ROS-responsive polyurethane fibrous patches loaded with methylprednisolone (MP) for restoring structures and functions of infarcted myocardium in vivo

Yuejun Yao; Jie Ding; Zhaoyi Wang; Haolan Zhang; Jieqi Xie; Yingchao Wang; Liangjie Hong; Zhengwei Mao; Jianqing Gao; Changyou Gao

doi:10.1016/j.biomaterials.2019.119726

ROS-responsive polyurethane fibrous patches loaded with methylprednisolone (MP) for restoring structures and functions of infarcted myocardium in vivo

Biomaterials. 2020 Feb:232:119726. doi: 10.1016/j.biomaterials.2019.119726. Epub 2019 Dec 26.

Authors

Affiliations

¹ MOE Key Laboratory of Macromolecular Synthesis and Functionalization, Department of Polymer Science and Engineering, Zhejiang University, Hangzhou, 310027, China.
² Pharmaceutical Informatics Institute, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, 310058, China.
³ MOE Key Laboratory of Macromolecular Synthesis and Functionalization, Department of Polymer Science and Engineering, Zhejiang University, Hangzhou, 310027, China. Electronic address: zwmao@zju.edu.cn.
⁴ Pharmaceutical Informatics Institute, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, 310058, China; Dr. Li Dak Sum & Yip Yio Chin Center for Stem Cell and Regenerative Medicine, Zhejiang University, Hangzhou, 310058, China.
⁵ MOE Key Laboratory of Macromolecular Synthesis and Functionalization, Department of Polymer Science and Engineering, Zhejiang University, Hangzhou, 310027, China; Dr. Li Dak Sum & Yip Yio Chin Center for Stem Cell and Regenerative Medicine, Zhejiang University, Hangzhou, 310058, China. Electronic address: cygao@zju.edu.cn.

PMID: 31901502
DOI: 10.1016/j.biomaterials.2019.119726

Abstract

Reactive oxygen species (ROS) play an important role in the pathogenesis of numerous diseases including atherosclerosis, diabetes, inflammation and myocardial infarction (MI). In this study, a ROS-responsive biodegradable elastomeric polyurethane containing thioketal (PUTK) linkages was synthesized from polycaprolactone diol (PCL-diol ), 1,6-hexamethylene diisocyanate (HDI), and ROS-cleavable chain extender. The PUTK was electrospun into fibrous patches with the option to load glucocorticoid methylprednisolone (MP), which were then used to treat MI of rats in vivo. The fibrous patches exhibited suitable mechanical properties and high elasticity. The molecular weight of PUTK was decreased significantly after incubation in 1 mM H₂O₂ solution for 2 weeks due to the degradation of thioketal bonds on the polymer backbone. Both the PUTK and PUTK/MP fibrous patches showed good antioxidant property in an oxidative environment in vitro. Implantation of the ROS-responsive polyurethane patches in MI of rats in vivo could better protect cardiomyocytes from death in the earlier stage (24 h) than the non ROS-responsive ones. Implantation of the PUTK/MP fibrous patches for 28 days could effectively improve the reconstruction of cardiac functions including increased ejection fraction, decreased infarction size, and enhanced revascularization of the infarct myocardium.

Keywords: Fibrous patch; Methylprednisolone; Myocardial infarction; Polyurethane; ROS-Responsive.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Hydrogen Peroxide
Methylprednisolone*
Myocardium
Polyurethanes*
Rats
Reactive Oxygen Species

Substances

Polyurethanes
Reactive Oxygen Species
Hydrogen Peroxide
Methylprednisolone