title: Chondroitin sulfate coatings display low platelet but high endothelial cell adhesive properties favorable for vascular implants.
abstract: This study highlights the advantages of chondroitin sulfate (CS) as a sublayer combining selective low-fouling properties, low-platelet adhesion and pro-adhesive properties on endothelial cells, making CS promising for vascular graft applications. These properties were evaluated by comparing CS with well-known low-fouling coatings such as poly(ethylene glycol) (PEG) and carboxymethylated dextran (CMD), which were covalently grafted on primary amine-rich plasma polymerized (LP) films. Protein adsorption studies by quartz crystal microbalance with dissipation monitoring (QCM-D) and fluorescence measurements showed that CS is as effective as PEG in reducing fibrinogen adsorption (~90% reduction). CS also largely reduced adsorption of bovine serum albumin (BSA) as well as fetal bovine serum (FBS) but to a lower extent than PEG and CMD surfaces (72% vs 85% for BSA and 66% vs 89% for FBS). Whole blood perfusion assays indicated that, while LP surfaces were highly reactive with platelets, PEG, CMD, and CS grafted surfaces drastically decreased platelet adhesion and activation to levels significantly lower than polyethylene terephthalate (PET) surfaces. Finally, while human umbilical vein endothelial cell (HUVEC) adhesion and growth were found to be very limited on PEG and CMD, they were significantly increased on CS compared to that on bare PET and reached similar values as those for tissue culture polystyrene positive controls. Interestingly, HUVEC retention during perfusion with blood was found to be excellent on CS but poor on PET. Overall, our results suggest that the CS surface has the advantage of promoting HUVEC growth and resistance to flow-induced shear stress while preventing fibrinogen and platelet attachment. Such a nonthrombogenic but endothelial-cell adhesive surface is thus promising to limit vascular graft occlusion.
authors.affiliation: Laboratory of Endovascular Biomaterials (LBeV), Centre hospitalier de l'Université de Montréal (CRCHUM) , 900 Saint Denis, Tour Viger, 11th Floor, Montreal, QC, H2X 0A9, Canada.
authors.forename: Pradeep K
authors.initials: PK
authors.lastname: Thalla
authors.forename: Hicham
authors.initials: H
authors.lastname: Fadlallah
authors.forename: Benoit
authors.initials: B
authors.lastname: Liberelle
authors.forename: Pauline
authors.initials: P
authors.lastname: Lequoy
authors.forename: Gregory
authors.initials: G
authors.lastname: De Crescenzo
authors.forename: Yahye
authors.initials: Y
authors.lastname: Merhi
authors.forename: Sophie
authors.initials: S
authors.lastname: Lerouge
mesh_terms: D001792:Blood Platelets / Q000187:drug effects*; D001807:Blood Vessel Prosthesis; D002448:Cell Adhesion / Q000187:drug effects*; D002809:Chondroitin Sulfates / Q000737:chemistry* / Q000494:pharmacology; D020099:Coated Materials, Biocompatible / Q000737:chemistry* / Q000494:pharmacology; D003911:Dextrans / Q000737:chemistry; D042783:Endothelial Cells / Q000187:drug effects / Q000378:metabolism; D005340:Fibrinogen / Q000737:chemistry; D061307:Human Umbilical Vein Endothelial Cells; D006801:Humans; D010973:Platelet Adhesiveness / Q000187:drug effects; D011092:Polyethylene Glycols / Q000737:chemistry; D011093:Polyethylene Terephthalates / Q000737:chemistry; D011137:Polystyrenes / Q000737:chemistry; D011506:Proteins / Q000737:chemistry; D058525:Quartz Crystal Microbalance Techniques; D012710:Serum Albumin, Bovine / Q000737:chemistry
chemical_list: D020099:Coated Materials, Biocompatible; D003911:Dextrans; D011093:Polyethylene Terephthalates; D011137:Polystyrenes; D011506:Proteins; D012710:Serum Albumin, Bovine; D011092:Polyethylene Glycols; D005340:Fibrinogen; D002809:Chondroitin Sulfates; C014392:carboxymethyl dextran