The microbotic technology for delivering stem cell therapies could also have applications in cardiology, oncology and wound healing.
Illustration of how microrobots are fabricated on a lab-on-a-chip (LoC). (Image courtesy of ETH Zurich)
Researchers in Zurich say they have developed a method to use microrobots delivering stem cell therapies to treat spinal cord injuries.
According to ETH Zurich and the University of Zurich (UZH), modern therapies for spinal cord injuries attempt to influence implanted stem cells using electrical stimulation, promoting the growth of new nerve cells. However, researchers say the approach requires implanted electrodes, while transplanted cells may not always survive or integrate properly into existing tissue.
To address this, the research team say they found a novel approach to treating spinal cord injuries (SCIs). They use controllable microrobots to deliver stem cells directly to the site of an injury. There, they promote nerve cell regeneration. The researchers say that animal experiments showed that the approach significantly improved mobility.
Combining therapeutic stem cells with magnetoelectric nanoparticles, the researchers can guide cells magnetically to the precise site of an injury to stimulate the stem cells and accelerate repair. They created a biohybrid microrobot to achieve this, combining living neural progenitor cells (NPCs) with a technical component in the form of specially engineered nanoparticles. The researchers derived the NPCs from induced pluripotent stem (iPS) cells, which are regular body cells reprogrammed in the laboratory to regain stem cell properties. Nanoparticles feature an inner layer that responds to magnetic fields and an outer layer that converts the response into electrical signals.
Schematic illustration of nerve cell recovery in zebrafish and mice. (Image courtesy of ETH Zurich)
Altogether, the researchers say they fabricate what they label “NPCbots.” They create the NPCbots in specialized labs on a surface totaling just one square centimeter. Each measuring about six micrometers in size, the NPCbots are ready to use after just 30 minutes.
“We place a reservoir in the centre where we trap the cells. Then we inject the nanoparticles and wait for the two components to bind,” said Professor Salvador Pané i Vidal of the Multi-Scale Robotics Lab at ETH Zurich.
Testing the microrobot technology in animals and beyond
The researchers tested the microrobots on zebrafish larvae with SCI. They injected them precisely into the injury site and generated the electromagnetic fields. In just three days, the zebrafish exhibited nearly normal swimming and exploratory behavior.
Following this test, the researchers used the microrobots in mice with completely severed spinal cords. After 28 days, the animals’ nerve cells had reconnected at the injury site. During this period, the researchers say the treated mice demonstrated increasingly normal movement patterns. Gait, stride length, coordination and exploratory behavior all improved significantly, they noted. The significance with the outcomes in mice, the researchers say, is that their spinal cords don’t normally regenerate, unlike zebrafish. All animals also tolerated the treatment well, with no evidence of adverse effects or immune reactions.
The researchers say the electrical stimulation of stem cells made the successes in these studies possible. They only needed to apply external magnetic fields around the injury site when using the microrobots. This eliminated the need for implanted electrodes or cables. Meanwhile, magnetic fields can penetrate tissue easily, while their frequency and field strength can be flexibly adjusted.
Once the progenitor cells have been stimulated and differentiated into nerve cells, the microrobots essentially dissolve within the tissue. The researchers expect the nanoparticles to remain stable and minimally reactive due to their barium titanate coating. Future studies are set to evaluate how the particles degrade or are excreted over the long term.
The researchers say that, despite promising results, they require further research before testing the NPCbots in humans. Potential applications could include biomedical areas, such as cardiology, oncology and wound healing.
