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Giving and taking--to whom and from whom? People's attitudes toward transplantation of organs and tissue from different sources.

The aims of the study were: 1) to describe the willingness of the public to receive material of different origins in one's own body; 2) to compare the willingness to donate and receive body material; 3) to compare the willingness to donate while alive and after death; 4) to compare the willingness to donate to a next-of-kin and unknown recipients. A random sample of 1500 inhabitants, 18 to 70 yr old, in the county of Uppsala, Sweden, were sent a questionnaire asking about their opinion on transplantation and transfusion issues. The response rate was 71%. Ninety-five percent accepted to receive blood transfusion, 89% bone-marrow transplantation, and 85% transplantation of a solid organ. Organs from living donors were preferred (77%), then organs from decreased donors (69%), then artificial organs (63%), and last animal organs (40%). More than half of those accepting transplants made exceptions for some types of organs. The youngest and those with higher education were more positive toward receiving all types of organs than the older ones and those with lower education. Women were less prepared than men to accept animal organs. Those who accepted organs from animals usually also accepted all other types of organs, and were willing to donate organs and tissue more often than those who did not accept to receive animal organs. The readiness to support a sick family member by giving bone-marrow and even a kidney was considerable, 89 and 81%, respectively. The attitudes were less positive with regard to giving blood and bone-marrow to unknown recipients, 54 and 41%, respectively. Sixty-one percent of the respondents were positive toward donating their own organs after death. Of those who were positive, 10% made exceptions for special organs that they did not want to donate, mostly heart, eyes, and brain. Individuals with higher education and young people were more often positive than those with lower education and old people regarding donation of blood and organs, and bone-marrow donation to a relative. Women were somewhat more accepting to donate while alive than males. Thirty-one percent, more often women than men, had signed a donor card and/or registered with the Swedish Organ Donation Registry. The results with regard to receiving organs and tissue are discussed in terms of two different sets of explanations, which can be seen as different sides of the same coin, and mutually strengthening the reactions. The great readiness to donate to a family member as well as the discrepancy between giving in life and after death is commented upon.

Adolescent↗

Collagen gel immobilisation provides a suitable cell matrix for long term human hepatocyte cultures in hybrid reactors.

An easy to apply culture technique is presented that protects a monolayer configuration of liver cells within an extracellular matrix. The Immobilising Gel (IG)-Technique not only preserves hepatocyte morphology and supports a variety of differentiated cell functions over long term periods, but also offers higher resistance of IG-culture systems against shear forces of fluids in a hybrid reactor device, as compared to other culture techniques. Human hepatocyte cultures in IG-Technique: DNA-normalised levels for the total production of cholinesterase, albumin, urea and lactate remained high throughout the investigational period (50 days). Glutamic-Pyruvic-Transaminase (GPT) release decreased after peak values during early culture adaptation. Electron Microscopic (EM) findings after the shear forces experiment revealed undisturbed subcellular structures and a preserved intercellular morphology, including bile canaliculi and desmosomes. We conclude that the IG-technique is of considerable advantage as compared to other culture systems, especially in the field of dynamic applications, e.g. hybrid reactors for artificial organ development.

Alanine Transaminase↗

Transplantation of microencapsulated hepatocytes for liver function replacement.

Recent advances in cell biology and biotechnology have lead the way for a greater understanding of cell function and the potential therapeutic use of transplanted cells for treating a wide array of illnesses. Treatment of disease by transplantation of normal healthy cells, for the replacement of specific biological deficiencies or as a form of auxiliary support for a failing organ, offers important therapeutic applications and also serves as a model for assessing cellular physiology. In the long-term, cell transplantation may also have potential in the development of artificial organ support systems for sustaining patients with severe and chronic diseases such as diabetes, liver failure, endocrine and exocrine disorders, neurological abnormalities, and congenital metabolic defects. Several groups have demonstrated the feasibility and efficacy of cell transplantation in providing specific function in various experimental animal models of human disease. However, without adequate immunosuppression, complications due to tissue rejection remain a significant problem. Microencapsulation of cells within a synthetic semipermeable membrane, prior to transplantation, has been proposed for circumventing immunological complications following transplantation. The microcapsule's semipermeable membrane allows permeant molecules to freely diffuse across while preventing the microencapsulated cells from escaping. This membrane also keeps unwanted substances, such as cells and antibodies, from entering the microcapsule. Thus, microencapsulation provides an innovative and unique technique for the transplantation of foreign tissue and cells without the need for immunosuppression.

