Page 171 - Biomedical Engineering and Design Handbook Volume 2, Applications

150 MEDICAL DEVICE DESIGN

bound to the hydroxyl groups. This modified cellulose is marketed under the trade name Hemophan.
While cellulose acetate membranes induce significant platelet activation, platelet activation with
Hemophan membranes is not as pronounced. 25,26,28
Synthetically modified cellulose is produced by replacing some hydroxyl groups with benzyl
groups by ether bonds. These membranes offer a combination of hydrophobic (benzyl groups) to
reduce complement activation and hydrophilic (hydroxyl groups) to reduce protein adsorption. In
another type of synthetic modification, the surface hydroxyl groups are replaced by grafting polyethe-
29
lene glycol. Although there is an improved compatibility with the modified cellulose membranes, the
improvement is far from the desired.
Advantages of cellulose and it’s derivatives include uniform pore size, ability to form thin mem-
branes of the order of 5 to 15 μm, high mechanical strength, chemical stability and high tenacity even
in the wet state, reduced tendency for protein adsorption, and excellent permeability to small molecules.
Disadvantages of the cellulose and modified cellulose membranes include complement activation,
leucopenia, and inability to eliminate toxic middle molecules such as β -microglobulin. Vitamin
2
E–bonded cellulose available under the trade name Excebrane has improved blood compatibility and
microglobulin clearance when compared to cellulose. 30,31 In addition, oxidative DNA damage has been
less pronounced when compared to cellulose membranes. However, more pronounced leukopenia was
observed with vitamin E–modified cellulose when compared to synthetic polysulfone membranes. 32
Synthetic membranes offer superior blood compatibility and middle molecule clearance. Synthetic
membranes, in general, are more hydrophobic than cellulose-based membranes. Polysulfone is the most
widely used synthetic membrane. Polysulfone membranes have high water permeability and signifi-
cantly improved biocompatibility. 33 Polysulfone is used for both low flux and high flux dialysis.
Helixone is a commercially available polysulfone high flux membrane which efficiently removes mid-
dle molecules, such as β -microglobulin, in a narrow range without the loss of albumin. This is achieved
2
by uniform pore in Helixone membranes, which are produced by nanocontrolled spinning techniques.
Polyethersulfone membranes available under the trade name Diapes are thin (30 m) and have higher
water permeability with increased middle molecule (β -microglobulins and AGE) clearance. 25,34,35
2
Polymethylmethacrylate (PMMA) membranes have good middle molecule clearance, and have
excellent biocompatibility. Both polysulfone membranes and PMMA membranes effectively eliminate
several immunogenic products, including neutrophil elastase. Immunoglobulin light chains are uremic
toxins which are effectively eliminated by PMMA membranes. 25,36–38
Polyacrylonitrile-based membranes have very good biocompatibility and enhanced permeability.
AN69 is a commercially available high flux membrane made from copolymer of acrylonitrile and
sodium methyl sulfonate. 39 AN69 has excellent blood compatibility due to its negative surface
charge, and has high permeability with pores in the range of 25 to 55 Å. AN69 membrane effectively
removes β -microglobulin AGE peptides by convection (high flux) and adsorption. In addition AN69
2
eliminates immunogenic substances such as C3a and C5a, and factor D, etc., by adsorption. However,
AN69 membranes lead to severe adverse reaction in patients who are on medical treatment with
angiotensin-converting enzyme (ACE) inhibitors. 40,41
In general, high flux synthetic membranes have increased biocompatibility, blood compatibility,
and increased middle molecule clearance when compared to membranes made of cellulose and its
derivatives. Clinical studies have revealed lower mortality, lower microglobulin and triglyceride val-
ues, and lower incidence of amyloid disease in synthetic high flux membranes (polysulfone, AN69,
and PMMA, etc.) when compared to cellulose-derived membranes. 25 However, the clearance of
these middle molecule toxins, even with the high flux dialysis, using synthetic membranes is much
lower when compared to the clearance in the natural kidney.

5.4.1 The Dialysis System

Blood flows through hollow fibers and dialysate fluid flows outside the hollow fibers, and the hollow
fiber wall acts as a membrane separating the blood and the dialysate fluid. Therefore, there are three
distinct circulation components: the dialysis circuit; the blood circuit, and the hollow fiber which
interfaces both. Figure 5.3 describes the dialysis system for low flux dialysis. The basics of
42
hemodialysis machine are well described by Misra. The dialysis fluid forms a major component of