Preventing Muscle Atrophy – Harvard Scientists Have Developed an Adhesive That Makes Muscles Move

An adhesive that may stimulate muscle groups to stretch and contract has been developed – and it has the potential to forestall and allow restoration from muscle atrophy.

Muscles can turn into weak and waste away as a result of a scarcity of train, resembling when a limb is immobilized in a forged, or progressively as individuals age. This situation, often called muscle atrophy, may also happen on account of neurological problems like ALS and MS, or as a response to sure ailments together with most cancers and diabetes.

Mechanotherapy, a sort of remedy that makes use of handbook or mechanical strategies, is believed to have the potential to help in tissue restore. Massage, which makes use of compressive stimulation to calm down muscle groups, is probably the most well-known type of mechanotherapy, nonetheless, it isn’t clear whether or not stretching and contracting muscle groups via exterior means may also be efficient as a remedy. There have been two main obstacles to learning this chance: a scarcity of mechanical techniques that may evenly apply stretching and contraction forces to muscle groups alongside their whole size, and the inefficient supply of those mechanical stimuli to the floor and deeper layers of muscle tissue.

This picture exhibits examples of MAGENTA prototypes fabricated with a “shape memory alloy” spring and an elastomer, and the way their sizes evaluate to that of a one-cent coin. Credit: Wyss Institute at Harvard University

Now, bioengineers on 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 a mechanically lively adhesive named MAGENTA, which capabilities as a tender robotic system and solves this two-fold downside. In an animal mannequin, MAGENTA efficiently prevented and supported the restoration from muscle atrophy. The workforce’s findings are printed in Nature Materials.

“With MAGENTA, we developed a new integrated multi-component system for the mechanostimulation of muscle that can be directly placed on muscle tissue to trigger key molecular pathways for growth,” mentioned senior creator and Wyss Founding Core Faculty member David Mooney, Ph.D. “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.” Mooney leads the Wyss Institute’s Immuno-Materials Platform and can also be the Robert P. Pinkas Family Professor of Bioengineering at SEAS.

An adhesive that may make muscle groups transfer

One of MAGENTA’s main elements is an engineered spring comprised of nitinol, a sort of steel often called “form reminiscence alloy” (SMA) that enables MAGENTA’s rapid actuation when heated to a certain temperature. The researchers actuated the spring by electrically wiring it to a microprocessor unit that allows the frequency and duration of the stretching and contraction cycles to be programmed. The other components of MAGENTA are an elastomer matrix that forms the body of the device and insulates the heated SMA, and a “tough adhesive” that enables the device to be firmly adhered to muscle tissue.

In this way, the device is aligned with the natural axis of muscle movement, transmitting the mechanical force generated by SMA deep into the muscle. Mooney’s group is advancing MAGENTA, which stands for “mechanically active gel-elastomer-nitinol tissue adhesive,” as one of several Tough Gel Adhesives with functionalities tailored to various regenerative applications across multiple tissues.

After designing and assembling the MAGENTA device, the team tested its muscle-deforming potential, first in isolated muscles ex vivo and then by implanting it on one of the major calf muscles of mice. The device did not induce any serious signs of tissue inflammation and damage and exhibited a mechanical strain of about 15% on muscles, which matches their natural deformation during exercise.

Next, to evaluate its therapeutic efficacy, the researchers used an in vivo model of muscle atrophy by immobilizing a mouse’s hind limb in a tiny cast-like enclosure for up to two weeks after implanting the MAGENTA device on it. “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,” said first-author and Wyss Technology Development Fellow Sungmin Nam, Ph.D. “Our approach could also promote the recovery of muscle mass that already had been lost over a three-week period of immobilization, and induce the activation of the major biochemical mechanotransduction pathways known to elicit protein synthesis and muscle growth.”

Facets of mechanotherapy

In a previous study, Mooney’s group in collaboration with Wyss Associate Faculty member Conor Walsh’s group found that regulated cyclical compression (as opposed to stretching and contraction) of acutely injured muscles, using a different soft robotic device, reduced inflammation and enabled the repair of muscle fibers in acutely injured muscle. In their new study, Mooney’s team asked whether those compressive forces could also protect from muscle atrophy. However, when they directly compared muscle compression via the previous device to muscle stretching and contraction via the MAGENTA device, only the latter had clear therapeutic effects in the mouse atrophy model.

“There is a good chance that distinct soft robotic approaches with their unique effects on muscle tissue could open up disease or injury-specific mechano-therapeutic avenues,” said Mooney.

To further expand the possibilities of MAGENTA, the team explored whether the SMA spring could also be actuated by laser light, which had not been shown before and would make the approach essentially wireless, broadening its therapeutic usefulness. Indeed, they demonstrated that an implanted MAGENTA device without any electric wires could function as a light-responsive actuator and deform muscle tissue when irradiated with laser light through the overlying skin layer. While laser actuation did not achieve the same frequencies as electrical actuation, and especially fat tissue seemed to absorb some laser light, the researchers think that the demonstrated light sensitivity and performance of the device could be further improved.

“The general capabilities of MAGENTA and the 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 mechanotransduction,” said Nam.

“The growing realization that mechanotherapy can address critical unmet needs in regenerative medicine in ways that drug-based therapies simply cannot, has stimulated a new area of research that connects robotic innovations with human physiology down to the level of the molecular pathways that are transducing different mechanical stimuli,” said Wyss Founding Director Donald Ingber, M.D., Ph.D. “This study by Dave Mooney and his group is a very elegant and forward-looking example of how this type of mechanotherapy could be used clinically 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.

Reference: “Active tissue adhesive activates mechanosensors and prevents muscle atrophy” by Sungmin Nam, Bo Ri Seo, Alexander J. Najibi, Stephanie L. McNamara and David J. Mooney, 10 November 2022, Nature Materials.
DOI: 10.1038/s41563-022-01396-x

 The study was funded by the National Institute of Dental and Craniofacial Research, the Eunice Kennedy Shriver National Institute of Child Health and Human Development, and the National Science Foundation’s Materials Research Science and Engineering Center at Harvard University.