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53-1120: [REDACTED] Look up SPAD  or spad in Wiktionary, the free dictionary. SPAD may refer to: Science and technology [ edit ] Signal passed at danger by a train Simple Plastic Airplane Design , a type of radio-controlled model airplane Single-photon avalanche diode , a photodetector Single Pass Albumin Dialysis , liver dialysis Military [ edit ] SPAD VII , SPAD S.XII and SPAD S.XIII , French fighter planes of World War I produced by Société Pour L'Aviation et ses Dérivés A-1 Skyraider , nicknamed Spad , an attack aircraft (1950s and 1960s) Self-propelled air defence , weapons Other uses [ edit ] Société Pour L'Aviation et ses Dérivés , also Société Provisoire des Aéroplanes Deperdussin and Blériot-SPAD, French aircraft manufacturer (1912–1921) Special adviser (UK) ,

106-440: A bioartificial liver device , it is a form of artificial extracorporeal liver support. A critical issue of the clinical syndrome in liver failure is the accumulation of toxins not cleared by the failing liver . Based on this hypothesis, the removal of lipophilic , albumin-bound substances such as bilirubin , bile acids , metabolites of aromatic amino acids , medium-chain fatty acids and cytokines should be beneficial to

159-467: A critical role in providing structural support and facilitating cell attachment and proliferation in BAL systems. Recent studies have investigated the use of natural and synthetic materials, such as hydrogels, alginate, and decellularized liver scaffolds, to create biomimetic environments conducive to liver cell growth and function. Bioreactor Designs: Innovative bioreactor designs have been developed to enhance

212-562: A formidable challenge, as it necessitates the intricate optimization of cell colonization, biomaterial scaffold design, and BAL fluid dynamics. Expanding upon prior research indicating its potential as a blood perfusion device for detoxification, some studies have explored the application of Arg-Gly-Asp (RGD)-containingPoly(2-hydroxyethyl methacrylate) (pHEMA)-alginate cryogels as scaffolds for BAL. These cryogels, incorporating alginate to mitigate protein fouling and functionalized with an RGD-containing peptide to enhance hepatocyte adhesion, represent

265-688: A government post Suruhanjaya Pengangkutan Awam Darat , the Land Public Transport Commission of Malaysia See also [ edit ] Spade (disambiguation) Topics referred to by the same term [REDACTED] This disambiguation page lists articles associated with the title SPAD . If an internal link led you here, you may wish to change the link to point directly to the intended article. Retrieved from " https://en.wikipedia.org/w/index.php?title=SPAD&oldid=1243407240 " Category : Disambiguation pages Hidden categories: Short description

318-601: A government post Suruhanjaya Pengangkutan Awam Darat , the Land Public Transport Commission of Malaysia See also [ edit ] Spade (disambiguation) Topics referred to by the same term [REDACTED] This disambiguation page lists articles associated with the title SPAD . If an internal link led you here, you may wish to change the link to point directly to the intended article. Retrieved from " https://en.wikipedia.org/w/index.php?title=SPAD&oldid=1243407240 " Category : Disambiguation pages Hidden categories: Short description

371-442: A healthy one. In hyperacute and acute liver failure, the clinical picture develops rapidly with progressive encephalopathy and multiorgan dysfunction such as hyperdynamic circulation , coagulopathy , acute kidney injury and respiratory insufficiency , severe metabolic alterations, and cerebral edema that can lead to brain death. In these cases the mortality without liver transplantation (LTx) ranges between 40-80%. LTx

424-413: A human liver using a 20-inch-long, 4-inch-wide plastic cylinder filled with cellulose fibers and pig liver cells. Blood was routed outside the patient's body and through the artificial liver before being returned to the body. Dr. Kenneth Matsumara's work on the BAL led it to be named an invention of the year by Time magazine in 2001. Liver cells obtained from an animal were used instead of developing

477-566: A photodetector Single Pass Albumin Dialysis , liver dialysis Military [ edit ] SPAD VII , SPAD S.XII and SPAD S.XIII , French fighter planes of World War I produced by Société Pour L'Aviation et ses Dérivés A-1 Skyraider , nicknamed Spad , an attack aircraft (1950s and 1960s) Self-propelled air defence , weapons Other uses [ edit ] Société Pour L'Aviation et ses Dérivés , also Société Provisoire des Aéroplanes Deperdussin and Blériot-SPAD, French aircraft manufacturer (1912–1921) Special adviser (UK) ,

