A team of scientists from South Korea and Switzerland conducted collaborative research, published in the journal little, to develop a technology capable of producing more than 100 microrobots per minute that can be disintegrated in the body. The goal is to use the devices as minimally invasive targeted precision therapy.
According to the website Physical, they can be made in different ways. The most common of these is an ultra-fine 3D printing technology called two-photon polymerization, a method that triggers the formation of macromolecules by intercepting two lasers in a synthetic resin.
This technology can produce a structure with nanometric precision. However, there is a downside: producing a microrobot is time-consuming because the voxels (pixels made by 3D printing) must be successively polymerized. In addition, the magnetic nanoparticles contained in the device can block the passage of light during the two-photon polymerization process. In this case, the result may not be uniform when using high concentration magnetic nanoparticles.
To overcome the limitations of the method, the research team of Professor Hongsoo Choi, from the Daegu Gyeongbuk Institute of Science and Technology, has developed a mechanism capable of creating microrobots at a high speed of 100 per minute, running a mixture of magnetic nanoparticles and gelatin methacrylate, which is biodegradable and can be cured by light in the microfluidic chip. This is more than 10,000 times faster than the existing two-photon polymerization method.
Next, the prototype of the microrobot produced with this technology was cultured with turbocharged human nasal stem cells to induce adhesion to the surface of the device. With this process, a stem cell was made that carried microrobots as the magnetic nanoparticles within them responded to an external magnetic field and could be moved to the desired position from a real-time electromagnetic field control system.
The research team conducted an experiment to see if the stem cell carrying the microrobot could reach the target point through a maze-like microchannel, which was confirmed.
In addition, the degradability of the device was tested by incubating the stem cell carrying the microrobot using a degenerative enzyme. After six hours of incubation, the microrobot completely disintegrated, and the magnetic nanoparticles inside were collected by the magnetic field generated by the control system.
Stem cells proliferated at the site where the microrobot disintegrated. Subsequently, they were induced to detach in nerve cells to confirm normal differentiation, which occurred after approximately 21 days.
This experiment confirmed that the delivery of stem cells to a desired location using a microrobot is possible and that the delivered stem cells can serve as a precisely targeted therapeutic agent, exhibiting proliferation and differentiation.
The purpose of this study is to ensure that the stem cells delivered by the robot normally perform their bridging function in a state in which the link between existing nerve cells is disconnected.
To confirm this, hippocampal neurons extracted from mouse embryos emitting electrical signals were used. The corresponding cell was attached to the surface of the microrobot, cultured on a microelectrode, and electrical signals were observed from hippocampal neurons after 28 days. With this, the microrobot has been verified to properly fulfill its role as a cell delivery platform.
“We hope that the technologies developed in this study, such as mass production of microrobots, precise operation by electromagnetic fields, and stem cell delivery and differentiation, will significantly increase the effectiveness of precision-targeted therapy at the future,” Choi said.
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