Diabetes is one of the most prevalent, costly, and debilitating diseases in the world. Although traditional insulin therapy has alleviated the short-term effects, long-term complications are ubiquitous and harmful. For these reasons, alternative treatment options are being developed. This review investigates one appealing area: cell replacement using encapsulated islets. Encapsulation materials, encapsulation methods, and cell sources are presented and discussed. In addition, the major factors that currently limit cell viability and functionality are reviewed, and strategies to overcome these limitations are examined. This review is designed to introduce the reader to cell replacement therapy and cell and tissue encapsulation, especially as it applies to diabetes.
Diabetes is one of the most prevalent, costly, and debilitating diseases in the world. Although traditional insulin therapy has alleviated the short-term effects, long-term complications are ubiquitous and harmful. For these reasons, alternative treatment options are being developed. This review investigates one appealing area: cell replacement using encapsulated islets. Encapsulation materials, encapsulation methods, and cell sources are presented and discussed. In addition, the major factors that currently limit cell viability and functionality are reviewed, and strategies to overcome these limitations are examined. This review is designed to introduce the reader to cell replacement therapy and cell and tissue encapsulation, especially as it applies to diabetes.
High-flux dialysis membranes used with bicarbonate dialysis fluid increase the risk of back diffusion of bacterial endotoxin into the blood during hemodialysis. Endotoxin transfer of various synthetic fiber membranes was tested with bacterial culture filtrates using an in vitro system testing both diffusive and convective conditions. Membranes were tested in a simulated dialysis mode with endotoxin challenge material (approximately 420 EU/mL) added to the dialysis fluid, with saline used to model both blood and dialysis fluid. Samples were taken of both blood and dialysis fluid, and analyzed using a kinetic turbidimetric Limulus amoebocyte lysate assay. Endotoxin was found in all of the blood circuit samples, except for the Fresenius Optiflux F200NR(e) and thick-wall membranes. All membranes tested removed approximately 95% of the endotoxin from solution, with the residual approximately 5% recirculating within the dialysis fluid compartment. Endotoxin distribution through the fiber membrane was examined using a fluorescent-labeled endotoxin conjugate. Fluorescence images indicate that adsorption occurs throughout the membrane wall, with the greatest concentration of endotoxin located at the inner lumen. Contact angle analysis was able to show that all membranes exhibit a more hydrophilic lumen and a more hydrophobic outer surface except for the polyethersulfone membranes, which were of equal hydrophobicity. Resulting data indicate that fiber geometry plays an important role in the ability of the membrane to inhibit endotoxin transfer, and that both adsorption and filtration are methods by which endotoxin is retained and removed from the dialysis fluid circuit.
Sterilized hollow-fiber membranes are used in hemodialysis, ultrafiltration, bioprocessing, and tissue engineering applications that require a stable and biocompatible surface. In this study, we demonstrated significant changes in the fiber physicochemical properties with different methods of sterilization. Commercial polysulfone (PS) hollow fibers containing poly(vinyl pyrrolidone) were subjected to standard ethylene oxide (ETO), sodium hypochlorite (bleach), and electron-beam (e-beam) sterilization techniques followed by analysis of the surface hydrophilicity, morphology, and water-retention ability. E-beam sterilization rendered more hydrophilic fibers with water contact angles near 47 compared to the ETO-and bleachtreated fibers, which were each near 56. Atomic force microscopy revealed lumen root mean square (rms) roughness values near 19 nm for all three sterilization methods;however, e-beam-sterilized and bleach-treated fibers had significantly higher ($ 106 nm) rms values for the outer wall compared to the ETO-sterilized fibers ($ 39 nm). The increased hydrophilicity and surface area of the e-beamsterilized fiber were reflected by a greater water evaporation rate than that of the ETO-treated fiber. These results demonstrate that common sterilization methods may significantly and distinctly alter the polymer membrane physicochemical properties, which may, in turn, impact the performance and, in particular, surface fouling. For tissue engineering and bioprocessing applications, these changes may be leveraged to promote cell adhesion and spreading.
During hemodialysis bacterial lipopolysaccharide (LPS) in contaminated dialysate solution may translocate across the hollow fiber membrane (HFM) to a patient's blood, resulting in fever and possible systemic shock. This study investigates LPS transfer across, and adsorption within, native and modified Fresenius Optiflux® F200NRe polysulfone (PS)/polyvinyl pyrrolidone (PVP) HFMs. Modifications include varied PVP content, addition of a PS‐poly(ethylene glycol) copolymer (PS‐PEG), and bleach sterilization. Under clinically relevant flow conditions LPS from >400 EU mL−1 spiked dialysate is not detected (<0.1 EU mL−1) in the lumens of native fibers, but is detected to varying degrees (0.2–15 EU mL−1) in the lumens of the modified fibers. Fluorescently labeled LPS predominantly adsorbs near the lumen of all membranes except the PS‐PEG containing membrane, where LPS localizes on the outer wall. Thus, addition of PS‐PEG may entrap LPS in the HFM spongy matrix, away from the blood‐contacting fiber lumen. © 2014 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2015, 132, 41550.
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