What are microrobots used for?

Magnetic beads with stem cells : Bio-micro robots could repair the knee joint

Once the cartilage is gone, it is said to be gone. Then only certain stem cells can help to rebuild it. Scientists have now succeeded in smuggling "microrobots" loaded with stem cells into the body, where they can guide them precisely to the injured knee joint.

They initially tested this on rabbits. Within two to three weeks, the micro-robots dismantled their bodies, the stem cells multiplied and helped to repair the broken cartilage, writes a team led by Gwangjun Go from the Korea Institute of Medical Microrobotics in the journal "Science Robotics".

There are so-called mesenchymal stem cells that can form cartilage. With their help, researchers and doctors have long tried to heal cartilage injuries. In arthritis, for example, the stem cells can help alleviate the inflammation. In the case of osteoarthritis - i.e. the destruction of the cartilage layer - you can ensure that a joint does not have to be replaced by an artificial joint until later or not at all.

The problem with these treatment approaches is usually to get the cells to the site of the injury - and then hold them there so that they can take effect. Usually, many cells have to be injected at the same time either directly on the spot or even scaffolds with the cells have to be brought there in an open operation.

Swiss cheese in mini format

Go and his team now want to solve this problem - with magnetic beads that they call microrobots. The small spheres measure around 200 to 300 micrometers and are criss-crossed with tons of pores in which they transport the stem cells. A mini-sized Swiss cheese, if you will - and a biodegradable one at that.

Most of the microrobots that have been developed for this purpose so far are not, they can be deposited in the body and cause inflammation. If the method is to reach the clinic at some point, biodegradability is a prerequisite.

To build the robots, the scientists first formed porous balls from the polymer PLGA, which is also used as surgical suture material and which the body can easily break down. But PLGA is not magnetic.

That is why the scientists then coated the spheres with a layer of two components: on the one hand, the iron-carbohydrate compound ferumoxytol, which is already used in contrast media for magnetic resonance imaging or as an active ingredient against iron deficiency. The other component is the biopolymer chitosan, derived from the widely used polysaccharide chitin. Overall, the researchers write, the microrobots thus consist of carbon, oxygen and iron.

First in the pig, then in the rabbit

Then they loaded the small spheres with human mesenchymal stem cells. The cells adhered to the pores of the microrobots, multiplied in this shell for up to 16 days in the laboratory and successfully converted into cartilage cells in a nutrient medium. It was time to start testing.

First, the researchers inserted one hundred microrobots into the knee joint of a dead pig. Using a specially developed magnet system, they guided the beads precisely to a four millimeter small defect in the cartilage and were able to hold them there - even against the force of gravity. Without the magnet system, however, the robots would swim aimlessly around the joint. So in principle it worked as planned.

Then came the core of the experiments. The researchers provided the joint space of living rabbits with a hundred microrobots each, loaded with human stem cells. Because of the narrow joint space in rabbits, they did not inject the beads, but instead performed an open operation.

Then they steered the magnetic spheres with the help of six coils that built up an electromagnetic field around the knee, so to speak by remote control, exactly to the point where the cartilage was injured. When they reached the goal, the researchers attached a small magnet to the rodent's knee. He was supposed to keep the robots at the site of the injury for a week so that the stem cells could do their work.

And that actually made sense: Without the use of magnets, the robots slowly swam away in the experiment - and with them the stem cells. After a while, the researchers found it no longer at the defect site, but in the surrounding tissue. However, if the magnet held them in place, they did exactly what they were designed to do: They slowly dissolved, releasing the stem cells. They could then begin repairing the articular cartilage.

The microrobots decomposed after two to three weeks

After two to three weeks, the scientists observed that some of the cartilage had grown back in those rabbits that were treated with the procedure. Nothing had changed in the untreated animals in the control group. "This means that the micro-robot system has improved cartilage regeneration through the supply of human stem cells, conclude Go and his colleagues.

But what happened to the microrobots in the joint? After two to three weeks, the magnetic framework had detached itself from the spherical base body and was noticeably falling apart. It was known from previous experiments that PLGA, which makes up the body of the microrobot, can attack the cartilage when it decomposes.

However, the scientists found no evidence of this. Likewise, they could not detect any inflammatory reaction. The rabbit's immune system did not react to the decomposing "garbage" in the joint space. The ferumoxytol does not dissolve, it is transported to the liver and then broken down. According to the researchers, the low concentration of the substance used in the tests had no noticeably negative effects.

If the researchers were able to test the microrobots in other animal models for a longer period of time, they could in future also be tested in humans, they write. In addition to the safety of the entire system, it would be crucial to be able to bring enough cells to an injury site.

At this point, the scientists are confident, since in their experiments the stem cells in the pores of the robots multiplied quickly and then attached themselves to the broken cartilage. In the study, the hundred microrobots were able to deliver around 80,000 stem cells within four hours.

That is much less than in most of the work that uses other methods of "stem cell delivery". Without the magnets, however, a large part of them would regularly be "lost" - precisely because the cells virtually swim past the defect that they are actually supposed to repair. As a further advantage, they cite that - should the method one day make it into clinical use - patients could recover quickly after such a minimally invasive procedure.

So far there is no device for spraying the balls

Until then, however, there are still some hurdles to be overcome. For example, there is still no device with which microrobots can be stably and safely injected into people's bodies in large quantities. In the study, the researchers used a normal cannula, which resulted in an irregular delivery of the robot balls. It is also still unclear how exactly the magnet should optimally be designed in humans, since the joints are significantly larger than those of a rabbit.

Therefore, and in order to better evaluate the safety of the new method, further experiments would first have to follow with larger animals whose joints are more similar to those of humans. Such tests are being planned, write Gwangjun Go and colleagues.

In any case, there would be enough grateful customers for an innovation in cartilage regeneration: Every year doctors in Germany implant around 190,000 knee prostheses - most of them because the articular cartilage no longer works.

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