Extracorporeal devices

Polyelectrolytes have been widely investigated as components of biocompatible materials. Biomaterials come into contact with blood when used as components in invasive instruments, implant devices, extracorporeal devices in contact with blood flow, implanted parts of hard structural elements, implanted parts of organs, implanted soft tissue substitutes and drug delivery devices. Approaches to the development of blood compatible materials include surface modification to give blood compatibility, polyelectrolyte-based systems which adsorb and/or release heparin as well as polyelectrolytes which mimic the biological activity of heparin. 

Cell Sourcing Cell Transplantation Tissue Engineered Implants Extracorporeal Devices... 

This chapter will review the current state of the art in this arena. We first discuss the current methods for treating liver failure, including cell transplant techniques. The primary physical characteristics of successful implantable and extracorporeal devices will be described. We will then cover the work of Matsushita et al. that meets most of the requirements for a successful device along with improvements that will result from the use of hydrophilic-grafted polyurethanes. 

The answer to the shortage of hver tissue is to evolve from a dependence on whole and partial organs to the use of hepatic cehs. Ceh therapies range from the injection of ceh colonies with the hope that they wih take up residence and become chnicahy active to the development of implantable or extracorporeal devices. Such approaches must consider both the sources of hepatocytes and stabilization of liver-specific functions. 

Extracorporeal devices to support a compromised liver were reviewed by Allen et al. and Strain and Neubcrgcr.Various nonbiological approaches such as hemodialysis or hemoperfusion over charcoal have met with limited success, presumably because these systems inadequately replaced the synthetic and metabolic functions of the liver. Conversely, biological approaches such as hollow fiber devices, flat plate systems, perfusion beds, and suspension reactors have shown encouraging results but are difficult to implement in a clinical setting. 

Yang et al. discussed the basic properties of an implantable or extracorporeal artificial liver. The article focused on implantable devices but other than biodegradability, the properties of implantable devices are also applicable to extracorporeal devices. The focus of the article on implantable devices reveals an unfortunate prejudice on the part of much of the scientific community. Most researchers in this field are working on devices intended to be placed in the body. 

Membrane separation in the medical field has been included in a chapter focused on medical extracorporeal devices, which illustrates the use of membranes for separation of biological fluids and for preparation of bioartificial organs able to accomplish ex vivo biological transformation (Part headed Transformation ). 

This chapter will focus on three types of membrane extracorporeal devices, hemodialyzers, plasma filters for fractionating blood components, and artificial liver systems. These applications share the same physical principles of mass transfer by diffusion and convection across a microfiltration or ultrafiltration membrane (Figure 18.1). A considerable amount of research and development has been undertaken by membrane and modules manufacturers for producing more biocompatible and permeable membranes, while improving modules performance by optimizing their internal fluid mechanics and their geometry. 

Development of an in vivo or extracorporeal device that supplements reduced tissue function. The in vivo device is encapsulated within a semi-permeable membrane to allow for provision of a therapeutic molecule to the site while protecting the cells from the host immune system. An externally positioned device would provide deficient tissue function compounds through a tube directed to the body site while avoiding cellular contact with the immune system. 

Cardiopulmonary bypass—The use of extracorporeal devices to pump blood and oxygenate the blood while the heart or lungs are not functional. Extracorporeal membrane oxygenation (ECMO) is a form of long-term cardiopulmonary b5 pass that is typically used for days to weeks. 

Within the next 5-10 years the use of ISE type devices for continuous monitoring during surgical procedures and at the bedside of critically ill patients should become commonplace. While there are still problems to overcome, recent experiments with animals have already demonstrated that such measurements are feasible. It is probable that biomedical instrument manufocturers will produce both extracorporeal (e.g., the Miles Biostator already mentioned) and catheter-type systems for continuous detection of blood electrolyte levels. The use of telemetry for monitoring ISE potentials will undoubtedly play a major role in the development of the catheter devices. Ideally, one can envision, in the near future, operating nrams equipped with in vivo or extracorporeal devices and video screens which continuously display the patient s electroijrte levels just as blood pressure and heart rates are currently monitored. 

Several other reactors for immobilized heparinase have been designed (53,54). The initial reactor (47) caused no more blood damage than conventionally used extracorporeal devices such as the artificial kidney machine (54a). By controlling the mode of immobilized enzyme bead suspension, all blood damage can be essentially eliminated (54). The FDA... 

During hyperthermia, terms representing the heat input to a specific tissue or whole body must be added to the proper system equation(s). For example, during whole-body or local hyperthermia induced by radiofrequency currents, microwaves, or ultrasound, a heat-generation term is added to the section of the body being heated. During hyperthermia with blood perfusion, the afferent blood temperature is set at a desired value, and the efferent blood is circulated to the central blood pool, or to the extracorporeal device used for heating the blood. Suitable numerical... 

Figure 7.36 L-Asparagine concentration vs. time in in vivo experiments performed on rats. The extracorporeal device is a "tube-and-shell" membrane reactor where asparaginase is bound to the outer surface of Cuprophan membranes.71...

We propose a new approach that would allow the full heparinization of the extracorporeal device, yet could enable, on-demand, elimination of heparin in the patient s bloodstream. This approach consists of a blood filter containing immobilized heparinase, which could be placed at the effluent of any extracorporeal device (Figure 1). Such a filter could theoretically be used to eliminate heparin after it had served its purpose in the extracorporeal device and before it returned to the patient. In this chapter we discuss our efforts to develop such a filter. Our work has focused on several areas (1) enzyme production (2) enzyme purification (3) characterization of heparinase (4) immobilization of heparinase and (5) in vitro testing of immobilized heparinase. 

Figure 1. Proposed heparin circuit. The extracorporeal device could be a renal dialysis unit or a pump-oxygenator. The heparinase reactor could be part of a blood filter to be used either continuously (in which case heparin would, be added, continuously at the start of the circuit) or at the end of an operation. Heparin could thus be confined to the extracorporeal circuit.

At present, synthetic blood filters are routinely placed at the effluent of extracorporeal devices such as the pump-oxygenator or artificial kidney to remove clots or aggregates formed during the perfusion. The filters used in oxygenators can be as large as 2 L, whereas those used in renal dialysis are only several milliliters. With further development, heparinase could be immobilized to polymers in these filters. In this case, the filter could remove both clots and heparin. 

Since membrane lungs as extracorporeal devices are in wide use, thoughts have turned to an implantable artificial lung prosthesis based on membrane technology. Developing such a device with the adequate characteristics and long-term reliability is a much more difficult task than encountered with the extracorporeal device developed for intermittent use. However, a small prototype device made of porous Teflon has been fabricated and tested by Richardson and Galletti. ... 

---