In this review article, we present the state-of-the-art approaches and recent advancements in the engineering of scaffold-free cardiac microtissues for myocardial repair.
The prevalence of cardiovascular
risk factors is expected
to increase
the occurrence of cardiovascular diseases (CVDs) worldwide. Cardiac
organoids are promising candidates for bridging the gap between in vitro experimentation and translational applications
in drug development and cardiac repair due to their attractive features.
Here we present the fabrication and characterization of isogenic scaffold-free
cardiac organoids derived from human induced pluripotent stem cells
(hiPSCs) formed under a supplement-deprivation regimen that allows
for metabolic synchronization and maturation of hiPSC-derived cardiac
cells. We propose the formation of coculture cardiac organoids that
include hiPSC-derived cardiomyocytes and hiPSC-derived cardiac fibroblasts
(hiPSC-CMs and hiPSC-CFs, respectively). The cardiac organoids were
characterized through extensive morphological assessment, evaluation
of cellular ultrastructures, and analysis of transcriptomic and electrophysiological
profiles. The morphology and transcriptomic profile of the organoids
were improved by coculture of hiPSC-CMs with hiPSC-CFs. Specifically,
upregulation of Ca2+ handling-related genes, such as RYR2
and SERCA, and structure-related genes, such as TNNT2 and MYH6, was
observed. Additionally, the electrophysiological characterization
of the organoids under supplement deprivation shows a trend for reduced
conduction velocity for coculture organoids. These studies help us
gain a better understanding of the role of other isogenic cells such
as hiPSC-CFs in the formation of mature cardiac organoids, along with
the introduction of exogenous chemical cues, such as supplement starvation.
In this paper, we report the development of a wireless,
passive,
biocompatible, and flexible system for stimulation of human induced
pluripotent stem cell derived cardiomyocytes (hiPSC-CMS). Fabricated
on a transparent parylene/PDMS substrate, the proposed stimulator
enables real-time excitation and characterization of hiPSC-CMs cultured
on-board. The device comprises a rectenna operating at 2.35 GHz which
receives radio frequency (RF) energy from an external transmitter
and converts it into DC voltage to deliver monophasic stimulation.
The operation of the stimulator was primarily verified by delivering
monophasic voltage pulses through gold electrodes to hiPSC-CMs cultured
on the Matrigel-coated substrates. Stimulated hiPSC-CMs beat in accordance
with the monophasic pulses when delivered at 0.5, 1, and 2 Hz pulsing
frequency, while no significant cell death was observed. The wireless
stimulator could generate monophasic pulses with an amplitude of 8
V at a distance of 15 mm. These results demonstrated the proposed
wireless stimulator’s efficacy for providing electrical stimulation
to engineered cardiac tissues. The proposed stimulator will have a
wide application in tissue engineering where a fully wireless stimulation
of electroconductive cells is needed. The device also has potential
to be employed as a cardiac stimulator by delivering external stimulation
and regulating the contractions of cardiac tissue.
Biofunctionalization of gold nanoribbons and their integration with stem cell-derived cardiac organoids show promising results for cardiac tissue engineering.
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