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.
Subject(s)
Blood Platelets/drug effects , Blood Vessel Prosthesis , Cell Adhesion/drug effects , Chondroitin Sulfates/chemistry , Coated Materials, Biocompatible/chemistry , Chondroitin Sulfates/pharmacology , Coated Materials, Biocompatible/pharmacology , Dextrans/chemistry , Endothelial Cells/drug effects , Endothelial Cells/metabolism , Fibrinogen/chemistry , Human Umbilical Vein Endothelial Cells , Humans , Platelet Adhesiveness/drug effects , Polyethylene Glycols/chemistry , Polyethylene Terephthalates/chemistry , Polystyrenes/chemistry , Proteins/chemistry , Quartz Crystal Microbalance Techniques , Serum Albumin, Bovine/chemistryABSTRACT
Polyethylene glycol (PEG) grafting has a great potential to create nonfouling and nonthrombogenic surfaces, but present techniques lack versatility and stability. The present work aimed to develop a versatile PEG grafting method applicable to most biomaterial surfaces, by taking advantage of novel primary amine-rich plasma-polymerized coatings. Star-shaped PEG covalent binding was studied using static contact angle, X-ray photoelectron spectroscopy (XPS), and quartz crystal microbalance with dissipation monitoring (QCM-D). Fluorescence and QCM-D both confirmed strong reduction of protein adsorption when compared to plasma-polymerized coatings and pristine poly(ethyleneterephthalate) (PET). Moreover, almost no platelet adhesion was observed after 15 min perfusion in whole blood. Altogether, our results suggest that primary amine-rich plasma-polymerized coatings offer a promising stable and versatile method for PEG grafting in order to create nonfouling and nonthrombogenic surfaces and micropatterns.
Subject(s)
Biocompatible Materials/chemistry , Polyethylene Glycols/chemistry , Adsorption , Blood Platelets/drug effects , Cardiovascular Diseases/therapy , Equipment Design , Humans , Microscopy, Electron, Scanning/methods , Microscopy, Fluorescence/methods , Platelet Adhesiveness , Polyethylene Terephthalates/chemistry , Polymers/chemistry , Proteins/chemistry , Spectrometry, Fluorescence/methods , Spectrophotometry/methods , Surface Properties , Water/chemistryABSTRACT
Bone health in men with prostate cancer on androgen deprivation therapy (ADT) has gained increased attention in recent years. Therapies that are becoming available to prevent bone loss and associated complications are changing practice for this patient population. In addition to basic vitamin D and calcium supplementation, bisphosphonates may be an option to treat these patients, and denosumab, a receptor activator of nuclear factor-κB ligand inhibitor, has been proven to be effective in preventing bone loss through a randomized clinical trial. This review examines the importance of bone health in patients on ADT, with an overview of available treatment modalities and guidelines for managing these patients.
