An Adhesive That Can Move Muscles

An Adhesive That Can Mobilize Muscles A programmable mechanically active adhesive enables muscle stretching and contraction, preventing atrophy and making it possible to address this problem. Muscle loss resulting from insufficient exercise develops rapidly in a fractured limb immobilized in plaster, and can also occur more slowly as age advances. The condition clinicians refer to as muscle atrophy is a debilitating symptom in individuals suffering from neurological diseases such as amyotrophic lateral sclerosis (ALS) and multiple sclerosis (MS). Muscle atrophy can be a systemic response developed against various other diseases, including cancer and diabetes. Mechanotherapy, a form of therapy administered manually or mechanically, is thought to have significant potential in tissue repair. The best-known example is massage, which applies compressive stimulation to muscles for relaxation. However, it remains unclear whether externally stretching and contracting muscles could also be a form of treatment. To date, two distinct problems can be identified that have hindered such research. These two problems are the insufficiency of mechanical systems capable of producing tension and contraction forces equally distributed along the length of muscles, and the inefficient transmission of these mechanical stimuli to the surface and deeper layers of muscle tissue. Bioengineers at the Wyss Institute for Biologically Inspired Engineering at Harvard University and the Harvard John A. Paulson School of Engineering and Applied Sciences (SEAS) have developed MAGENTA, a mechanically active adhesive that functions as a soft robotic device and addresses both of these challenges. MAGENTA succeeded in preventing and eliminating muscle atrophy in an animal model under study. The research team's findings were published in Nature Materials. David Mooney (Ph.D.), Wyss Founding Core Faculty Member and senior author of the study, stated: "The study provides the first proof-of-concept that externally provided stretching and contraction movements can prevent atrophy in an animal model, and we believe the device's fundamental design can be broadly adapted to various diseases where atrophy poses a significant problem." Mooney directs the Wyss Institute's Immuno-Materials Platform and is also the Robert P. Pinkas Professor of Bioengineering at SEAS. An Adhesive That Can Mobilize Muscles One of MAGENTA's main components is a spring made of nitinol, a metal type known as a "shape memory alloy" (SMA), which causes MAGENTA to move rapidly when brought to a specific temperature. The researchers operated the spring by electrically connecting it to a microprocessor unit that allowed programming of the frequency and duration of stretch and contraction cycles. MAGENTA's other components are an elastomer matrix that forms the device's body and insulates the heated SMA, and a rigid adhesive that ensures the device adheres firmly to muscle tissue. The device thus aligns with the natural axis of muscle movement and transmits the mechanical force produced by the SMA into the depths of the muscle. Mooney's research group is developing MAGENTA, which stands for "mechanically active gel-elastomer-nitinol tissue adhesive," as one of several rigid gel adhesives with functions adapted for various regenerative applications across multiple tissues. After designing and completing assembly of the MAGENTA device, the research team first tested its muscle deformation potential in isolated muscles outside the organism (ex vivo), then by implanting the device into one of the main calf muscles of mice. The device showed no signs of severe tissue inflammation or damage and produced approximately 15% mechanical strain on the muscles, matching natural deformations during exercise. The researchers then used an in vivo muscle atrophy model by immobilizing a mouse's hind limb in a small plaster-like cast after placing the MAGENTA device on it, for up to two weeks, to evaluate therapeutic efficacy. Sungmin Nam (Ph.D.), Wyss Technology Development Member and first author of the study, stated: "While untreated muscles and muscles treated with the device but not stimulated showed significant shrinkage during this period, actively stimulated muscles showed reduced muscle loss. Our approach can also facilitate the reactivation of major biochemical mechanotransduction pathways known to promote protein synthesis and muscle growth, while enabling recovery of muscle mass previously lost during a three-week immobilization period."

Different Faces of Mechanotherapy

Previously, in collaboration with Conor Walsh's group, formerly an assistant professor at Wyss, Mooney's research group discovered that regulated cyclic compression (as opposed to stretching and contraction) of acutely injured muscles, regulated using a different soft robotic device, reduced inflammation and enabled repair of muscle fibers in acutely injured muscles. In their new study, Mooney's team investigated whether these compressive forces could also protect against muscle atrophy. However, when they directly compared muscle compression via the previous device with muscle stretching and contraction via the MAGENTA device, they found that only the latter had clear therapeutic effects in the mouse atrophy model. Mooney stated: "With their unique effects on muscle tissue, different soft robotic approaches have a high likelihood of opening mechanical-therapeutic pathways in disease and injury." To further expand the use possibilities of MAGENTA, the research team examined whether the SMA spring could also be operated with laser light, investigating whether it would be possible to make the method wireless and enhance therapeutic utility. Indeed, they demonstrated that an implanted MAGENTA device without any electrical cables could function as a light-sensitive actuator and deform muscle tissue when irradiated with laser light through the overlying skin layer. While laser operation did not reach the same frequencies as electrical operation, and particularly because adipose tissue appears to absorb some of the laser light, the researchers believe that the device's demonstrated light sensitivity and performance can be further improved. Nam commented: "MAGENTA's general characteristics and the fact that the device can be easily scaled from millimeters to several centimeters allows it not only to enable treatment of atrophy but potentially also to accelerate regeneration of skin, heart, and other areas that could benefit from this form of mechanotransduction." Donald Ingber (M.D., Ph.D.), Wyss Founding Director, stated: "Growing awareness that mechanotherapies can address critical unmet needs in regenerative medicine in ways that drug-based therapies simply cannot has spurred a new research area that links robotic innovations to the molecular pathways through which human physiology transduces mechanical stimuli. This work by Dave Mooney and his group provides an excellent and forward-looking example of how such mechanotherapy could be clinically used in the future." Ingber is also the Judah Folkman Professor of Vascular Biology at Harvard Medical School and Boston Children's Hospital, and the Hansjörg Wyss Professor of Bioinspired Engineering at SEAS. Other authors in the study include Bo Ri Seo, Alexander Najibi, and Stephanie McNamara from Mooney's group at the Wyss Institute and SEAS. The study was funded by the National Institute of Dental and Craniofacial Research (Award # R01DE013349), the Eunice Kennedy Shriver National Institute of Child Health and Human Development (Award # P2CHD086843), and the Materials Research Science and Engineering Center at Harvard University of the National Science Foundation. Source: https://wyss.harvard.edu/news/wasting-muscles-built-back-better/