(H-282) An Injectable Reverse Thermal Gel Functionalized with Gold Nanoparticles Promotes Passive Electromechanical Conditioning which Improves Cardiac Spheroids Contractile Performance

Introduction:: The development of a mature in vitro cardiac tissue involves the design of a scaffold supporting a proper electrical communication, mechanosensing, and mechanotransduction of the cardiomyocytes, which are cells known for being electroactive. Moreover, a 3D environment is pivotal to create a myocardial model structured like a native tissue. Cardiac spheroids are simple, yet effective 3D structures made of cardiomyocyte that spontaneously aggregate to form a spheroidal body.

Materials and Methods:: In this work, we show that the contractile properties of neonatal rat cardiomyocytes can be improved by growing them for up to three weeks inside an injectable reverse thermal gel (RTG) functionalized with gold nanoparticles (RTG-AuNP); The RTG-AuNP transitions from a solution at room temperature to a three-dimensional (3D) gel-based matrix shortly after reaching body temperature, allowing for a 3D cell culture.

Results, Conclusions, and Discussions::

Cardiac spheroids that were grown into the nano-engineered RTG-AuNP showed signs of advanced maturation, including increased gap junction expression, improved synchronicity of beating, and increased twitch power, after undergoing mechanical loading. This work highlights the importance of a strong interplay between electrical and mechanical cues in the development of a mature, adult-like cardiomyocyte phenotype, thus paving the way for the development of new strategies aimed at creating physiological in vitro models for a variety of tissue engineering applications.

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