Implantable device functions as a flexible robot for the treatment of muscle atrophy
By the editors of HospiMedica International
Posted Nov 23, 2022
Muscles atrophy from lack of exercise, as happens rapidly with a broken limb immobilized in a cast, and more slowly in people who reach old age. Muscle wasting, as clinicians refer to the phenomenon, is also a debilitating symptom in patients with neurological disorders, such as amyotrophic lateral sclerosis (ALS) and multiple sclerosis (MS), and can be a systemic response to various other diseases, including cancer. and diabetes. Mechanotherapy, a form of therapy delivered by manual or mechanical means, is believed to have broad tissue repair potential. The best-known example is massage, which applies compressive stimulation to muscles for relaxation. However, it has been much less clear whether stretching and contracting muscles by external means can also be a treatment. Two major challenges have so far prevented such studies: limited mechanical systems capable of uniformly generating stretching and contracting forces along the entire length of muscles, and inefficient delivery of these mechanical stimuli at the surface and in deeper layers of muscle tissue.
Now, bioengineers from Harvard University’s Wyss Institute (Boston, MA, USA) have developed a mechanically active adhesive named MAGENTA, which functions as a flexible robotic device and solves this dual problem. In an animal model, MAGENTA successfully prevented and supported recovery from muscle atrophy. One of MAGENTA’s main components is a spring made from nitinol, a type of metal known as a “shape memory alloy” (SMA) that allows MAGENTA to act quickly when heated. at a certain temperature. The researchers actuated the spring by electrically connecting it to a microprocessor unit that allows the frequency and duration of the stretch and contraction cycles to be programmed.
Image: MAGENTA prototypes made with spring and “shape memory alloy” elastomer (Photo courtesy of Wyss Institute)
Other components of MAGENTA are an elastomeric matrix that forms the body of the device and insulates the heated SMA, and a “tough adhesive” that allows the device to firmly adhere to muscle tissue. This way, the device is aligned with the natural axis of muscle movement, transmitting the mechanical force generated by SMA deep into the muscle. Researchers are advancing MAGENTA, which stands for “mechanically active gel-elastomer-nitinol tissue adhesive”, as one of several tough gel adhesives with features suitable for various regenerative applications across multiple tissues.
After designing and assembling the MAGENTA device, the team tested its muscle deformation potential, first on isolated muscles ex vivo and then by implanting it on one of the major calf muscles of mice. The device induced no serious signs of inflammation and tissue damage and exhibited approximately 15% mechanical stress on the muscles, consistent with their natural deformation during exercise. Then, to assess its therapeutic efficacy, the researchers used an in vivo model of muscle atrophy by immobilizing the hind limb of a mouse in a tiny plaster-like enclosure for up to two weeks after implanting the MAGENTA device into it.
“While untreated muscles and muscles treated with the device but not stimulated significantly atrophied during this period, actively stimulated muscles showed reduced muscle wasting,” said Sungmin Nam, Ph.D., first author and Wyss Technology Development Fellow. “Our approach could also promote the recovery of already lost muscle mass during a three-week immobilization period and induce the activation of key biochemical mechanotransduction pathways known to trigger protein synthesis and muscle growth.”
“With MAGENTA, we have developed a new integrated, multi-component system for muscle mechanostimulation that can be directly placed on muscle tissue to trigger key molecular pathways for growth,” said David Mooney, Ph.D., author principal and founding faculty member of Wyss. . “Although 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 broadly adapted to various pathological contexts where atrophy is a major problem.”
Wyss Institute at Harvard University