麻豆淫院

A brand-new engineering approach to generate "designer" biological robots using human lung cells is underway in Carnegie Mellon University's Ren lab. Referred to as AggreBots, these microscale living robots may one day be able to traverse through the body's complex environments to deliver desired therapeutic or mechanical interventions, once greater control is achieved over their motility patterns. In new research published in Science Advances, the group provides a novel tissue engineering platform capable of achieving customizable motility in AggreBots by actively controlling their structural parameters.

Biobots are microscopic, man-made biological machines capable of autonomous movement and programmability to perform specific tasks or behaviors. Previously, enabling biobots' motility has been centered around using muscle fibers, which allow them to move by contracting and relaxing like real muscles.

A novel, alternative mechanism of actuation can be found by using cilia, the nanoscopic, hair-like, organic propellers that continuously move fluids in the body (like in the lungs) and help some aquatic creatures, like Paramecium or comb jellies, swim. However, a reliable way to control the exact shape and structure of a cilia-powered biobot (CiliaBot, for short), and thereby its motility outcome, has proven difficult to come by.

The Ren lab pioneered a novel modular assembly strategy for CiliaBots, using spatially controlled aggregation of tissue spheroids, which their lab engineers out of lung stem cells. Using the strategy, these aggregated CiliaBots (AggreBots) can incorporate stem cell spheroids bearing a genetic mutation that renders cilia in specific regions nonfunctional and immotile.

Dhruv Bhattaram, first author of the paper and biomedical engineering Ph.D. student, likened the process to taking away the oars at chosen locations on a rowboat while paddling.

"We're pushing forward an alternative method of powering biobot tissues with our AggreBots," explained Bhattaram. "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. This is a seminal step forward that we and others can invest time into for productive outcomes."

"The Aggrebots approach adds a new design dimension to these types of biobots and biohybrid robots," added Victoria Webster-Wood, associate professor of mechanical engineering. "Being able to combine different ciliated and non-ciliated elements modularly will allow future researchers to create biobots with specific engineered mobility patterns. 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."

As the Ren lab continues to build on the platform, they acknowledge the technology could benefit a wide range of audiences, including those in the biorobotics community, clinicians, and medical researchers who study how cilia work in diseases like primary ciliary dyskinesia or in the thick, high-viscosity mucus of cystic fibrosis. Notably, CiliaBots can be made from a patient's own cells, which could be used to generate personalized therapeutic delivery vehicles without running the risk of an immune rejection.

"Motility matters, because the body is a complex environment," elaborated Xi (Charlie) Ren, associate professor of biomedical engineering. "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. 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."