[The problem of hitherto know dialyzable toxins, removable from the organism by artificial kidney, hemoperfusion and forced diuresis].
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Damage or loss of a tissue or organ is common, costly, and tragic. Advances in mechanical artificial organs and organ transplantation have improved the treatment of organ failure, and advances in molecular immunology, tissue engineering, and stem cell biology offer the promise of even better therapeutic modalities for treating organ failure in the future. Enhancement of immune tolerance of transplanted tissues, improved understanding of cellular differentiation and tissue development, and advances in biomaterials may enable the de novo creation of implantable tissue and organs for transplantation. Innovative techniques for prevention and treatment of tissue loss and organ failure should improve the quality and length of life.
Artificial cells are being actively investigated for use in the replacement of cell and organ functions, especially related to metabolic functions. The earliest routine clinical use of artificial cells is in the form of coated activated charcoal for hemoperfusion. Implantation of encapsulated cells are being studied for the treatment of diabetes, liver failure, kidney failure and the use of encapsulated genetically engineered cells for gene therapy. Blood substitutes based on modified hemoglobin are already in Phase III clinical trials in patients with as much as 20 units 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. Artificial cell is also being investigated for drug delivery and for other uses in biotechnology, chemical engineering and medicine.
Organic artificial proteases with broad substrate specificity were synthesized by covering the surface of silica gel with aldehyde and the functional groups present in amino acids. The artificial proteases hydrolyzed ovalbumin, albumin, hemoglobin, gamma-globulin with half-lives as short as 50 min at 25 degrees C or 7 min at 50 degrees C.
Stem cells responsible for tissue maintenance and repair are found in a number of organs. However, hepatic stem cells assumed to play a key role in liver development and regeneration remain to be well characterized. To address this issue, we set up a culture system in which primitive hepatic progenitor cells formed colonies. By combining this culture system with fluorescence-activated cell sorting (FACS), cells forming colonies containing distinct hepatocytes and cholangiocytes were identified in the fetal mouse liver. These cells express both CD49f and CD29 (alpha6 and beta1 integrin subunits), but do not mark for hematopoietic antigens such as CD45, TER119, and c-Kit. When transplanted into the spleen, these cells migrated to the recipient liver and differentiated into liver parenchymal cells. Our data demonstrate that hepatic progenitor cells are enriched by FACS and suggest approaches to supplanting organ allografting and improving artificial-organ hepatic support.
The usefulness of hemoperfusion in ESRD therapy has not yet been proven in long-term studies. This negative assessment of results is not meant to impugn the efforts of the many investigators in this field. Their research has led to the development of sorbent cartridges, which have played a major life-saving role in acute poison therapy. Moreover, many futuristic artificial organs, such as the wearable artificial kidney and the prosthetic liver, will be lineal descendants of early sorbent research and their development will be facilitated further by current and future studies. Surely, for all those who are not prematurely discouraged by the negative results to date, hemoperfusion remains a challenging avenue for clinical innovation.
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It was hypothesized that an orientated cellular tissue for incorporation into vital, functioning hybrid artificial organs can be prepared by periodically applying mechanical stresses on a hybrid tissue. Therefore, the effect of cyclic stretching on the two-dimensional (2-D) orientation response of arterial smooth muscle cells (SMCs) was studied. Smooth muscle cells derived from bovine aortas were seeded onto transparent elastomeric membranes made of polyurethane, and subjected to periodical stretching with various amplitudes from 5-20% at frequencies of 15 to 120 RPM for up to 24 hours. Phase-contrast microscopic views of SMCs were time-lapse video recorded. The orientation angle to the direction of stretching (OA) and cellular longitudinal length (CLL) of individual cells were analyzed by a computerized image processor. After several hours, SMCs subjected to the stress exhibited orientation responses perpendicular to the direction of stretching, evidenced by a significant increase in OA. The responses were more rapid under operating conditions with higher amplitudes and frequencies of stretching. Meanwhile, little significant change in CLL was observed. These findings indicate that an applied mechanical stress induces a significant orientation response, without morphologic alteration of SMCs. The mechanically induced orientation response provides a fundamental basis for more structured hybrid organs and tissue engineering.
