title: The induction of thrombus generation on nanostructured neutral polymer brush surfaces.
abstract: Surface induced thrombus generation is a major clinical concern associated with vascular medical devices and implants. Here, we show that high graft density hydrophilic non-charged poly (N,N-dimethylacrylamide) (PDMA) brushes prevent the initiation of blood coagulation on synthetic surfaces. Using a multi-faceted analysis approach, we have identified that PDMA brushes greater than 0.27 chains/nm2 graft density showed this highly desired property. Non-specific protein adsorption is greatly reduced on high density brushes compared to bare surface as evident from isothermal titration calorimetry, gel electrophoresis, and proteomic analyses. We have identified approximately 129 proteins of various types on bare and PDMA brush coated surfaces at a range of surface concentrations. Thromboelastography, platelet activation, and aggregation analyses show that only high graft density brushes are neutral to blood coagulation. Since the polymer brush synthesis can be adapted to most currently used biomedical materials, these results have significant impact in the design of highly hemocompatible surfaces.
authors.affiliation: Centre for Blood Research and Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, BC, Canada.
authors.forename: Benjamin F L
authors.initials: BF
authors.lastname: Lai
authors.forename: A Louise
authors.initials: AL
authors.lastname: Creagh
authors.forename: Johan
authors.initials: J
authors.lastname: Janzen
authors.forename: Charles A
authors.initials: CA
authors.lastname: Haynes
authors.forename: Donald E
authors.initials: DE
authors.lastname: Brooks
authors.forename: Jayachandran N
authors.initials: JN
authors.lastname: Kizhakkedathu
mesh_terms: D000178:Acrylamides / Q000494:pharmacology*; D000327:Adsorption / Q000187:drug effects; D000818:Animals; D001777:Blood Coagulation / Q000187:drug effects; D001798:Blood Proteins / Q000737:chemistry / Q000378:metabolism; D001807:Blood Vessel Prosthesis; D002151:Calorimetry; D002645:Chickens; D004591:Electrophoresis, Polyacrylamide Gel; D006801:Humans; D013058:Mass Spectrometry; D049329:Nanostructures / Q000737:chemistry*; D015539:Platelet Activation / Q000187:drug effects; D010974:Platelet Aggregation / Q000187:drug effects; D053657:Platelet-Rich Plasma / Q000378:metabolism; D011485:Protein Binding / Q000187:drug effects; D040901:Proteomics; D013499:Surface Properties / Q000187:drug effects; D013916:Thrombelastography; D013927:Thrombosis / Q000139:chemically induced* / Q000473:pathology*
chemical_list: D000178:Acrylamides; D001798:Blood Proteins; C429790:poly(N,N-dimethylacrylamide)