Modular polymer design to regulate phenotype and oxidative response of human coronary artery cells for potential stent coating applications

Abstract

Polymer properties can be tailored by copolymerizing subunits with specific physico-chemical characteristics. Vascular stent materials require biocompatibility, mechanical strength, and prevention of restenosis. Here we copolymerized poly(ε-caprolactone) (PCL), poly(ethylene glycol) (PEG), and carboxyl-PCL (cPCL) at varying molar ratios and characterized the resulting material properties. We then performed a short-term evaluation of these polymers for their applicability as potential coronary stent coating materials with two primary human coronary artery cell types: smooth muscle cells (HCASMC) and endothelial cells (HCAEC). Changes in proliferation and phenotype were dependent upon intracellular reactive oxygen species (ROS) levels, and 4%PEG-96%PCL-0%cPCL was identified as the most appropriate coating material for this application. After 3days on this substrate HCASMC maintained a healthy contractile phenotype and HCAEC exhibited a physiologically relevant proliferation rate and a balanced redox state. Other test substrates promoted a pathological, synthetic phenotype of HCASMC and/or hyperproliferation of HCAEC. Phenotypic changes of HCASMC appeared to be modulated by the Young's modulus and surface charge of the test substrates, indicating a structure-function relationship that can be exploited for intricate control over vascular cell functions. These data indicate that tailored copolymer properties can direct vascular cell behavior and provide insights for further development of biologically instructive stent coating materials.