530-681: A piece of equipment for each function of the liver . The structure and function of the first device also resembles that of today's BALs. Animal liver cells are suspended in a solution and a patient's blood is processed by a semipermeable membrane that allow toxins and blood proteins to pass but restricts an immunological response. Advancements in bioengineering techniques in the decade after Matsumara's work have led to improved membranes and hepatocyte attachment systems. Cell sources now include primary porcine hepatocytes, primary human hepatocytes, human hepatoblastoma (C3A), immortalized human cell lines and stem cells . The purpose of BAL-type devices

583-405: A precipitating event such as variceal bleeding, sepsis and excessive alcohol intake among others that can lead to a condition referred to as acute-on-chronic liver failure (ACLF). Both types of hepatic insufficiency, ALF and ACLF, can potentially be reversible and liver functionality can return to a level similar to that prior to the insult or precipitating event. LTx has shown an improvement in

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636-423: A promising avenue for BAL scaffold development. Methods for characterizing internal flow within the porous cryogel matrix such as Particle Image Velocimetry (PIV), enables visualization of flow dynamics. PIV analysis revealed the laminar flow characteristics within cryogel pores, prompting the design of a multi-layered bioreactor consisting of spaced cryogel discs to optimize blood/hepatocyte mass exchange. Compared to

689-410: A reason why ELAD decreased survival chance over standard care. Unlike artificial ELS devices and HepatAssist, ELAD does not incorporate any filtration devices, such as charcoal columns and exchange resins. Therefore, it cannot replace the filtration capability of the kidneys and cannot compensate for multi-organ failure from more severe presentations of ACLF, resulting in increased mortality rates. While

742-459: A variety of tasks, including separation and purification of substances, along with acting as extracellular matrix for cell growth and proliferation. Immobilisation of specific ligands onto cryogels enables adsorption of specific substances, supporting their use as treatment options for toxins, for separation of haemoglobin from blood, and as a localised and sustained method for drug delivery. Developing an effective bioartificial liver (BAL) remains

795-541: A very high cost; it has been proposed that lowering the concentration of albumin in the dialysate does not seem to affect the detoxification capability of the procedure. Nevertheless, the most widely used systems today are based on hemodialysis and adsorption. These systems use conventional dialysis methods with an albumin containing dialysate that is later regenerated by means of adsorption columns, filled with activated charcoal and ion exchange resins. At present, there are two artificial extracorporeal liver support systems:

848-427: Is a BAL device containing porcine hepatocytes within a hollow-fibre bioreactor. These semi-permeable fibres act as capillaries, allowing the perfusion of plasma through the device, and across the hepatocytes surrounding the fibres. The system incorporates a charcoal column to act as a filter, removing additional toxins from the plasma. Demetriou et al. carried out a large, randomised, multicentre, controlled trial on

901-422: Is also supported by cryogels, enabling even distribution of nutrients and metabolite elimination, overcoming some of the shortcomings of hollow-fibre systems. Cryogel scaffolds demonstrate good mechanical strength and biocompatibility without triggering an immune response, improving their potential for long-term inclusion in BAL devices or in-vitro use. Another advantage of cryogels is their flexibility for use in

954-472: Is different from Wikidata All article disambiguation pages All disambiguation pages SPAD [REDACTED] Look up SPAD  or spad in Wiktionary, the free dictionary. SPAD may refer to: Science and technology [ edit ] Signal passed at danger by a train Simple Plastic Airplane Design , a type of radio-controlled model airplane Single-photon avalanche diode ,

1007-563: Is different from Wikidata All article disambiguation pages All disambiguation pages Single Pass Albumin Dialysis The primary functions of the liver include removing toxic substances from the blood, manufacturing blood proteins , storing energy in the form of glycogen , and secreting bile . The hepatocytes that perform these tasks can be killed or impaired by disease, resulting in acute liver failure (ALF) which can be seen in person with previously diseased liver or

1060-507: Is generally due to inherent design limitations, causing convectional transport issues, nutritional gradients, non-uniform seeding, inefficient immobilisation of cells, and reduced hepatocyte growth. As of writing, no cryogel-based devices have entered clinical trials. However, laboratory results have been promising, and hopefully trials will begin soon. The HepatAssist , developed at the Cedars-Sinai Medical Center,