Animals↗

[Control and diagnosis in the biotechnical systems of artificial clearance].

Controlling and diagnostic processes in the bioengineering artificial clearance systems despite of the procedures applied, their functional use and design seem to occur in the artificial organs, each of them consists of controlling and actuating processors ensuring their homogeneous (material, energy-producing, informational) or combined interaction with the patient's body. Centralized control over artificial clearance is proposed by using universal controlling processes which are informationally connected with the operator, the central computer and other controlling processes of the bioengineering system.

Artificial Organs↗

Hybrid artificial lung with interleukin-10 and endothelial constitutive nitric oxide synthase gene-transfected endothelial cells attenuates inflammatory reactions induced by cardiopulmonary bypass.

BACKGROUND: Recently, the research on hybrid artificial organs such as heart, liver, and kidney has been reported to yield new possibilities for clinical use. However, there have been few reports on the practical use of a hybrid artificial lung, primarily due to difficulties in the concept for its application and techniques for cell attachment. In this study, we investigated the possibility for developing a novel strategy: a hybrid artificial lung with constitutive nitric oxide synthase (NOS) and interleukin (IL)-10 gene-transfected endothelial cells to attenuate inflammatory reactions induced by cardiopulmonary bypass. METHODS AND RESULTS: First, we performed an in vitro study to confirm the efficacy of our gene transfection into endothelial cells. Constitutive nitric oxide synthase and IL-10 cDNA were transfected into endothelial cells according to the hemagglutinating virus of Japan-liposome method. Levels of nitric oxide released from the endothelial constitutive NOS (ecNOS)-transfected endothelial cells were significantly higher than those of control cells (24 hours after the stimulation by lipopolysaccharide: 284.5 +/- 54.0 versus 95.7 +/- 27.9 mumol/L, P = 0.0001). On the other hand, IL-8 levels in the transfected endothelial cells were significantly lower than those in the control group (48 hours after stimulation by tumor necrosis factor-alpha: 3.1 +/- 2.4 versus 62.1 +/- 1.3 ng/mL, P = 0.0002), and IL-10 was detected in the transfected group but not in the control group. Next, we performed an in vivo study to evaluate the possibility of developing a hybrid artificial lung. One-hour partial cardiopulmonary bypass with this lung was established in rats undergoing femorofemoral bypass. Artificial lungs with no cells (group C; n = 5), that were coated with untreated endothelial cells (group E; n = 5), or that were coated with ecNOS and IL-10 gene-transfected endothelial cells (group T; n = 3) were used. At 45 minutes after the initiation of cardiopulmonary bypass, group T showed higher nitric oxide levels than groups C and E (T versus C versus E: 75.2 +/- 6.8 versus 67.2 +/- 4.3 versus 68.6 +/- 5.2 mumol/L, P = NS). The serum IL-8 levels just after cardiopulmonary bypass in group T were significantly lower than those in group C (1728 +/- 282 versus 4275 +/- 145 pg/mL, P = 0.0151). The Pao2 levels in group T just after weaning from cardiopulmonary bypass were significantly higher than those in group C (271.3 +/- 41.7 versus 136.6 +/- 12.3 mm Hg, P = 0.0362). CONCLUSIONS: These results demonstrate that a hybrid artificial lung with IL-10 and ecNOS gene-transfected endothelial cells inhibited IL-8 release and increased nitric oxide production. This suggests the possibility of developing a hybrid artificial lung capable of preserving native lung function by attenuating cardiopulmonary bypass-induced inflammatory reactions via inhibition of IL-8 release and enhanced nitric oxide production.

