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At least 19 recordsLinked to original sources
PubMed1992

Bioartificial organs.

Bioartificial organs combine the physical aspects of implantable prostheses with the biological advantages of organ transplantation. Enclosing live cells in a permselective, synthetic envelope avoids rejection by an immunoincompatible host while the geometric limitation of the closed polymer capsule prevents overgrowth of the transplanted material. As a tenet bioartificial organs widen the range of therapeutics based on the biological activity of cell transplants and open an alternative path to gene therapy.

Animals↗
PubMed2000

Bioartificial organ support for hepatic, renal, and hematologic failure.

The current strategy to the treatment of SIRS and MODS uses a multidisciplinary approach that emphasizes supportive therapy. Herein, we have presented a futuristic approach that focuses on replacing the function of failed organs using bioartificial technology (Table 1). Bioartificial organ technology may allow the intensivist to provide physiologic organ replacement either as a bridge to transplantation or as a "time-buying" element until native organs that have become acutely dysfunctional or nonfunctional in a variety of clinical settings, can recover their function or regenerate their mass. As bioartificial organ technology matures, it is conceivable as an ultimate goal that non-immunogenic bioartificial organs would be miniaturized or redesigned and acutely placed within the intracorporeal space as replacement organs.

Bioartificial Organs↗
PubMed2001

Objectively assessing bioartificial organs.

The metrics used, thus far, to assess bioartificial organ function are shown to be subjective and requiring validation. Therefore, four categories of correlations are proposed based on, respectively, device, in vitro and in vivo evaluations, and clinical function. Examples are presented whereby the correlations among individual indicators are used as a means to expedite the development of immunoisolated cells. Specifically, a case study illustrating the validation of in vitro indicators of in vivo graft function for the bioartificial pancreas (microencapsulated islets) is summarized. This has revealed thresholds with respect to given metrics relating to in vivo device function, the necessity to couple bioartificial organ design with transplant site selection, as well as the lack of objectivity involved in the evaluation and establishment of hypotheses. Specific quantitative indicators illustrate the need for quality-controlled measures, for example, relating to the tolerance of microcapsule diameter and membrane thickness distributions. Qualitative indices representing fibrosis and device properties (e.g., sphericity) are also used to describe the need for in vitro experiments in the development of bioartificial organs.

Bioartificial Organs↗
PubMed2001

Bioartificial organs in the twenty-first century: nanobiological devices.

Bioartificial organs involve the design, modification, growth and maintenance of living tissues embedded in natural or synthetic scaffolds to enable them to perform complex biochemical functions, including adaptive control and the replacement of normal living tissues. Future directions in this area will lead to an abandonment of the trial-and-error implant optimization approach and a switch to the rational production of precisely formulated nanobiological devices. This will be accomplished with the help of three major thrusts: (1) use of molecularly manipulated nanostructured biomimetic materials; (2) application of microelectronic and nanoelectronic interfacing for sensing and control; and (3) application of drug delivery and medical nanosystems to induce, maintain, and replace a missing function that cannot be readily substituted with a living cell and to accelerate tissue regeneration. Biomimetics involves employment of microstructures and functional domains of organismal tissue function, correlation of processes and structures with physical and chemical processes, and use of this knowledge base to design and synthesize new materials for health applications. Nanostructured materials should involve biological materials (rather then synthetic ones) because their prefabricated structure is suitable for modular control of devices from existing materials. Nanostructured tools should encompass surface patterned molecular arrays, nanoscale synthetic scaffolding mimicking the cell-extracellular matrix microenvironment, precise positioning of molecules with specific signals to provide microheterogeneity, composites of bioinorganic and organic molecules, molecular layering (coating), and molecular and supramolecular self-assembly and self-organization (template-directed) assembly. The nanoelectronic interface includes electronic or optoelectronic biointerfaced devices based on individual cells, their aggregates and tissues, organelles, and molecules, such as enzyme-based devices, transport and ion-channel membrane proteins, and receptor-ligand structures, including nanostructured semiconductor chips and microfluidic components. Delivery nanosystems encompass both water and lipid core vehicles (for hydrophilic and lipophilic components) of various geometries: liposomes, micelles, nanoparticles, lipid shells (as imaging and contrasting agents), solid nanosuspensions, lipid nanospheres, and coated film surfaces (molecular layering), all for use in delivering drugs, proteins, cell modifiers, and genes. Nanoelectronic interface and delivery nanosystems will be used for sensing, feedback, control, and analysis of function of bioartificial organs.

