to support human patients with liver failure. All studies reported the patient's condition before therapy, duration of therapy, and outcome after therapy in order to be included in this review. Since the number of clinical trials is small at this time, animal studies were used to demonstrate application of other systems in the treatment of experimentally induced liver failure. Similar selection criteria were used to select animal studies for review. All initially identified human studies met these selection criteria. DATA EXTRACTION: Independent extraction by multiple observers. DATA SYNTHESIS: Liver failure, resulting from infection, drugs, or as a part of the multiple organ failure syndrome, remains a major cause of morbidity, mortality, and resource allocation. Current therapy is limited to supportive care, along with liver transplantation. Because of these therapeutic limitations, hybrid artificial liver systems have been proposed for temporary and long-term hepatic support. Several animal studies and a small number of preliminary human studies indicate that hepatocyte culture systems are capable of supporting nearly all essential hepatic functions and may supply biologically active substances that promote regeneration and repair of the damaged liver being supported. Hybrid systems may be constructed from materials that serve as immunoprotective barriers against host defenses. CONCLUSIONS: During the past decade, important progress has been made with hybrid artificial liver support systems. Cell culture technology has progressed sufficiently so that an artificial liver, composed of metabolically active hepatocytes, may be a potential reality in the foreseeable future. Both implantable and extracorporeal artificial liver support systems have been developed to provide metabolic support during acute liver failure, or to serve as a bridge to solid organ transplantation. Implantable hepatocyte systems, however, require a prolonged period for intraperitoneal engraftment and vascularization, not typically available to patients with acute liver failure. For this reason, extracorporeal hybrid designs offer the greatest hope for on-line treatment of acute liver failure. Such systems are entering the final stages of animal testing.

Animals↗
PubMedDate not supplied

Xenotransplantation: how to overcome the complement obstacle?

The xenotransplantation research is driven by the shortage of allografts for transplantation of patients with end-stage organ failure and by lack of success in developing suitable artificial organs. Pigs are now generally accepted to be the donor species of choice, although a possible risk for transmission of xenozoonoses, particularly pig endogenous retroviruses, should be born in mind. A vascular xenograft from pig to human is usually rejected hyperacutely due to naturally occurring antibodies and complement. This hyperacute rejection can be prevented by manipulating with either of these systems. In this review we briefly describe the hyperacute rejection and how it can be prevented by complement modulation. Pigs made transgenic for human complement regulatory proteins seem very promising for future clinical experiments. Control of fluid-phase complement activation should be obtained as well. The latter is discussed based on our own recent studies in this field.

Animals↗
PubMed1998

Some politico-economic aspects of organ shortage in transplantation medicine.

Transplantation of solid organs has become a widely performed and accepted procedure. This type of high-performance medicine has led to vigorous debates on ethical and economic issues and most of this discussion can be seen as an example of the different opinions about highly individualised and technologised approaches in health care. The paper focuses on the rising gap in the demand for suitable organs for transplantation and the levelling off, or even fall, in the supply of these organs. Despite the rather demanding requirements for organ donation, there appear to be a sufficient number of deaths under suitable circumstances to satisfy the annual demand of transplantable organs--if the collection rates are adequate. It has been shown that there are great differences in the rate of organ procurement efficiency within different regions. The question then is how to set appropriate incentives to obtain organs in sufficient quantities from eligible donors to meet the demand. This paper discusses the different medical and societal approaches as well as the economic proposals to overcome the organ shortage. The theory of Public Choice is used to develop a specific policy that can be applied to organ procurement efforts. This is a different approach, whereby political and economic considerations of ethical dilemmas focus on setting appropriate and widely accepted frameworks and rules, in which individuals may then decide about their behaviour. In an appendix, the economic consequences of transplantation medicine are discussed if more organs were to be made available and the impacts of relaxing the simplifying assumptions on effectiveness of organ replacement therapy and on the allocation system are considered. Ultimately, artificial organs or genetically transformed animal organs may be used but it is highly likely that a vigorous debate on the ethics and especially financial implications of these interventions will take place beforehand.

Commerce↗
PubMed2003

Artificial fish schools: collective effects of school size, body size, and body form.

Individual-based models of schooling in fish have demonstrated that, via processes of self-organization, artificial fish may school in the absence of a leader or external stimuli, using local information only. We study for the first time how body size and body form of artificial fish affect school formation in such a model. For a variety of group sizes we describe how school characteristics (i.e., group form, spread, density, polarization, turning rate, and speed) depend on body characteristics. Furthermore, we demonstrate that the nearest neighbor distance and turning rate of individuals are different for different regions in the group, although the agents are completely identical. Our approach shows the significance of both self-organization and embodiment in modeling of schools of artificial fish and, probably, in structuring schools of real fish.

