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Excitement Over Tiny Things: Microbots

Let’s start with a thought experiment. Suppose we have a patient with a damaged liver, and we want to repair the damage. How do we achieve that? Probably the simplest answer to the problem would be this: replace the damaged liver cells with healthy liver cells. As with life, things are more complicated than they look, and this happens to be the case here as well. While the basic idea is simple, we need to overcome a few obstacles to achieve our objective. How can we, for example, generate healthy liver cells? We can’t just take cells from the skin and dump them on the liver, so where do we get the healthy liver cells from? With the recent advances in stem cell research, the answer to this question is rather simple: we can make liver cells from stem cells—these stem cells that can be biochemically “programmed” to become liver cells. We can take cells from the patient’s other tissues, skin, for example, and convert the skin cells to stems cells and then convert these stem cells to liver cells under an appropriate condition in a dish. Since we are using the patient’s own cells, the host’s immune cells won’t attack and kill these programmed liver cells. But we face a few problems with that approach as well. Growing these cells in a dish and injecting them onto the patient’s liver is not an option because the cells grown in a dish—in a 2D culture—quickly lose their function and physical attributes. And how do we deliver the cells have generated to our patient? In a recent paper, Li and colleagues (Science Robotics, 27 Jun 2018: Vol. 3, Issue 19) provided us with a rather interesting solution to these problems.
Let’s take the delivery problem first. The researchers created tiny, tiny porous, thorny spheres made from resin, SU-8, using 3D Laser lithography (go here and here for more details about SU-8 and photolithography, respectively). These spheres, called microbots by the researchers, were coated with Nickel (Ni) and Titanium (Ti) (I will explain shortly why), and these microbots are small enough to travel through some major veins and arteries. The reason why the researchers chose spheres instead of cubes is that at a given volume, spheres have more surface area, and thus more cells can be loaded on these microbots. But how can these be delivered to a particular region inside the body since these microbots are not really micro-robots? That’s where Ni coating comes in: these Ni-coated microbots can be guided by a magnetic force (the spherical nature also enhances these microbots’ magnetic response). Ti, on the other hand, ensures that these microbots are biocompatible and aren’t harmful to the host. Furthermore, cells can be grown on these sterilized microbots directly, and cells grown on these 3D structures won’t lose their characteristics.
Let’s now see if these microbots do what they are designed to do. To show that cells remain viable on these devices, the researches grew two different cells types on the microbots and found the cells thriving. To show that the microbots can be controlled by a magnetic force, the scientists injected these devices into zebrafish embryos and guided them to specific locations using a magnet. What is so good about Zebrafish embryos? Because these embryos are transparent, the researchers could follow the movement of the microbots under a microscope. Finally, the researchers showed that once loaded and guided to a particular location, the microbots could spontaneously release the cells they carry. To show this in animals, they delivered fluorescently labeled cancer cells using the microbots in nude mice. They showed that tumor formed at the location they guided the microbots to. Thus, theoretically, at least, it’s possible that we could guide these microbots, carrying manufactured liver cells, to our patient’s liver, and expect the cells to be released onto the liver spontaneously.
However, we are not done: we still face a few problems and questions. For example, it’s one thing to guide these microbots in an embryo, but it’s quite different to guide them through various blood vessels in an animal. Can it be done smoothly? How can we tell where these microbots are going since we obviously aren’t transparent like zebrafish embryos? Can healthy cells be incorporated in an organ like the liver if delivered this way? And last but not least, how do we get rid of the microbots once the delivery is complete? While we may be years away from helping our unfortunate patient by this approach, these microbots do clear away some obstacles, and that is what makes this paper exciting.

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