Theranostics 2018; 8(10):2752-2764. doi:10.7150/thno.22599
Polypyrrole-chitosan conductive biomaterial synchronizes cardiomyocyte contraction and improves myocardial electrical impulse propagation
1. Toronto General Hospital Research Institute, Division of Cardiovascular Surgery, University Health Network, Toronto, Ontario, Canada
2. Department of Surgery, Division of Cardiac Surgery, University of Toronto, Toronto, Ontario, Canada
3. Department of Chemical Engineering, National Tsing Hua University, Hsinchu, Taiwan
Background: The post-myocardial infarction (MI) scar interrupts electrical impulse propagation and delays regional contraction, which contributes to ventricular dysfunction. We investigated the potential of an injectable conductive biomaterial to restore scar tissue conductivity and re-establish synchronous ventricular contraction.
Methods: A conductive biomaterial was generated by conjugating conductive polypyrrole (PPY) onto chitosan (CHI) backbones. Trypan blue staining of neonatal rat cardiomyocytes (CMs) cultured on biomaterials was used to evaluate the biocompatibility of the conductive biomaterials. Ca2+ imaging was used to visualize beating CMs. A cryoablation injury rat model was used to investigate the ability of PPY:CHI to improve cardiac electrical propagation in the injured heart in vivo. Electromyography was used to evaluate conductivity of scar tissue ex vivo.
Results: Cell survival and morphology were similar between cells cultured on biomaterials-coated and uncoated-control dishes. PPY:CHI established synchronous contraction of two distinct clusters of spontaneously-beating CMs. Intramyocardial PPY:CHI injection into the cryoablation-induced injured region improved electrical impulse propagation across the scarred tissue and decreased the QRS interval, whereas saline- or CHI-injected hearts continued to have delayed propagation patterns and significantly reduced conduction velocity compared to healthy controls. Ex vivo evaluation found that scar tissue from PPY:CHI-treated rat hearts had higher signal amplitude compared to those from saline- or CHI-treated rat heart tissue.
Conclusions: The PPY:CHI biomaterial is electrically conductive, biocompatible and injectable. It improved synchronous contraction between physically separated beating CM clusters in vitro. Intra-myocardial injection of PPY:CHI following cardiac injury improved electrical impulse propagation of scar tissue in vivo.
Keywords: conductive polymer, cardiac injury, electrical impulse conduction, optical mapping
Cui Z, Ni NC, Wu J, Du GQ, He S, Yau TM, Weisel RD, Sung HW, Li RK. Polypyrrole-chitosan conductive biomaterial synchronizes cardiomyocyte contraction and improves myocardial electrical impulse propagation. Theranostics 2018; 8(10):2752-2764. doi:10.7150/thno.22599. Available from http://www.thno.org/v08p2752.htm