Vascularized and Perfusable Human Heart‐on‐a‐Chip Model Recapitulates Aspects of Myocardial Ischemia and Enables Analysis of Nanomedicine Delivery
Abstract
Abstract Cardiovascular diseases (CVDs) are the leading cause of death worldwide. However, the pathophysiological mechanisms of CVDs are not yet fully understood, and animal models do not accurately replicate human heart function. Heart‐on‐a‐chip technologies with increasing complexity are being developed to mimic aspects of native human cardiac physiology for mechanistic studies and as screening platforms for drugs and nanomedicines. Here, a 3D human myocardial ischemia‐on‐a‐chip platform incorporating perfusable vasculature in direct contact with myocardial regions is designed. Infusing a vasoconstrictor cocktail, including angiotensin II and phenylephrine, into this heart‐on‐a‐chip model leads to increased arrhythmias in cardiomyocyte pacing, fibroblast activation, and damage to blood vessels, all of which are hallmarks of ischemic heart injury. To verify the potential of this platform for drug and nanocarrier screening, a proof‐of‐concept study is conducted with cardiac homing peptide‐conjugated liposomes containing Alamandine. This nanomedicine formulation enhances targeting to the ischemia model, alleviates myocardial ischemia‐related characteristics, and improves cardiomyocyte beating. This confirms that the vascularized chip model of human myocardial ischemia provides both functional and mechanistic insights into myocardial tissue pathophysiology and can contribute to the development of cardiac remodeling medicines.
Article Details
Authors (15)
Junyoung Kim
Xuening Zhang
Richard Wang
Laboratory of Molecular and Mechanistic Cell Signaling, Lindsley F. Kimball Research Institute, New York Blood Center
Adrian Najer
Department of Materials, Department of Bioengineering and Institute of Biomedical Engineering Imperial College London Prince Consort Road London SW7 2AZ UK
Qiao You Lau
Department of Materials, Department of Bioengineering and Institute of Biomedical Engineering Imperial College London Prince Consort Road London SW7 2AZ UK
Ana Cammack‐Najera
Department of Materials, Department of Bioengineering and Institute of Biomedical Engineering Imperial College London Prince Consort Road London SW7 2AZ UK
Jang Ah Kim
Department of Materials, Department of Bioengineering and Institute of Biomedical Engineering Imperial College London Prince Consort Road London SW7 2AZ UK
Yoo Kyung Kang
Department of Materials, Department of Bioengineering and Institute of Biomedical Engineering Imperial College London Prince Consort Road London SW7 2AZ UK
Ruoxiao Xie
Department of Materials, Department of Bioengineering and Institute of Biomedical Engineering Imperial College London Prince Consort Road London SW7 2AZ UK
Hyemin Kim
Kai Xie
Hyeonji Lim
Tae‐Eun Park
Department of Biomedical Engineering Ulsan National Institute of Science and Technology (UNIST) Ulsan 44919 Republic of Korea
Jinmyoung Joo
Department of Biomedical Engineering Ulsan National Institute of Science and Technology (UNIST) Ulsan 44919 Republic of Korea
Molly M. Stevens