Implantable Device That Stimulates Muscles Prevents Atrophy in Mice
MAGENTA device was able to apply stretching, contracting forces to muscle tissue
A soft robotic implantable device that can exert mechanical force on muscles was shown to reduce muscle atrophy in a mouse model in a recent study.
Based on the findings, researchers believe the device may be able to be applied in diseases such as amyotrophic lateral sclerosis (ALS) that are marked by muscle wasting.
“While the study provides first proof-of-concept that externally provided stretching and contraction movements can prevent atrophy in an animal model, we think that the device’s core design can be broadly adapted to various disease settings where atrophy is a major issue,” said David Mooney, PhD, a professor at Harvard University and co-author of the study, in a university news release.
The study, “Active tissue adhesive activates mechanosensors and prevents muscle atrophy,” was published in Nature Materials.
Muscles are built to move — the mechanical processes of muscle cells stretching and contracting triggers biomechanical processes that are essential for maintaining muscle health. When a muscle is unmoved for an extended period, it begins to atrophy, or waste away, and this process tends to accelerate the longer it is motionless.
A feature of ALS is the progressive damage and death of motor neurons, the nerve cells that normally secrete chemical signals telling muscles when to contract. Without these signals, the muscles don’t move, ultimately leading to the atrophy that characterizes the disease.
Theoretically, using medical devices to prompt muscle movement — for example, physically stretching and contracting muscle cells using an implanted robot — could help prevent or reverse atrophy.
Prompting muscle movement to prevent wasting
A team of scientists at Harvard set out to create such a device, calling it MAGENTA, short for mechanically active gel–elastomer–nitinol tissue adhesive. It consists of a soft, springy material called shape memory alloy (SMA) that’s attached to a tough, biologically compatible adhesive called a hydrogel. Changing the temperature of the SMA causes it to act as an actuator, exerting mechanical force that’s transferred to the tissue through the attaching adhesive.
“Our SMA-based actuators provide a simple and versatile approach to implementing tissue stretching/contraction with a biocompatible actuation mechanism and scalable design,” the researchers wrote.
The MAGENTA system can be remote controlled using a laser to regulate the temperature of the SMA, though most experiments used direct electrical control of the device, as this tended to yield more consistent results.
“While remote control systems typically involve complex electrical circuits … and require a large physical space to mount the additional equipment, the wireless actuation of MAGENTA is possible without additional electrical components or complex application systems,” the scientists said, noting future studies could aim at improving the wireless setup’s reliability.
The researchers showed through experiments that the MAGENTA device could apply stretching and contracting forces to muscle tissue, as designed. The forces were generated along the length of the muscle and also affected deeper muscle tissue beneath where the device was attached.
Testing on muscle atrophy in mouse model
They also tested the device in experiments with mice. In one experiment, the MAGENTA device was attached to the atrophied calf muscles of some of them to provide mechanical stimulation while their legs were immobilized. In the other, the animal were first immobilized for several weeks, and then treated with MAGENTA. The experiments suggested the device can help slow ongoing atrophy as well as prevent it from developing in the first place.
With MAGENTA, we developed a new integrated multi-component system for the [mechanic stimulation] of muscle that can be directly placed on muscle tissue to trigger key molecular pathways for growth.
The mice treated with the MAGENTA device showed larger muscles capable of generating more force, indicating less atrophy. Biochemical analyses of the muscle tissue indicated less atrophy in MAGENTA-treated mice and suggested increases in pathways that promote muscle growth.
“While untreated muscles and muscles treated with the device, but not stimulated significantly, wasted away during this period, the actively stimulated muscles showed reduced muscle wasting. Our approach could also promote the recovery of muscle mass that already had been lost over a three-week period of immobilization,” said Sungmin Nam, PhD, a research fellow at Harvard and co-author of the study.
These anti-atrophy effects were not seen with a different mechanical stimulation device that was applied over the mice’s skin. “This highlights the effectiveness of MAGENTA despite the required implantation procedure,” the researchers wrote. Other results suggested the implanted device did not induce substantial inflammation.
“The general capabilities of MAGENTA and fact that its assembly can be easily scaled from millimeters to several centimeters could make it interesting as a central piece of future mechanotherapy not only to treat atrophy, but perhaps also to accelerate regeneration in the skin, heart, and other places that might benefit from this form of [mechanic stimulation],” Nam said.
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