Researchers at the University of California, San Diego, Sanford Stem Cell Institute have devised an innovative technique to stimulate and mature human brain organoids utilising graphene, a monolayer of carbon atoms. The study, published in Nature Communications, presents Graphene-Mediated Optical Stimulation (GraMOS), a safe, non-genetic, biocompatible, and non-invasive method for modulating brain activity over periods of days to weeks. This method expedites the formation of brain organoids, which is particularly crucial for modelling age-associated disorders such as Alzheimer’s disease, and enables real-time control of robotic equipment.

“This is a game-changer for brain research,” said Alysson Muotri, Ph.D., corresponding author, professor of pediatrics, and director of the UC San Diego Sanford Stem Cell Institute Integrated Space Stem Cell Orbital Research Center. “We can now speed up brain organoid maturation without altering their genetic code, opening doors for disease research, brain–machine interfaces and other systems combining living brain cells with technology.”

An innovative approach to cultivating neural tissue in vitro

Brain organoids—three-dimensional, stem cell-derived representations of the human brain—are crucial for investigating neurological disorders; nevertheless, their protracted maturation process constrains their applicability for problems that evolve over decades. To date, stimulation techniques have either necessitated genetic modification (optogenetics) or the application of direct electrical currents, which may harm delicate neurones.

GraMOS utilises the distinctive optoelectronic capabilities of graphene to transform light into subtle electrical signals that promote neuronal connectivity and communication. This stimulation replicates the environmental input that actual brains experience, promoting development without invasive methods.

“Using graphene and light, we were able to nudge the neurons to form connections and mature more rapidly, without traditional optogenetic tools,” said Elena Molokanova, Ph.D., co-corresponding author and chief executive officer and inventor of GraMOS technology at NeurANO Bioscience. “It’s like giving them a gentle push to grow up faster — essential for studying age-related diseases in a dish.”

Key findings:

• Accelerated development: Consistent use of GraMOS facilitated the formation of robust connections, enhanced network organisation, and improved neuronal transmission in brain organoids, including those derived from Alzheimer’s patients.
• Graphene is safe and biocompatible, exhibiting no detrimental effects on neurones or organoid structure, even over extended durations.
• Improved disease modelling: Early-stage Alzheimer’s organoids demonstrated distinct functional variations in network connectivity and excitability upon stimulation.
• Robotic integration: Graphene-stimulated organoids were connected to a basic robot in a closed feedback loop, allowing it to react to visual stimuli.

From laboratory to Alzheimer’s research and beyond

Stimulation expedites neuronal maturation, enabling researchers to investigate disease progression earlier and within a more physiologically pertinent environment. This may enhance drug testing timeframes and offer new perspectives on how disorders such as Alzheimer’s modify brain circuitry.

“Our technology bridges a critical gap in organoid research,” said Alex Savchenko, Ph.D., co-senior author and chief executive officer of Nanotools Bioscience. “It offers a reliable, repeatable way to activate neurons, which can transform both fundamental neuroscience and translational studies.”

Cerebral interaction with technology

Graphene-interfaced brain organoids exhibit environmental responsiveness and can modify their neural networks in reaction to light. The acquired neuroplasticity provides a significant advantage over computer chips in future artificial intelligence (AI) applications by enhancing the capacity of AI systems to address complex, unanticipated challenges while ensuring increased fault tolerance and dependability in important applications.

The team demonstrated a compelling proof-of-concept by linking graphene-interfaced brain organoids to a sensor-equipped robotic system. Upon detecting an obstruction, the robot transmitted a signal to activate the organoid, which subsequently produced a neural pattern that prompted the robot to alter its trajectory, so completing the loop in less than 50 milliseconds.

This integration suggests the potential for future neuro-biohybrid systems, wherein living neural tissue and robots collaborate for enhanced prosthetics, adaptive interfaces, or novel computational methods.

This research represents a significant advancement in harnessing the capabilities of graphene within neuroscience, nanotechnology, and neuroengineering. This technique may facilitate novel methods for interlinking increasingly intricate brain-like tissues, as well as connecting them to the brain itself. The capacity to regulate and expedite brain organoid growth facilitates their utilisation as robust models for evaluating therapeutics for neurodegenerative and developmental brain illnesses, wherein impaired connections might hinder the brain’s capacity to process and respond to information.

This methodology could extend beyond illness research to tissue engineering, providing a noninvasive and precise means to activate many types of lab-cultivated tissues. By connecting living neural networks to machines, researchers may uncover how the brain’s resilience and learning might improve computers and robots, perhaps leading to future applications in artificial intelligence.

“This is only the beginning,” said Muotri. “The combination of graphene’s versatility and brain organoid biology could redefine what’s possible in neuroscience, from understanding the brain to creating entirely new technological paradigms.”

The study includes additional co-authors: Mariana S.A. Ferraz, Angels Almenar-Queralt, Georgia Chaldaiopoulou, Janaina Sena de Souza, Francesca Puppo, and Pinar Mesci from UC San Diego School of Medicine; Teng Zhou, Michael Reiss, Honieh Hemati, Francisco Downey, and Omowuyi O. Olajide from UC San Diego School of Engineering; Pragna Vasupal from NeurANO Bioscience; Volodymyr P. Cherkas from the Institute of Bioorganic Chemistry at the Polish Academy of Sciences and the Bogomoletz Institute of Physiology; Prashant Narute and Dmitry Kireev from the University of Massachusetts, Amherst; Carolina Thörn Perez from Universidade Federal do ABC; and Samuel L. Pfaff from the Salk Institute for Biological Studies.

The research received partial funding from the National Institutes of Health (A.S.: 1R43MH124563; A.R.M: 1R01MH128365, R01NS123642, 1R01ES033636, MH123828, MH127077, NS105969; EM: 1R43NS122666, 1R43AG076088, 5R44DA050393), the Department of Defence W81XWH2110306 (to A.R.M.), the California Institute of Regenerative Medicine (DISC2-13866 to A.S.), and the long-term support program for Ukrainian research teams at the Polish Academy of Sciences, conducted in collaboration with the U.S. National Academy of Sciences, with financial backing from external partners for V.C.

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