Animals↗
PubMed2003

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.

Arteries↗
PubMed2004

Cloning and transgenesis in mammals: implications for xenotransplantation.

Availability of suitable organs for transplantation remains of major concern and projections indicate that the problem will continue to increase. Therefore, alternatives to the use of human organs for transplantation, continue to be explored including use of stem cells, artificial organs, and organs from other species (xenotransplantation). In xenotransplantation, the species of choice remains the pig due to its physiological similarities to humans, reduced costs, ease of manipulation, and reduced ethical concerns to its use. However, in order to develop pig organs that are suitable for xenotransplantation, complex genetic modification need to be undertaken. These modifications require the introduction of precise genetic changes into the pig that can only be accomplished at this time using somatic cell nuclear transfer. We cover in this review advances in transgenic manipulation and cloning in swine and how the development of these two technologies is critical to the eventual utilization of the pig as a human organ donor.

Animals↗
PubMed2004

Artificial cells for cell and organ replacements.

The artificial cell is a Canadian invention (Chang, Science, 1964). This principle is being actively investigated for use in cell and organ replacements. The earliest routine clinical use of artificial cells is in the form of coated activated charcoal for hemoperfusion for use in the removal of drugs, and toxins and waste in uremia and liver failure. Encapsulated cells are being studied for the treatment of diabetes, liver failure, and kidney failure, and the use of encapsulated genetically-engineered cells is being investigated for gene therapy. Blood substitutes based on modified hemoglobin are already in Phase III clinical trials in patients, with as much as 20 units being infused into each patient during trauma surgery. Artificial cells containing enzymes are being developed for clinical trial in hereditary enzyme deficiency diseases and other diseases. The artificial cell is also being investigated for drug delivery and for other uses in biotechnology, chemical engineering, and medicine.

Artificial Organs↗
PubMed2004

Performance of diffusion gradient in thin films to evaluate the toxic fraction of copper to Daphnia magna.

This study investigates the relevance of the diffusion gradient in thin films technique (DGT) to measure copper's induced lethality on Daphnia magna in natural water spiked with various organic ligands. Ethylenediaminetetraacetic acid (EDTA), nitrilotriacetic acid (NTA), and glycine were used as artificial organic ligands in controlled solutions of mineral water. With EDTA, DGT measurement makes it possible to predict the toxicity of the mixture because Cu-EDTA complexes are inert, whereas DGT is of no help in the case of NTA, because Cu-NTA complexes are fully labile. The Cu-glycine complexes appear as partly labile and toxic. Humic acids as well as fresh and aged algae extracts also were used as models for natural dissolved organic matters. All three of them form copper complexes that are not toxic to Daphnia magna and appear as partly labile with open-pored DGT. However, the use of restricted gels in DGT greatly reduces the contribution of labile complexes, at least for humic acids and aged algae copper complexes. The DGT with restrictive gels, therefore, appears to be a powerful tool for measuring bioavailable copper in natural water bodies, especially when the dissolved organic matter mostly is of humic origin. The DGTs potential ability to mimic the lability induced by the biological uptake also is discussed.

Animals↗
PubMed1994

[What future for clinical xenograft of the liver?].

In the cyclosporine era liver orthotopic allotransplantation has shown to be very effective in the treatment of many end-stage liver diseases. Currently, the major limitation in clinical transplantation is the shortage of donor organs unlikely solvable by alternative policies or approaches such as living donors and artificial organs. Animals have been considered as an alternative source of organs offering the following advantages: availability of a predictable and ready supply of donor organs, opportunity to practice transplantation as an elective procedure, possibility to match the size of the graft recipient. However, immunologic barriers are thought to make xenotransplantation impractical between widely divergent (discordant) species. Hyperacute xenograft rejection, in fact, consists of an immediate, diffuse intravascular coagulopathy followed by an aggressive cellular reaction. Recipient preformed natural antibodies and complement are involved in the humoral phase of hyperacute rejection. The violence of this reaction depends on the titer of natural antibodies and on the divergency of the species involved. Species more closely related (concordant) exhibit a less aggressive reaction characterized by an acute cellular rejection. Hepatic allografts and xenografts, though, are unusually resistant to humoral injury and undergo a combination of both humoral and cellular rejection. Preliminary studies have demonstrated a prolonged reduction in natural antibodies accomplished by plasmapheresis and cyclophosphamide combined treatment. Furthermore, new therapeutic agents such as FK 506, rapamycin and deoxyspergualin may find widespread application in clinical transplantation. FK 506 has shown to possess a remarkable efficacy in reversing refractory hepatic allograft rejection as well as ability to inhibit humorally mediated immunity.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