title: Novel high-throughput polymer biocompatibility screening designed for SAR (structure-activity relationship): application for evaluating polymer coatings for cardiovascular drug-eluting stents.
abstract: The development of stents has been a major advancement over balloon angioplasty, improving vessel revascularization in obstructive coronary artery disease. The development of drug-eluting stents (DES) was the next breakthrough, designed to prevent the development of neointimal hyperplasia (restenosis) following percutaneous coronary interventions (PCI). Several DES are currently in various stages of clinical development; these DES use different stent platforms, different antiproliferative drugs and different polymeric coatings that carry the drugs and control their delivery kinetics. Following DES implantation, when the entire drug is released, the polymeric coating is still retained on the stent and can influence subsequent tissue response and vascular healing. Therefore, the biocompatibility of the polymeric coatings is an important component of DES safety and needs to be thoroughly evaluated. Here we describe the development of a high-throughput screening platform for the evaluation of polymer biocompatibility, assaying whether a polymeric coating triggers inflammation in vascular cells. The data generated by these assays provides a structure-activity relationship (SAR) that can guide polymer chemists in polymer design. We have also applied this methodology to evaluate the components of a novel polymer system (BioLinx polymer system) designed in-house. In addition, we assayed other polymeric coatings similar to those currently used on various DES. The results of this evaluation reveal a remarkable correlation between polymer hydrophobicity and its ability to provoke inflammatory response.
authors.affiliation: Medtronic CardioVascular, Santa Rosa, CA 95403, USA. ayala.hezi-yamit@medtronic.com
authors.forename: Ayala
authors.initials: A
authors.lastname: Hezi-Yamit
authors.forename: Carol
authors.initials: C
authors.lastname: Sullivan
authors.forename: Jennifer
authors.initials: J
authors.lastname: Wong
authors.forename: Laura
authors.initials: L
authors.lastname: David
authors.forename: Mingfei
authors.initials: M
authors.lastname: Chen
authors.forename: Peiwen
authors.initials: P
authors.lastname: Cheng
authors.forename: David
authors.initials: D
authors.lastname: Shumaker
authors.forename: Josiah
authors.initials: J
authors.lastname: Wilcox
authors.forename: Kishore
authors.initials: K
authors.lastname: Udipi
mesh_terms: D002448:Cell Adhesion; D002478:Cells, Cultured; D020099:Coated Materials, Biocompatible; D003328:Coronary Thrombosis / Q000235:genetics; D003331:Coronary Vessels / Q000166:cytology; D015195:Drug Design; D054855:Drug-Eluting Stents; D006801:Humans; D007249:Inflammation / Q000235:genetics; D015394:Molecular Structure; D013329:Structure-Activity Relationship; D013499:Surface Properties
chemical_list: D020099:Coated Materials, Biocompatible