Bioengineering in Development of the Hybrid Artificial Pancreas

Colton, Clark K.; Avgoustiniatos, Efstathios S.

doi:10.1115/1.2891229

Cited by 199 publications

(96 citation statements)

References 0 publications

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“…This approach was found to be rather successful because these devices implanted as high flow arteriovenous fistulas could remain patent for periods of 7 weeks in the absence of systemic anticoagulant therapy [12]. This success can be explained in part by the high flow rates through the device which prevents adhesion of cells to the membranes or collection of those cells in the immediate vicinity [13]. However, high flow arteriovenous fistulas are not without risk and much longer patency rates are required for effective applicability.…”

Section: Macroencapsulation Of Pancreatic Isletsmentioning

confidence: 99%

“…The hollow fibre geometry is usually preferred over the planar membranes for their smaller foreign body response [30]. Most studies on hollow fibres use fibres made of PAN-PVC [13,31], similar to those used in intravascular devices. They have been produced with a smooth and fenestrated outer skin with the same spongy matrix as applied in the intravascular.…”

Section: Macroencapsulation Of Pancreatic Isletsmentioning

confidence: 99%

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Considerations for successful transplantation of encapsulated pancreatic islets

2002

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A major challenge in the treatment of Type I (insulindependent) diabetes mellitus is the prevention of late complications, and thereby improvement of the quality of patient life. There is no dispute that euglycaemia is of essential importance to reach that goal. Euglycaemia can be achieved by insulin treatment and the results of the Diabetes control and complications trial clearly show that insulin treatment delays the onset and reduces the progression of diabetic complications [1]. Intensified treatment, however, is not a simple chore because it requires multiple daily injections, frequent monitoring, dosage adaptations and, thus, patient compliance. It is also associated with frequent episodes of severe hypoglycaemia and with glycaemic unawareness. A different approach to euglycaemia is to provide the diabetic patient with an endogenous rather than an exogenous source of insulin by the transplantation of the endocrine pancreatic tissue. Pancreatic organ transplantation is now an es- Diabetologia (2002) AbstractEncapsulation of pancreatic islets allows for transplantion in the absence of immunosuppression. The technology is based on the principle that transplanted tissue is protected for the host immune system by an artificial membrane. Encapsulation offers a solution to the shortage of donors in clinical islet transplantation because it allows animal islets or insulin-producing cells engineered from stem cells to be used. During the past two decades three major approaches to encapsulation have been studied. These include intravascular macrocapsules, which are anastomosed to the vascular system as AV shunt; extravascular macrocapsules, which are mostly diffusion chambers transplanted at different sites; and extravascular microcapsules transplanted in the peritoneal cavity. The advantages and pitfalls of these three approaches are discussed and compared in the light of their applicability to clinical islet transplantation. All systems have been shown to be successful in preclinical studies but not all approaches meet the technical or physiological requirements for application in human beings. The extravascular approach has advantages over the intravascular because since it is associated with less complications such as thrombosis and infection. Microcapsules, due to their spatial characteristics, have a better diffusion capacity than macrocapsules. Recent progress in biocompatibility of microcapsules has brought this technology close to clinical application. Critical issues such as limitations in the functional performance and survival are being discussed. The latest results show that both issues can be solved by the transplantation of microencapsulated islets close to blood vessels in prevascularized solid supports. [Diabetologia (2002) 45: 159±173]

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Section: Macroencapsulation Of Pancreatic Isletsmentioning

confidence: 99%

Section: Macroencapsulation Of Pancreatic Isletsmentioning

confidence: 99%

Considerations for successful transplantation of encapsulated pancreatic islets

2002

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“…It is realized that suf®cient diffusion of insulin and simultaneous blockage of IgG is not a trivial parameter in the design of a successful biocapsule membrane. Although the IgG molecule has a molecular weight of approximately 150 kDa, studies have disagreed on the actual dimensions of the molecule, estimated to be tens of nanometers or less [20,21]. For example, Wang et al [22] investigated permeability of relevant immune molecules to sodium alginate/poly-L-lysine capsules and found that signi®cant amounts of IgG (close to 40%) passed through both 230 and 110 kDa membranes in 24 h.…”

Section: Discussionmentioning

confidence: 99%

Characterization of micromachined silicon membranes for immunoisolation and bioseparation applications

Desai

Hansford

Ferrari

1999

Journal of Membrane Science

141

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The application of microfabrication technology to create precise separation and isolation membranes for biomedical applications is described. By utilizing fabrication techniques commonly employed in the microelectronics industry (MEMS), membranes can be fabricated with well-controlled and uniform pore sizes, allowing the optimization of membrane parameters for biomedical applications in cell immunoisolation and viral ®ltration. Using bulk and surface micromachining to create diffusion membranes, pore sizes down to 18 nm have been attained through deposition and subsequent etching of sacri®cial layers on silicon. Membranes were shown to be suf®ciently permeable to small biomolecules such as oxygen, glucose, and insulin, while excluding the passage of larger proteins such as immunoglobulin G (IgG). The semipermeability of microfabricated membranes, their biocompatibility, ease in sterilization, along with their thermal and chemical stability, may provide a signi®cant advantages for biomedical applications. Microfabrication technology may also be applied to other materials of interest for the development of highly controlled membranes. #

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“…Some substances like transferrin may even be retained as the consequence of its incompatible conformation or its large molecular weight. Furthermore, the low oxygen tension [36][37][38] and low concentrations of essential minerals [36][37][38][39] in the peritoneal fluid may also contribute to a gradual decrease of the size of the islet graft and, therefore, limit the lifespan of the graft. The significance of the lack of vascular access for the viability of the encapsulated islets and for the occurrence of graft failure is illustrated by our observations that the diameters of encapsulated islets become smaller with time and that islets gradually develop necrotic zones.…”

Section: Discussionmentioning

confidence: 99%