Cardiovascular disease (CVD) is the leading cause of death around the world, resulting in more than 17.9 million deaths in 2016. Thus, it is vitally important to advance therapies and drugs that can help in the treatment of CVD. Even with an uptick in R&D efforts toward CVD therapies, success has been limited, with many efforts thwarted in the preclinical stages. Preclinical models have a difficult time recreating and simulating the in vivo dynamics of the heart and surrounding environment.
Recently organ on chip technologies have emerged as powerful systems for disease modeling, tissue development, drug screening, therapy design and potentially organ replacement. While there has been increased activity in the development of 3D or heart on chip platforms, these models have yet to produce physiologically relevant anisotropic cardiac tissue, and are unable to induce or mimic physiological conditions of specific cardiac diseases. Further, none of these platforms have provided precise mechanistic insight into the phenotypic signatures of cardiac cells and the physiological alterations of myocardium from a healthy to diseased state.
Researchers at Arizona State University have developed a physiologically relevant 3D cardiac tissue microfluidic platform with precisely engineered architecture and surface topography. This platform enables 3D tissue culture with optimized tissue-level alignment, similar to that seen in native human myocardium, over an extended period of time. It provides physiologically relevant disease modeling and drug testing as well as sample collection for appropriate phenotypic and genotypic analyses. Pathological events involved in the transition of healthy to diseased cardiac tissue can be better studied with this model. Additionally, the design allows it to recapitulate specific disease conditions such as acute and chronic ischemia.
This platform overcomes the technical limitations of existing heart on chip systems and provides a powerful approach for both mechanistic studies and pre-clinical applications.
Potential Applications
• Cardiac injury/disease modeling
• Fundamental biological discovery
• Real-time monitoring of cardiac tissue in healthy or injured/diseased state
• Drug screening/testing for safety, efficacy & cardiotoxicity
• Genotypic/phenotypic/cardiac marker analyses
• Use of siRNA to block genes and assess outcome on tissue physiology
• Additional cell layers can be incorporated for more complex and fundamental studies
Benefits and Advantages
• Specially designed and engineered to more accurately mimic the tissue of the human myocardium including co-culturing of cardiomyocytes and non-myocytes
• 3D cellular and tissue-level alignment
• Enables cell sample collection for phenotypic/genotypic analyses to define the underlying mechanisms of disease at the molecular level
o Media can also be sampled to analyze secreted cytokines/proteins
• Able to create specific cardiac injury/disease models
o Allows for specific and directed application of insults such as drugs or environmental factors
• Provides continuous, real-time monitoring of the cardiac tissue in both healthy and injured or diseased state
• The platform is versatile and scalable
For more information about the inventor(s) and their research, please see
Dr. Nikkhah’s laboratory webpage