Animals↗

The artificial lung facility at Brown: more than a dozen years with Pierre Galletti.

Beginning in 1969, Pierre Galletti and his colleagues established a laboratory at Brown University, which, initially and for many years, was involved with artificial lungs. Various projects budded out of this, including the following: the establishment of standards for oxygenator performance, which anticipated Food and Drug Administration requirements; studies of thrombosis and other pathologies, which could be reduced by design changes; long-term, pumpless arterio-venous (A-V) bypass; early hybrid pancreas and other artificial organs; implantable lungs; and spin off companies. The current report outlines the history, philosophy, collaborations, and major results of the laboratory, as well as how the principal investigators simultaneously moved into research areas outside of artificial lungs in the late 1980s.

Animals↗

Sustained release of basic fibroblast growth factor and angiogenesis in a novel covalently crosslinked gel of heparin and alginate.

The construction of organs by tissue engineering and regenerative engineering, using an artificial extracellular matrix, is an innovative method that is expected to replace artificial organs and organ transplantation. We have produced an artificial extracellular matrix of alginate and demonstrated that the matrix stimulated the regeneration of skin, nerve, and bone. In this report, the new matrix, which consists of heparin and alginate covalently crosslinked with ethylenediamine, was produced to stabilize and control the release of growth factors. Heparin content of the new matrix was confirmed by toluidine blue absorption, elementary analysis, and Fourier transform infrared spectrum. In vitro experiments showed that the new matrix significantly suppressed the initial burst of basic fibroblast growth factor, which is a representative member of heparin-binding growth factors, and released biologically active basic fibroblast growth factor for 1 month under physiological conditions. Obvious cellular infiltration and angiogenesis were shown to occur in the new matrix which was implanted subcutaneously in the dorsal area of rat with 1 microg of basic fibroblast growth factor for 2 weeks. This new matrix may be useful for not only the construction of transplantable blood vessels of small diameter, but also the induction of angiogenesis in regenerated skin constructed by tissue engineering.

3T3 Cells↗

There isn't an ideal smooth-surface material--yet: the history and future of urologic materials.

Indwelling and implantable urologic devices did not become commercially available until the late 1970s. The first such device was a ureteral stent made of silicone. Other materials-polyethylene, polyurethane, C-Flex, and Percuflex-have since been introduced. Each of these materials is rated for a particular indwell time, after which the material may begin to break down. Various methods of modifying the surface to make it more slippery or to prevent infection have been tested. Attempts have been made to create artificial organs and have not been entirely successful, and the future may lie with tissue-engineered materials such as small intestinal submucosa.

Artificial Organs↗

In vivo tissue engineering: Part I. Concept genesis and guidelines for its realization.

A loss of function of an organ often represents a life-threatening situation. Transplantations are successful, but "replacement" availability, its compatibility with the host, and subsequent healing often pose serious questions. Tissue engineering, where a carefully prepared scaffold is populated, in vitro, by cells to form an artificial organ, addresses some of the problems mentioned above. Trauma associated with the implant introduction to the host often complicates the process. The novel concept of in vivo tissue engineering which is designed to mediate the healing and tissue regeneration process by providing an in vitro formed porous, microcellular scaffold is proposed. The scaffold (part or entire organ) is then populated by cells either spontaneously (the surrounding cells will spread and populate to inhabit the scaffold) or by cellular augmentation (encapsulated cells are delivered to this in statu nascendi scaffold). Minimally traumatic arthroscopic surgery combined with a unique polymer delivery system is envisioned for the introduction of this implant to a site to be repaired. Such an approach will require the formation of polymer in-situ, in a reasonable time. The scaffold-forming polymers will be, in principle, biodegradable. We propose to utilize biodegradable polyurethane systems for in vivo tissue engineering. Diversity of their structure/property relationships, relative "ease" of their preparation, and excellent biocompatibility predetermine polyurethanes to be the materials of choice. This paper describes the genesis of this concept and potentials for its realization. It is intended to initiate and stimulate discussion among the related scientific disciplines to form a basis for this field. The synthesis, application, and biodegradation of selected polyurethanes and variety of its medical utilization will be discussed in upcoming papers.

