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International Journal of Bioprinting Printed organoids for medicine

which can generate multiple gradients simultaneously and ganglion cell activity. This approach not only validated
with higher precision, further improving the ability to developmental patterns of inner retinal signaling but also
control organoid development. 191–193 revealed critical insights into early-stage neural organoid
modeling of retinal degeneration. The findings underscore
5.2. Sensory accessories for real-time monitoring the technology’s utility in dissecting disease mechanisms
Incorporating sensors into 3D printed accessories through dynamic, cell-type-specific observations. Both
allows non-invasive monitoring of organoid physiology, studies leverage liquid metal’s mechanical adaptability to
including metabolic activity, electrical signals, and overcome the limitations of rigid conventional electrodes,
mechanical strain. 194 yet their designs diverge to address distinct challenges.

5.2.1. Biosensors for metabolite detection Park’s approach emphasizes scalability and dynamic
Printable conductive materials, like carbon nanotubes stability for cardiac electrophysiology, whereas Lee’s work
and graphene oxide, can be integrated into scaffolds to prioritizes submillimeter precision for neural circuit
create electrochemical sensors. For instance, a glucose- interrogation. This complementary framework establishes
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sensitive sensor printed within a pancreatic islet organoid a modular toolkit for organoid electrophysiology, enabling
scaffold continuously monitored insulin secretion in researchers to tailor electrode configurations to specific
response to glucose challenges, providing real-time data for experimental demands. Integration with multimodal
diabetes research. 196,197 Similarly, lactate sensors in printed sensing technologies could further advance applications
brain organoid cultures correlated metabolic activity in organ development studies, disease progression
with neuronal network maturation, offering insights into modeling, and personalized medicine, paving the way
neurodevelopmental disorders. 196,198 These biosensors for unprecedented insights into biological systems at
have the potential to revolutionize the field of organoid the organoid scale. The elucidation of brain function in
research by providing real-time, non-invasive monitoring neural organoids necessitates precise electrophysiological
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of organoid function, which can help to better understand monitoring of neuronal activity. To this end, 3D-printed
the underlying mechanisms of disease and develop more microelectrodes, coated with biocompatible polymers,
effective treatments. have been engineered to penetrate cerebral organoids,
enabling the detection of action potentials and synaptic
5.2.2. Electrophysiological probes for connectivity. A pioneering study by Acha et al.
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neural organoids employed printed multi-electrode arrays (MEAs) to
Traditional organoid research has been constrained by the systematically map electrical signals in cortical organoids.
limitation of surface-level signal acquisition, rendering Their findings revealed spontaneous network oscillations
the spatiotemporal dynamics of internal physiological resembling those observed in fetal brain development,
activities inaccessible, which is a critical drawback, underscoring the utility of these systems in modeling
particularly in cardiac and neural organoid studies. To neurodevelopmental dynamics. 203-205 The research
address this challenge, Park et al. developed a soft introduced shell-like MEA configurations analogous
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bioelectrode platform based on liquid metal 3D printing. to electroencephalography caps, designed to interface
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This system enables customizable geometric parameters with the surface of neural organoids while enabling 3D
(height, diameter) to accommodate diverse organoid spatiotemporal recording. This design not only facilitated
structures while maintaining mechanical compliance non-invasive longitudinal monitoring of neuronal firing
comparable to biological tissues. This compatibility but also demonstrated a statistically significant increase in
prevents mechanical damage to cardiac organoids action potential generation following external stimulation.
during contraction or fluidic movement, enabling stable, Crucially, the biocompatible architecture preserved
long-term monitoring. The electrode array further organoid viability, thereby supporting prolonged in vitro
facilitates simultaneous electrophysiological monitoring studies of neurodevelopmental processes.
of 32 organoids, successfully capturing drug-induced A novel microfabrication technique has further
electrophysiological responses. This scalable capability advanced this field by addressing the mechanical
establishes a robust platform for high-throughput drug constraints of traditional MEAs. By depositing material
screening and disease modeling. layers over a sacrificial template and strategically releasing

Lee et al. extended the potential of liquid metal internal stresses, researchers constructed vertically
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microelectrodes through high-resolution 3D printing. By protruding cantilever microelectrodes. These slender
precisely embedding electrodes into specific inner layers of beams extend over 200 µm from their base, allowing
retinal organoids, the researchers achieved spatiotemporally deep penetration into organoid interiors. This innovation
controlled electrophysiological recordings of retinal enables the recording of local field potentials from deeply

Volume 11 Issue 4 (2025) 85 doi: 10.36922/IJB025190184