1113-404: Is injected into a series of hollow fibers. In the case of collagen, the suspension is then gelled within the fibers, usually by a temperature change. The hepatocytes then contract the gel by their attachment to the collagen matrix, reducing the volume of the suspension and creating a flow space within the fibers. Nutrient media is circulated through the fibers to sustain the cells. During use, plasma

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1166-419: Is not to permanently replace liver functions , but to serve as a supportive device, either allowing the liver to regenerate properly upon acute liver failure , or to bridge the individual's liver functions until a transplant is possible. BALs are essentially bioreactors , with embedded hepatocytes (liver cells ) that perform the functions of a normal liver . They process oxygenated blood plasma , which

1219-459: Is poor and therefore they must be used combined with other systems to mitigate this deficiency. Today, its use is limited to centers with high experience in their application. A bioartificial liver device (BAL) is an artificial extracorporeal liver support (ELS) system for an individual who is suffering from acute liver failure (ALF) or acute-on-chronic liver failure (ACLF). The fundamental difference between artificial and BAL systems lies in

1272-441: Is removed from the patients blood. The patient's plasma is fed into the space surrounding the fibers. The fibers, which are composed of a semi-permeable membrane, facilitate transfer of toxins, nutrients and other chemicals between the blood and the suspended cells. The membrane also keeps immune bodies, such as immunoglobulins , from passing to the cells to prevent an immune system rejection. Currently, hollow-fibre bioreactors are

1325-512: Is responsible for procuring and implanting a new liver, or a part (lobe) of one, if and when it becomes available in time and the patient is eligible. Because of the need for these experts, as well as the relative newness of the procedure in certain areas, it is usually available only in larger hospitals, such as level I trauma center teaching hospitals connected with medical schools. Between the different albumin dialysis modalities, single pass albumin dialysis (SPAD) has shown some positive results at

1378-518: Is separated from the other blood constituents. Several types of BALs are being developed, including hollow fiber systems and flat membrane sheet systems. Various types of hepatocytes are used in these devices. Porcine hepatocytes are often used due to ease of acquisition and cost; however, they are relatively unstable and carry the risk of cross-species disease transmission. Primary human hepatocytes sourced from donor organs present several problems in their cost and difficulty to obtain, especially with

1431-422: Is the only effective treatment for these patients although it requires a precise indication and timing to achieve good results. Nevertheless, due to the scarcity of organs to carry out liver transplantations, it is estimated that one third of patients with ALF die while waiting to be transplanted. On the other hand, a patient with a chronic hepatic disease can suffer acute decompensation of liver function following

1484-411: Is used with patients of specific aetiology. The Extracorporeal Liver Assist Device (ELAD) is a human-cell based treatment system. A catheter removes blood from the patient, and an ultrafiltrate generator separates the plasma from the rest of the blood. This plasma is then run through a separate circuit containing cartridges filled with C3A cells, before being returned to the main circuit and re-entering

1537-459: The 96 patients in the ELAD group, 45 completed the full 120 hours of treatment – the rest were unable to complete the full regimen due to a variety of reasons, including withdrawal of consent or severe adverse events, though 37 completed >72 hours of treatment, with results showing minimal difference in mortality between those receiving either >72 hours or the full 120 hours of treatment. The study

1590-504: The Molecular Adsorbents Recirculating System (MARS) from Gambro and Fractionated Plasma Separation and Adsorption (FPSA), commercialised as Prometheus (PROM) from Fresenius Medical Care . Of the two therapies, MARS is the most frequently studied, and clinically used system to date. While the technique is in its infancy, the prognosis of patients with liver failure remains guarded. Liver dialysis

1643-401: The clinical course of a patient in liver failure. This led to the development of artificial filtration and absorption devices. Liver dialysis is performed by physicians and surgeons and specialized nurses with training in gastroenterological medicine and surgery, namely, in hepatology , alongside their colleagues in the intensive or critical care unit and the transplantation department, which

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1696-456: The column configuration, the stacked bioreactor demonstrated significantly elevated production of albumin and urea, alongside enhanced cell colonization and proliferation over time. Recent developments in bioartificial liver (BAL) using living liver cells have shown promising advancements in the field of liver support and regeneration. These developments focus on utilizing various cell sources, scaffold materials, and bioreactor designs to enhance

