Ionic liquid-derived blood-compatible composite membranes for kidney dialysis

Abstract

A novel heparin- and cellulose-based biocomposite is fabricated by exploiting the enhanced dissolution of polysaccharides in room temperature ionic liquids (RTILs). This represents the first reported example of using a new class of solvents, RTILs, to fabricate blood-compatible biomaterials. Using this approach, it is possible to fabricate the biomaterials in any form, such as films or membranes, fibers (nanometer- or micron-sized), spheres (nanometer- or micron-sized), or any shape using templates. In this work, we have evaluated a membrane film of this composite. Surface morphological studies on this biocomposite film showed the uniformly distributed presence of heparin throughout the cellulose matrix. Activated partial thromboplastin time and thromboelastography demonstrate that this composite is superior to other existing heparinized biomaterials in preventing clot formation in human blood plasma and in human whole blood. Membranes made of these composites allow the passage of urea while retaining albumin, representing a promising blood-compatible biomaterial for renal dialysis, with a possibility of eliminating the systemic administration of heparin to the patients undergoing renal dialysis.

Figure 1

Schematic representation for the preparation of heparin–cellulose composite biomaterials. [Color figure can be viewed in the online issue, which is available at www.interscience.wiley.com.]

Figure 2

Surface morphology of the cellulose and the heparin–cellulose composite films. (a, b) FESEM; (c, d) AFM topography; and (e, f) AFM phase images of the cellulose-only film (a, c, and e) and heparin–cellulose composite film (b, d, and f). FESEM images are presented at ×30,000 magnification. [Color figure can be viewed in the online issue, which is available at www.interscience.wiley.com.]

Figure 3

The concentration of heparin measured, releasing out of film, plotted as a function of time. [Color figure can be viewed in the online issue, which is available at www.interscience.wiley.com.]

Figure 4

Clotting properties of heparin–cellulose composite membrane. (a) APTT values of the cellulose and heparin–cellulose composite membranes compared with existing heparinized biomaterials. (b) TEGs of blood alone (control in red), cellulose film (black), leached heparinized biofilm (pink) and intact heparinized biofilm (green); The characteristics of the pink TEG (elongated clotting time, reduced clot formation, formation of weaker clot, and slower rate of clot formation) clearly demonstrates heparin is present in its bioactive form. [Color figure can be viewed in the online issue, which is available at www.interscience.wiley.com.]

Figure 5

Dialysis properties of heparin–cellulose composite membrane. Equilibrium dialysis of urea and BSA across the heparin–cellulose composite film from high concentration side (H) to the low concentration side (L).