Bioartificial Organs↗
PubMed2002

Oxygen and inulin transport measurements in a planar tissue-engineered bioartificial organ.

In vivo oxygen and inulin transport rates were measured in a planar tissue-engineered bioartificial organ implanted in a rat. A compartmental model was used to describe the transport of oxygen and inulin between the cell chamber, across the immunoisolation membrane, and within the neovascularized region adjacent to the immunoisolation membrane. A nonlinear regression analysis of the plasma inulin levels and the oxygen transport rate into the device provided information on the degree of vascularization in the region adjacent to the bioartificial organ. Key parameters that were obtained from the analysis of the in vivo transport data included the average capillary blood oxygen partial pressure, the Krogh tissue cylinder radius, the extracellular volume fraction, and the capillary blood residence time. These four parameters are important indicators for assessing the degree of vascularization in the tissue adjacent to the immunoisolation membrane in the bioartificial organ. The oxygen and inulin transport technique reported here is a useful tool for describing the in vivo transport characteristics of a bioartificial organ and for assessment of the vascularization within tissue engineered structures.

Animals↗
PubMed1999

In vivo measurement of solute transport rates in a bioartificial organ.

A radioactive tracer technique was used to evaluate the in vivo mass transfer properties of a tissue engineered bioartificial organ. To obtain these measurements, bioartificial organs were first implanted in ten rats and allowed to vascularize for 4 weeks. After vascularization, radioactive inulin was placed within the cell chamber of the device. Following the addition of tracer, blood samples were taken over a 4-h time period and inulin levels were determined. The results of these experiments were interpreted using a compartmental model that describes the transport of inulin from the cell chamber, across the immunoisolation membrane, and into the neovascularized region contained within the adjacent scaffold material. Nonlinear regression analysis of the plasma inulin levels using a four-compartment pharmacokinetic model provided estimates of the membrane permeability, the product of the capillary wall surface area and capillary permeability, and the glomerular filtration rate (GFR). The permeability of the membrane was found to be 3.50 x 10(-5) +/- 1.15 x 10(-5) cm/sec (95% confidence interval, n = 10), which compares favorably to previous in vitro permeability data for this membrane. The capillary wall permeability was found to be 0. 0087 6 0.0029 cm(3)/sec/100 g of tissue. This compares well to a reported value for inulin of 0.01 cm(3)/sec/100 g of tissue. The GFR was found to be 0.44 +/- 0.07 ml/h/g BW, which compares well with a reported value of 0.40 ml/hr/g BW. The inulin tracer technique reported here is a useful tool for assessing the in vivo transport characteristics of a bioartificial organ as well as the vascularization within tissue engineered structures.

Animals↗
PubMedDate not supplied

Promotion of neovascularization around hollow fiber bioartificial organs using biologically active substances.

A limiting factor of the long-term function of bioartificial organs is oxygen delivery to the encapsulated tissue. This study determined whether incorporation of endothelial cell growth factor (ECGF) into the alginate core of a hollow fiber bioartificial organ will induce neovascularization around the hollow fiber. Polyethersulfone (PES) and polyvinylidine difluoride (PVDF) hollow fibers were examined. Endothelial cell growth factor was incorporated into sodium alginate, extruded into the lumen of hollow fibers, and cured in calcium chloride. Samples without ECGF were fabricated and used as controls. Hollow fibers were implanted into 16 rats. For each rat, two implants were placed subcutaneously and two intraperitoneally, one with and one without ECGF at each site. Implants were placed on opposite sides of each animal. Implants were removed 65 days later and examined using immunohistochemical methods and light microscopy to determine the extent of neovascularization. A total of 64 implants were used. Most intraperitoneal implants were found free floating but were encased within a 100-microm thick avascular fibrotic reaction. This finding was independent from the presence of ECGF. Hollow fibers without ECGF, implanted subcutaneously, also had an avascular fibrotic reaction surrounding each implant. Subcutaneous implants with incorporation of ECGF within the alginate core had marked neovascularization within the fibrotic overgrowth that surrounded these implants. This was most prevalent in hollow fibers, with the thin separation layer facing the fiber lumen irrespective of limiting pore size. Potent angiogenic factors, such as ECGF, incorporated into diffusion chamber bioartificial organs can promote neovascularization around the subcutaneously implanted hollow fiber and may improve oxygen delivery to the tissue encapsulated within devices based on this technology.