We have developed an artificial organ conditioning system in order not only to condition but also evaluate the viability for transplant graft of kidneys which have been stored for a long time and damaged by warm ischaemia following cardiac arrest. The conditioning system consisted of an artificial lung, a roller pump, an organ chamber and perfusate. The perfusate was prepared with electrolytes, fluorocarbon, amino acid, glucose, an oxygen scavenger and so on. Conditioning was performed by continuous perfusion under mild hypothermia at 24 degrees C. Mildly damaged kidneys (0 and 30 minutes warm ischaemia rabbit kidneys) were well conditioned but severely damaged kidneys failed to produce urination. Our device successfully exposed the viability of stored kidneys and the successful conditioning of damaged kidneys due to warm ischaemia avoiding transplantation. By establishing our method, the harvesting of kidneys following cardiac arrest will be feasible.
Applicability of different forms of chitosan in medicine and biomedical engineering has been discussed on the basis of a literature survey. Attention was paid to the use of chitosan as a drug carrier and as a pharmacological agent in the treatment of hypercholesterolemia. Suitability of the polymer was proved in the process of blood purification (LDL-apheresis, haemoperfusion, dialysis) and wound healing (dressings). A possibility of using it in biohybrid artificial organs and as athrombogenic surfaces was also mentioned.
This study reports in vivo testing of ULTI carbon coated dacron grafts in the dog's 4 mm carotid artery, and showed 97.5% patency at 21 days in 40 grafts compared to 33% in 6 control grafts. Physical properties of the dacron substrates were not altered after ULTI carbon deposition. The carbon coated grafts must be carefully cleaned and maintained in that condition. This initial study with the modified pyrolytic carbon adds a new dimension to vascular prosthetics and artificial organ development.
Cultures of the minimal deviation rat hepatoma cell line H4-11-E derived from the Reuber hepatoma were grown on bundles of artificial capillaries. Sections of those cells grown in circumfusion culture on acrylic copolymer and polysulfone capillaries were prepared. Light, transmission and scanning electron micrographs disclosed variations in cell viability in different parts of the bundle, variations in capillary wall structure affecting the proximity of cells to capillary lumen, and intraluminal sediment deposits derived from pump tubes used for circulating the culture medium. These sediments, by obstructing capillaries, inhibited cell growth and caused focal necrosis of cells. The importance of monitoring the morphology of cell cultures grown on bundles of artificial capillaries which are to be used as artificial organs is emphasized.
This review discusses the factors important in the incorporation or integration of biomaterials and devices by tissue. Methods for surface modification and surface-sensitive techniques for analysis are cited. In vitro methods to evaluate the biocompatibility or efficacy of certain biomaterials and devices are presented. Present and future directions in neural prostheses, cardiovascular materials, blood or bone substitutes, controlled drug delivery, orthopedic prostheses, dental materials, artificial organs, plasma- and cytapheresis, and dialysis are discussed.
Medicine owes much to nephrology. Indeed many of the practical and doctrinal acquisitions, through nephrology have derived their first intuitions, explanations and applications which have become epochal conquests of scientific progress. This article is a historical reconstruction of six of the milestones which have marked the medical and scientific human progress: Galeno, the ligature of the ureters and the birth of experimental medicine; uroscopy and the introduction of laboratory exams; the synthesis of urea in the laboratory and the beginnings of biothecnology; the kidney and the introduction of systematic parenteral antibiotic therapy; the kidney and the first artificial organs; the kidney and the start of the transplantation era.
Since the mid-1990s, numerous studies on the treatment of drinking water by photocatalysis have been reported. Once optimised, the photocatalytic process can completely degrade numerous natural and artificial organic compounds. In this study, a hybrid photocatalysis/membrane process was used as a polishing treatment of surface water containing a small concentration of natural organic matters (i.e. total organic carbon (TOC) concentration of around 3mg/L) which may be difficult to remove using conventional filtration or coagulation. An optimum pH of 4.5 and a TiO(2) concentration of 0.1g/L were found to lead to the highest removal efficiencies. The relative effect of the individual processes featuring in the hybrid system (UV radiation, TiO(2) adsorption and membrane filtration) was also assessed for different pH values. The membrane separation process was accounted to remove around 18% of the initial TOC concentration, while TiO(2) adsorption alone was generally responsible for less than 5% of TOC removal during the 120 min of the experiments. However, when the natural water was only radiated by UV light, up to 70% of TOC was removed. A synergetic effect was observed when the three processes (TiO(2), UV and membrane) were used together. Comparison of removal efficiencies obtained during real and model (International Humic Substance Society) waters treatment by photocatalysis is also presented, revealing the importance of the nature of the feed in this type of treatment.
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