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International Journal of Bioprinting Printed organoids for medicine

as artificial cardiac tissues to mimic cardiac structures for over 6 months in vitro (Figure 3B). By combining
and functions by adjusting their size, shape, and cardiomyocytes, endothelial cells, and conductive bioinks,
configuration. The reconstruction of functional cardiac researchers have achieved synchronized contractions and
organoids requires biomimetic architectures that emulate action potential propagation in bioprinted cardiac patches.
the electromechanical coupling and vascularization These models replicate the helical myocardial fiber
of native heart tissue. Human cardiac organoids are orientation critical for ventricular ejection dynamics.
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created through the self-assembly of differentiating Nevertheless, limitations in scalability and
cardiomyocytes from human pluripotent stem cells.
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Consequently, cardiac organoids serve as promising electrophysiological maturity remain, as current cardiac
models for replicating native cardiac elements, including organoids lack the structural complexity of adult
inflow-outflow territories, cardiac chamber architecture, myocardium. Emerging strategies, such as 4D bioprinting
and heart-related regulation. with shape-memory hydrogels, aim to dynamically align
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cells into anisotropic tissue geometries under physiological
Recent breakthroughs in multi-material bioprinting stimuli. 46,47 Additionally, the integration of organoid-
have allowed for the recreation of complex cardiac derived pacemaker cells could advance arrhythmia
structures, enabling the fabrication of ventricle models modeling and personalized drug testing. This synthesis
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with perfusable vascular networks, a feat unattainable of bioprinting and organoid technologies represents
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with traditional 3D printing methods. Fang et al. have a paradigm shift in cardiovascular research, offering
successfully developed Sequential Printing in a Reversible unprecedented opportunities to model congenital heart
Ink Template technology, enabling the fabrication of defects, ischemic injury, and pharmacogenomic responses
ventricle models with hierarchical vascular networks with physiological fidelity.
by combining sacrificial ink printing with microgel-
enhanced bioinks. This approach allows sequential 2.3. Brain organoids
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deposition of structural bioinks to form cardiac chambers, Conventional self-assembly methods often yield structurally
followed by sacrificial ink removal to create perfusable inconsistent neural spheroids with limited vascularization
channels. The resulting constructs exhibit synchronized and incomplete regional specification. 49,50 Pioneered in
contractions and action potential propagation, mimicking 2009, early cerebral organoids derived from embryonic
the helical fiber orientation critical for ventricular ejection stem cells and iPSCs demonstrated self-organized cortical
dynamics (Figure 3A). Despite structural progress, regions, neural progenitor zones, and rudimentary laminar
achieving electrophysiological maturity comparable to organization. These primitive models laid the groundwork
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adult myocardium remains challenging. Current cardiac for investigating neurodevelopmental trajectories,
organoids often lack the ion channel density and calcium interspecies divergence, and pathological mechanisms.
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handling capacity required for sustained rhythmic activity. The convergence of 3D bioprinting with cerebral organoid
To overcome this obstacle, 4D bioprinting with shape- technology has revolutionized our capacity to replicate
memory hydrogels has been employed to spatiotemporally human neurodevelopment in vitro. Cadena et al. printed
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align cardiomyocytes into anisotropic architectures in a high-throughput, adjustable, and repeatable scaffold for
response to physiological stimuli, enhancing action precisely controlling the development and patterns of brain
potential propagation velocity by 2.3-fold compared to static organoids, achieving real-time monitoring of calcium
cultures. Additionally, the incorporation of organoid- signaling and synaptic plasticity. It was confirmed that the
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derived pacemaker cells into bioprinted patches has fabricated scaffold exhibited stiffness values comparable
enabled arrhythmia modeling, demonstrating abnormal to the developing human brain. The organoids cultured
conduction patterns under β-adrenergic stimulation. long-term within the bioprinted scaffold remain healthy
Intriguingly, Zhang et al. have further advanced and exhibit expected neuroectodermal differentiation.
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vascular integration using six-axis robotic bioprinters, which In addition, the endothelial cells within the printed
enable omnidirectional cell deposition on complex arterial channel structures demonstrated the ability to migrate
scaffolds. By employing a mineral oil-based suspension and infiltrate the embedded brain organoids. Advanced
system, endothelial cells adhere to vascular scaffolds bioprinting strategies enable the spatial orchestration of
without shear stress, forming confluent monolayers that neural progenitor cells within tunable ECMs, achieving
subsequently sprout capillaries under angiogenic factors. unprecedented control over cortical layering and synaptic
This “print-culture” iterative strategy, where alternating connectivity patterns. 54,55 Innovative bioink formulations
layers of cardiomyocytes and endothelial cells are cultured combining decellularized brain ECM with thermo-
to promote vascular network maturation, has yielded responsive hydrogels have demonstrated enhanced
myocardial tissues that maintain rhythmic contractions neurite outgrowth (2.3-fold increase versus Matrigel

Volume 11 Issue 4 (2025) 71 doi: 10.36922/IJB025190184