Animals↗
PubMed1999

Method for measuring in vivo oxygen transport rates in a bioartificial organ.

Oxygen transport is crucial for the proper functioning of a bioartificial organ. In many cases, the immunoisolation membrane used to protect the transplanted cells from the host's immune system can be a significant barrier to oxygen transport. A method is described for measuring the in vitro and in vivo oxygen transport characteristics of a planar immunoisolation membrane. The in vitro oxygen permeability of the membrane was found to equal 9.22 x 10(-4) cm/sec and was essentially the same as the in vivo value of 9.51 x 10(-4) cm/sec. The fact that the in vitro and in vivo membrane permeabilities are identical indicates that any fibrotic tissue adjacent to the immunoisolation membrane did not present a significant resistance to the transport of oxygen. The measured oxygen permeability was also found consistent with the solute permeabilities obtained in a previous study for larger molecules. Based on the oxygen permeability results, theoretical calculations for this particular membrane indicate that about 1,100 islets of Langerhans/cm2 of membrane area can be sustained at high tissue densities and only 660 islets/cm2 can be supported at low tissue densities.

Animals↗
PubMed1998

New technologies for bioartificial organs.

Each year several hundred thousand Americans die because of organ failure. Organ transplantations have achieved remarkable success, but the source of human organs is limited. Only a small portion of patients can benefit annually from this method of treatment. Immunoisolated living cells as bioartificial organs can be transplanted into humans without the need for immunosuppression and its accompanying side effects. Immunoisolation allows cells from nonhuman species to be used, thereby overcoming the limited supply of human cells available for encapsulation, and the capsule can serve as an ideal cage to keep animal viruses from contacting the human host. To achieve this promise, we have incorporated the pore size distribution into a new design of capsule for the immunoisolation of living cells. In this model the capsule wall is thicker and the pores are bigger than in the current systems. The larger pores will allow the immune system to enter the membrane, and the smaller pores inside the membrane will act as the traps to prevent or delay most of the immune system from passing all the way through to the inner volume of the capsule where the living cells reside. Limited animal studies have supported the advantages of this new entrapment model over the current model. Systematic studies to determine optimal capsule design for human transplantation are now feasible.

Alginates↗
PubMedDate not supplied

A device to measure the oxygen uptake rate of attached cells: importance in bioartificial organ design.

Quantification of the dependence of cellular oxygen uptake rate (OUR) on oxygen partial pressure is useful for the design and testing of bioartificial devices which utilize cells. Thus far, this information has only been obtained from suspended cells and from cells attached to microcarriers. In this work, a device was developed to obtain the dependence of OUR on oxygen partial pressure for anchorage-dependent cells cultured in standard culture dishes. The device is placed and sealed on the top of the culture dish, and holds a Clark polarographic mini-electrode flush with the bottom surface of the device. It also houses a motor to spin a magnetic stir bar within the cell chamber to insure that the medium is well-mixed. Several characteristics of the device--such as oxygen leakage into the device chamber, electrode-lag time, and linearity of the electrode at low oxygen partial pressures--were quantified and their potential effect on the values of Vm (maximal OUR) and K0.5 (oxygen partial pressure at which OUR is half-maximal) were evaluated. Comparison of Vm and K0.5 values obtained with this device with previously published values for suspended rat hepatocytes, Bacillus cereus, and E. coli indicated that the technique provides values accurate within 30% as long as the cell under study has a K0.5 greater than approximately 1.0 mmHg. For hepatocytes cultured on 0.05 mm thickness collagen gel for 1 day (n = 4) and 3 days (n = 6), Vm was found to be 0.38 +/- 0.12 and 0.25 +/- 0.09 nmol O2/S/10(6) cells, respectively, and K0.5 was found to be 5.6 +/- 0.5 and 3.3 +/- 0.6 mmHg, respectively. This technique should aid in predicting bioreactor conditions such as flow rate, cell density, distance of cell from flow, and gas phase oxygen partial pressure which can lead to oxygen limitations. In addition, further studies of the effect of factors such as extracellular matrix composition, metabolic substrate, and drugs on the dependence of OUR on oxygen partial pressure for many anchorage-dependent cell types can be pursued with this technique.

