Engineered cardiac organoid chambers: toward a functional biological model ventricle.
A growing area in the field of tissue engineering is the development of tissue equivalents as model systems for in vitro experimentation and high-throughput screening applications. Although a variety of strategies have been developed to enhance the structure and function of engineered cardiac tissues, an inherent limitation with traditional myocardial patches is that they do not permit evaluation of the fundamental relationships between pressure and volume that characterize global contractile function of the heart. Therefore, in the following study we introduce fully biological, living engineered cardiac organoids, or simplified heart chambers, that beat spontaneously, develop pressure, eject fluid, contain residual stress, exhibit a functional Frank-Starling mechanism, and generate positive stroke work. We also demonstrate regional variations in pump function following local cryoinjury, yielding a novel engineered tissue model of myocardial infarction. With the unique ability to directly evaluate relevant pressure-volume characteristics and regulate wall stress, this organoid chamber culture system provides a flexible platform for developing a controllable biomimetic cardiac niche environment that can be adapted for a variety of high-throughput and long-term investigations of cardiac pump function.
Lee
Eun Jung
EJ
Department of Anesthesiology, Yale University, New Haven, Connecticut, USA.
Kim
Do Eun
DE
Azeloglu
Evren U
EU
Costa
Kevin D
KD
D000818:Animals; D000831:Animals, Newborn; D004195:Disease Models, Animal; D016014:Linear Models; D009203:Myocardial Infarction / Q000378:metabolism / Q000503:physiopathology / Q000628:therapy; D009206:Myocardium / Q000166:cytology / Q000378:metabolism*; D009940:Organoids / Q000254:growth & development*; D051381:Rats; D017207:Rats, Sprague-Dawley; D023822:Tissue Engineering / Q000379:methods*