Researchers at Carnegie Mellon University have developed a groundbreaking class of microscopic robots constructed entirely from human lung cells, offering a new approach to targeted drug delivery that could transform precision medicine. These living machines, dubbed AggreBots, represent a fusion of biology and robotics that harnesses the natural propulsion mechanisms of human cells to navigate complex bodily environments.
Revolutionary Biobot Design Using Natural Cell Propulsion
The AggreBots are self-assembled from tracheal cells harvested from human lungs, which naturally form multicellular aggregates propelled by cilia—tiny hair-like structures that enable controlled movement across surfaces or through fluids. Unlike traditional mechanical robots that rely on external power sources like magnetic fields or ultrasound, AggreBots utilize the innate cilia of lung cells for autonomous propulsion.
"We're pushing forward an alternative method of powering biobot tissues with our AggreBots," explained Dhruv Bhattaram, first author of the research published in Science Advances and biomedical engineering Ph.D. student. "Through the process of fusing together different spheroids into different shapes, together with the inclusion of nonfunctional spheroids, we can precisely control the location and abundance of cilia propellers on the tissue's surface to direct CiliaBot behavior for the first time."
Modular Assembly Strategy Enables Precise Movement Control
The Ren Lab at Carnegie Mellon pioneered a novel modular assembly strategy for these cilia-powered biobots, using spatially controlled aggregation of tissue spheroids engineered from lung stem cells. The strategy incorporates stem cell spheroids bearing genetic mutations that render cilia in specific regions nonfunctional and immotile, allowing researchers to dictate movement patterns with unprecedented precision.
Bhattaram likened the process to "taking away the oars at chosen locations on a rowboat while paddling." By manipulating structural design elements such as the number and arrangement of cell clusters, researchers can control how AggreBots move—whether in straight lines, circles, or more complex patterns. This level of control is crucial for navigating the body's intricate environments, including viscous mucus in airways or turbulent bloodstream flow.
Enhanced Biocompatibility and Therapeutic Applications
What distinguishes AggreBots from synthetic nanorobots is their biological origin, which enhances biocompatibility and reduces immune rejection risks. The biobots measure mere fractions of a millimeter, making them ideal for minimally invasive applications. Victoria Webster-Wood, associate professor of mechanical engineering, noted that "because the Aggrebots are made entirely from biological materials, they are naturally biodegradable and biocompatible, which may enable their direct application in medical settings in the future."
Envisioned therapeutic applications include delivering chemotherapy directly to lung cancer sites to minimize systemic side effects, clearing mucus in cystic fibrosis patients, and repairing damaged airways. Notably, CiliaBots can be manufactured from a patient's own cells, enabling personalized therapeutic delivery vehicles without immune rejection concerns.
Clinical Potential and Future Development
The technology could benefit multiple audiences, including the biorobotics community, clinicians, and medical researchers studying ciliary diseases like primary ciliary dyskinesia. Xi (Charlie) Ren, associate professor of biomedical engineering, emphasized the importance of controlled motility: "Cellular delivery of therapeutics has great potential, but without a proper propulsion mechanism, cells can easily get stuck. We've laid down a path that people can use to control CiliaBot motility."
The research team acknowledges that transitioning from laboratory prototypes to clinical applications will require addressing challenges including long-term cell viability, precise targeting mechanisms, and ensuring safety in vivo to prevent unintended tissue interactions. The modular design approach allows bots to be tailored for specific therapies, representing a significant step toward personalized medicine applications.
"From helping us understand the health impact of environmental hazards to facilitating in vivo therapeutic delivery, CiliaBots have a swath of potential uses, and it's exciting to be part of their evolution," Ren concluded.