Animals↗
PubMed1998

The move from dead to living membranes: bioartificial organ support of failing systems.

Several studies show that the diagnosis of acute renal failure still is predictive of high mortality. The reasons for this dismal prognosis despite improvements in dialytic methodologies and critical care are not entirely clear. Continuous renal replacement therapies have to date not shown improved outcome. Dialysis is conceptually not truly a "renal replacement therapy," because the many reabsorptive, metabolic, synthetic, and endocrine functions that occur in the kidney are not duplicated. This dilemma is applicable in varying degrees to other failing organs. Another therapeutic approach to a variety of organ failure conditions could be the transplantation of specific cell types to replace specific functions in the diseased host. The phenomenon of bioencapsulation with synthetic semipermeable membranes offers the possibility of allowing transplanted cells to function while sequestering them from the host's immune system. At this time, a bioartificial kidney is being developed that can be placed in series with a hemofilter and consists of proximal tubular cells layered on the surface of the hollow fibers of a dialyzer. Metabolic and transport functions appear to be intact. Further testing and refinement of this model will occur, which represents a potentially revolutionary form of therapy for renal disease.

Acute Kidney Injury↗
PubMedDate not supplied

A new tracheal bioartificial organ: evaluation of a tracheal allograft with minimal antigenicity after treatment by detergent.

The aim of this study was to reduce the antigenicity of tracheal allografts by detergent treatment. We attempted to apply these grafts to tracheal immunosuppressant-free allotransplantation. Fresh tracheal grafts were harvested from donor beagle dogs and treated with a detergent at 4 degrees C for 48 hours. By using treated grafts, we have performed tracheal immunosuppressant-free transplantation in six dogs at an intrathoracic five-ring defect. Implanted grafts were covered with an omental pedicle. In five of the six grafts, complete removal of the epithelium and mixed glands was recognized with both light microscopy and scanning electron microscopy. The appearance of the cartilage cells in the grafts was similar to those in fresh trachea. Five dogs that received detergent treated grafts survived uneventfully. The grafts had been incorporated by the host trachea without stenosis. On the one tracheal graft in which removal of the epithelium was incomplete (noted after implantation), moderate stenosis occurred 1 month after placement. These results suggest that removal of the tracheal epithelium and mixed glands can remarkably reduce tracheal antigenicity. A tracheal graft that has its epithelium and mixed glands removed can be used in tracheal immunosuppressant-free allotransplantation.

Animals↗
PubMedDate not supplied

New type of tracheal bioartificial organ treated with detergent: maintaining cartilage viability is necessary for successful immunosuppressant free allotransplantation.

The present investigation examined the key factors in the preparation of low-antigenic tracheal allografts by detergent treatment in dogs. In group 1 (n = 5), the grafts were treated by detergent at room temperature for 48 h and rinsed with running water until use. In group 2 (n = 4), detergent treatment was performed at 4 degrees C for 48 h, but the rinsing step was omitted. In group 3 (n = 6), the grafts were treated at 4 degrees C for 48 h, rinsed thoroughly with physiologic saline, and stored at 4 degrees C. The grafts were then used for tracheal replacement without immunosuppressant in dogs. The epithelium and mixed glands had been removed completely from the grafts in groups 1 and 2, and in five of the six grafts of group 3. In groups 1 and 2, cartilage viability appeared to have been lost and all animals died of airway stenosis within 38 days. In group 3, the chondrocytes were viable and all animals survived uneventfully. These results suggest that maintaining cartilage viability in a tracheal graft is necessary for successful immunosuppressant-free allotransplantation and, consequently, to maintain an open airway. The treatment temperature and sufficient rinsing are key factors for maintaining cartilage viability of grafts.

Airway Obstruction↗