Pancreas, artificial, development

FIGURE 51 Schematic of artificial pancreas under development based on a membrane unit (Circe Biomedical, Inc., Lexington, MA). 

Kim SW and Jacobs HA. Self-regulated insuhn dehvery—artificial pancreas. Drug Development and Industrial Pharmacy 1994 20 575-580. 

Artificial organs that perform the physical and biochemical functions of the heart, hver, pancreas, or lung are one class of organ replacements. A rather different target of opportunity is the development of biologieal materials that play a more passive role in the body for example,... 

Present perfect-passive An artificial pancreas has been developed. (From Tyon, 2000)... 

Other recently developed biomaterials will be used for quite different purposes in tissue engineering such as artificial pancreas and liver, artificial skin, nerve regeneration, gene therapy vascular grafts, cornea replacement and others.3... 

This chapter will review current activities and proposed research related to the development of artificial organs and organ-assist devices. While we will focus on the human liver, the discussion is applicable to other organs. The pancreas and the endocrine functions of the kidney follow the same basic path — the culturing of cells on a scaffold. The cells, of course, must function as they do in a natural uncompromised slate while the scaffold provides a permanent or temporary template on which the cells attach and proliferate. 

Development of Subcutaneous-Type Glucose Sensors for Implantable or Portable Artificial Pancreas... 

The closed-loop type artificial pancreas (specifically 8-cell), which consists of an automatic continuous monitor of blood glucose level (BGL) and an automatic injector of insulin which are coupled with feed-back system, has great potential for prevention of diabetic complication such as micro-angiopathies(l). A large-scale closed-loop type artificial pancreas for bedside use has already been developed and is clinically used at some laboratories and hospitals (2-4). However, this device is limited to only bedside use. On the other hand, the open-loop type artificial pancreas which consists of only a insulin injecting pump without an automatic continuous monitor of BGL, has been developed and is going to be clinically used(5-7). This system, however, can not completely control BGL as well as the bare pancreas in a normal body and often causes lower BGL(8-9). 

In order to provide for the complete therapy of diabetic patients, an implantable or portable closed-loop type artificial pancreas must be developed. The key factor in the development of such system is development of a small-size glucose sensor which is able to measure directly up to 500-700 mg/dl of BGL in a blood stream or in a body fluid. 

About ten years ago, Bessman et al(10), University of Southern California, developed a glucose sensor of enzyme electrode type with glucose oxidase (G0X) for an artificial pancreas. This sensor had... 

On the commercial front, an artificial liver system has reached advanced clinical trial stage. Based on pig hep-atocytes immobilized in a hollow-fiber membrane module, this system provides temporary life support until a liver from a human donor is available for transplantation (Fig. 50). Also under development is an artificial pancreas intended as a permanent replacement of the native organ (Fig. 51). 

The application of an artificial endocrine pancreas (AEP=Biostator) with feedback control could be useful in the clinical management of unstable diabetics (Ohno et al., 1983). Former early closed-loop devices were large bedside machines (Pfeiffer et al., 1974) with only limited application for long-term use. More recent research has developed small glucose sensors which, however, have had only preliminarily testing for clinical application. External insulin pumps must be further miniaturized and technical failure... 

There are various clinical conditions where administration of cultured whole cells or tissue may be desirable. The sources of these tissues are as diverse as the disease targets. For example, cultured fibroblasts from human prepuces are being developed as artificial skin for the treatment of leg ulcers and bums (Advanced Tissue Sciences, La Jolla, California Smith and Nephew, Romford, UK). Other companies are developing implantable pancreas generated from isolated pancreatic islet cells. Unlike matched transplantations, such therapies may involve treatment of large numbers of patients from a limited or sole initial human source or may be autologous albeit after some ex vivo manipulation and culturing of the cell mass before reimplantation. 

Biomedical materials include metals, ceramics, natural polymers (biopolymers), and synthetic polymers of simple or complex chemical and/or physical structure. This volume addresses, to a large measure, fundamental research on phenomena related to the use of synthetic polymers as blood-compatible biomaterials. Relevant research stems from major efforts to investigate clotting phenomena related to the response of blood in contact with polymeric surfaces, and to develop systems with nonthrombogenic behavior in short- and long-term applications. These systems can be used as implants or replacements, and they include artificial hearts, lung oxygenators, hemodialysis systems, artificial blood vessels, artificial pancreas, catheters, etc. 

Unlike the bedside or portable insulin delivery systems for which commercially available peristaltic or syringe pumps may be used, the key component of an implantable (open-loop) artificial pancreas is the specially developed miniature insulin pump. 

Glucose is probably the most frequently assayed nonionic analyte in clinical chemistry, but only recently have reliable sensors been developed for this species [66, 67]. At present, the lack of a suitable glucose sensor can be regarded as the rate-limiting step in the development of an artificial pancreas. 

One major interesting application of Biosensor has been the development of a wearable artificial pancreas and the studies associated with development. This devise has never reached the market stage even if several scientists addressed the problem and demonstrated the possibility to resolve it. In 1976 Clemens et al incorporated an electrochemical glucose biosensor in a bedside artificial pancreas . It was later marketed by Miles (Elkhart) as the Biostator Glucose-Controlled Insulin Infusion System (60 Kg, 42 x 46 x 46 cm) (Rg. 1). 

The second system, based on polymer 24 is water-soluble as its sodium salt, but crosslinks ionically in the presence of di- or tri-valent cations such as calcium or aluminum ions [43], to form hydrogels. This polymer Is under development as a component for the microencapsulation of hybridoma mammalian cells to allow their use in prototype artificial liver or pancreas devices, or in biotechnology [44-46]. 

An interesting strategy in tissue engineering is the encapsulation or immunoisolation of pancreatic and hepatic cells [ 162] (Fig. 25.4). Langerhans islets have been enclosed in chitosan/calcium alginate capsules with the aim of developing an artificial pancreas for the treatment of diabetes mellitus [163]. 

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