Evolution of synthetic membranes for blood purification: the case of the Polyflux family.

Abstract

Transport in biological systems is controlled by membranes functioning as barriers between compartments with various degrees of specificity. In 1972, Singer andNicolson [1] introduced a breakthrough view on structures of cell membranes with their fluid mosaic model. Their findings emerged along colloid chemistrybased organization of hydrophilic–hydrophobic polymer molecules and structures to form the cell membrane. Obviously, these principles also influenced the design of artificial membranes for therapeutic purposes. The general functional features involved in membrane separation processes, whether a natural cell membrane or an artificial membrane, concern either the process or the structure of the barrier, i.e. diffusion and convection of solutes along a pressure or concentration gradient, adsorption to generate a barrier for certain molecules, patch-like or mosaic-like structures to prevent or limit unspecific interaction, short transport channels for fast transport, nanoand micro-dimensions to suppress unspecific interaction and enable selectivity, narrow pore distribution to sharpen cut-off profiles, and optimized cross-filtration flux. In biological organisms, a number of additional functional elements of membranes are applied: active epithelial layers supported by basement membrane structures such as glomerular membranes, confluent tightly connected layers of endothelial cells, and strictly ordered hydrophilic–hydrophobic molecular arrangements in cellular bi-layer membranes. The function of the artificial kidney has relied from the beginning on principles laid down in renal physiology or, later, in biophysical principles in synthetic membranes whose functions were approaching those of the human glomerular membrane. Diffusion and convection predominantly have been combined to achieve the desired blood purification. Today, haemodialysis is basically divided into two categories: blood purification by low-flux and high-flux dialysis membranes [2–13]. Low-flux dialysis includes the standard haemodialysis technique in which dialysers with low hydraulic permeability are utilized. Blood and dialysate flows are at 250 and 500ml/min, respectively, and the average duration is 4 h. When dialyser surface area is increased, blood and dialysate flows are increased up to 400 and 800ml/min, respectively, and the treatment is defined in these circumstances as high efficiency haemodialysis. In this treatment, the clearance for small molecules is remarkably increased and the treatment time can generally be shortened, but the clearance for medium to large molecules is still very low due to the sieving characteristics of the membrane [14–30]. Classic cellulosic membranes such as Cuprophan were typically hydrogel-type low-flux membranes (i.e. permeability to water in the range of 5–6ml/h mmHg m), strongly hydrophilic and remarkably thin (6–12 mm) to permit an optimal utilization in diffusive transport of water-soluble solutes for treatments such as haemodialysis. On the other hand, classic high-flux synthetic membranes were originally fully hydrophobic, strongly asymmetric and with a wall thickness of 40–60 mm. They were originally employed in convective therapies such as haemofiltration [31] due to their high hydraulic permeability (i.e. 30–40ml/h mmHg m) and their elevated sieving coefficients. In a subsequent step, membrane structures have been adapted to fulfil the demand for increased diffusive permeability matched with tailored convective properties. This was achieved by (i) using polymer blends of hydrophilic and hydrophobic polymers; (ii) reduction of the wall thickness; and (iii) structural modifications Correspondence and offprint requests to: Claudio Ronco, Department of Nephrology, St Bortolo Hospital, Viale Rodolfi, 36100 Vicenza, Italy. E-mail: cronco@goldnet.it