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Published on: June 16, 2020
Vascularized and Perfusable Human Heart-on-a-Chip Model Recapitulates Aspects of Myocardial Ischemia and Enables
Junyoung Kim1,2, Xuening Zhang1, Richard Wang1
1Department of Materials, Department of Bioengineering and Institute of Biomedical Engineering, Imperial College London, Prince Consort Road, London, SW7 2AZ, UK.
Insights
A new 3D heart-on-a-chip model replicates human myocardial ischemia, revealing disease mechanisms. This platform aids in developing new cardiac drugs and nanomedicines for cardiovascular diseases (CVDs).
Area of Science:
- Biomedical Engineering
- Cardiovascular Research
- Organ-on-a-Chip Technology
Background:
- Cardiovascular diseases (CVDs) are a leading global cause of mortality.
- Existing animal models fail to accurately replicate human cardiac physiology and disease.
- Heart-on-a-chip systems offer advanced platforms for studying cardiac function and disease.
Purpose of the Study:
- To develop a 3D human myocardial ischemia-on-a-chip platform with integrated vasculature.
- To investigate the pathophysiological mechanisms of myocardial ischemia using this advanced model.
- To evaluate the platform's utility for screening cardiac drugs and nanomedicines.
Main Methods:
- Design and fabrication of a 3D heart-on-a-chip device with perfusable vasculature.
- Induction of ischemic conditions using a vasoconstrictor cocktail (angiotensin II, phenylephrine).
- Assessment of cardiomyocyte pacing, fibroblast activation, and vascular integrity.
- Proof-of-concept drug screening using cardiac homing peptide-conjugated liposomes with Alamandine.
Main Results:
- The model successfully replicated key features of ischemic heart injury, including arrhythmias and vascular damage.
- Fibroblast activation was observed, contributing to the understanding of cardiac remodeling.
- Nanomedicine delivery using targeted liposomes alleviated ischemia-related characteristics and improved cardiomyocyte function.
Conclusions:
- The vascularized 3D heart-on-a-chip platform provides functional and mechanistic insights into myocardial ischemia.
- This technology serves as a valuable tool for understanding cardiac pathophysiology.
- The platform demonstrates potential for accelerating the development of novel therapeutics for cardiovascular diseases.
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.