Artificial Organs↗

How to comply with the Food and Drug Administration's "Investigational Device Exemption (IDE)" regulations including an application form (revised January 1982).

This is a revision of the IDE Application Form, "How to Comply with the Food and Drug Administration's New 'Investigational Device Exemption (IDE)' Regulations, Including an Application Form" originally published in Artificial Organs, Volume 4, Number 4, November 1980. This publication updates the IDE application form to facilitate compliance with the amended investigational device exemption regulations now in effect.

Artificial Organs↗

Synthetic artificial peptidases and nucleases using macromolecular catalytic systems.

Effective artificial enzymes have been designed by adopting macromolecular systems for catalyst-substrate complexes. Artificial active sites comprising two or more organic functional groups were built on macromolecular backbones, leading to several types of organic artificial proteases. The activity of metal centers for peptide or DNA hydrolysis was greatly enhanced by attachment to polystyrene, leading to artificial metallopeptidases with substrate selectivity as well as artificial metallonucleases with high catalytic activity for double stranded DNA. A small artificial protease selective for a macromolecular target protein was synthesized. Target-specific artificial proteases can be used as protein-cleaving catalytic drugs.

Catalysis↗

Remarkable proteolytic activity of imidazoles attached to cross-linked polystyrene.

The insoluble resins synthesized by attaching imidazoles to poly(chloromethylstyrene-co-divinylbenzene) effectively hydrolyzed albumin with half-life as short as 20 min at pH 7 and 25 degrees C. Thus, peptide hydrolysis was accomplished with imidazole in an artificial system for the first time. The imidazole-based artificial proteinases manifested optimum activity at pH 7-8. The proteolytic activity of the imidazole-based artificial proteinases exceeded that of previously reported organic artificial proteinases including catalytic antibodies. High proteolytic activity was observed when imidazole was attached to the resin through the C-2 atom instead of the N atom. The catalytic activity was greatly reduced when the content of imidazole was lowered. This indicates catalytic cooperation of at least two proximal imidazole moieties attached to the resin. Possible mechanisms for the effective protein hydrolysis by the proximal imidazoles are presented.

Cross-Linking Reagents↗

Biomaterials in Urology II: future usage and management.

It seems likely, and indeed inevitable, that medical device usage will continue its rapid increase over the next 10 to 20 years and beyond. For surgeons, these new inventions will come in many forms but should take into account biocompatibility and resistance to encrustations and to microorganisms. This review focuses on research under way at present in vitro and in vivo on materials and coatings, use of bioelectrics, use of artificial organs and tissues, application of indigenous bacteria, and other alternative device management techniques, which could well become part of clinical practice in the future. By necessity, some of these citations are speculative, but supporting documentation for their inclusion is presented.

Animals↗

Micromachining technology and biomedical engineering.

Medical science and clinical medicine include many microscopic environments. Recent micromachining techniques fit the microscopic environments and are applied to microsurgery, fiberscopic operation, micromanipulation, artificial organs, and drug delivery systems. Microactuators, microsensors, and micro mechanical parts will be prepared for such medical devices and techniques. Virtual reality, stereovision, and fiber imaging support handling of cells and small targets of living body. The paper reports some perspectives of microtechnologies in biomedical engineering.

Angioplasty, Laser↗

In vitro production of functionally mature hepatocytes from prospectively isolated hepatic stem cells.

Hepatocyte transplantation and artificial organ hepatic support require a number of functionally mature hepatocytes. However, their growth activity and functional behaviors are much smaller in culture after isolation from the liver. We examined whether continuously differentiating hepatocytes from multipotent hepatic stem cells that were isolated by using flow cytometry and propagated clonally in culture could be a source of clinical application. They actually gave rise to cells that were functionally equal to mature hepatocytes found in the adult liver, which secreted albumin into culture medium and metabolized harmful ammonium into urea. These data suggest that stem cell-derived hepatocytes are a useful cell source for developing therapeutic strategies, such as cell transplantation, gene therapy, and artificial liver organ to treat various liver disorders.