1749-453: The cryogel precursors in the solution to increase, initiating the cryogelation process and forming the polymer walls. As the cryogel warms, the solvent crystals thaw, leaving cavities that form the pores. Cryogel pores range in size from 10-100 μm in size, forming an interconnected network that mimics a capillary system with a very large surface area to volume ratio, supporting large numbers of immobilised cells. Convection mediated transport

1802-469: The cultivation of new types of human hepatocytes capable of improved longevity and efficacy in a bioreactor over currently used cell types, that do not pose the risk of transfer of malignancy or infection, such as the HepZ cell line created by Werner et al. . Similar to kidney dialysis , hollow fiber systems employ a hollow fiber cartridge. Hepatocytes are suspended in a gel solution such as collagen , which

1855-422: The current lack in transplantable tissue. In addition, questions have been raised about tissue collected from patients transmitting malignancy or infection via the BAL device. Several lines of human hepatocytes are also used in BAL devices, including C3A and HepG2 tumour cell lines, but due to their origin from hepatomas, they possess the potential to pass on malignancy to the patient. There is ongoing research into

1908-558: The device can be connected to artificial liver dialysis devices in order to further increase the effectiveness of the device in filtration of toxins. The inclusion of functioning hepatocytes in the reactor allows the restoration of some of the synthetic functions that the patient’s liver is lacking. The first bioartificial liver device was developed in 1993 by Dr. Achilles A. Demetriou at Cedars-Sinai Medical Center. The bioartificial liver helped an 18-year-old southern California woman survive without her own liver for 14 hours until she received

1961-400: The difference was not significant. However, when patients with PNF are excluded from the results there is a 44% reduction in mortality for BAL treated patients, a statistically significant advantage. The investigators noted that exclusion of PNF patients is justifiable due to early retransplantation and lack of intercranial hypertension, so HepatAssist would give little benefit to this group. For

2014-644: The failing liver. Bio-artificial liver (BAL) Hepatassist 2000 uses porcine hepatocytes whereas ELAD system employs hepatocytes derived from human hepatoblastoma C3A cell lines. Both techniques can produce, in fulminant hepatic failure (FHF), an improvement of hepatic encephalopathy grade and biochemical parameters. Potential side effects that have been documented include immunological issues (porcine endogenous retrovirus transmission), infectious complications, and tumor transmigration. Other biological hepatic systems are Bioartificial Liver Support (BLSS) and Radial Flow Bioreactor (RFB). Detoxification capacity of these systems

2067-427: The functionality and viability of BAL systems. Key advancements include: Cell Sources: Researchers have explored different cell sources for BAL, including primary hepatocytes, stem cell-derived hepatocyte-like cells, and immortalized liver cell lines. Efforts have been made to optimize cell culture conditions to maintain cell viability and functionality within BAL systems. Scaffold Materials: Biomaterial scaffolds play

2120-472: The functionality of liver cells within BAL systems more accurately. These techniques include measuring the secretion of liver-specific biomarkers, such as albumin, urea, and bile acids, as well as evaluating metabolic activity, drug metabolism, and detoxification capacity. There have been numerous clinical studies involving hollow-fibre bioreactors. Overall, they show promise but do not provide statistically significant evidence supporting their effectiveness. This

2173-413: The inclusion of hepatocytes into the reactor, often operating alongside the purification circuits used in artificial ELS systems. The overall design varies between different BAL systems, but they largely follow the same basic structure, with patient blood or plasma flow through an artificial matrix housing hepatocytes. Plasma is often separated from the patient’s blood to improve efficiency of the system, and

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2226-425: The most commonly accepted design for clinical use due to their capillary-network allowing for easy perfusion of plasma across cell populations. However, these structures have their limitations, with convectional transport issues, nutritional gradients, non-uniform seeding, inefficient immobilisation of cells, and reduced hepatocyte growth restricting their effectiveness in BAL designs. Researchers are now investigating

2279-408: The overall findings were not statistically significant, when the aetiology of the patients was taken into account the BAL group gained a statistically significant reduction in mortality over the control group. This suggests that while the device may not be applicable to patients as an overall treatment for liver dysfunction, it can provide an advantage when the heterogeneity of patients is considered and

