Development of novel membranes for blood purification therapies based on copolymers of N-vinylpyrrolidone and n-butylmethacrylate.

Developments in membrane based blood purification therapies often come with longer treatment times and therefore longer blood-material contact, which requires long-term membrane biocompatibility. In this study, we develop for the first time membranes for blood purification using the material SlipSkin™, which is a copolymer, made from N-vinylpyrrolidone (NVP) and butylmethacrylate (BMA). Specific attention is focused on understanding the mechanism of pore formation and the tailoring of the membrane mechanical and transport properties to obtain the optimal membrane for blood purification therapies. Polymer composition, solvent type and solvent evaporation time influence membrane morphology and membranes with sieving properties of cascade filters in plasma fractionation applications are developed. The new membranes have very good blood compatibility properties; in fact compared to benchmark flat membranes currently used in the clinic, they have lower platelet adhesion while all other properties (contact activation, thrombogenicity, leukocyte adhesion, hemolysis and complement activation) are also very good and comparable to the benchmarks.

[1]  M. N. Levy,et al.  Principles of Physiology , 1990 .

[2]  William J. Koros,et al.  Phase separation, vitrification, and the manifestation of macrovoids in polymeric asymmetric membranes , 1996 .

[3]  T. Miyasaka,et al.  Effects of fluid flow on elution of hydrophilic modifier from dialysis membrane surfaces , 2008, Journal of Artificial Organs.

[4]  A. Garg,et al.  Survival with three-times weekly in-center nocturnal versus conventional hemodialysis. , 2012, Journal of the American Society of Nephrology : JASN.

[5]  L. Koole,et al.  Thrombus formation at the surface of guide-wire models: effects of heparin-releasing or heparin-exposing surface coatings. , 2007, Journal of vascular and interventional radiology : JVIR.

[6]  A. Denizli,et al.  Poly(hydroxyethyl methacrylate) based affinity membranes for in vitro removal of anti-dsDNA antibodies from SLE plasma. , 2010, International journal of biological macromolecules.

[7]  Zhen-liang Xu,et al.  Polyethersulfone (PES) hollow fiber ultrafiltration membranes prepared by PES/non-solvent/NMP solution , 2004 .

[8]  Shuvo Roy,et al.  Hemocompatibility of Silicon-Based Substrates for Biomedical Implant Applications , 2011, Annals of Biomedical Engineering.

[9]  Y. Ikada,et al.  Simple method for platelet counting. , 1995, Biomaterials.

[10]  C. Ronco,et al.  Effects of different membranes and dialysis technologies on patient treatment tolerance and nutritional parameters. The Italian Cooperative Dialysis Study Group. , 1996, Kidney international.

[11]  H. Coenraad Hemker,et al.  Calibrated Automated Thrombin Generation Measurement in Clotting Plasma , 2003, Pathophysiology of Haemostasis and Thrombosis.

[12]  Bernd Krause,et al.  Polymeric membranes for medical applications , 2003 .

[13]  M. Walport Complement. First of two parts. , 2001, The New England journal of medicine.

[14]  S. Itoh,et al.  Platelet activation through interaction with hemodialysis membranes induces neutrophils to produce reactive oxygen species. , 2006, Journal of biomedical materials research. Part A.

[15]  B. Stegmayr,et al.  A survey of blood purification techniques. , 2005, Transfusion and apheresis science : official journal of the World Apheresis Association : official journal of the European Society for Haemapheresis.

[16]  J. Lai,et al.  Formation and gas flux of asymmetric PMMA membranes , 1996 .

[17]  M J Lysaght,et al.  Effect of membrane composition and structure on solute removal and biocompatibility in hemodialysis. , 1999, Kidney international.

[18]  Matthias Wessling,et al.  A novel approach for blood purification: mixed-matrix membranes combining diffusion and adsorption in one step. , 2012, Acta biomaterialia.

[19]  Andrew Davenport,et al.  A wearable haemodialysis device for patients with end-stage renal failure: a pilot study , 2007, The Lancet.

[20]  S. Nakaji,et al.  Membranes for therapeutic apheresis. , 2002, Therapeutic apheresis : official journal of the International Society for Apheresis and the Japanese Society for Apheresis.

[21]  Matthias Wessling,et al.  Medical applications of membranes: Drug delivery, artificial organs and tissue engineering , 2008 .

[22]  Ayusman Sen,et al.  Disruption and activation of blood platelets in contact with an antimicrobial composite coating consisting of a pyridinium polymer and AgBr nanoparticles. , 2009, ACS applied materials & interfaces.

[23]  J. van Limbeek,et al.  Mechanisms of intra-dialyser granulocyte activation: a sequential dialyser elution study. , 1997, Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association.

[24]  A. Meyrier,et al.  In vivo intracellular cytokine production by leukocytes during haemodialysis. , 2000, Cytokine.

[25]  Christopher T. Chan,et al.  Survival among nocturnal home haemodialysis patients compared to kidney transplant recipients. , 2009, Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association.

[26]  San-Yuan Chen,et al.  Hemocompatibility and anaphylatoxin formation of protein-immobilizing polyacrylonitrile hemodialysis membrane. , 2005, Biomaterials.

[27]  J. Maessen,et al.  The relationship between the antimicrobial effect of catheter coatings containing silver nanoparticles and the coagulation of contacting blood. , 2009, Biomaterials.

[28]  Pengli Bai,et al.  Modification of polyethersulfone membrane by grafting bovine serum albumin on the surface of polyethersulfone/poly(acrylonitrile-co-acrylic acid) blended membrane , 2009 .

[29]  M. Storr,et al.  Blood material interactions at the surfaces of membranes in medical applications , 1998 .

[30]  A. Sjöholm,et al.  Functional analysis of the classical, alternative, and MBL pathways of the complement system: standardization and validation of a simple ELISA. , 2005, Journal of immunological methods.

[31]  S. Kadam,et al.  The biocompatibility and separation performance of antioxidative polysulfone/vitamin E TPGS composite hollow fiber membranes. , 2011, Biomaterials.

[32]  J. Vienken,et al.  Blood compatibility and permeability of heparin-modified polysulfone as potential membrane for simultaneous hemodialysis and LDL removal. , 2011, Macromolecular bioscience.

[33]  M. Lysaght Hemodialysis membranes in transition. , 1988, Contributions to nephrology.

[34]  J. Vienken,et al.  Score model for the evaluation of dialysis membrane hemocompatibility. , 2008, Artificial organs.

[35]  F. H. van der Veen,et al.  Metallic wires with an adherent lubricious and blood-compatible polymeric coating and their use in the manufacture of novel slippery-when-wet guidewires: possible applications related to controlled local drug delivery. , 1999, Journal of biomedical materials research.

[36]  C. Figdor,et al.  Extracellular Ca2+ modulates leukocyte function-associated antigen-1 cell surface distribution on T lymphocytes and consequently affects cell adhesion , 1994, The Journal of cell biology.

[37]  J. Caro,et al.  Basic Principles of Membrane Technology , 1998 .