A recent study showed that a flexible implantable robotic device that can exert mechanical force on muscles reduced muscle atrophy in a mouse model.
Based on the results, the researchers believe the device could be applied in diseases such as amyotrophic lateral sclerosis (ALS) which are characterized by muscle wasting.
“While the study provides the first proof-of-concept that externally delivered stretching and contraction movements can prevent atrophy in an animal model, we believe that the basic design of the device can be widely extended. suitable for a variety of pathological settings where atrophy is a major problem,” said David Mooney, PhD, professor at Harvard University and co-author of the study, in an academic press release.
The study, “Active tissue adhesive activates mechanosensors and prevents muscle atrophywas published in Natural materials.
Muscles are built to move – the mechanical processes of stretching and contracting muscle cells trigger biomechanical processes essential to maintaining muscle health. When a muscle remains immobile for an extended period, it begins to atrophy or waste away, and this process tends to accelerate the longer it remains immobile.
A hallmark of ALS is the progressive damage and death of motor neurons, the nerve cells that normally secrete chemical signals that tell muscles when to contract. Without these signals, the muscles do not move, which ultimately leads to the atrophy that characterizes the disease.
Theoretically, using medical devices to induce muscle movement — for example, physically stretching and contracting muscle cells using an implanted robot — could help prevent or reverse atrophy.
Stimulation of muscle movements to prevent wasting
A team of Harvard scientists set out to create such a device, calling it MAGENTA, short for Mechanically Active Gel-Elastomeric-Nitinol Tissue Adhesive. It consists of a soft, elastic material called a shape memory alloy (SMA) that is attached to a strong, biologically compatible adhesive called a hydrogel. Changing the temperature of the SMA causes it to act as an actuator, exerting a mechanical force that is transferred to the tissue through the fixation adhesive.
“Our SMA-based actuators offer a simple and versatile approach to implementing tissue stretch/contraction with a biocompatible actuation mechanism and scalable design,” the researchers wrote.
The MAGENTA system can be controlled remotely using a laser to regulate the temperature of the SMA, although most experiments used direct electrical control of the device, as this tended to give more consistent results .
“While remote control systems typically involve complex electrical circuits…and require a large physical space to mount the additional equipment, wireless actuation of MAGENTA is possible without additional electrical components or complex application systems,” said the scientists, noting that future studies may aim to improve the reliability of the wireless setup.
The researchers showed through experiments that the MAGENTA device could apply stretching and contracting forces to muscle tissue, as expected. The forces were generated along the entire length of the muscle and also affected deeper muscle tissue below where the device was attached.
Muscle atrophy test in a 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 was first immobilized for several weeks and then treated with MAGENTA. Experiments have suggested that the device can help slow ongoing atrophy and prevent it from developing in the first place.
With MAGENTA, we have developed a new integrated multi-component system for the [mechanic stimulation] of muscle that can be placed directly on muscle tissue to trigger key molecular pathways for growth.
Mice treated with the MAGENTA device showed larger muscles capable of generating more force, indicating less atrophy. Biochemical analyzes of 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 significantly stimulated, atrophied during this time, actively stimulated muscles showed reduced muscle wasting. Our approach may also promote recovery from muscle mass that had already been lost during a three-week immobilization period,” said Sungmin Nam, PhD, a Harvard researcher and co-author of the study.
These anti-atrophy effects were not observed with a different mechanical stimulation device applied to the skin of mice. “This highlights the effectiveness of MAGENTA despite the required implantation procedure,” the researchers wrote. Other results suggest that the implanted device does not induce substantial inflammation.
“MAGENTA’s general capabilities and the fact that its assembly can be easily scaled from a few millimeters to several centimeters could make it interesting as a centerpiece of future mechanotherapy not only to treat atrophy, but perhaps- also be to accelerate the regeneration of the skin, heart and other places that could benefit from this form of [mechanic stimulation]”Nam said.
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