2332-576: The patient. Thompson et al. performed a large open-label trial, measuring the effectiveness of ELAD on patients with severe alcoholic hepatitis resulting in ACLF. Their study involved patients screened at 40 sites across the US, UK, and Australia, and enrolled a total of 203 patients. Patients were then randomised into either ELAD (n=96) or standard medical care (n=107) groups, with even distribution for patients in terms of sex, MELD score, and bilirubin levels. Of

2385-425: The patient’s liver. A randomized, phase 3 trial of the ELAD device in patients with severe alcoholic hepatitis failed to show benefit on overall survival and development was discontinued. Artificial liver support systems are aimed to temporarily replace native liver detoxification functions and they use albumin as scavenger molecule to clear the toxins involved in the physiopathology of the failing liver. Most of

2438-438: The performance of BAL systems by optimizing mass transfer, fluid dynamics, and cell-matrix interactions. These designs include perfusion-based bioreactors, microfluidic devices, and three-dimensional (3D) bioprinted constructs, which aim to mimic the physiological microenvironment of the liver and promote liver cell function and survival. Functional Assessment: Advances in bioanalytical techniques have enabled researchers to assess

2491-1090: The prognosis and survival with severe cases of ALF. Nevertheless, cost and donor scarcity have prompted researchers to look for new supportive treatments that can act as “bridge” to the transplant procedure. By stabilizing the patient's clinical state, or by creating the right conditions that could allow the recovery of native liver functions, both detoxification and synthesis can improve, after an episode of ALF or ACLF. Three different types of supportive therapies have been developed: bio-artificial, artificial and hybrid liver support systems (Table 2). Extracorporeal liver assist device Molecular adsorbent recirculating system Bioartificial Liver Support System Fractionated plasma separation and adsorption system TECA-Hybrid Artificial Liver Support System Radial Flow Bioreactor Single-pass albumin dialysis Modular Extracorporeal Liver Support Bioartificial Liver Selective plasma filtration therapy Bioartificial liver devices are experimental extracorporeal devices that use living cell lines to provide detoxification and synthesis support to

2544-513: The results of the study cannot provide conclusive evidence to suggest that a BAL device like ELAD improves the outcome of severe ACLF, it does suggest that it can aid the survival of patients with a less severe form of the disease. In those patients with a MELD <28, beneficial effects were seen 2–3 weeks post treatment, suggesting that while C3A incorporating BAL devices are unable to provide short-term aid like artificial albumin filtration devices, they instead provide more long-term aid in recovery of

2597-539: The safety and efficacy of the HepatAssist device. 171 patients with ALF stemming from viral hepatitis, paracetamol overdose or other drug complications, primary non-function (PNF), or of indeterminate aetiology, were involved in the study and were randomly assigned to either the experimental or control groups. The study found that at the primary end-point 30-day post admission mark, there was an increased survival rate in BAL patients over control patients (71% vs 62%), but

2650-405: The secondary end-point of time-to-death, in patients with ALF of known aetiology there was a significant difference between BAL and control groups, with BAL patients surviving for longer. There was no significant difference for patients of unknown aetiology, however. The conclusions of the study suggest that such a device has potentially significant importance when used as a treatment measure. While

2703-500: The toxins that accumulate in the plasma of patients with liver insufficiency are protein bound, and therefore conventional renal dialysis techniques, such as hemofiltration , hemodialysis or hemodiafiltration are not able to adequately eliminate them. Liver dialysis has shown promise for patients with hepatorenal syndrome . It is similar to hemodialysis and based on the same principles, but hemodialysis does not remove toxins bound to albumin that accumulate in liver failure. Like

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2756-403: The use of cryogels to replace hollow-fibres as the cell carrier components in BAL systems. Cryogels are super-macroporous three-dimensional polymers prepared at sub-zero temperatures, by the freezing of a solution of cryogel precursors and solvent. The pores develop during this freezing process – as the cryogel solution cools, the solvent begins to form crystals. This causes the concentration of

2809-686: Was unable to complete its goal, finding no statistically significant improvement in mortality rates for patients that received ELAD treatment over those receiving standard care at 28 and 91 days (76.0% versus 80.4% and 59.4% versus 61.7%, respectively). Biomarker measurements showed a significantly reduced level of bilirubin and alkaline phosphatase in ELAD patients, though neither improvement translated into increased survivability rates. Outcomes for patients with MELD score <28 showed trends towards improved survival on ELAD, whereas those with MELD >28 had decreased survivability on ELAD. These patients presented with raised creatinine from kidney failure, suggesting

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