Peptide-Mediated PEGylation of Polysulfone Reduces Protein Adsorption and Leukocyte Activation

The exposure of blood to bioincompatible materials used for dialysis triggers leukocyte activation and protein adsorption. We describe a single-step, postmanufacturing method for surface modification to create biomaterials used in medical devices and dialysis with altered surface characteristics. Peptides derived from the receptor-binding domain of the type IV pilin of Pseudomonas aeruginosa were synthesized using L and D-amino acids to generate L-K122-4, enantiomer D-K122-4, and D-retroinverso RI-K122-4 peptides. L-K122-4, D-K122-4, and RI-K122-4 peptides, but not control peptides, bound durably to the surfaces of materials used in medical devices and dialysis including silicone and polysulfone. D-K122-4 enantiomeric peptides were protease resistant on polysulfone and could remain bound to the surface for up to 28 days. To demonstrate that K122-4 peptides could be used to modify material surfaces, D-K122-4 peptide was conjugated to polyethylene glycol (D-K122-4-PEG) and applied to polysulfone. When compared with untreated material, D-K122-4-PEG reduced the surface adsorption of albumin or immunoglobulin G to polysulfone. In coincubation experiments, although uncoated polysulfone induced pro-interleukin-1β cytokine expression in leukocytes, cellular activation was prevented when leukocytes were incubated with D-K122-4-PEG-modified polysulfone. These data demonstrate the proof of principle that K122-4 peptides can be applied to modify the surface characteristics of materials used for dialysis.