Novel high-throughput polymer biocompatibility screening designed for SAR (structure-activity relationship): application for evaluating polymer coatings for cardiovascular drug-eluting stents.
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.
Hezi-Yamit
Ayala
A
Medtronic CardioVascular, Santa Rosa, CA 95403, USA. ayala.hezi-yamit@medtronic.com
Sullivan
Carol
C
Wong
Jennifer
J
David
Laura
L
Chen
Mingfei
M
Cheng
Peiwen
P
Shumaker
David
D
Wilcox
Josiah
J
Udipi
Kishore
K
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
D020099:Coated Materials, Biocompatible