Albumins↗

Where are we going?

Searching for answers to "Where are we going?" 10 predictions for the coming decade follow: 1. Recombinant agents. 2. Preimplantation genetic diagnosis and gene therapy. 3. Advances in basic science research. 4. Disappearance of gynecologic surgery for infertility. 5. Development of artificial organs: tubes, womb, and spermatoceles. 6. Investigation of male factors: identification of specific defects in spermatogenesis and functions of the epididymis. 7. Central nervous system manipulation through drugs. 8. Computer systems to diagnose and treat infertility. 9. Ethical issues will be resolved and managed more readily. 10. The electronic journal. I have speculated broadly and humbly apologize for my myopia, which will be far more evident with the inevitable arrival of many other important advances in the coming decade.

Artificial Organs↗

Biomedical applications of polyurethanes: a review of past promises, present realities, and a vibrant future.

Polyurethanes, having extensive structure/property diversity, are one of the most bio- and blood-compatible materials known today. These materials played a major role in the development of many medical devices ranging from catheters to total artificial heart. Properties such as durability, elasticity, elastomer-like character, fatigue resistance, compliance, and acceptance or tolerance in the body during the healing, became often associated with polyurethanes. Furthermore, propensity for bulk and surface modification via hydrophilic/hydrophobic balance or by attachments of biologically active species such as anticoagulants or biorecognizable groups are possible via chemical groups typical for polyurethane structure. These modifications are designed to mediate and enhance the acceptance and healing of the device or implant. Many innovative processing technologies are used to fabricate functional devices, feeling and often behaving like natural tissue. The hydrolytically unstable polyester polyurethanes were replaced by more resistant but oxidation-sensitive polyether polyols based polyurethanes and their clones containing silicone and other modifying polymeric intermediates. Chronic in vivo instability, however, observed on prolonged implantation, became a major roadblock for many applications. Presently, utilization of more oxidation resistant polycarbonate polyols as soft segments, in combination with antioxidants such as Vitamin E, offer materials which can endure in the body for several years. The applications cover cardiovascular devices, artificial organs, tissue replacement and augmentation, performance enhancing coatings and many others. In situ polymerized, cross-linked systems could extend this biodurability even further. The future will expand this field by revisiting chemically-controlled biodegradation, in combination with a mini-version of RIM technology and minimally invasive surgical procedures, to form, in vivo, a scaffold, by delivery of reacting materials to the specific site in the body and polymerizing the mass in situ. This scaffold will provide anchor for tissue regeneration via cell attachment, proliferation, control of inflammation, and healing.

Animals↗

Changes in surface roughness of erythrocytes due to shear stress: atomic force microscopic visualization of the surface microstructure.

Blood cells are subject to various kinds of stresses in flow fields. Hemolysis is the phenomenon in which a higher stress than normal damages the erythrocyte membrane and results in the leakage of its contents. Even if the stress is not strong enough to cause cell lysis, however, the cell membrane may sustain some damage. Therefore, to further improve the blood compatibility of artificial organs, the mechanisms of sublethal damage must be investigated. As a first step, we have analyzed the fine surface structure of sheared erythrocytes from a microscopic viewpoint by using an atomic force microscope (AFM) featuring nano meter-scale visualization. Sheep erythrocytes were sheared by a conventional cylindrical viscometer under sublethal shearing conditions. The duration of shear was set at 10 s, and the shearing rate was set at 0 (as control), 10000, and 50000/s. After being stressed, the cell surfaces were visualized by an AFM and the surface roughness was measured. As a result, the roughness value was found to increase with the shearing rate: 4.5 +/- 1.5 nm (0/s, control), 6.9 +/- 2.1 nm (10000/s, P < 0.01), and 10.1 +/- 2.4 nm (50000/s, P < 0.01).

Animals↗