Researchers have developed a bioresorbable acoustic microrobot (BAM) crafted from hydrogel, a remarkable innovation in targeted therapy. Featured in Science Robotics, this microrobot is designed for precise navigation within the human body, offering a new frontier in medical treatments.
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Background
Microrobots could change how we approach precision medicine, offering a way to deliver drugs and perform treatments with pinpoint accuracy. Unlike traditional drug delivery methods, these tiny devices are designed to travel directly to the problem area in the body. This targeted approach reduces side effects and improves treatment outcomes. But despite decades of research, getting them to work reliably in real-world conditions has been a tough nut to crack.
Over the last 20 years, researchers have developed various micro and nanorobots to tackle specific medical challenges. These efforts have shed light on some major hurdles. For instance, steering microrobots through complex fluids like blood or saliva is no small feat—these fluids are thick and constantly moving, making navigation tricky. Then there’s the question of safety: the robots need to be biocompatible so they don’t harm the body, and they also need to break down harmlessly after their job is done. On top of that, ensuring they release drugs only at the right spot remains a persistent challenge.
To tackle these issues, this study introduces BAMs, a new type of microrobot designed to check all the boxes.
These microrobots use focused ultrasound for propulsion, which allows them to move smoothly through biofluids. They also feature a clever use of microbubbles, which not only help with real-time tracking via ultrasound imaging but also ensure precise control and localization. Even better, BAMs release their drugs only at the target site, boosting efficiency while reducing unintended side effects. Made from biocompatible hydrogels, they safely dissolve in the body once their job is done.
Engineering the Hydrogel-Based Microrobots
To build these microrobots, the researchers used a hydrogel called poly(ethylene glycol) diacrylate as the foundation. Hydrogels are fascinating materials that can transition from liquid to solid when their polymer network becomes cross-linked. This unique property enables them to hold large amounts of fluid, making them both biocompatible and well-suited for use in the human body.
The outer layer of the hydrogel was specifically designed to carry therapeutic agents, ensuring the microrobots could deliver drugs directly to the intended site. To achieve this precise structure, the team used a method called TPP lithography, a sophisticated additive manufacturing process. This technique employs infrared laser pulses to cross-link photosensitive polymers, creating intricate, highly detailed structures layer by layer.
Each microrobot was fabricated as a spherical structure about 30 microns in diameter—roughly the width of a human hair.
Crafting these tiny robots was no easy feat. The team had to overcome challenges like preventing the delicate spheres from collapsing during fabrication and incorporating essential biofunctional elements, such as therapeutic drugs and magnetic nanoparticles. The magnetic nanoparticles allowed the microrobots to be steered using external magnetic fields, while the drugs diffused passively once the robots reached their target. This careful design ensured effective drug delivery with minimal side effects.
Advanced Design for Stability and Functionality
Navigating the body’s complex biological environments is no small task, but these microrobots were designed with innovative features to tackle the challenge.
One key advancement was the use of dual-surface chemical modifications to enhance both stability and functionality. The outer layer of the robots was made hydrophilic, helping them avoid clumping together as they moved through biofluids. At the same time, the interior surface was hydrophobic, which allowed them to retain air bubbles essential for propulsion.
This clever asymmetric design was created through a two-step process. First, hydrophobic long-chain carbon molecules were attached to the hydrogel. Then, the outer surface was selectively treated with oxygen plasma etching to remove those molecules, leaving the desired hydrophilic properties on the outside. This approach significantly extended bubble stability in biofluids—from just minutes to several days—a critical improvement for reliable movement and tracking.
The functionality of the microrobots didn’t stop there. They featured a dual-opening design, with one cylindrical opening at the top and another on the side. These openings were key to their propulsion mechanism. When exposed to ultrasound, vibrations from the trapped bubbles created fluid streams that propelled the robots through thick, viscous environments at impressive speeds, outperforming single-opening designs.
In addition to propulsion, the bubbles also served another purpose: acting as contrast agents for ultrasound imaging. This allowed the robots to be tracked in real-time within the body. Testing in mice with bladder tumors demonstrated just how effective these microrobots could be. They delivered drugs more efficiently than traditional methods, leading to better tumor shrinkage and highlighting their potential for precise and targeted treatments.
Conclusion
This research presents hydrogel-based, imaging-guided BAMs as a promising step forward in precision medicine. These microrobots tackle critical challenges head-on, from navigating complex biofluids to delivering drugs with pinpoint accuracy. Designed with dual-surface modifications for stability and propelled by ultrasound, they move efficiently and reliably through the body’s intricate environments.
In preclinical tests with mice, these microrobots delivered drugs more effectively than traditional methods, leading to significant tumor shrinkage. This demonstrates their potential to make targeted therapies safer, more efficient, and less invasive.
BAMs represent a practical solution to longstanding challenges in medicine. While more work is needed to bring them into clinical use, they offer a glimpse of how advanced engineering can improve patient care in meaningful ways.
Journal Reference
Han et al., 2024. Imaging-guided bioresorbable acoustic hydrogel microrobots. Science Robotics, 9(97). DOI:10.1126/scirobotics.adp3593 https://www.science.org/doi/10.1126/scirobotics.adp3593
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